168 results on '"Carvalho KC"'
Search Results
2. Comparative study of laser action GaAlInP and high-frequency generator in the treatment of skin wounds in rats: an experimental study.
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Sá HP, Nunes HM, do Santo LAE, de Oliveira GC Jr., da Silva JMN, Carvalho KC, and Alves WS
- Abstract
Copyright of ConScientiae Saúde is the property of Nove de Julho University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2010
3. Study of the strength of healing skin of rats treated with phototherapy in laser.
- Author
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Carvalho KC, Nicolau RA, Maia ALM, Barja PR, de Sá HP, do Santo LAV, and da Rocha GM
- Published
- 2010
4. Genetic profile of Brazilian patients with LAMA2-related dystrophies.
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Camelo CG, Moreno CAM, Artilheiro MDC, Fonseca ATQM, Gurgel Gianetti J, Barbosa AV, Donis KC, Saute JAM, Pessoa A, Van der Linden H Jr, Gonçalves ARA, Kulikowski LD, Kok F, and Zanoteli E
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- Humans, Male, Brazil epidemiology, Female, Child, Child, Preschool, Adolescent, Adult, Genetic Profile, Phenotype, Retrospective Studies, Muscular Dystrophies genetics, Mutation, Young Adult, Genetic Predisposition to Disease, Infant, Genotype, Middle Aged, Laminin genetics, Genetic Association Studies
- Abstract
LAMA2-related dystrophies (LAMA2-RD) constitute a rare neuromuscular disorder with a broad spectrum of phenotypic severity. Our understanding of the genotype-phenotype correlations in this condition remains incomplete, and reliable clinical data for clinical trial readiness is limited. In this retrospective study, we reviewed the genetic data and medical records of 114 LAMA2-RD patients enrolled at seven research centers in Brazil. We identified 58 different pathogenic variants, including 21 novel ones. Six variants were more prevalent and were present in 81.5% of the patients. Notably, the c.1255del, c.2049_2050del, c.3976 C>T, c.5234+1G>A, and c.4739dup variants were found in patients unable to walk and without cortical malformation. In contrast, the c.2461A>C variant was present in patients who could walk unassisted. Among ambulatory patients, missense variants were more prevalent (p < 0.0001). Although no specific hotspot regions existed in the LAMA2, 51% of point mutations were in the LN domain, and 88% of the missense variants were found within this domain. Functional analysis was performed in one intronic variant (c.4960-17C>A) and revealed an out-of-frame transcript, indicating that the variant creates a cryptic splicing site (AG). Our study has shed light on crucial phenotype-genotype correlations and provided valuable insights, particularly regarding the Latin American population., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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5. Nutritional Value of the Larvae of the Black Soldier Fly ( Hermetia illucens ) and the House Fly ( Musca domestica ) as a Food Alternative for Farm Animals-A Systematic Review.
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da-Silva WC, Silva ÉBRD, Silva JARD, Martorano LG, Belo TS, Sousa CEL, Camargo-Júnior RNC, Andrade RL, Santos AGS, Carvalho KC, Lobato ADSM, Rodrigues TCGC, Araújo CV, Lima JS, Neves KAL, Silva LKX, and Lourenço-Júnior JB
- Abstract
Dietary alternatives using insect-based products as an alternative for farm animal nutrition have been the object of study due to the high nutritional value of these feeds and the costs related to both their production and consequently their commercialization. Thus, the use of flies, especially larvae, has a high content of proteins and lipids (fat), as well as minerals and essential nutrients for development and growth, directly impacting the production of these animals, whether meat or milk. Therefore, the objective of this study was to compile data from the literature on the nutritional value of adults and larvae of Black soldier ( Hermetia illucens ) and housefly ( Musca domestica ) as a dietary alternative for animal feed. The Prisma checklist was used. After reviewing the data found in the literature, following the systematic review, it was noted that studies emerge that larvae of black soldier flies and domestic flies of the order Diptera obtain essential sources in the nutrition of ruminants, in addition to obtaining rapid digestibility, thus adhering to reproduction with high nutritional content, due to incident levels of protein, lipids, and minerals in M. domestica and Lucilia sericata , making it a target for inclusion in the diet of farm animals. In addition, it is concluded that both species are studied for their sustainable potential as well as for offering greater economic and nutritional viability when compared to ingredients present in production animal feed.
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- 2024
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6. Diagnostic Yield of NGS Tests for Hereditary Ataxia: a Systematic Review.
- Author
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Tenorio RB, Camargo CHF, Donis KC, Almeida CCB, and Teive HAG
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- Humans, Genetic Testing methods, Ataxia genetics, Ataxia diagnosis, High-Throughput Nucleotide Sequencing methods
- Abstract
Next-generation sequencing (NGS), comprising targeted panels (TP), exome sequencing (ES), and genome sequencing (GS) became robust clinical tools for diagnosing hereditary ataxia (HA). Determining their diagnostic yield (DY) is crucial for optimal clinical decision-making. We conducted a comprehensive systematic literature review on the DY of NGS tests for HA. We searched PubMed and Embase databases for relevant studies between 2016 and 2022 and manually examined reference lists of relevant reviews. Eligible studies described the DY of NGS tests in patients with ataxia as a significant feature. Data from 33 eligible studies showed a median DY of 43% (IQR = 9.5-100%). The median DY for TP and ES was 46% and 41.9%, respectively. Higher DY was associated with specific phenotype selection, such as episodic ataxia at 68.35% and early and late onset of ataxia at 46.4% and 54.4%. Parental consanguinity had a DY of 52.4% (p = 0.009), and the presumed autosomal recessive (AR) inheritance pattern showed 62.5%. There was a difference between the median DY of studies that performed targeted sequencing (tandem repeat expansion, TRE) screening and those that did not (p = 0.047). A weak inverse correlation was found between DY and the extent of previous genetic investigation (rho = - 0.323; p = 0.065). The most common genes were CACNA1A and SACS. DY was higher for presumed AR inheritance pattern, positive family history, and parental consanguinity. ES appears more advantageous due to the inclusion of rare genes that might be excluded in TP., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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7. Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy.
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Yang Q, Madueke-Laveaux OS, Cun H, Wlodarczyk M, Garcia N, Carvalho KC, and Al-Hendy A
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- Humans, Female, Prognosis, Molecular Targeted Therapy, Biomarkers, Tumor metabolism, Leiomyosarcoma diagnosis, Leiomyosarcoma pathology, Leiomyosarcoma therapy, Leiomyosarcoma drug therapy, Leiomyosarcoma genetics, Uterine Neoplasms diagnosis, Uterine Neoplasms drug therapy, Uterine Neoplasms pathology, Uterine Neoplasms genetics, Uterine Neoplasms therapy
- Abstract
Uterine leiomyosarcoma (uLMS) is the most common subtype of uterine sarcomas. They have a poor prognosis with high rates of recurrence and metastasis. The five-year survival for uLMS patients is between 25 and 76%, with survival rates approaching 10-15% for patients with metastatic disease at the initial diagnosis. Accumulating evidence suggests that several biological pathways are involved in uLMS pathogenesis. Notably, drugs that block abnormal functions of these pathways remarkably improve survival in uLMS patients. However, due to chemotherapy resistance, there remains a need for novel drugs that can target these pathways effectively. In this review article, we provide an overview of the recent progress in ascertaining the biological functions and regulatory mechanisms in uLMS from the perspective of aberrant biological pathways, including DNA repair, immune checkpoint blockade, protein kinase and intracellular signaling pathways, and the hedgehog pathway. We review the emerging role of epigenetics and epitranscriptome in the pathogenesis of uLMS. In addition, we discuss serum markers, artificial intelligence (AI) combined with machine learning, shear wave elastography, current management and medical treatment options, and ongoing clinical trials for patients with uLMS. Comprehensive, integrated, and deeper insights into the pathobiology and underlying molecular mechanisms of uLMS will help develop novel strategies to treat patients with this aggressive tumor.
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- 2024
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8. Thermal Comfort of Nelore Cattle ( Bos indicus ) Managed in Silvopastoral and Traditional Systems Associated with Rumination in a Humid Tropical Environment in the Eastern Amazon, Brazil.
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da Silva WC, da Silva JAR, Martorano LG, da Silva ÉBR, de Carvalho KC, Sousa CEL, Neves KAL, Júnior RNCC, Belo TS, de Santos AGS, Araújo CV, Joaquim LA, Rodrigues TCGC, and Lourenço-Júnior JB
- Abstract
The objective of this study was to evaluate the thermal comfort of Nelore cattle ( Bos indicus ) managed in silvopastoral and traditional systems associated with rumination behavior in a humid tropical environment in the Eastern Amazon, Brazil. The study was carried out on a rural property in Mojuí dos Campos, Pará, Brazil, during the transition period of the year, from June to July 2023. Over these two months, six consecutive data collection days were held. We selected 20 clinically healthy non-castrated male Nelore cattle, aged between 18 and 20 months, with an average weight of 250 kg and body condition score of 3.5 (1-5). These animals were randomly divided into two groups: traditional system (TS) and silvopastoral system (SS). The physiological variables evaluated included RR, RT and BST. The variables were analyzed using the linear mixed model. For agrometeorological variables, higher values were observed between 10:00 a.m. (33 °C) and 6:00 p.m. (30 °C), with the highest temperature observed at 4:00 p.m. (40 °C). The RR showed interactions ( p = 0.0214) between systems and times; in general, higher RR were obtained in the Traditional. The animals' RT showed no significant difference ( p < 0.05) between the production systems, but there was a statistically significant difference in relation to the time of collection ( p < 0.0001). In the BGHI, it was possible to observe that there was mild stress in the period from 22:00 at night to 6:00 in the morning and moderate stress in the period of greatest increase in temperature, from 10:00 in the morning to 18:00 at night. BST showed no statistical difference between the regions studied or between the SP (35.6 °C) and TS (36.25 °C) systems. RT in the TS showed a positive correlation with AT (r = 0.31507; p = 0.0477). RT in the SP showed a positive correlation with THI (r = 35583; p = 0.0242). On the other hand, RT in the SP (r = 0.42873; p = 0.0058) and ST (r = 0.51015; p = 0.0008) showed a positive correlation with BGHI. RR in the TS showed a positive correlation with BGHI (r = 0.44908; p = 0.0037). The greatest amounts of rumination were carried out by animals in the SP system, generally ruminating lying down ( p < 0.05). With regard to rumination behavior in the morning and afternoon, there were higher numbers of WS and LD in the TS ( p > 0.05). Most of the time, the cattle were LD during the morning and afternoon shifts, and at night and dawn they were WS in the TS. Therefore, the SP offers more thermal comfort advantages compared to the TS system.
- Published
- 2024
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9. FOXO3a deregulation in uterine smooth muscle tumors.
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de Almeida TG, Ricci AR, Dos Anjos LG, Soares Junior JM, Maciel GAR, Baracat EC, and Carvalho KC
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- Humans, Female, Middle Aged, Adult, Immunohistochemistry, Gene Expression Regulation, Neoplastic genetics, Leiomyosarcoma genetics, Leiomyosarcoma pathology, Leiomyosarcoma metabolism, Smooth Muscle Tumor genetics, Smooth Muscle Tumor pathology, Smooth Muscle Tumor metabolism, Up-Regulation, MicroRNAs genetics, MicroRNAs metabolism, Prognosis, Aged, Myometrium metabolism, Myometrium pathology, Forkhead Box Protein O3 metabolism, Forkhead Box Protein O3 genetics, Uterine Neoplasms genetics, Uterine Neoplasms pathology, Uterine Neoplasms metabolism, Leiomyoma genetics, Leiomyoma pathology, Leiomyoma metabolism
- Abstract
Objective: The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis., Methods: The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes., Results: This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated., Conclusions: In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest and funding disclosures., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)
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- 2024
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10. Treatment with Raloxifene Induces the Expression of Kisspeptin, Insulin, and Androgen Receptors in Bones of Castrated Adult Female Rats.
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Condi FLF, Fuchs LFP, Carvalho KC, and Baracat EC
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Objective To evaluate the effects of estrogen, raloxifene and genistein on the expression of KISS1 (kisspeptin), KISS1R (kisspeptin receptor), AR (androgen receptor) and INSR (insulin receptor) in the bones of ovariectomized rats. Methods Forty-eight adult rats were randomly divided into 6 groups, containing 8 animals each: G1-nonovariectomized control; G2-ovariectomized and treated with conjugated equine estrogens (50 µg/Kg/day); G3-ovariectomized and treated with raloxifene (0.75 mg/kg/day); G4-ovariectomized animal that received soy extract with genistein (300 mg/kg/day); G5-ovariectomized animal that received estrogen and genistein; and G6-ovariectomized animal that received estrogen and raloxifene. Three months after surgery, the castrated animals received the drugs orally daily for 120 days. All animals were sacrificed after this period, by deepening the anesthesia. The left tibia was removed for total RNA extraction and analysis of gene expression of KISS1 , KISS1R , AR and INSR , by quantitative real-time polymerase chain reaction (qRT-PCR). Results KISS1 was not detected in any of the treated groups. KISS1R , INSR and AR showed higher expression in the G3 group ( p < 0.001), while lower levels of transcripts for these genes were observed in G4 and G5. G2 animals showed hypoexpression of the evaluated genes. Conclusion The results indicate that raloxifene, alone or combined with estrogen, was able to induce the expression of genes associated with the recovery of bone tissue homeostasis in ovariectomized rats., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)
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- 2024
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11. An adult with cystathionine beta-synthase deficiency, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, and deafness: A case report.
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Donis KC, Kalil MAB, Poswar F, Kok F, Kohem CL, Poloni S, Borsatto T, Vairo FPE, Pinheiro FC, and Schwartz IVD
- Abstract
Massive sequencing platforms allow the identification of complex clinical phenotypes involving more than one autosomal recessive disorder. In this study, we report on an adult patient, born to a related couple (third degree cousins), referred for genetic evaluation due to ectopia lentis, deafness and previous diagnosis of juvenile idiopathic arthritis. He was biochemically diagnosed as having Classic Homocystinuria (HCU); Sanger sequencing of the CBS gene showed the genotype NM_000071.2(CBS):c.[833T>C];[833T>C], compatible with the diagnosis of pyridoxine-responsive HCU. As he also had symptoms not usually associated with HCU, exome sequencing was performed. In addition to the variants found in the Sanger sequencing, the following variants were identified: NM_001256317.1(TMPRSS3):c.[413C>A];[413C>A]; and the NM_005807.6(PRG4):c.[3756dup]:[3756dup], confirming the diagnosis of autosomal recessive nonsyndromic deafness and Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome (CACP), respectively. Genomic analysis allowed the refinement of the diagnosis of a complex case and improvement of the patient's treatment.
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- 2024
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12. Empowerment of genetic information by women at-risk of being carriers of Duchenne and Becker muscular dystrophies.
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Hoefel AML, Weschenfelder CA, Rosa BF, Donis KC, and Saute JAM
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The emergence of therapies acting on specific molecular targets for Duchenne and Becker muscular dystrophies (DBMD) led to expanded access of diagnostic DMD analysis. However, it is unclear how much of these advances have also improved healthcare and access to genetic testing for women at-risk of being carriers. This study evaluates the process of genetic counseling and empowerment of genetic information by women from DBMD families. We carried out a cross-sectional study between February and June 2022 in Brazil. The online survey with items regarding sociodemographic data; family history; access to health services; reproductive decisions; and the Genomic Outcome Scale was answered by 123 women recruited from a rare diseases reference service and a nationwide patient advocacy group. Genetic counseling was reported by 77/123 (62.6%) of women and 53.7% reported having performed genetic analysis of DMD. Although the majority knew about the risks for carriers of developing heart disease and muscle weakness, only 35% of potential carriers have had cardiac studies performed at least once in their lives. Country region, type of kinship, number of affected males in the family, age, notion of genetic risk, education level, and participation in advocacy groups were the main factors associated with adequate healthcare access to women and empowerment of genetic information. Education to health professionals and policies to expand access to carrier genetic testing, whether public policies or regulation of pharmaceutical companies' diagnostic programs, is paramount to improve the care of families with DBMD in Brazil., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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13. Co-Occurrence of Myotonic Dystrophy Type 1 and Limb-Girdle Muscular Dystrophy Type 2B: A Case Report.
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Hauschild LA, Seixas Maia da Silva T, Winckler PB, Moreira Cardoso-Júnior L, Saute JAM, and Donis KC
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Introduction: Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disease whose pattern of weakness is predominantly distal. Limb-girdle muscular dystrophy type 2B/R2-dysferlin-related (LGMD2B/R2) is another neuromuscular disease, which presents an autosomal recessive inheritance and is marked by proximal muscle weakness. Even if uncommon, comorbid inherited pathologies must be considered in cases of atypical presentations, especially in those with family history of consanguinity., Case Presentation: Herein, we report the unique case of a patient diagnosed with both DM1 and LGMD2B/R2: a 38-year-old woman in follow-up of DM1 in a neuromuscular disease service presenting prominent proximal weakness. The patient's parents were consanguineous, and creatine kinase levels were elevated. A multi-gene panel test was performed and revealed the diagnosis of LGMD2B/R2., Conclusion: Genetic diseases with atypical presentations should raise the possibility of a second disorder, prompting an appropriate investigation. Overlooking a second diagnosis can implicate in not offering adequate genetic counseling, support, or specific treatment., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)
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- 2024
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14. Impact of the Pandemic Time on the Mental Health of People with Dementia and Their Family Caregivers in Brazil and Chile: One-Year Follow-Up.
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Olavarría L, Caramelli P, Lema J, Andrade CB, Pinto A, Azevedo LVDS, Thumala D, Vieira MCS, Rossetti AP, Generoso AB, Carmona KC, Sepúlveda-Loyola W, Pinto LAC, Barbosa MT, and Slachevsky A
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- Humans, Caregivers psychology, Pandemics, Mental Health, Follow-Up Studies, Chile epidemiology, Brazil epidemiology, Dementia epidemiology, Dementia psychology, COVID-19 epidemiology
- Abstract
Background: Previous studies reported the negative impact of social isolation on mental health in people with dementia (PwD) and their caregivers, butlongitudinal studies seem scarcer., Objective: To describe a one-year follow-up impact of the COVID-19 pandemic on PwD and their caregivers in both Brazil and Chile., Methods: This study analyzed the impact of the pandemic on the psychological and physical health of PwD and their family caregivers after one year of follow-up in three outpatient clinics in Brazil (n = 68) and Chile (n = 61)., Results: In both countries, PwD reduced their functional capacity after one year of follow-up (p = 0.017 and p = 0.009; respectively) and caregivers reported worse physical and mental health (p = 0.028 and p = 0.039). Only in Chile, caregivers reported more sadness associated with care (p = 0.001), and reduced time sleeping (p = 0.07)., Conclusions: In conclusion, the COVID-19 pandemic appears to have had a long-lasting impact on PwD and their caregivers. However, it is essential to acknowledge that the inherent progression of dementia itself may also influence changes observed over a year.
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- 2024
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15. Adapting lean management to prevent healthcare-associated infections: a low-cost strategy involving Kamishibai cards to sustain bundles' compliance.
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Saavedra Bravo MA, Santos GCSD, Petenate AJ, Westphal PJ, Souza LGA, Marques RG, Morosov EDM, Gushken AKF, Franco FF, Silva WG, de Moura RM, de Lima AL, Dos Santos RG, Andrade KC, Hamada APS, Cristalda CMR, Ue LY, de Barros CG, and Vernal S
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- Child, Infant, Newborn, Adult, Humans, Infection Control methods, Intensive Care Units, Intensive Care Units, Neonatal, Guideline Adherence, Delivery of Health Care, Cross Infection prevention & control, Catheter-Related Infections prevention & control
- Abstract
Lean healthcare visual management has been successfully integrated into infection control programs, leading to lower healthcare-associated infection (HAI) rates and greater provider compliance with evidence-based prevention practices; however, its implementation during quality improvement (QI) initiatives in limited-resource settings has not yet been well exploited. We aimed to describe a low-cost strategy involving Kamishibai cards to sustain bundles' adherence to prevent HAIs in a middle-income country. This descriptive case study evaluated the implementation of a lean healthcare visual management tool-Kamishibai board (K-board)-during a nationwide QI collaborative preventing three critical HAIs in 189 adult and pediatric/neonatal intensive care units (ICUs) from September 2021 to January 2023. Considering a limited-resource setting, our team adapted a K-board using simple, cheap, and easy-to-handle materials for routine monitoring of QI procedures, including safety bundles' compliance. After test prototypes, the final K-board version was implemented. The chart materials and assembly cost BRL 80.00 (USD 15.48). Before launching, expert working group meetings were held to shape the contents, refine technical issues, and prepare the ICU teams for implementation. After starting, plan-do-study-act cycles were conducted according to the Breakthrough Series model. Participating ICU teams, including leaders and front-line health workers, performed bedside audits following a weekly chronogram. Two indicators were calculated: the percentage of ICUs in which K-boards were being implemented and whether bundles' compliance was addressed in the K-board. Audit data were recorded in 'SimpleQI'. After 17 months of this initiative, 177 (93.7%) participating ICUs had included this visual management tool in their daily care routines. When more than 94 (>50%) ICUs posted K-board data, the mean compliance for the bundles for each HAI was sustained above 85%. A lean healthcare visual management tool can be adapted to local settings, including healthcare facilities with limited resources. K-board seems to be a feasible method for auditing evidence-based practices in medical care, including safety bundles to simultaneously prevent three types of HAIs., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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16. Neonatal screening for spinal muscular atrophy: A pilot study in Brazil.
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Oliveira Netto AB, Brusius-Facchin AC, Lemos JF, Pasetto FB, Brasil CS, Trapp FB, Saute JAM, Donis KC, Becker MM, Wiest P, Coutinho VLS, Castro S, Ferreira J, Silveira C, Bittar MFR, Wang C, Lana JM, França Junior MC, and Giugliani R
- Abstract
Spinal muscular atrophy (SMA) is considered one of the most common autosomal recessive disorders, with an estimated incidence of 1 in 10,000 live births. Testing for SMA has been recommended for inclusion in neonatal screening (NBS) panels since there are several therapies available and there is evidence of greater efficacy when introduced in the pre/early symptomatic phases. In Brazil, the National Neonatal Screening Program tests for six diseases, with a new law issued in 2021 stating that it should incorporate more diseases, including SMA. In the present study, dried blood spot (DBS) samples collected by the Reference Services of Neonatal Screening of RS and SP, to perform the conventional test were also screened for SMA, using real-time PCR, with SALSA MC002 technique. A total of 40,000 samples were analyzed, enabling the identification of four positive cases of SMA, that were confirmed by MLPA. Considering our sampling, Brazil seems to have an incidence comparable to the described in other regions. This work demonstrated that the use of the MC002 technique in samples routinely collected for the conventional NBS program is suitable to screen for SMA in our conditions and can be included in the expansion of the neonatal screening programs.
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- 2023
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17. Blood biochemical, hormonal, and hematological responses of native sheep submitted to different environmental conditions.
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Rodrigues RCM, Furtado DA, Ribeiro NL, de Sousa Silva R, da Costa Silva JAP, da Silva MR, Mascarenhas NMH, Cavalcanti CR, Ayres GDJ, Dornelas KC, Lima PR, and de Figueiredo CFV
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- Sheep, Animals, Cholesterol, Glucose, Urea, Hydrocortisone, Magnesium
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The aim of this study was to evaluate the biochemical, hormonal, and hematological blood responses of native sheep subjected to five temperatures (20°, 24°, 28°, 32°, and 36 °C), using 24 sheep of the following breeds: Santa Inês (SI), Morada Nova (MN), Soinga (SO) and no defined racial pattern (NDRP), kept in collective pens inside the climatic chamber. The experimental design was completely randomized, in a 5 × 4 factorial scheme (5 temperatures and 4 breeds) with 6 animals of each breed at each temperature. There was interaction for urea (P < .0001), glucose (P < .0001), cholesterol (P < .0001), and magnesium (P < .0001) as a function of breed and air temperature. Urea (P = .001), glucose (P < .0001), triglycerides (P = .033), cholesterol (P = .004), and magnesium (P < .0001) showed differences according to breed. It was observed that T4 (P < .0001) and cortisol (P < .0001) showed an interaction between breed and temperature, while T4 (P = .001) and cortisol (P = .001) an effect of breed. The highest magnesium concentration was observed in MN, and the lowest was in NDRP, SO, and SI, which are statistically similar, and SI and NDRP are statistically similar. The hormones showed a significant effect (P < .0001) for temperature, where cortisol increased, and thyroid hormones decreased with increasing temperature. Temperatures of 32° and 36 °C contribute to changes in blood, hormone, and hematological biochemical responses of native sheep., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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18. [Proinsulin: physiology, measurement, and interest in clinical biology].
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Alves KC, Bonnet-Serrano F, Laguillier C, Akiki V, Dehghani L, Larger É, Leguy MC, and Guibourdenche J
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The proinsulin molecule results from the cleavage of pre-pro-insulin, produced in pancreatic beta cells. Its subsequent -cleavage allows the release of insulin, the key hormone of glycemia regulation and C-peptide in equimolar proportions. During fasting trial, insulinoma diagnosis relies on inadequately high insulin and C-peptide serum levels concomitant with an hypoglycemia. In this context, proinsulin assay can be interesting in the cases of discrepancy between the two parameters. In diabetes, endoplasmic reticulum stress and beta cells inflammation, lead to the secretion of misfolded proinsulin molecules. Thus, in type 2 diabetes, proinsulin/insulin ratio increases with the degree of insulin resistance. In type 1 diabetes, proinsulin/C-peptide ratio could predict the onset of diabetes in relatives. In our practice, serum pro-insulin determined using an Elisa immunoassay (Millipore®) during fasting trial can be complementary to C-peptide and insulin assays in relation to glycemia to label an hypoglycemia. In case of glucose intolerance and diabetes, proinsulin could thus be measured.
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- 2023
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19. Photochemoprevention of topical formulation containing purified fraction of Inga edulis leaves extract.
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Costa KC, Cuelho CHF, Figueiredo SA, Vilela FMP, and Fonseca MJV
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- Animals, Epidermis, Ultraviolet Rays, Plant Extracts pharmacology, Plant Extracts chemistry, Plant Leaves, Antioxidants pharmacology, Skin radiation effects
- Abstract
Natural antioxidants have attracted attention for their therapeutic use as photochemopreventive agents. Inga edulis leaves extract and its purified fraction have high polyphenolic content and high antioxidant capacity. In addition, they presented UV photostability and low citotoxicity in fibroblast cells. In this context, this study first aimed at development of topical formulation containing purified fraction of I. edulis extract and the evaluation of skin penetration of the compounds. Moreover, the photoprotective/photochemopreventive potential of the formulation containing I. edulis purified fraction were investigated in vitro and in vivo. The topical formulation containing 1% of the purified fraction of I. edulis increased the endogenous antioxidant potential of the skin, and vicenin-2 and myricetin compounds were able to penetrate the epidermis and dermis. Additionally, the purified fraction (25 and 50 mg/mL) showed a photoprotective effect against UVA and UVB radiation in L929 fibroblast cells. In vivo studies have shown that the formulation added with purified fraction provided an anti-inflammatory effect on the skin of animals after UVB exposure, since it was observed a reduction in MPO activity, IL-1β and TNF-α cytokines, and CXCL1/KC chemokine concentrations. In conclusion, the purified fraction of I. edulis, rich in phenolic compounds, when incorporated in topical formulation, appears as an alternative to prevent skin damages induced by UV radiation, due to its antioxidant and anti-inflammatory properties., (© 2023. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)
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- 2023
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20. Cardiovascular autonomic dysfunction in "Long COVID": pathophysiology, heart rate variability, and inflammatory markers.
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Marques KC, Quaresma JAS, and Falcão LFM
- Abstract
Long COVID is characterized by persistent signs and symptoms that continue or develop for more than 4 weeks after acute COVID-19 infection. Patients with Long COVID experience a cardiovascular autonomic imbalance known as dysautonomia. However, the underlying autonomic pathophysiological mechanisms behind this remain unclear. Current hypotheses include neurotropism, cytokine storms, and inflammatory persistence. Certain immunological factors indicate autoimmune dysfunction, which can be used to identify patients at a higher risk of Long COVID. Heart rate variability can indicate autonomic imbalances in individuals suffering from Long COVID, and measurement is a non-invasive and low-cost method for assessing cardiovascular autonomic modulation. Additionally, biochemical inflammatory markers are used for diagnosing and monitoring Long COVID. These inflammatory markers can be used to improve the understanding of the mechanisms driving the inflammatory response and its effects on the sympathetic and parasympathetic pathways of the autonomic nervous system. Autonomic imbalances in patients with Long COVID may result in lower heart rate variability, impaired vagal activity, and substantial sympathovagal imbalance. New research on this subject must be encouraged to enhance the understanding of the long-term risks that cardiovascular autonomic imbalances can cause in individuals with Long COVID., Competing Interests: JASQ is a member of the editorial board of Frontiers in Cardiovascular Medicine. This had no impact on the peer review process and the final decision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Marques, Quaresma and Falcão.)
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- 2023
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21. Characterization of Thermal Patterns Using Infrared Thermography and Thermolytic Responses of Cattle Reared in Three Different Systems during the Transition Period in the Eastern Amazon, Brazil.
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Silva WCD, Silva JARD, Silva ÉBRD, Barbosa AVC, Sousa CEL, Carvalho KC, Santos MRPD, Neves KAL, Martorano LG, Camargo Júnior RNC, and Lourenço-Júnior JB
- Abstract
In the Lower Amazon mesoregion, there are basically three types of production systems: the traditional (without shade and no bathing area), the silvopastoral (with shade and no bathing area), and the integrated (with shade and bathing area). It is considered that the type of production system influences the thermal comfort and productivity of cattle, so this research aims to evaluate the influence of these three types of production systems on the thermoregulation of Nellore cattle. The experiment was carried out on a rural property for raising cattle, located in Mojuí dos Campos, Pará, Brazil, during the transition period (June/July). Thirty bovine males (not castrated, aged between 18 and 20 months, average weight of 250 ± 36 kg, body condition score of 3.5, clinically healthy) were randomly divided into three groups: Silvopastoral System-SS ( n = 10), Traditional System-TS ( n = 10), and Integrated System-IS ( n = 10). Climate variables were collected (air temperature (AT °C), relative humidity (RH %), wind speed (WS, m/s), solar radiation (SR), black globe temperature (BGT °C), and physiological parameters, such as respiratory rate (RR) and rectal temperature (RT)) at 6 a.m., 12 p.m., 6 p.m., and 12 a.m. to determine the thermal comfort situation of the animals. Thermographic images of the environment and animals were captured in order to obtain the body surface temperature (BST) through infrared thermography. The Benezra Thermal Comfort Index (BTCI), Environmental Stress Index (ESI), Equivalent Temperature Index (ETI), and Iberian Heat Tolerance Index (Iberian HTI) were used. The results showed that the silvopastoral system, with shading by chestnut trees and an ample vegetative area, presented better thermal conditions, with an average of 28.98 °C, in comparison with the traditional system (35.93 °C) and the integrated one (34.11 °C). It was observed that the body surface temperature of cattle did not differ significantly between the anatomical regions of the body and the studied systems ( p > 0.05). As for the respiratory rate, the traditional system registered higher values, with an average of 41 movements per minute, indicating possible thermal stress ( p < 0.05). The thermal comfort indices revealed that all systems presented moderate stress conditions during times of higher solar intensity. It is concluded that the silvopastoral system proved to be more favorable for cattle, providing shade and reducing thermal stress, which may have a positive impact on animal welfare and productivity in this region.
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- 2023
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22. Thermal stress index for native sheep.
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Mascarenhas NMH, Furtado DA, Fonsêca VFC, de Souza BB, de Oliveira AG, Leal Morais FT, Silva RS, Silva MRD, Batista LF, Dornelas KC, Bezerra CVC, and Costa Silva JAPD
- Subjects
- Sheep, Animals, Heat-Shock Response, Hot Temperature, Body Temperature, Heat Stress Disorders veterinary
- Abstract
The first objective of this study was to develop a thermal stress index for sheep based on environmental and animal data collected in a climate chamber under various environmental conditions. The second objective was to compare published indices of thermal comfort and the proposed index, testing them with the data from this study, with the objective of pointing out the most adequate index to be used by breeders when choosing management procedures. A total of 3024 data were obtained for the physiological variables of the sheep exposed to the eight thermal conditions in the climatic chamber and in ambient condition, kept three days in each thermal condition. A principal component analysis summarized the measurements of physiological variables into only one variable (y1). Using SigmaPlot software, multiple regression of y1 with the environmental variables and their combinations produced a number of indices. The equation chosen was the heat stress index for sheep, TSI = 24.153 - (0.0523*A
T ) + (0.746*BGT ) + (4.104*Vp), with R2 = 0.668. The correlations presented high values, where these correlation values were assumed to indicate the efficiency of each index as indicators of the animals' response to the environment. Thus, it was assumed that the TSI presents a high efficiency., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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23. Granulosa cells and follicular development: a brief review.
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Cavalcanti GS, Carvalho KC, Ferreira CDS, Alvarez PAC, Monteleone PAA, Baracat EC, and Soares Júnior JM
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- Humans, Female, Granulosa Cells, Ovarian Follicle
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- 2023
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24. Diagnostic Delay of Hereditary Ataxias in Brazil: the Case of Machado-Joseph Disease.
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Dos Santos Pinheiro J, Sena LS, Donis KC, Furtado GV, Saraiva-Pereira ML, and Jardim LB
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- Humans, Delayed Diagnosis, Brazil, Machado-Joseph Disease, Spinocerebellar Degenerations, Spinocerebellar Ataxias
- Abstract
Background: Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a rare disease with diagnosis offered by the Unified Health System in Brazil. Our aim was to investigate the diagnostic delay in an interval of 23 years in a public university hospital, and some potentially determining factors., Methods: A retrospective review of the medical records of subjects identified at our institution between 1999 and 2017 was carried out, including residents of Rio Grande do Sul. The diagnostic delay was equivalent to the difference between age at onset of symptoms and age at molecular diagnosis. Calendar years, educational level, sex, distance between the household and the clinics, age and being the index case were studied as modifying factors., Results: SCA3/MJD had a median diagnostic delay of 5 years. Index cases had delays of 6 versus 4 years (p<0.001) for subsequent family members. Delay correlated with age (rho=0.346, p<0.001), but not with age at disease onset (rho=0.005, p=0.91). No change was observed with the level of education of individuals or with the distance between household and hospital from 1999 to 2017., Discussion: The diagnostic delay of SCA3/MJD is high in our region, where its occurrence has been reported for years. Failure to change the delay over the years suggests ineffective dissemination to the population, but a smaller lag among younger people can portray the effect of digital inclusion., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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25. Editorial: Emerging researchers in frontiers in pharmacology: obstetric and pediatric pharmacology 2022.
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Yang Q, Carvalho KC, Shirazi R, and Falahati A
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2023
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26. Subjective Visual Vertical and Vestibular Evoked Myogenic Potential in Meniere's disease.
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Ferreira MM, Lopes KC, Grigol TAAES, Ganança MM, and Caovilla HH
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- Male, Humans, Female, Adult, Middle Aged, Neck, Meniere Disease, Vestibular Evoked Myogenic Potentials physiology, Vestibule, Labyrinth
- Abstract
Objective: To evaluate otolith function by comparing the findings of the Subjective Visual Vertical, the cervical Vestibular Evoked Myogenic Potential and the ocular Vestibular Evoked Myogenic Potential tests in patients in the inter-crisis period of unilateral definite Meniere's disease., Methods: The sample consisted of an experimental group (n=22; 10 men and 12 women, mean age 47.32±12.82 years) with definite unilateral Meniere's disease and a control group (n=14; 5 men and 9 women, with a mean age of 41.64±13.45 years). They all underwent vestibular evaluation by means of Subjective Visual Vertical with the bucket method and, cervical and ocular Vestibular Evoked Myogenic Potential tests. The data were collected and subjected to statistical analysis., Results: The results of the comparison of the Subjective Visual Vertical, the cervical Vestibular Evoked Myogenic Potential, the ocular Vestibular Evoked Myogenic Potential and, the association of cervical Vestibular Evoked Myogenic Potential with the ocular Vestibular Evoked Myogenic Potential showed no significant difference, indicating concordance among the tests., Conclusion: The identified abnormalities and the concordance between the combined proportion of the Subjective Visual Vertical, the cervical Vestibular Evoked Myogenic Potential and the ocular Vestibular Evoked Myogenic Potential findings indicate that the association of these three tests contributes to the identification of sustained and transient otolith dysfunction in the inter-crisis of unilateral definite Meniere's disease., (Copyright © 2022. Published by Elsevier España, S.L.U.)
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- 2023
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27. Copy number variations in SPAST and ATL1 are rare among Brazilians.
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Fussiger H, Pereira BLDS, Padilha JPD, Donis KC, Siebert M, Brusius-Facchin AC, Baldo G, and Saute JAM
- Subjects
- Humans, Brazil epidemiology, Cohort Studies, Mutation, Proteins genetics, DNA Copy Number Variations genetics, Spastic Paraplegia, Hereditary epidemiology, Spastic Paraplegia, Hereditary genetics, Spastic Paraplegia, Hereditary diagnosis, Spastin genetics
- Abstract
Copy number variations (CNV) may represent a significant proportion of SPG4 and SPG3A diagnosis, the most frequent autosomal dominant subtypes of hereditary spastic paraplegias (HSP). We aimed to assess the frequency of CNVs in SPAST and ATL1 and to update the molecular epidemiology of HSP families in southern Brazil. A cohort study that included 95 Brazilian index cases with clinical suspicion of HSP was conducted between April 2011 and September 2022. Multiplex Ligation Dependent Probe Amplification (MLPA) was performed in 41 cases without defined diagnosis by different massive parallel sequencing techniques (MPS). Diagnosis was obtained in 57/95 (60%) index cases, 15/57 (26.3%) being SPG4. Most frequent autosomal recessive HSP subtypes were SPG7 followed by SPG11, SPG76 and cerebrotendinous xanthomatosis. No CNVs in SPAST and ATL1 were found. Copy number variations are rare among SPG4 and SPG3A families in Brazil. Considering the possibility of CNVs detection by specific algorithms with MPS data, we consider that this is likely the most cost-effective approach to investigate CNVs in these genes in low-risk populations, with MLPA being reserved as an orthogonal confirmatory test., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2023
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28. Quantifying microplastics in fishes: The first case study contrasting the perspective of untrained and experienced researchers.
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Costa LL, Arueira VF, Silva TN, da Silva Oliveira A, Dos Santos Nascimento L, Sant'Anna MEAS, Viana CF, da Silva KC, Gunner B, Leite V, and da Costa ID
- Subjects
- Animals, Microplastics, Plastics metabolism, Environmental Monitoring, Fishes metabolism, Water Pollutants, Chemical analysis, Tilapia metabolism
- Abstract
Microplastic studies hold a low explored potential for citizen science and environmental education, but methodological issues challenge data produced by non-specialists. We compared microplastic abundance and diversity in the red tilapia Oreochromis niloticus recovered by untrained students with those recovered by researchers that have experience of three years studying the incorporation of this pollutant by aquatic organisms. Seven students dissected 80 specimens and performed digestion of digestive tract in hydrogen peroxide. The solution was filtered and inspected under a stereomicroscope by the students and by two expert researchers. A control treatment consisted of 80 samples handled only by experts. The students overestimated the abundance of fibers and fragments. Striking differences in abundance and richness of microplastics were verified between the fish dissected by students and by expert researchers. Therefore, citizen science projects involving the uptake of microplastics by fish should provide training until a satisfactory level of expertise is reached., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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29. Molecular dynamics simulations of aqueous systems of inhibitor candidates for adenosine-5'-phosphosufate reductase.
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da Silva TU, Pougy KC, Albuquerque MG, Lima CHDS, and Machado SP
- Subjects
- Molecular Docking Simulation, Ligands, Protein Binding, Molecular Dynamics Simulation, Oxidoreductases
- Abstract
Molecular dynamics (MD) simulations were used to evaluate some chelating agents as potential candidates to inhibitors for dissimilatory adenosine-5'-phosphosulfate reductase (APSrAB). Molecular docking methods were used to evaluate the best binding modes of these molecules to the enzyme at two binding sites: of the substrate (enzyme active site) by mean the redocking protocol of substrate; and of one of the [Fe
4 S4 ]2+ groups by mean of the clusterization protocol. The best docking poses were selected by criteria such as low energy and RMSD (redocking) and the cluster with the higher number of similar poses (clusterization), which were submitted to MD simulations. RMSD, RDF, and hydrogen bonds results revelated that all ligands left the cube site, while in the active site, some ligands remained in their docking region, pointing to the enzyme active site as the best target for the selected ligands. The binding energy results of ligands hydroxamic acid (HXA) and catechol (CAT) showed that they bonded favorably to the enzyme and key residues of the active site contributed significantly to the protein-ligand bind, indicating HAX and CAT may compete with the substrate for interactions with these residues and displaying potential as candidates for experimental studies about APSrAB inhibitors.Communicated by Ramaswamy H. Sarma.- Published
- 2023
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30. Chemical behavior of 20%-22% carbamide peroxide gels in at-home bleaching: Randomized crossover in situ trial.
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Mailart MC, Dos Santos KC, Torres CRG, and Borges AB
- Subjects
- Humans, Carbamide Peroxide, Gels, Hydrogen Peroxide, Peroxides chemistry, Urea chemistry, Cross-Over Studies, Tooth Bleaching methods, Tooth Bleaching Agents chemistry
- Abstract
Objective: To evaluate if distinct 20%-22% carbamide peroxide bleaching gels present similar decomposition pattern and pH during the clinical use in both arches, as well as gels viscosity., Methods: Participants randomly received treatments with carbamide peroxide gels (n = 10): OPF (OpalescencePF-20%); PNT (Polanight-22%); and WPC (Whiteness Perfect-22%) in three different days, with 2-day washout. Decomposition pattern was assessed by peroxide concentration. Both PC and pH of bleaching gels were measured in different time points in upper and lower trays during a total of 120 min of clinical use. Viscosity of bleaching gels was measured in triplicate. ANOVA and Tukey's test were applied (α = 0.05)., Results: Regarding decomposition pattern, no significant differences were observed for the interaction between gel, time, and tray position factors. The peroxide concentration progressively reduced until 120 min of trays use (p < 0.001), being overall more notable in lower trays (p < 0.001). Regarding pH, the lowest values were verified in WPC within time. At 120 min, an increase of pH was observed for both WPC and OPF (p < 0.001) compared to baseline means. PNT exhibited constant pH values over time. The values of viscosity were: OPF (1.682.000 ± 19 cP)a, WPC (1.388.667 ± 172.63 cP)ab, PNT (579.567 ± 0.98 cP)b., Conclusions: The bleaching gels presented overall decomposition pattern clinically equivalent, being more notable in lower trays over time. Nevertheless, distinct pH and viscosities were observed among the products., Clinical Significance: Although the manufacturers recommend different times of use for bleaching gels with similar peroxide concentrations, the commercial products tested did not exhibit clinically relevant difference in the decomposition pattern during the 120 min of clinical procedure., (© 2022 Wiley Periodicals LLC.)
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- 2023
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31. Chicken bed reuse.
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Dornelas KC, Mascarenhas NMH, Dos Santos da Rocha PA, Ton APS, do Amaral AG, Schneider RM, Dos Santos Lima de Brito AN, Furtado DA, and do Nascimento JWB
- Subjects
- Animals, Chickens, Poultry
- Abstract
Aviculture is a developed and important industry worldwide. However, it is an industry that produces solid waste such as bedding. As an attempt to reduce environmental impact and productive activity costs, beds are reused by several consecutive lots which can increase microorganism concentration and lead to unsanitary conditions. In this regard, it is essential to adopt a litter pre-treatment during the gap sanitary period between lots to avoid passing problems to the birds from the current flock to the subsequent flock and to guarantee the litter quality. Several factors must be considered to guarantee that there is minimal damage to chicken production. Therefore, this literature review aims to approach the main factors that affect the thermal comfort and chicken litter quality, as well as alternatives used as an alternative biological treatment to guarantee its reuse quality., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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32. High performance older adults in a population-based sample with low education: Pietà study.
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Carmona KC, Resende EPF, Guimarães HC, Machado TH, Amaral-Carvalho V, Santos ELD, Barbosa MT, and Caramelli P
- Subjects
- Humans, Female, Aged, Aged, 80 and over, Educational Status, Neuropsychological Tests, Mental Recall, Aging psychology, Mental Disorders
- Abstract
Background: Healthy brain aging can be defined as aging without neurological or psychiatric disorders, sustaining functional independence. In addition to the absence of disease and preserved functionality, there are individuals who stand out for their superior performance to that considered normal for their age in cognitive tests. These individuals are called "high-performance older adults" (HPOA)., Objectives: To investigate the presence of HPOA in an oldest-old population with low education, and if present, to investigate associations with sociodemographic, clinical, and lifestyle variables., Methods: We evaluated 132 cognitively healthy individuals from the Pietà Study, a population-based investigation with 639 participants. We used the delayed recall from the Rey Auditory-Verbal Learning Test to verify the existence of HPOA and to classify participants based on their performance. Sociodemographic, clinical, and lifestyle variables associated with HPOA were investigated., Results: We identified 18 individuals fulfilling HPOA criteria (age: 77.4 ± 2.6 years old; 14 women; education: 4.6 ± 3.4 years). The other participants, 114 total (age: 79.8 ± 4.5 years old; 69 women; education: 3.0 ± 2.7 years) were classified as "standard performance older adults" (SPOA). In multivariate analysis, younger age (odds ratio [OR] = 0.672; 95% confidence interval [CI]: 0.462-0.979; p = 0.037) and lower scores on the Geriatric Depression Scale (OR = 0.831; 95%CI: 0.688-0.989; p = 0.038) were associated with HPOA., Conclusions: The present study identifies for the first time HPOA with low educational level, thereby reinforcing the existence of biological substrates related to this condition. Furthermore, the data suggest an association between younger age and less depressive symptoms with HPOA., Competing Interests: The authors have no conflict of interests to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)
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- 2023
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33. Morphology of coat and skin of small ruminants reared in the Brazilian semi-arid region.
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Henrique Mascarenhas NM, Furtado DA, Benício de Souza B, Brilhante de Sousa O, Lima da Costa AN, Feitosa JV, Rodrigues da Silva M, Batista LF, and Dornelas KC
- Subjects
- Animals, Female, Male, Brazil, Goats, Sheep, Sweating, Skin anatomy & histology, Sweat Glands
- Abstract
The structure of the coat and integument of small ruminants reared in semi-arid regions have valuable characteristics that favor their adaptation to the region. The objective of this study was to evaluate the structural characteristics of the coat and integument and sweating capacity of goats and sheep in the Brazilian semi-arid region, using 20 animals, 10 of each breed, 5 males and 5 females of each species, grouped in a completely randomized design in a 2 x 2 factorial scheme (2 species and 2 genders) with 5 replicates. The animals were already being kept under the influence of high temperatures and levels of direct solar radiation before the day of the collections. At the time of the evaluations, ambient temperature was high, with low relative humidity. The pattern of epidermal thickness and sweat glands per body region was superior in sheep (P < 0.05), and the number of hair follicles and sweat rate were similar (P > 0.05) between the species. There was no difference (P > 0.05) in the evaluated characteristics between the genders, showing that they are not influenced by hormones. The morphology of the coat and skin of these animals showed a superiority of goats compared to sheep., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2023
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34. Gene Expression Profile of Uterine Leiomyoma from Women Exposed to Different Air Pollution Levels in Metropolitan Cities of Sao Paulo, Brazil.
- Author
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Dos Anjos LG, de Almeida BC, Baracat EC, Al-Hendy A, Yang Q, and Carvalho KC
- Subjects
- Pregnancy, Humans, Female, Cities, Brazil epidemiology, Transcriptome, Air Pollutants toxicity, Air Pollutants analysis, Air Pollution adverse effects, Air Pollution analysis, Infertility, Leiomyoma etiology, Leiomyoma genetics
- Abstract
Leiomyomas (LMs) are the most frequent uterine benign tumors, representing the leading cause of hysterectomy indications worldwide. They are highly associated with women's reproductive complications, and endocrine disruptors may influence their etiology. In this sense, air pollution represents a relevant hormonal disruptor that acts on key signaling pathways, resulting in tumor development and infertility. Our goal was to evaluate submucosal LM samples from patients living in the metropolitan and Sao Paulo city regions, focusing on genes involved in tumor development and infertility features. Twenty-four patients were selected based on their region of residence and clinical information availability. Several genes were differentially expressed between women living in metropolitan areas and Sao Paulo city. Significant associations were observed between BCL-2 , DVL1 , FGFR3 , and WNT5b downregulation and contraceptive use in the samples from women living in Sao Paulo city. ESR1 and HHAT downregulation was associated with ethnicity. WNT5b and GREM were associated with LM treatment and related pathologies, respectively. In the samples from women living in other cities of the metropolitan region, abortion occurrence was associated with BMP4 upregulation. Although further studies may be necessary, our results showed that air pollution exposure influences the expression of genes related to LM development and female reproductive features.
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- 2023
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35. Could be FOXO3a, miR-96-5p and miR-182-5p useful for Brazilian women with luminal A and triple negative breast cancers prognosis and target therapy?
- Author
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Mendes DCC, Filho CMCC, Garcia N, Ricci MD, Soares JM Júnior, Carvalho KC, and Baracat EC
- Subjects
- Female, Humans, Biomarkers, Tumor genetics, Brazil, Carcinogenesis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Prognosis, Phenobarbital metabolism, Breast Neoplasms genetics, Breast Neoplasms pathology, MicroRNAs genetics, MicroRNAs metabolism, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms pathology
- Abstract
FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. Their potential prognostic role for the patients was also evaluated. We identified the miRNAs miR-96-5p and miR-182-5p, de-scribed as negative regulators of FOXO3A, with differential expression both in LA and TN tumors when compared to normal tissue. The miR-96-5p and miR-182-5p miRNAs were upregulated in LA (7.82 times, p < 0.005; 6.12 times, p < 0.005, respectively) and TN breast cancer samples (9.42 times, p < 0.0001; 8.51 times, p < 0.0001) compared to normal tissues. The samples with higher miR-96-5p and miR-182-5p expression (FR ≥ 4) were submitted for FOXO3a immunostaining. Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)
- Published
- 2023
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36. Oral Dantrolene Reduces Myalgia and Hyperckemia in a Child with RYR1-Related Exertional Myalgia/Rhabdomyolysis.
- Author
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de Lima Silva EV, Donis KC, Machado FRC, Simão Medeiros L, Aschoff CAM, de Souza CFM, Poswar FO, and Saute JAM
- Subjects
- Humans, Child, Child, Preschool, Myalgia drug therapy, Myalgia etiology, Ryanodine Receptor Calcium Release Channel genetics, Muscles, Dantrolene therapeutic use, Rhabdomyolysis drug therapy, Rhabdomyolysis complications
- Abstract
RYR1-related exertional myalgia/rhabdomyolysis (ERM) is an underrecognized condition, which can cause limiting muscle symptoms, and may account for more than one-third of undiagnosed rhabdomyolysis cases. Dantrolene has shown promising results in controlling muscle symptoms in individuals with ERM, however, its use in children remains poorly documented. This case report presents the successful treatment of a 5-year-old patient with ERM using oral dantrolene. The patient experienced notable improvements, including a reduction in the frequency and intensity of myalgia episodes, no hospitalizations due to rhabdomyolysis, a substantial decrease in creatine phosphokinase (CPK) levels, and enhanced performance on the 6-minute walk test. The use of dantrolene was well-tolerated, and no significant adverse effects were observed. This report adds to the existing evidence supporting the effectiveness of oral dantrolene in managing ERM, and, to the best of our knowledge, this is the first report of the use of dantrolene in a pediatric patient for controlling anesthesia-independent muscle symptoms.
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- 2023
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37. Management of laryngopharyngeal reflux in Brazil: a national survey.
- Author
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Lechien JR, Perazzo PS, Ceccon FP, Eckley CA, Lopes KC, Maunsell R, Avelino MAG, Akst LM, Sant'Anna GD, and Imamura R
- Subjects
- Humans, Brazil epidemiology, Otolaryngologists, Proton Pump Inhibitors therapeutic use, Laryngopharyngeal Reflux diagnosis, Laryngopharyngeal Reflux drug therapy, Otolaryngology
- Abstract
Introduction: Studies assessing the management of laryngopharyngeal reflux by otolaryngologists have reported an important heterogeneity regarding the definition, diagnosis, and treatment, which leads to discrepancies in the management of the patient. Information about the current knowledge and practices of Brazilian otolaryngologists in laryngopharyngeal reflux is lacking., Objective: To investigate the trends in management of laryngopharyngeal reflux disease among Brazilian otolaryngologists., Methods: A survey was sent by email to the members of the Brazilian Association of Otolaryngology-Head Neck Surgery. This survey has initially been conducted by the laryngopharyngeal reflux study group of young otolaryngologists of the International Federation of Otolaryngological Societies., Results: According to the survey responders, the prevalence of laryngopharyngeal reflux was estimated to be 26.8% of patients consulting in otolaryngology and the most common symptoms were globus sensation, throat clearing, cough and stomach acid reflux. Nasal obstruction, Eustachian tube dysfunction, acute and chronic otitis media, vocal fold nodules and hemorrhage were considered not associated with laryngopharyngeal reflux by the majority of responders. About 2/3 of Brazilian otolaryngologists based the diagnosis of laryngopharyngeal reflux on the assessment of both symptoms and findings and a positive response to empiric therapeutic trials. Proton pump inhibitor utilized once or twice daily, was the most commonly used therapeutic scheme. Only 21.4% of Brazilian otolaryngologists have heard about nonacid and mixed laryngopharyngeal reflux and the awareness about the usefulness of multichannel intraluminal impedance pH monitoring (MII-pH) was minimal; 30.5% of responders did not consider themselves as well-informed about laryngopharyngeal reflux., Conclusion: Although the laryngopharyngeal reflux-related symptoms, main diagnostic and treatment approaches referred by Brazilian otolaryngologists are consistent with the literature, the survey identified some limitations, such as the insufficient awareness of the role of laryngopharyngeal reflux in many otolaryngological conditions and of the possibility of non-acid or mixed reflux in refractory cases. Future studies are needed to establish international recommendations for the management of laryngopharyngeal reflux disease., (Copyright © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)
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- 2022
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38. Vestibular function assessment in sudden hearing loss.
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Maia NPD, Lopes KC, and Ganança FF
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- Humans, Adult, Middle Aged, Dizziness diagnosis, Dizziness etiology, Prospective Studies, Head Impulse Test, Caloric Tests, Vertigo, Hearing Loss, Sudden diagnosis, Vestibular Evoked Myogenic Potentials physiology
- Abstract
Objectives: To perform vestibular assessment using cervical and ocular vestibular evoked myogenic potential, video head impulse test and caloric testing in patients with sudden hearing loss. Moreover, to evaluate the correlation of dizziness with vestibular tests and the correlation of vestibular tests with hearing prognosis., Methods: This is an observational, longitudinal and prospective study, including participants diagnosed with sudden hearing loss. The participants underwent cervical and ocular vestibular evoked myogenic potential, video head impulse test and caloric testing. The audiometric assessment was performed at the beginning and at the end of the follow-up. A value of p≤0.05 was considered statistically significant., Results: Seventeen patients were included in the study sample, with a mean age of 45.4±11.1 years. Five participants (29.41%) had dizziness and 15 (88.23%) had tinnitus. All participants underwent vestibular evaluation through cervical and ocular vestibular evoked myogenic potential and video head impulse test, and 13 of them were evaluated through caloric testing. The cervical vestibular evoked myogenic potential was considered altered in five (29.41%) participants, while 11 (64.71%) showed alterations at the ocular vestibular evoked myogenic potential. The video head impulse test and the caloric testing were considered altered in seven (41.18%) and five (38.46%) participants, respectively. There was no statistically significant correlation between the clinical data and the results of vestibular tests or hearing recovery, nor between the results of vestibular tests and hearing recovery., Conclusion: The assessment through vestibular evoked myogenic potential, video head impulse test and caloric testing showed vestibular involvement in some participants. However, it cannot be stated that the results of the vestibular tests are related to the hearing prognosis of sudden hearing loss., (Copyright © 2022 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)
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- 2022
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39. Epigenetic Features in Uterine Leiomyosarcoma and Endometrial Stromal Sarcomas: An Overview of the Literature.
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de Almeida BC, Dos Anjos LG, Dobroff AS, Baracat EC, Yang Q, Al-Hendy A, and Carvalho KC
- Abstract
There is a consensus that epigenetic alterations play a key role in cancer initiation and its biology. Studies evaluating the modification in the DNA methylation and chromatin remodeling patterns, as well as gene regulation profile by non-coding RNAs (ncRNAs) have led to the development of novel therapeutic approaches to treat several tumor types. Indeed, despite clinical and translational challenges, combinatorial therapies employing agents targeting epigenetic modifications with conventional approaches have shown encouraging results. However, for rare neoplasia such as uterine leiomyosarcomas (LMS) and endometrial stromal sarcomas (ESS), treatment options are still limited. LMS has high chromosomal instability and molecular derangements, while ESS can present a specific gene fusion signature. Although they are the most frequent types of "pure" uterine sarcomas, these tumors are difficult to diagnose, have high rates of recurrence, and frequently develop resistance to current treatment options. The challenges involving the management of these tumors arise from the fact that the molecular mechanisms governing their progression have not been entirely elucidated. Hence, to fill this gap and highlight the importance of ongoing and future studies, we have cross-referenced the literature on uterine LMS and ESS and compiled the most relevant epigenetic studies, published between 2009 and 2022.
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- 2022
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40. Evaluation of circulating microRNA profiles in Brazilian women with polycystic ovary syndrome: A preliminary study.
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De Nardo Maffazioli G, Baracat EC, Soares JM, Carvalho KC, and Maciel GAR
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- Androgens, Biomarkers, Brazil epidemiology, Cross-Sectional Studies, Female, Gene Expression Profiling, Humans, Steroids, Circulating MicroRNA genetics, Insulins, MicroRNAs genetics, MicroRNAs metabolism, Polycystic Ovary Syndrome genetics, Polycystic Ovary Syndrome metabolism
- Abstract
Objective: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy, which etiology encompasses complex genetic traits associated with epigenetic factors, including differences in microRNA (miRNA) expression in a variety of tissues. The circulating form of these molecules is raising attention in the syndrome not only as potential biomarkers of PCOS but also as possible therapeutic targets. The aim of this study was to explore the circulating miRNA profiles present in a cohort of Brazilian women with and without PCOS and to evaluate the potential role of miRNAs in the pathophysiology of the syndrome., Methods: Cross-sectional study of 36 well-characterized PCOS women and 16 healthy controls. Clinical, hormone and metabolic data were recorded and evaluated. The expression profile of the 201 circulating miRNA selected were analyzed by taqman quantitative real time polymerase chain reactions (RT-PCR) using a customized Open Array platform. Statistical and bioinformatic analyzed were performed., Results: Circulating miR-21-5p, miR-23a-3p and miR-26a-5p were upregulated, and miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p were downregulated in women with PCOS compared to healthy normo-ovulatory controls. miR-21-5p, miR-103a-3p and miR-376a-3p levels correlated positively with androgen levels. These miRNAs, in combination, were related to pathways involved in insulin signaling, steroids biosynthesis and endothelial regulation as well as in folliculogenesis., Conclusion: In this study, we identified a specific circulating miRNA signature in Brazilian women with PCOS. According to our data, circulating miR-21-5p, miR-23a-3p, miR-26a-5p, miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p may represent potential candidates for differential diagnosis of PCOS in the future., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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41. Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia.
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Calame DG, Herman I, Maroofian R, Marshall AE, Donis KC, Fatih JM, Mitani T, Du H, Grochowski CM, Sousa SB, Gijavanekar C, Bakhtiari S, Ito YA, Rocca C, Hunter JV, Sutton VR, Emrick LT, Boycott KM, Lossos A, Fellig Y, Prus E, Kalish Y, Meiner V, Suerink M, Ruivenkamp C, Muirhead K, Saadi NW, Zaki MS, Bouman A, Barakat TS, Skidmore DL, Osmond M, Silva TO, Murphy D, Karimiani EG, Jamshidi Y, Jaddoa AG, Tajsharghi H, Jin SC, Abbaszadegan MR, Ebrahimzadeh-Vesal R, Hosseini S, Alavi S, Bahreini A, Zarean E, Salehi MM, Al-Sannaa NA, Zifarelli G, Bauer P, Robson SC, Coban-Akdemir Z, Travaglini L, Nicita F, Jhangiani SN, Gibbs RA, Posey JE, Kruer MC, Kernohan KD, Morales Saute JA, Houlden H, Vanderver A, Elsea SH, Pehlivan D, Marafi D, and Lupski JR
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- Dysarthria, Humans, Mutation genetics, Paraplegia genetics, Pedigree, Phenotype, Apyrase genetics, Intellectual Disability genetics, Spastic Paraplegia, Hereditary genetics, White Matter diagnostic imaging, White Matter pathology
- Abstract
Objective: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia is associated with >80 genes, with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in ENTPD1, a gene previously linked to spastic paraplegia 64 (Mendelian Inheritance in Man # 615683)., Methods: Individuals with biallelic ENTPD1 variants were recruited worldwide. Deep phenotyping and molecular characterization were performed., Results: A total of 27 individuals from 17 unrelated families were studied; additional phenotypic information was collected from published cases. Twelve novel pathogenic ENTPD1 variants are described (NM 001776.6): c.398_399delinsAA; p.(Gly133Glu), c.540del; p.(Thr181Leufs*18), c.640del; p.(Gly216Glufs*75), c.185 T > G; p.(Leu62*), c.1531 T > C; p.(*511Glnext*100), c.967C > T; p.(Gln323*), c.414-2_414-1del, and c.146 A > G; p.(Tyr49Cys) including 4 recurrent variants c.1109 T > A; p.(Leu370*), c.574-6_574-3del, c.770_771del; p.(Gly257Glufs*18), and c.1041del; p.(Ile348Phefs*19). Shared disease traits include childhood onset, progressive spastic paraplegia, intellectual disability (ID), dysarthria, and white matter abnormalities. In vitro assays demonstrate that ENTPD1 expression and function are impaired and that c.574-6_574-3del causes exon skipping. Global metabolomics demonstrate ENTPD1 deficiency leads to impaired nucleotide, lipid, and energy metabolism., Interpretation: The ENTPD1 locus trait consists of childhood disease onset, ID, progressive spastic paraparesis, dysarthria, dysmorphisms, and white matter abnormalities, with some individuals showing neurocognitive regression. Investigation of an allelic series of ENTPD1 (1) expands previously described features of ENTPD1-related neurological disease, (2) highlights the importance of genotype-driven deep phenotyping, (3) documents the need for global collaborative efforts to characterize rare autosomal recessive disease traits, and (4) provides insights into disease trait neurobiology. ANN NEUROL 2022;92:304-321., (© 2022 American Neurological Association.)
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- 2022
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42. Observation of the Decay Λ_{b}^{0}→Λ_{c}^{+}τ^{-}ν[over ¯]_{τ}.
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Aaij R, Abdelmotteleb ASW, Beteta CA, Abudinén F, Ackernley T, Adeva B, Adinolfi M, Afsharnia H, Agapopoulou C, Aidala CA, Aiola S, Ajaltouni Z, Akar S, Albrecht J, Alessio F, Alexander M, Albero AA, Aliouche Z, Alkhazov G, Cartelle PA, Amato S, Amey JL, Amhis Y, An L, Anderlini L, Andersson M, Andreianov A, Andreotti M, Archilli F, Artamonov A, Artuso M, Arzymatov K, Aslanides E, Atzeni M, Audurier B, Bachmann S, Bachmayer M, Back JJ, Rodriguez PB, Balagura V, Baldini W, Baptista de Souza Leite J, Barbetti M, Barlow RJ, Barsuk S, Barter W, Bartolini M, Baryshnikov F, Basels JM, Bashir S, Bassi G, Batsukh B, Battig A, Bay A, Beck A, Becker M, Bedeschi F, Bediaga I, Beiter A, Belavin V, Belin S, Bellee V, Belous K, Belov I, Belyaev I, Bencivenni G, Ben-Haim E, Berezhnoy A, Bernet R, Berninghoff D, Bernstein HC, Bertella C, Bertolin A, Betancourt C, Betti F, Bezshyiko I, Bhasin S, Bhom J, Bian L, Bieker MS, Biesuz NV, Bifani S, Billoir P, Biolchini A, Birch M, Bishop FCR, Bitadze A, Bizzeti A, Bjørn M, Blago MP, Blake T, Blanc F, Blusk S, Bobulska D, Boelhauve JA, Garcia OB, Boettcher T, Boldyrev A, Bondar A, Bondar N, Borghi S, Borisyak M, Borsato M, Borsuk JT, Bouchiba SA, Bowcock TJV, Boyer A, Bozzi C, Bradley MJ, Braun S, Rodriguez AB, Brodzicka J, Gonzalo AB, Brundu D, Buonaura A, Buonincontri L, Burke AT, Burr C, Bursche A, Butkevich A, Butter JS, Buytaert J, Byczynski W, Cadeddu S, Cai H, Calabrese R, Calefice L, Cali S, Calladine R, Calvi M, Gomez MC, Magalhaes PC, Campana P, Quezada AFC, Capelli S, Capriotti L, Carbone A, Carboni G, Cardinale R, Cardini A, Carli I, Carniti P, Carus L, Akiba KC, Vidal AC, Caspary R, Casse G, Cattaneo M, Cavallero G, Celani S, Cerasoli J, Cervenkov D, Chadwick AJ, Chapman MG, Charles M, Charpentier P, Barajas CAC, Chefdeville M, Chen C, Chen S, Chernov A, Chobanova V, Cholak S, Chrzaszcz M, Chubykin A, Chulikov V, Ciambrone P, Cicala MF, Vidal XC, Ciezarek G, Clarke PEL, Clemencic M, Cliff HV, Closier J, Cobbledick JL, Coco V, Coelho JAB, Cogan J, Cogneras E, Cojocariu L, Collins P, Colombo T, Congedo L, Contu A, Cooke N, Coombs G, Corredoira I, Corti G, Sobral CMC, Couturier B, Craik DC, Crkovská J, Torres MC, Currie R, Da Silva CL, Dadabaev S, Dai L, Dall'Occo E, Dalseno J, D'Ambrosio C, Danilina A, d'Argent P, Dashkina A, Davies JE, Davis A, Francisco OA, De Bruyn K, De Capua S, De Cian M, Da Graca UFC, De Lucia E, De Miranda JM, De Paula L, De Serio M, De Simone D, De Simone P, De Vellis F, de Vries JA, Dean CT, Debernardis F, Decamp D, Dedu V, Del Buono L, Delaney B, Dembinski HP, Denysenko V, Derkach D, Deschamps O, Dettori F, Dey B, Di Cicco A, Di Nezza P, Didenko S, Maronas LD, Dijkstra H, Dobishuk V, Dong C, Donohoe AM, Dordei F, Dos Reis AC, Douglas L, Dovbnya A, Downes AG, Dudek MW, Dufour L, Duk V, Durante P, Durham JM, Dutta D, Dziurda A, Dzyuba A, Easo S, Egede U, Egorychev V, Eidelman S, Eisenhardt S, Ek-In S, Eklund L, Ely S, Ene A, Epple E, Escher S, Eschle J, Esen S, Evans T, Falcao LN, Fan Y, Fang B, Farry S, Fazzini D, Féo M, Prieto AF, Fernez AD, Ferrari F, Lopes LF, Rodrigues FF, Sole SF, Ferrillo M, Ferro-Luzzi M, Filippov S, Fini RA, Fiorini M, Firlej M, Fischer KM, Fitzgerald DS, Fitzpatrick C, Fiutowski T, Fkiaras A, Fleuret F, Fontana M, Fontanelli F, Forty R, Foulds-Holt D, Lima VF, Sevilla MF, Frank M, Franzoso E, Frau G, Frei C, Friday DA, Fu J, Fuehring Q, Gabriel E, Galati G, Torreira AG, Galli D, Gambetta S, Gan Y, Gandelman M, Gandini P, Gao Y, Garau M, Martin LMG, Moreno PG, García Pardiñas J, Plana BG, Rosales FAG, Garrido L, Gaspar C, Geertsema RE, Gerick D, Gerken LL, Gersabeck E, Gersabeck M, Gershon T, Gerstel D, Giambastiani L, Gibson V, Giemza HK, Gilman AL, Giovannetti M, Gioventù A, Gironell PG, Giugliano C, Gizdov K, Gkougkousis EL, Gligorov VV, Göbel C, Golobardes E, Golubkov D, Golutvin A, Gomes A, Fernandez SG, Abrantes FG, Goncerz M, Gong G, Gorbounov P, Gorelov IV, Gotti C, Grabowski JP, Grammatico T, Cardoso LAG, Graugés E, Graverini E, Graziani G, Grecu A, Greeven LM, Grieser NA, Grillo L, Gromov S, Cazon BRG, Gu C, Guarise M, Guittiere M, Günther PA, Gushchin E, Guth A, Guz Y, Gys T, Hadavizadeh T, Haefeli G, Haen C, Haimberger J, Haines SC, Halewood-Leagas T, Hamilton PM, Hammerich JP, Han Q, Han X, Hansen EB, Hansmann-Menzemer S, Harnew N, Harrison T, Hasse C, Hatch M, He J, Hecker M, Heijhoff K, Heinicke K, Henderson RDL, Hennequin AM, Hennessy K, Henry L, Heuel J, Hicheur A, Hill D, Hilton M, Hollitt SE, Hou R, Hou Y, Hu J, Hu J, Hu W, Hu X, Huang W, Huang X, Hulsbergen W, Hunter RJ, Hushchyn M, Hutchcroft D, Hynds D, Ibis P, Idzik M, Ilin D, Ilten P, Inglessi A, Ishteev A, Ivshin K, Jacobsson R, Jage H, Jakobsen S, Jans E, Jashal BK, Jawahery A, Jevtic V, Jiang X, John M, Johnson D, Jones CR, Jones TP, Jost B, Jurik N, Kadavath SHK, Kandybei S, Kang Y, Karacson M, Karpenkov D, Karpov M, Kautz JW, Keizer F, Keller DM, Kenzie M, Ketel T, Khanji B, Kharisova A, Kholodenko S, Kirn T, Kirsebom VS, Kitouni O, Klaver S, Kleijne N, Klimaszewski K, Kmiec MR, Koliiev S, Kondybayeva A, Konoplyannikov A, Kopciewicz P, Kopecna R, Koppenburg P, Korolev M, Kostiuk I, Kot O, Kotriakhova S, Kozachuk A, Kravchenko P, Kravchuk L, Krawczyk RD, Kreps M, Kretzschmar S, Krokovny P, Krupa W, Krzemien W, Kubat J, Kucharczyk M, Kudryavtsev V, Kuindersma HS, Kunde GJ, Kvaratskheliya T, Lacarrere D, Lafferty G, Lai A, Lampis A, Lancierini D, Lane JJ, Lane R, Lanfranchi G, Langenbruch C, Langer J, Lantwin O, Latham T, Lazzari F, Le Gac R, Lee SH, Lefèvre R, Leflat A, Legotin S, Leroy O, Lesiak T, Leverington B, Li H, Li P, Li S, Li Y, Li Z, Liang X, Lin T, Lindner R, Lisovskyi V, Litvinov R, Liu G, Liu H, Liu Q, Liu S, Salvia AL, Loi A, Lollini R, Castro JL, Longstaff I, Lopes JH, Soliño SL, Lovell GH, Lu Y, Lucarelli C, Lucchesi D, Luchuk S, Martinez ML, Lukashenko V, Luo Y, Lupato A, Luppi E, Lupton O, Lusiani A, Lyu X, Ma L, Ma R, Maccolini S, Machefert F, Maciuc F, Macko V, Mackowiak P, Maddrell-Mander S, Madejczyk O, Mohan LRM, Maev O, Maevskiy A, Maisuzenko D, Majewski MW, Malczewski JJ, Malde S, Malecki B, Malinin A, Maltsev T, Malygina H, Manca G, Mancinelli G, Manuzzi D, Marangotto D, Maratas J, Marchand JF, Marconi U, Mariani S, Benito CM, Marinangeli M, Marks J, Marshall AM, Marshall PJ, Martelli G, Martellotti G, Martinazzoli L, Martinelli M, Santos DM, Vidal FM, Massafferri A, Materok M, Matev R, Mathad A, Matiunin V, Matteuzzi C, Mattioli KR, Mauri A, Maurice E, Mauricio J, Mazurek M, McCann M, Mcconnell L, Mcgrath TH, Mchugh NT, McNab A, McNulty R, Mead JV, Meadows B, Meier G, Melnychuk D, Meloni S, Merk M, Merli A, Garcia LM, Mikhasenko M, Milanes DA, Millard E, Milovanovic M, Minard MN, Minotti A, Mitchell SE, Mitreska B, Mitzel DS, Mödden A, Mohammed RA, Moise RD, Mokhnenko S, Mombächer T, Monroy IA, Monteil S, Morandin M, Morello G, Morello MJ, Moron J, Morris AB, Morris AG, Mountain R, Mu H, Muheim F, Mulder M, Müller K, Murphy CH, Murray D, Murta R, Muzzetto P, Naik P, Nakada T, Nandakumar R, Nanut T, Nasteva I, Needham M, Neri N, Neubert S, Neufeld N, Newcombe R, Niel EM, Nieswand S, Nikitin N, Nolte NS, Normand C, Nunez C, Oblakowska-Mucha A, Obraztsov V, Oeser T, O'Hanlon DP, Okamura S, Oldeman R, Oliva F, Olivares ME, Onderwater CJG, O'Neil RH, Goicochea JMO, Ovsiannikova T, Owen P, Oyanguren A, Ozcelik O, Padeken KO, Pagare B, Pais PR, Pajero T, Palano A, Palutan M, Pan Y, Panshin G, Papanestis A, Pappagallo M, Pappalardo LL, Pappenheimer C, Parker W, Parkes C, Passalacqua B, Passaleva G, Pastore A, Patel M, Patrignani C, Pawley CJ, Pearce A, Pellegrino A, Altarelli MP, Perazzini S, Pereima D, Castro AP, Perret P, Petric M, Petridis K, Petrolini A, Petrov A, Petrucci S, Petruzzo M, Pham TTH, Philippov A, Piandani R, Pica L, Piccini M, Pietrzyk B, Pietrzyk G, Pili M, Pinci D, Pisani F, Pizzichemi M, Resmi PK, Placinta V, Plews J, Casasus MP, Polci F, Lener MP, Poliakova M, Poluektov A, Polukhina N, Polyakov I, Polycarpo E, Ponce S, Popov D, Popov S, Poslavskii S, Prasanth K, Promberger L, Prouve C, Pugatch V, Puill V, Punzi G, Qi H, Qian W, Qin N, Quagliani R, Raab NV, Trejo RIR, Rachwal B, Rademacker JH, Rajagopalan R, Rama M, Pernas MR, Rangel MS, Ratnikov F, Raven G, Reboud M, Redi F, Reiss F, Alepuz CR, Ren Z, Renaudin V, Ribatti R, Ricci AM, Ricciardi S, Rinnert K, Robbe P, Robertson G, Rodrigues AB, Rodrigues E, Lopez JAR, Rodriguez ERRR, Rollings A, Roloff P, Romanovskiy V, Lamas MR, Vidal AR, Roth JD, Rotondo M, Rudolph MS, Ruf T, Fernandez RAR, Vidal JR, Ryzhikov A, Ryzka J, Silva JJS, Sagidova N, Sahoo N, Saitta B, Salomoni M, Gras CS, Santacesaria R, Rios CS, Santimaria M, Santovetti E, Saranin D, Sarpis G, Sarpis M, Sarti A, Satriano C, Satta A, Saur M, Savrina D, Sazak H, Smead LGS, Scarabotto A, Schael S, Scherl S, Schiller M, Schindler H, Schmelling M, Schmidt B, Schmitt S, Schneider O, Schopper A, Schubiger M, Schulte S, Schune MH, Schwemmer R, Sciascia B, Sellam S, Semennikov A, Soares MS, Sergi A, Serra N, Sestini L, Seuthe A, Shang Y, Shangase DM, Shapkin M, Shchemerov I, Shchutska L, Shears T, Shekhtman L, Shen Z, Sheng S, Shevchenko V, Shields EB, Shimizu Y, Shmanin E, Shupperd JD, Siddi BG, Coutinho RS, Simi G, Simone S, Skidmore N, Skuza R, Skwarnicki T, Slater MW, Slazyk I, Smallwood JC, Smeaton JG, Smith E, Smith M, Snoch A, Lavra LS, Sokoloff MD, Soler FJP, Solovev A, Solovyev I, De Almeida FLS, De Paula BS, Spaan B, Norella ES, Spradlin P, Stagni F, Stahl M, Stahl S, Stanislaus S, Steinkamp O, Stenyakin O, Stevens H, Stone S, Strekalina D, Suljik F, Sun J, Sun L, Sun Y, Svihra P, Swallow PN, Swientek K, Szabelski A, Szumlak T, Szymanski M, Taneja S, Tanner AR, Tat MD, Terentev A, Teubert F, Thomas E, Thompson DJD, Thomson KA, Tilquin H, Tisserand V, T'Jampens S, Tobin M, Tomassetti L, Tong X, Machado DT, Tou DY, Trifonova E, Trilov SM, Trippl C, Tuci G, Tully A, Tuning N, Ukleja A, Unverzagt DJ, Ursov E, Usachov A, Ustyuzhanin A, Uwer U, Vagner A, Vagnoni V, Valassi A, Valenti G, Canudas NV, van Beuzekom M, Van Dijk M, Van Hecke H, van Herwijnen E, van Veghel M, Gomez RV, Regueiro PV, Sierra CV, Vecchi S, Velthuis JJ, Veltri M, Venkateswaran A, Veronesi M, Vesterinen M, Vieira D, Diaz MV, Viemann H, Vilasis-Cardona X, Figueras EV, Villa A, Vincent P, Volle FC, Bruch DV, Vorobyev A, Vorobyev V, Voropaev N, Vos K, Waldi R, Walsh J, Wang C, Wang J, Wang J, Wang J, Wang J, Wang M, Wang R, Wang Y, Wang Z, Wang Z, Wang Z, Ward JA, Watson NK, Websdale D, Weisser C, Westhenry BDC, White DJ, Whitehead M, Wiederhold AR, Wiedner D, Wilkinson G, Wilkinson MK, Williams I, Williams M, Williams MRJ, Wilson FF, Wislicki W, Witek M, Witola L, Wormser G, Wotton SA, Wu H, Wyllie K, Xiang Z, Xiao D, Xie Y, Xu A, Xu J, Xu L, Xu M, Xu Q, Xu Z, Xu Z, Yang D, Yang S, Yang Y, Yang Z, Yang Z, Yao Y, Yeomans LE, Yin H, Yu J, Yuan X, Yushchenko O, Zaffaroni E, Zavertyaev M, Zdybal M, Zenaiev O, Zeng M, Zhang D, Zhang L, Zhang S, Zhang S, Zhang Y, Zhang Y, Zharkova A, Zhelezov A, Zheng Y, Zhou T, Zhou X, Zhou Y, Zhovkovska V, Zhu X, Zhu X, Zhu Z, Zhukov V, Zou Q, Zucchelli S, Zuliani D, and Zunica G
- Abstract
The first observation of the semileptonic b-baryon decay Λ_{b}^{0}→Λ_{c}^{+}τ^{-}ν[over ¯]_{τ}, with a significance of 6.1σ, is reported using a data sample corresponding to 3 fb^{-1} of integrated luminosity, collected by the LHCb experiment at center-of-mass energies of 7 and 8 TeV at the LHC. The τ^{-} lepton is reconstructed in the hadronic decay to three charged pions. The ratio K=B(Λ_{b}^{0}→Λ_{c}^{+}τ^{-}ν[over ¯]_{τ})/B(Λ_{b}^{0}→Λ_{c}^{+}π^{-}π^{+}π^{-}) is measured to be 2.46±0.27±0.40, where the first uncertainty is statistical and the second systematic. The branching fraction B(Λ_{b}^{0}→Λ_{c}^{+}τ^{-}ν[over ¯]_{τ})=(1.50±0.16±0.25±0.23)% is obtained, where the third uncertainty is from the external branching fraction of the normalization channel Λ_{b}^{0}→Λ_{c}^{+}π^{-}π^{+}π^{-}. The ratio of semileptonic branching fractions R(Λ_{c}^{+})≡B(Λ_{b}^{0}→Λ_{c}^{+}τ^{-}ν[over ¯]_{τ})/B(Λ_{b}^{0}→Λ_{c}^{+}μ^{-}ν[over ¯]_{μ}) is derived to be 0.242±0.026±0.040±0.059, where the external branching fraction uncertainty from the channel Λ_{b}^{0}→Λ_{c}^{+}μ^{-}ν[over ¯]_{μ} contributes to the last term. This result is in agreement with the standard model prediction.
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- 2022
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43. Impact of the prolactin levels in breast cancer: a systematic review and meta-analysis.
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Aranha AF, Dos Anjos LG, Turri JAO, Simões RS, Maciel GAR, Baracat EC, Soares-Júnior JM, and Carvalho KC
- Subjects
- Female, Humans, Prolactin, Breast Neoplasms epidemiology, Breast Neoplasms pathology
- Abstract
Prolactin (PRL) acts stimulating the mammary glands development, and its deregulation has been associated to the emergence of several types of tumors, including breast cancer. Breast cancer represents the most prevalent malignancy in women, and the second cause of death in several countries. This tumor can be arise due to several molecular alterations, among them PRL has been the object of increasing interest from researchers worldwide., Objective: To assess the association between elevated levels of plasma prolactin and breast cancer development., Methods: A total of 158 studies were found in search databases (48 from PubMed, 69 from Scopus, 88 from Cochrane, 25 from Embase and 10 retrieved from the gray literature) after removing duplicates. Of these, 104 studies were excluded after title and abstract reading, and 54 studies were then read in full, of which only 14 were selected for this review because they had evaluated the association between PRL and breast cancer. Meta-analysis was carried out using the relative risk (RR), mean and standard deviation, confidence interval (95% CI), and the total number of patients for each study. Fixed- and random-effect models were used as applicable and, for the analysis., Results: The meta-analysis showed a positive association between elevated levels of PRL and breast cancer occurrence (RR 1.26; 95%CI 1.15-1.37). Additionally, the patient sub-group analyses showed a positive association between PRL and invasive breast cancer (1.42; 1.24-1.60), ER+/PR+ (1.49; 1.23-1.75), and post-menopausal status (1.29; 1.16-1.43)., Conclusion: The results showed a positive association between plasma prolactin levels and breast cancer, especially in women with ER+/PR + tumors, of post-menopausal age and those with invasive cancer.
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- 2022
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- View/download PDF
44. Development of parameters compatible with the CHARMM36 force field for [Fe 4 S 4 ] 2+ clusters and molecular dynamics simulations of adenosine-5'-phosphosulfate reductase in GROMACS 2019.
- Author
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da Silva TU, Pougy KC, Albuquerque MG, da Silva Lima CH, and Machado SP
- Subjects
- Adenosine, Iron, Oxidoreductases, Molecular Dynamics Simulation, Sulfur
- Abstract
DFT calculations were used to obtain parameters compatible with the CHARMM36 force field for iron-sulfur clusters (Fe-S) of the type [Fe
4 S4 ]2+ that are coordinated to dissimilatory adenosine-5'-phosphosulfate reductase (APSrAB). Classical molecular dynamics (MD) simulations were performed on two APSrAB systems to validate the parameters and verify the stability of the studied systems. The time analysis of the parameters inserted into the force field was in reasonable agreement with the experimental X-ray diffraction data. The analysis of the time evolution of the studied systems indicated that these systems and, in particular, the clusters in their respective cavities had a good stability and were in agreement with what was observed in previous works. The parameters obtained provide the basis for the study of APSrAB as well as other systems that contain [Fe4 S4 ]2+ through the CHARMM36 force field.- Published
- 2022
- Full Text
- View/download PDF
45. Reduction of Cardiac Autonomic Modulation and Increased Sympathetic Activity by Heart Rate Variability in Patients With Long COVID.
- Author
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Marques KC, Silva CC, Trindade SDS, Santos MCS, Rocha RSB, Vasconcelos PFDC, Quaresma JAS, and Falcão LFM
- Abstract
Although several clinical manifestations of persistent long coronavirus disease (COVID-19) have been documented, their effects on the cardiovascular and autonomic nervous system over the long term remain unclear. Thus, we examined the presence of alterations in cardiac autonomic functioning in individuals with long-term manifestations. The study was conducted from October 2020 to May 2021, and an autonomic assessment was performed to collect heart rate data for the heart rate variability (HRV) analysis. The study participants were divided into the long COVID clinical group, the intragroup, which included patients who were hospitalized, and those who were not hospitalized and were symptomatic for different periods (≤3, >3, ≤6, and >6 months), with and without dyspnoea. The control group, the intergroup, comprised of COVID-free individuals. Our results demonstrated that the long COVID clinical group showed reduced HRV compared with the COVID-19-uninfected control group. Patients aged 23-59 years developed COVID symptoms within 30 days after infection, whose diagnosis was confirmed by serologic or reverse-transcription polymerase chain reaction (swab) tests, were included in the study. A total of 155 patients with long COVID [95 women (61.29%), mean age 43.88 ± 10.88 years and 60 men (38.71%), mean age 43.93 ± 10.11 years] and 94 controls [61 women (64.89%), mean age 40.83 ± 6.31 and 33 men (35.11%), mean age 40.69 ± 6.35 years] were included. The intragroup and intergroup comparisons revealed a reduction in global HRV, increased sympathetic modulation influence, and a decrease in parasympathetic modulation in long COVID. The intragroup showed normal sympathovagal balance, while the intergroup showed reduced sympathovagal balance. Our findings indicate that long COVID leads to sympathetic excitation influence and parasympathetic reduction. The excitation can increase the heart rate and blood pressure and predispose to cardiovascular complications. Short-term HRV analysis showed good reproducibility to verify the cardiac autonomic involvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marques, Silva, Trindade, Santos, Rocha, Vasconcelos, Quaresma and Falcão.)
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- 2022
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46. Evaluation of Hedgehog Pathway Inhibitors as a Therapeutic Option for Uterine Leiomyosarcoma Using the Xenograft Model.
- Author
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Garcia N, Ulin M, Ali M, Al-Hendy A, Carvalho KC, and Yang Q
- Subjects
- Animals, Cell Line, Tumor, Female, Humans, Leiomyosarcoma metabolism, Mice, Mice, Nude, Phenotype, Signal Transduction, Uterine Neoplasms metabolism, Xenograft Model Antitumor Assays, Biphenyl Compounds pharmacology, Hedgehog Proteins antagonists & inhibitors, Hedgehog Proteins metabolism, Leiomyosarcoma drug therapy, Pyridines pharmacology, Pyrimidines pharmacology, Uterine Neoplasms drug therapy
- Abstract
Uterine leiomyosarcoma (LMS) contributes to a significant proportion of uterine cancer deaths. It is a rare and high-risk gynecological cancer. LMS is challenging to the treatment due to the resistance of several therapies. The activation of the Hedgehog (HH) pathway has been reported in several types of female cancers. Uterine LMS presents an upregulation of the crucial HH signaling pathway members such as SMO and GLI1. Although targeting the HH pathway exhibited a potent inhibitory effect on the phenotype of uterine LMS in vitro, the effect of the HH inhibitors on LMS growth in vivo has not been identified. The present study aimed to assess the effect of Hedgehog pathway inhibitors (SMO-LDE225 and GLI-Gant61) as a therapeutic option in the xenograft model of uterine LMS. The results demonstrated that LDE225 treatment did not show any inhibitory effect on LMS tumor growth; however, treatment with GLI inhibitor (Gant61) induced a remarkable tumor regression with a significant decrease in Ki67 expression, compared to control (p < 0.01). Moreover, administration of Gant61 decreased the expression of GLI1, GLI target genes BMP4 and c-MYC (p < 0.05), indicating that the HH pathway is implicated in the LMS experimental model. In conclusion, our studies demonstrate for the first time that GLI inhibitor (Gant61), but not SMO inhibitor (LDE225), shows a potent inhibitory effect on LMS tumor growth and concomitantly suppresses the expression of GLI1- and GLI-targeted genes using the xenograft model of uterine LMS., (© 2021. The Author(s).)
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- 2022
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- View/download PDF
47. Study of Z Bosons Produced in Association with Charm in the Forward Region.
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Aaij R, Abdelmotteleb ASW, Beteta CA, Gallego FJA, Ackernley T, Adeva B, Adinolfi M, Afsharnia H, Agapopoulou C, Aidala CA, Aiola S, Ajaltouni Z, Akar S, Albrecht J, Alessio F, Alexander M, Albero AA, Aliouche Z, Alkhazov G, Cartelle PA, Amato S, Amey JL, Amhis Y, An L, Anderlini L, Andreianov A, Andreotti M, Archilli F, Artamonov A, Artuso M, Arzymatov K, Aslanides E, Atzeni M, Audurier B, Bachmann S, Bachmayer M, Back JJ, Rodriguez PB, Balagura V, Baldini W, Leite JB, Barbetti M, Barlow RJ, Barsuk S, Barter W, Bartolini M, Baryshnikov F, Basels JM, Bashir S, Bassi G, Batsukh B, Battig A, Bay A, Beck A, Becker M, Bedeschi F, Bediaga I, Beiter A, Belavin V, Belin S, Bellee V, Belous K, Belov I, Belyaev I, Bencivenni G, Ben-Haim E, Berezhnoy A, Bernet R, Berninghoff D, Bernstein HC, Bertella C, Bertolin A, Betancourt C, Betti F, Bezshyiko I, Bhasin S, Bhom J, Bian L, Bieker MS, Bifani S, Billoir P, Birch M, Bishop FCR, Bitadze A, Bizzeti A, Bjørn M, Blago MP, Blake T, Blanc F, Blusk S, Bobulska D, Boelhauve JA, Garcia OB, Boettcher T, Boldyrev A, Bondar A, Bondar N, Borghi S, Borisyak M, Borsato M, Borsuk JT, Bouchiba SA, Bowcock TJV, Boyer A, Bozzi C, Bradley MJ, Braun S, Rodriguez AB, Brodzicka J, Gonzalo AB, Brundu D, Buonaura A, Buonincontri L, Burke AT, Burr C, Bursche A, Butkevich A, Butter JS, Buytaert J, Byczynski W, Cadeddu S, Cai H, Calabrese R, Calefice L, Diaz LC, Cali S, Calladine R, Calvi M, Gomez MC, Magalhaes PC, Campana P, Quezada AFC, Capelli S, Capriotti L, Carbone A, Carboni G, Cardinale R, Cardini A, Carli I, Carniti P, Carus L, Akiba KC, Vidal AC, Casse G, Cattaneo M, Cavallero G, Celani S, Cerasoli J, Cervenkov D, Chadwick AJ, Chapman MG, Charles M, Charpentier P, Chatzikonstantinidis G, Barajas CAC, Chefdeville M, Chen C, Chen S, Chernov A, Chobanova V, Cholak S, Chrzaszcz M, Chubykin A, Chulikov V, Ciambrone P, Cicala MF, Vidal XC, Ciezarek G, Clarke PEL, Clemencic M, Cliff HV, Closier J, Cobbledick JL, Coco V, Coelho JAB, Cogan J, Cogneras E, Cojocariu L, Collins P, Colombo T, Congedo L, Contu A, Cooke N, Coombs G, Corredoira I, Corti G, Sobral CMC, Couturier B, Craik DC, Crkovská J, Torres MC, Currie R, Da Silva CL, Dadabaev S, Dai L, Dall'Occo E, Dalseno J, D'Ambrosio C, Danilina A, d'Argent P, Davies JE, Davis A, Francisco OA, De Bruyn K, De Capua S, De Cian M, De Miranda JM, De Paula L, De Serio M, De Simone D, De Simone P, De Vellis F, de Vries JA, Dean CT, Debernardis F, Decamp D, Dedu V, Del Buono L, Delaney B, Dembinski HP, Dendek A, Denysenko V, Derkach D, Deschamps O, Desse F, Dettori F, Dey B, Di Cicco A, Di Nezza P, Didenko S, Maronas LD, Dijkstra H, Dobishuk V, Dong C, Donohoe AM, Dordei F, Dos Reis AC, Douglas L, Dovbnya A, Downes AG, Dudek MW, Dufour L, Duk V, Durante P, Durham JM, Dutta D, Dziurda A, Dzyuba A, Easo S, Egede U, Egorychev V, Eidelman S, Eisenhardt S, Ek-In S, Eklund L, Ely S, Ene A, Epple E, Escher S, Eschle J, Esen S, Evans T, Falabella A, Fan J, Fan Y, Fang B, Farry S, Fazzini D, Féo M, Prieto AF, Fernez AD, Ferrari F, Lopes LF, Rodrigues FF, Sole SF, Ferrillo M, Ferro-Luzzi M, Filippov S, Fini RA, Fiorini M, Firlej M, Fischer KM, Fitzgerald DS, Fitzpatrick C, Fiutowski T, Fkiaras A, Fleuret F, Fontana M, Fontanelli F, Forty R, Foulds-Holt D, Lima VF, Sevilla MF, Frank M, Franzoso E, Frau G, Frei C, Friday DA, Fu J, Fuehring Q, Gabriel E, Galati G, Torreira AG, Galli D, Gambetta S, Gan Y, Gandelman M, Gandini P, Gao Y, Garau M, Martin LMG, Moreno PG, Pardiñas JG, Plana BG, Rosales FAG, Garrido L, Gaspar C, Geertsema RE, Gerick D, Gerken LL, Gersabeck E, Gersabeck M, Gershon T, Gerstel D, Giambastiani L, Gibson V, Giemza HK, Gilman AL, Giovannetti M, Gioventù A, Gironell PG, Giubega L, Giugliano C, Gizdov K, Gkougkousis EL, Gligorov VV, Göbel C, Golobardes E, Golubkov D, Golutvin A, Gomes A, Fernandez SG, Abrantes FG, Goncerz M, Gong G, Gorbounov P, Gorelov IV, Gotti C, Govorkova E, Grabowski JP, Grammatico T, Cardoso LAG, Graugés E, Graverini E, Graziani G, Grecu A, Greeven LM, Grieser NA, Grillo L, Gromov S, Cazon BRG, Gu C, Guarise M, Guittiere M, Günther PA, Gushchin E, Guth A, Guz Y, Gys T, Hadavizadeh T, Haefeli G, Haen C, Haimberger J, Halewood-Leagas T, Hamilton PM, Hammerich JP, Han Q, Han X, Hancock TH, Hansen EB, Hansmann-Menzemer S, Harnew N, Harrison T, Hasse C, Hatch M, He J, Hecker M, Heijhoff K, Heinicke K, Hennequin AM, Hennessy K, Henry L, Heuel J, Hicheur A, Hill D, Hilton M, Hollitt SE, Hou R, Hou Y, Hu J, Hu J, Hu W, Hu X, Huang W, Huang X, Hulsbergen W, Hunter RJ, Hushchyn M, Hutchcroft D, Hynds D, Ibis P, Idzik M, Ilin D, Ilten P, Inglessi A, Ishteev A, Ivshin K, Jacobsson R, Jage H, Jakobsen S, Jans E, Jashal BK, Jawahery A, Jevtic V, Jiang F, John M, Johnson D, Jones CR, Jones TP, Jost B, Jurik N, Kadavath SHK, Kandybei S, Kang Y, Karacson M, Karpov M, Keizer F, Keller DM, Kenzie M, Ketel T, Khanji B, Kharisova A, Kholodenko S, Kirn T, Kirsebom VS, Kitouni O, Klaver S, Kleijne N, Klimaszewski K, Kmiec MR, Koliiev S, Kondybayeva A, Konoplyannikov A, Kopciewicz P, Kopecna R, Koppenburg P, Korolev M, Kostiuk I, Kot O, Kotriakhova S, Kravchenko P, Kravchuk L, Krawczyk RD, Kreps M, Kress F, Kretzschmar S, Krokovny P, Krupa W, Krzemien W, Kucharczyk M, Kudryavtsev V, Kuindersma HS, Kunde GJ, Kvaratskheliya T, Lacarrere D, Lafferty G, Lai A, Lampis A, Lancierini D, Lane JJ, Lane R, Lanfranchi G, Langenbruch C, Langer J, Lantwin O, Latham T, Lazzari F, Le Gac R, Lee SH, Lefèvre R, Leflat A, Legotin S, Leroy O, Lesiak T, Leverington B, Li H, Li P, Li S, Li Y, Li Y, Li Z, Liang X, Lin T, Lindner R, Lisovskyi V, Litvinov R, Liu G, Liu H, Liu Q, Liu S, Salvia AL, Loi A, Castro JL, Longstaff I, Lopes JH, Solino SL, Lovell GH, Lu Y, Lucarelli C, Lucchesi D, Luchuk S, Martinez ML, Lukashenko V, Luo Y, Lupato A, Luppi E, Lupton O, Lusiani A, Lyu X, Ma L, Ma R, Maccolini S, Machefert F, Maciuc F, Macko V, Mackowiak P, Maddrell-Mander S, Madejczyk O, Mohan LRM, Maev O, Maevskiy A, Maisuzenko D, Majewski MW, Malczewski JJ, Malde S, Malecki B, Malinin A, Maltsev T, Malygina H, Manca G, Mancinelli G, Manuzzi D, Marangotto D, Maratas J, Marchand JF, Marconi U, Mariani S, Benito CM, Marinangeli M, Marks J, Marshall AM, Marshall PJ, Martelli G, Martellotti G, Martinazzoli L, Martinelli M, Santos DM, Vidal FM, Massafferri A, Materok M, Matev R, Mathad A, Matiunin V, Matteuzzi C, Mattioli KR, Mauri A, Maurice E, Mauricio J, Mazurek M, McCann M, Mcconnell L, Mcgrath TH, Mchugh NT, McNab A, McNulty R, Mead JV, Meadows B, Meier G, Meinert N, Melnychuk D, Meloni S, Merk M, Merli A, Garcia LM, Mikhasenko M, Milanes DA, Millard E, Milovanovic M, Minard MN, Minotti A, Minzoni L, Mitchell SE, Mitreska B, Mitzel DS, Mödden A, Mohammed RA, Moise RD, Mokhnenko S, Mombächer T, Monroy IA, Monteil S, Morandin M, Morello G, Morello MJ, Moron J, Morris AB, Morris AG, Mountain R, Mu H, Muheim F, Mulder M, Müller D, Müller K, Murphy CH, Murray D, Muzzetto P, Naik P, Nakada T, Nandakumar R, Nanut T, Nasteva I, Needham M, Neri I, Neri N, Neubert S, Neufeld N, Newcombe R, Niel EM, Nieswand S, Nikitin N, Nolte NS, Normand C, Nunez C, Oblakowska-Mucha A, Obraztsov V, Oeser T, O'Hanlon DP, Okamura S, Oldeman R, Oliva F, Olivares ME, Onderwater CJG, O'Neil RH, Goicochea JMO, Ovsiannikova T, Owen P, Oyanguren A, Padeken KO, Pagare B, Pais PR, Pajero T, Palano A, Palutan M, Pan Y, Panshin G, Papanestis A, Pappagallo M, Pappalardo LL, Pappenheimer C, Parker W, Parkes C, Passalacqua B, Passaleva G, Pastore A, Patel M, Patrignani C, Pawley CJ, Pearce A, Pellegrino A, Altarelli MP, Perazzini S, Pereima D, Castro AP, Perret P, Petric M, Petridis K, Petrolini A, Petrov A, Petrucci S, Petruzzo M, Pham TTH, Philippov A, Pica L, Piccini M, Pietrzyk B, Pietrzyk G, Pili M, Pinci D, Pisani F, Pizzichemi M, K RP, Placinta V, Plews J, Casasus MP, Polci F, Lener MP, Poliakova M, Poluektov A, Polukhina N, Polyakov I, Polycarpo E, Ponce S, Popov D, Popov S, Poslavskii S, Prasanth K, Promberger L, Prouve C, Pugatch V, Puill V, Pullen H, Punzi G, Qi H, Qian W, Qin J, Qin N, Quagliani R, Quintana B, Raab NV, Trejo RIR, Rachwal B, Rademacker JH, Rama M, Pernas MR, Rangel MS, Ratnikov F, Raven G, Reboud M, Redi F, Reiss F, Alepuz CR, Ren Z, Renaudin V, Ribatti R, Ricciardi S, Rinnert K, Robbe P, Robertson G, Rodrigues AB, Rodrigues E, Lopez JAR, Rodriguez ERRR, Rollings A, Roloff P, Romanovskiy V, Lamas MR, Vidal AR, Roth JD, Rotondo M, Rudolph MS, Ruf T, Fernandez RAR, Vidal JR, Ryzhikov A, Ryzka J, Silva JJS, Sagidova N, Sahoo N, Saitta B, Salomoni M, Gras CS, Santacesaria R, Rios CS, Santimaria M, Santovetti E, Saranin D, Sarpis G, Sarpis M, Sarti A, Satriano C, Satta A, Saur M, Savrina D, Sazak H, Smead LGS, Scarabotto A, Schael S, Scherl S, Schiller M, Schindler H, Schmelling M, Schmidt B, Schmitt S, Schneider O, Schopper A, Schubiger M, Schulte S, Schune MH, Schwemmer R, Sciascia B, Sellam S, Semennikov A, Soares MS, Sergi A, Serra N, Sestini L, Seuthe A, Shang Y, Shangase DM, Shapkin M, Shchemerov I, Shchutska L, Shears T, Shekhtman L, Shen Z, Shevchenko V, Shields EB, Shimizu Y, Shmanin E, Shupperd JD, Siddi BG, Coutinho RS, Simi G, Simone S, Skidmore N, Skwarnicki T, Slater MW, Slazyk I, Smallwood JC, Smeaton JG, Smetkina A, Smith E, Smith M, Snoch A, Soares M, Lavra LS, Sokoloff MD, Soler FJP, Solovev A, Solovyev I, De Almeida FLS, De Paula BS, Spaan B, Norella ES, Spradlin P, Stagni F, Stahl M, Stahl S, Stanislaus S, Steinkamp O, Stenyakin O, Stevens H, Stone S, Straticiuc M, Strekalina D, Suljik F, Sun J, Sun L, Sun Y, Svihra P, Swallow PN, Swientek K, Szabelski A, Szumlak T, Szymanski M, Taneja S, Tanner AR, Tat MD, Terentev A, Teubert F, Thomas E, Thompson DJD, Thomson KA, Tisserand V, T'Jampens S, Tobin M, Tomassetti L, Tong X, Machado DT, Tou DY, Trifonova E, Trippl C, Tuci G, Tully A, Tuning N, Ukleja A, Unverzagt DJ, Ursov E, Usachov A, Ustyuzhanin A, Uwer U, Vagner A, Vagnoni V, Valassi A, Valenti G, Canudas NV, van Beuzekom M, Van Dijk M, Van Hecke H, van Herwijnen E, Van Hulse CB, van Veghel M, Gomez RV, Regueiro PV, Sierra CV, Vecchi S, Velthuis JJ, Veltri M, Venkateswaran A, Veronesi M, Vesterinen M, Vieira D, Diaz MV, Viemann H, Vilasis-Cardona X, Figueras EV, Villa A, Vincent P, Volle FC, Bruch DV, Vorobyev A, Vorobyev V, Voropaev N, Vos K, Waldi R, Walsh J, Wang C, Wang J, Wang J, Wang J, Wang J, Wang M, Wang R, Wang Y, Wang Z, Wang Z, Wang Z, Ward JA, Watson NK, Weber SG, Websdale D, Weisser C, Westhenry BDC, White DJ, Whitehead M, Wiederhold AR, Wiedner D, Wilkinson G, Wilkinson M, Williams I, Williams M, Williams MRJ, Wilson FF, Wislicki W, Witek M, Witola L, Wormser G, Wotton SA, Wu H, Wyllie K, Xiang Z, Xiao D, Xie Y, Xu A, Xu J, Xu L, Xu M, Xu Q, Xu Z, Xu Z, Yang D, Yang S, Yang Y, Yang Z, Yang Z, Yao Y, Yeomans LE, Yin H, Yu J, Yuan X, Yushchenko O, Zaffaroni E, Zavertyaev M, Zdybal M, Zenaiev O, Zeng M, Zhang D, Zhang L, Zhang S, Zhang S, Zhang Y, Zhang Y, Zharkova A, Zhelezov A, Zheng Y, Zhou T, Zhou X, Zhou Y, Zhovkovska V, Zhu X, Zhu X, Zhu Z, Zhukov V, Zonneveld JB, Zou Q, Zucchelli S, Zuliani D, and Zunica G
- Abstract
Events containing a Z boson and a charm jet are studied for the first time in the forward region of proton-proton collisions. The data sample used corresponds to an integrated luminosity of 6 fb^{-1} collected at a center-of-mass energy of 13 TeV with the LHCb detector. In events with a Z boson and a jet, the fraction of charm jets is determined in intervals of Z-boson rapidity in the range 2.0
- Published
- 2022
- Full Text
- View/download PDF
48. Clinical and molecular characterization of a large cohort of childhood onset hereditary spastic paraplegias.
- Author
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Giordani GM, Diniz F, Fussiger H, Gonzalez-Salazar C, Donis KC, Freua F, Ortega RPM, de Freitas JL, Barsottini OGP, Rosemberg S, Kok F, Pedroso JL, França MC Jr, and Saute JAM
- Subjects
- Adolescent, Adult, Age of Onset, Alleles, Brazil epidemiology, Child, Cohort Studies, Disease Management, Disease Susceptibility, Female, Genetic Predisposition to Disease, Genotype, High-Throughput Nucleotide Sequencing, Humans, Magnetic Resonance Imaging, Male, Phenotype, Population Surveillance, Spastic Paraplegia, Hereditary epidemiology, Spastin genetics, Symptom Assessment, Young Adult, Spastic Paraplegia, Hereditary diagnosis, Spastic Paraplegia, Hereditary etiology
- Abstract
The present study aimed to characterize clinical and molecular data of a large cohort of subjects with childhood-onset hereditary spastic paraplegias (HSPs). A multicenter historical cohort was performed at five centers in Brazil, in which probands and affected relatives' data from consecutive families with childhood-onset HSP (onset < 12 years-old) were reviewed from 2011 to 2020. One hundred and six individuals (83 families) with suspicion of childhood-onset HSP were evaluated, being 68 (50 families) with solved genetic diagnosis, 6 (5 families) with candidate variants in HSP-related genes and 32 (28 families) with unsolved genetic diagnosis. The most common childhood-onset subtype was SPG4, 11/50 (22%) families with solved genetic diagnosis; followed by SPG3A, 8/50 (16%). Missense pathogenic variants in SPAST were found in 54.5% of probands, favoring the association of this type of variant to childhood-onset SPG4. Survival curves to major handicap and cross-sectional Spastic Paraplegia Rating Scale progressions confirmed the slow neurological deterioration in SPG4 and SPG3A. Most common complicating features and twenty variants not previously described in HSP-related genes were reported. These results are fundamental to understand the molecular and clinical epidemiology of childhood-onset HSP, which might help on differential diagnosis, patient care and guiding future collaborative trials for these rare diseases., (© 2021. The Author(s).)
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- 2021
- Full Text
- View/download PDF
49. Thiamine deficiency and recovery: impact of recurrent episodes and beneficial effect of treatment with Trolox and dimethyl sulfoxide.
- Author
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Gomes KC, Lima FWB, da Silva Aguiar HQ, de Araújo SS, de Cordova CAS, and de Cordova FM
- Subjects
- Animals, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents pharmacology, Antioxidants administration & dosage, Antioxidants pharmacology, Behavior, Animal drug effects, Chromans administration & dosage, Dimethyl Sulfoxide administration & dosage, Disease Models, Animal, Locomotion drug effects, Male, Mice, Recurrence, Spatial Memory drug effects, Chromans pharmacology, Dimethyl Sulfoxide pharmacology, Thiamine administration & dosage, Thiamine Deficiency drug therapy
- Abstract
At present, thiamine deficiency (TD) is managed with administration of high doses of thiamine. Even so, severe and permanent neurological disorders can occur in recurrent episodes of TD. In this study, we used a murine model to assess the efficacy of TD recovery treatments using thiamine with or without additional administration of the antioxidant Trolox or the anti-inflammatory dimethyl sulfoxide (DMSO) after a single or recurrent episode of TD. TD was induced for 9 days with deficient chow and pyrithiamine, and the recovery period was 7 days with standard amounts of chow and thiamine, Trolox, and/or DMSO. After these periods, we evaluated behavior, histopathology, and ERK1/2 modulation in the brain. Deficient animals showed reductions in locomotor activity, motor coordination, and spatial memory. Morphologically, after a single episode of TD and recovery, deficient mice showed neuronal vacuolization in the dorsal thalamus and, after two episodes, a reduction in neuronal cell number. These effects were attenuated or reversed by the recovery treatments, mainly in the treatments with thiamine associated with Trolox or DMSO. Deficient animals showed a strong increase in ERK1/2 phosphorylation in the thalamus, hippocampus, and cerebral cortex after one deficiency episode and recovery. Interestingly, after recurrent TD and recovery, ERK1/2 phosphorylation remained high only in the deficient mice treated with thiamine and/or Trolox or thiamine with DMSO. Our data suggest that a protocol for TD treatment with thiamine in conjunction with Trolox or DMSO enhances the recovery of animals and possibly minimizes the late neurological sequelae., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2021
- Full Text
- View/download PDF
50. Insights into the activation of oral keratinocyte cell death by Candida albicans and Staphylococcus aureus biofilms.
- Author
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Dias KC, Barbugli PA, and Vergani CE
- Subjects
- Biofilms, Cell Death, Keratinocytes, Candida albicans, Staphylococcus aureus
- Abstract
Polymicrobial biofilms comprising Candida albicans and Staphylococcus aureus can increase the frequency and severity of oral diseases. This study assessed oral keratinocyte cell death, apoptosis and/or necrosis, promoted by soluble factors from single and dual biofilms of S. aureus and C. albicans . The soluble factors were obtained from the 16-h biofilm growth media. Cell viability was assessed by MTT and cell membrane damage by LDH. SEM was used for morphology changes. Assessment of apoptosis and necrosis was performed using annexin V and propidium iodide and caspases -2, -3, -6, -8 and -9. Statistical analysis was conducted with ANOVA and Tukey tests (α = 5%). Dual biofilms promoted the greatest harmful effect on oral cells, with a viability rate of 31.76%, damage to cell membranes and LDH released. Dual biofilms also induced higher percentages of necrotic cells (24.95%). Apoptosis was associated with caspases -2, -3, -6 and -8 activation.
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- 2021
- Full Text
- View/download PDF
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