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A Doença Meningocócica tem sido um sério problema de saúde pública no município do Rio de Janeiro nos últimos 10 anos, com altas taxas de incidência em crianças de baixa idade, elevada letalidade e predomínio do sorogrupo B. Em dezembro de 1994 foi realizada a segunda campanha de vacinação anti-meningocócica contra os sorogrupos B e C, visando à imunização de crianças de 6 meses a 13 anos de idade. Foram vacinadas com duas doses cerca de 950 mil crianças. A vacina utilizada foi a produzida pelo Instituto Finlay de Cuba. Em 1995 foi observada uma modificação no comportamento da doença, quando passou a predominar o sorogrupo C e aumentou a incidência global da doença, particularmente entre os menores de 1 ano, adolescentes e adultos jovens. Nos grupos etários vacinados, a incidência foi menor que no ano de 1994, em função da diminuição do sorogrupo B. Não foram observadas modificações importantes no comportamento da letalidade.

Purpose: Oral squamous cell carcinoma (OSCC) is a significant public health challenge associated with high mortality rates primarily due to its invasive and metastatic behavior. This study aimed to evaluate the expression patterns of five critical biomarkers: β-catenin, E-cadherin, podoplanin (PDPN), CXCR4, and p53 in OSCC tissues and to investigate their correlations with clinicopathologic features and patient outcomes., Methods: We conducted an immunohistochemical analysis utilizing tissue microarrays (TMAs) from 95 patients diagnosed with primary OSCC. The expression levels of the five biomarkers were quantified using H-scores. Statistical analyses, including Kruskal-Wallis tests, Dunn's post-hoc tests, and correlation analyses, were performed to explore the associations between biomarker expression, clinicopathologic parameters, and overall patient survival., Results: The study found that loss of E-cadherin and β-catenin expression was significantly associated with increased tumor depth and lymphatic invasion, corroborating their role in the process of epithelial-mesenchymal transition (EMT). High levels of PDPN were noted in both early and late-stage OSCC, indicating its potential involvement in initiating invasive behaviors. Notably, CXCR4 expression exhibited positive correlations with E-cadherin and β-catenin, suggesting a hybrid invasion phenotype incorporating both EMT and collective invasion strategies. Although Cox regression analysis did not reveal significant associations between biomarker expression and overall survival (OS) or disease-specific survival (DSS), factors such as alcohol consumption, tumor size, lymph node involvement, and advanced clinical stage emerged as significant negative predictors of both OS and DSS., Conclusion: The expression profiles of β-catenin, E-cadherin, PDPN, CXCR4, and p53 in OSCC tissues provide valuable insights into a hybrid model of invasion that integrates mechanisms of EMT with an important rule in the tumor invasion. This nuanced understanding of OSCC progression highlights the potential of PDPN and CXCR4 as novel therapeutic targets, emphasizing the need for further investigation into their roles in OSCC biology and the development of targeted treatments that could improve patient outcomes and survival rates., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective  To evaluate the effects of the botulinum toxin (BTX-A) on muscle tone and joint mobility in children with congenital Zika syndrome (CZS). Methods  This was a longitudinal case series carried out in a Support Center for Children with Microcephaly, located in Northeastern Brazil. We collected data from the institution's medical records, containing information about muscle tone and passive joint mobility measured at least 3 months before and 4 weeks after BTX-A application. Results  We evaluated 13 children (9 boys) with a mean age of 77 ± 7.1 months. After BTX-A application, a bilateral reduction in the hypertonia level was observed in the elbow flexor ( p  < 0.01) and hip abductor ( p  < 0.05) muscles. Conclusion  No changes were observed in joint mobility and no adverse effects were reported by caregivers after application. The use of BTX-A can reduce hypertonia in CZS children, with no impact on joint mobility., Competing Interests: Conflitos de Interesse Os autores não têm conflito de interesses a declarar., (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/ ).)

Split hand-foot malformation (SHFM) is a congenital limb malformation affecting primarily the central rays of the hands and/or feet, with variable expressivity, incomplete penetrance and syndromic forms. It is genetically heterogeneous, including point mutations and structural variants in different loci. Five individuals with SHFM were clinically evaluated in a Tertiary Center in Brazil: four of them presented additional, nonskeletal findings, including one individual with split foot, hand syndactyly, and ectodermal findings. Structural variants and point mutations in genes associated with SHFM were identified in all individuals. Our results highlight genetic heterogeneity observed in this group of skeletal disorders, alongside incomplete penetrance, a challenging task imposed on genetic counseling. Of note, an individual harboring a recurrent heterozygous variant in MAP3K20 presented a phenotype reminiscent of TP63-related disorders, contrary to the one recently reported in the literature with prominent facial dysmorphisms, expanding the phenotypic spectrum of this newly recognized syndromic form of SHFM., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study aimed to assess the immediate effects of transcutaneous spinal direct current stimulation (tsDCS) on pain outcomes, measured using the visual analog scale (VAS) and pressure pain thresholds in a cohort of 55 participants experiencing chronic pain using a controlled, randomized trial with 55 participants allocated into 2 groups: 2 mA and 0.5 mA of tsDCS for 20 min. Anodal stimulation was applied on the 12th thoracic vertebra, with the cathode positioned on the 7th cervical vertebra. Pain outcomes were assessed before and post intervention using the VAS and pressure algometry. Between- and within-group differences, along with chi-square tests, were used to determine the differences and responsiveness. Significance was established at p < 0.05. Findings showed significant temporal effects for both VAS ( p < 0.001) and pressure algometry ( p = 0.04). However, no between-group differences were noted for the time × group factor for VAS ( p = 0.46) and pressure algometry ( p = 0.78). No significant between-group differences were observed for the responsiveness analysis. The results indicate that a single 20-min session of 2 and 0.5 mA tsDCS improves pain scores for both intensities equally. However, there were no statistically significant between-group differences in pain perception or pressure pain threshold.

Salicylic acid (SA) is a bioregulator well-known for mitigating salinity damage in plants. However, no studies have examined the interaction between SA and salinity in Dizygostemon riparius , a species rich in bioactive molecules. Therefore, we aimed to evaluate the effect of SA application on Dizygostemon riparius under different salinity levels. A completely randomized experiment was conducted in a 2 × 3 factorial design (two SA concentrations of 0 and 100 µM and three salinity concentrations of 0, 200, and 400 mM NaCl) with five replicates. At 400 mM NaCl, leaf temperature increased by 11%, while relative water content and total soluble carbohydrates decreased by 30% and 35%, respectively, leading to reduced biomass accumulation. Notably, the SA application mitigated these effects by restoring relative water content under 400 mM NaCl and improving carboxylation efficiency and intrinsic water-use efficiency under 200 mM NaCl. Additionally, dry biomass was maintained under both 200 and 400 mM NaCl with SA treatment. These findings suggest that SA has a promising potential to alleviate salt stress in Dizygostemon riparius . Our results could inform cultivation practices, opening new perspectives on the use of SA as an attenuator of salinity stress.

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics., (© 2024 Wiley Periodicals LLC.)

Transcranial direct current stimulation (tDCS) is often reported to have positive effects on brain hemodynamics as well as cognitive performance. Binaural beats (BBs) have also shown the potential to improve cognitive performance. However, we could not find any studies assessing prefrontal hemodynamics using a combination of these techniques or assessing the effects on hemodynamic response at different intensity levels of tDCS (two and three mA). This study aimed to compare the immediate hemodynamic responses to tDCS at different intensities (two and three mA) with and without 40 Hz BBs. Sixty-eight healthy young individuals of both sexes were split into four groups: the tDCS 2 mA group; tDCS 3 mA group; tDCS 2 mA + BB group; and tDCS 3 mA + BB group. All groups received 20 min tDCS (F3-Fp2) alone or combined with BBs. The hemodynamic effect was assessed using a functional near-infrared intracranial spectroscope (fNIRS) positioned on the left supraorbital region (Fp1). The mean values of rates of oxygen saturation (SatO 2 ) were recorded at baseline, during the intervention period, and post-stimulation. The oxygenated hemoglobin rates (HbO) were also extracted. No between-group differences were observed. The within-group analysis did not show significant differences in terms of the time×groups factor. However, the time factor showed significant within-group differences. No differences were found for the HbO rates. The present findings showed that two and three mA tDCS had effects on pre-frontal cortex SatO 2 ; however, the use of additional BBs did not change the SatO 2 levels compared to the use of tDCS alone.

The present study aimed to evaluate under dairy farm conditions the predisposing factors, impact on milk production and productivity, and the role of Rhipicephalus microplus in the epidemiology of tick fever agents in Holstein calves grazing in a tropical region. A total of 4292 pure female Holsteins were evaluated at a commercial farm. Until April 2020, calves had contact with R. microplus for between 3 and 24 months, while after April 2020, no animal had further contact with ticks. Three times a week the rectal temperature (RT) of all animals was determined, and blood samples were collected for evaluation of tick fever (TF) agents from those that showed RT >39.3 °C. Specific treatment was performed against Anaplasma marginale, Babesia bigemina and Babesia bovis when these TF agents were diagnosed in the blood smears. The number of relapses and treatments for TF agents were sub-classified into scales (1, 2, 3, 4, 5, 6 or 7-10 treatments or relapses, and animals that received blood transfusions). Within each sub-class, the health data of calves during lactation along with productivity data were analyzed. Based in the results, whether an animal received colostrum enriched with powdered colostrum substitute, whether the animal was an embryo transfer calf, and the weight at which each calf was weaned were ascertained as factors leading to more recurrences or treatments against TF agents in post-weaned calves. On average, each recurrence of TF agents that a heifer presented between three and seven months decreased milk production by 213.5 liters in the first lactation. Calves that received a blood transfusion had lower milk production at first lactation; lower weight at first fixed-time artificial insemination (FTAI); older age at first FTAI; older age at first, second, and third calving; and delayed age at third calving by 140 days compared to the farm average. R. microplus was the main agent causing clinical cases of TF on the farm, and 10,770 treatments against TF agents were carried out when calves aged between three and seven months had contact with this tick species (2018 and 2019). When the animals no longer had contact with ticks (2022 and 2023), there were no recurrences or treatments against TF agents despite the presence on the farm of S. calcitrans, which can maintain the transmission of A. marginale to the herd., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Health disparities present a barrier to successful oncology treatment. The potential for precision oncology to reduce health disparities has not previously been analyzed. We performed a retrospective analysis of 12,627 patients from six major cancer centers whose tumors underwent molecular testing at Caris Life Sciences between 2010 and 2020. Kaplan-Meier and Cox regression were used to describe and analyze overall survival. The molecular and demographic features of the cohort were analyzed by χ2 and ANOVA tests. Black patients composed 25% of the cohort and White patients 63%. Among this molecularly-tested cohort, there were minimal outcome differences based on race, geographic location, or poverty level. When analyzing the interaction of age, race, and sex, racial-based disparities were noted primarily for young non-White women in the study cohort but were more pronounced for men and women of all ages in the broader patient population within the Surveillance, Epidemiology, and End Results database. Mutations in five genes-APC, EGFR, STK11, TP53, and KRAS-were found to affect overall survival among our cohort, and their prevalence varied by race in specific tumor types. Real-world outcomes data in mutation-defined cohorts also provided additional context to previously reported therapeutic response trends. Our study shows that patients who undergo molecular testing display reduced racial health disparities compared with the general population, whereas persistent racial disparities are influenced by age and sex. Genomic-driven racial disparities should be examined at a tumor lineage-specific level. Increased access to molecular testing for all eligible patients may play a role in improving health equity. Significance: This study is the largest of its kind to analyze health disparities and genomic features among a diverse multiinstitutional cohort of patients who underwent molecular testing. Continuing to increase awareness of and access to molecular testing approaches may help to reduce cancer health disparities and improve outcomes for all patients., (©2024 The Authors; Published by the American Association for Cancer Research.)

Levodopa-induced dyskinesia (LID) refers to involuntary motor movements of chronic use of levodopa in Parkinson's disease (PD) that negatively impact the overall well-being of people with this disease. The molecular mechanisms involved in LID were investigated through whole-blood transcriptomic analysis for differential gene expression and identification of new co-expression and differential co-expression networks. We found six differentially expressed genes in patients with LID, and 13 in patients without LID. We also identified 12 co-expressed genes exclusive to LID, and six exclusive hub genes involved in 23 gene-gene interactions in patients with LID. Convergently, we identified novel genes associated with PD and LID that play roles in mitochondrial dysfunction, dysregulation of lipid metabolism, and neuroinflammation. We observed significant changes in disease progression, consistent with previous findings of maladaptive plastic changes in the basal ganglia leading to the development of LID, including a chronic pro-inflammatory state in the brain., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Heliozela pitangavora Moreira & Fochezato sp. nov. (Lepidoptera: Adeloidea: Heliozelidae), a leaf miner of Eugenia uniflora L. (Myrtaceae) is described in southern Brazil. Larvae, pupae and adults are characterized using optical and scanning electron microscopy, in association with data on their life history. Mitochondrial DNA (COI) sequences are provided and compared with closely related species. Individual mines initially appear as small blotches on the adaxial surface of leaves during the summer, progressively enlarging as larvae feed on leaf parenchyma. Mature larvae build typical dehiscent shields by cutting the leaf lamina, and moulting into the final, highly modified, non-feeding instar. Pupation occurs later within these shields, in the soil litter, during autumn-winter. This is the first report for Heliozela Herrich-Säffer in Brazil, and the first record of such a host-plant species for the family worldwide.

Microcephaly is characterized by an occipitofrontal circumference at least two standard deviations below the mean for age and sex. Neurodevelopmental disorders (NDD) are commonly associated with microcephaly, due to perturbations in brain development and functioning. Given the extensive genetic heterogeneity of microcephaly, managing patients is hindered by the broad spectrum of diagnostic possibilities that exist before conducting molecular testing. We investigated the genetic basis of syndromic microcephaly accompanied by NDD in a Brazilian cohort of 45 individuals and characterized associated clinical features, as well as evaluated the effectiveness of whole-exome sequencing (WES) as a diagnostic tool for this condition. Patients previously negative for pathogenic copy number variants underwent WES, which was performed using a trio approach for isolated index cases (n = 31), only the index in isolated cases with parental consanguinity (n = 8) or affected siblings in familial cases (n = 3). Pathogenic/likely pathogenic variants were identified in 19 families (18 genes) with a diagnostic yield of approximately 45%. Nearly 86% of the individuals had global developmental delay/intellectual disability and 51% presented with behavioral disturbances. Additional frequent clinical features included facial dysmorphisms (80%), brain malformations (67%), musculoskeletal (71%) or cardiovascular (47%) defects, and short stature (54%). Our findings unraveled the underlying genetic basis of microcephaly in half of the patients, demonstrating a high diagnostic yield of WES for microcephaly and reinforcing its genetic heterogeneity. We expanded the phenotypic spectrum associated with the condition and identified a potentially novel gene (CCDC17) for congenital microcephaly., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Case Report: This case report describes the multidisciplinary approach performed in a 9-year-old male patient with dental agenesia affecting teeth 21 and 22. Autotransplantation of the right upper second premolar with incomplete rhizogenesis to the missing area was combined with coronary reshaping with resin composite and orthodontic therapy. The treatment began with the extraction of the deciduous upper left central incisor, bone preparation for the recipient site of the donor tooth, atraumatic extraction of the right upper second premolar and immediate autotransplantation in the surgically prepared recipient site. Subsequently, sutures to reposition the flap and a rigid splint were performed. After 12 months, coronary reshaping of the autotransplanted tooth with resin composite was carried out. Orthodontic treatment involving the use of a fixed appliance was used to correct the interdental spaces and achieve adequate occlusion. Clinical and radiographic follow-up 10 years after tooth autotransplantation and 9 years after reshaping revealed partial obliteration of the pulp chamber, root resorption, ankylosis and the presence of endodontic treatment., Conclusions: The long-term outcomes highlighted that tooth autotransplantation represents a biologically and cost-effective procedure for replacing missing teeth in young patients, particularly in cases of incomplete rhizogenesis of the autotransplanted tooth., Clinical Significance: This case report discusses tooth autotransplantation and resin composite reshaping as viable and long-term clinical options for treating young patients with dental agenesis., (© 2024 Wiley Periodicals LLC.)

Excessive weight (overweight and obesity) is a common disorder involving genetic and environmental factors, associated with cardiovascular diseases, type-2 diabetes, and others. NOTCH1 is critical for the maintenance of stem cells and adult tissues, being reported as a key player in metabolism and adipogenesis in animals. Thus, we test the hypothesis that NOTCH1 Single Nucleotide Polymorphisms (SNPs) are associated with excessive weight. Participants from the census-based cohort SABE (Saúde, Bem Estar e Envelhecimento-Health, Well-Being, and Aging), carried out in the city of São Paulo-Brazil, were stratified into cases and controls according to BMI. We filter the SNPs located at the start and end positions of NOTCH1 and 50 Kb on both sides. We selected SNPs with minor allelic frequency (MAF) greater than or equal to 0.01 and Hardy-Weinberg equilibrium (p > 0.05) and r 2  ≥ 0.8. We performed an association study with genotypes and haplotypes, as well as in silico functional analysis of the identified SNPs. We observed an association of the SNP rs9411207 with the risk of excessive weight, under log-additive model, and the genotype distribution showed an increased frequency of homozygous TT (OR 1.50, CI 1.20-1.88; p = 0.0002). The haplotype GAT constructed from this and other SNPs in high Linkage Disequilibrium was more frequent in excessive-weight individuals (p = 0.003). In silico analyses suggested that these SNPs are likely to affect the transcription of NOTCH1 and other genes involved in adipogenesis and metabolism. This is the first study reporting association between NOTCH1 SNPs and the risk of excessive weight. Considering the possibility of NOTCH1 modulation, additional population studies are important to replicate these data and confirm the usefulness of risk genotypes for management strategies of excessive weight., (© 2024. The Author(s).)

The fungus Phyllosticta citricarpa is a quarantine phytopathogen responsible for causing citrus black spot (CBS) disease. To export fruits to CBS-free countries, they must undergo a sanitation process to ensure disease control. In this study, neem essential oil (NEO) was tested against P. citricarpa for the first time as an alternative sanitizer. In vitro experiments were conducted to determine the inhibition concentration of NEO for P. citricarpa , and the mode of action of the essential oil was evaluated. In vivo assays were performed to simulate the sanitization process used in packinghouses. NEO was characterized by GC-MS/MS. The results revealed that NEO at 100  μ L·mL -1 exhibited a similar inhibitory effect as copper oxychloride, suppressing 89.68 ± 1.14% of fungal mycelium growth. Fluorescence microscopy experiments demonstrated that NEO functions by disrupting the cytoplasmic membrane of fungal hyphae, leading to their death within 30 minutes of contact with NEO. GC-MS/MS characterization revealed a high presence of phenolic compounds, which serve as the primary antifungal agents responsible for the action against fungal hyphae. In vivo assays showed that NEO at 100  μ L·mL -1 also reduced microorganisms (CFU mL -1 ) by 93.00 ± 3.88% compared to the negative control. Overall, the results demonstrate that NEO can effectively serve as an alternative sanitizer against P. citricarpa in citrus packinghouses. Our findings allow future studies to explore the use of NEO for sanitizing other fruits and combating different phytopathogens to broaden its potential application in fruit sanitation for export., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 Joyce Maria Schuch et al.)

Introduction: Solid pseudopapillary tumor is a low-grade malignancy of the pancreas and predominantly affects young women. This neoplasm is a rare pancreatic entity with vague clinical presentation. Diagnosis is often incidental through imaging or even during surgical approach for another condition., Case Presentation: A 22-year-old Brazilian female with gastrointestinal symptoms was diagnosed with achalasia and underwent Heller myotomy. Intraoperatory findings included an enlarging mass in the distal pancreas. During follow-up for the surgical approach of achalasia, a hypothesis of Frantz's tumor was stated, and spleen-preserving distal pancreatectomy was performed., Discussion: The pathological pathways of Frantz's tumor is still unclear, and its connection with chromosomal abnormalities is under investigation. Although the tumor has been reclassified over the years to solid pseudopapillary tumor, surgical resection remains the standard treatment., Conclusion: Despite a surgical challenge, surgery presents a great prognosis in these patients and long-term survival. High suspicion and proper investigation are fundamental to diagnosis and early treatment., Competing Interests: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Providing accurate, evidence-based information to women with Zika infection during pregnancy was problematic because of the high degree of uncertainty in the diagnosis of the infection and the associated risk. The 2015-17 Zika virus epidemic overwhelmingly affected women in countries with limited access to safe abortion. Understanding women's perspectives on risk communication during pregnancy in the context of an emerging pathogen can help inform risk communication in response to future outbreaks that affect fetal or child development. We conducted a cross-sectional qualitative interview study with 73 women from 7 locations in Brazil, Colombia, and Puerto Rico to understand women's experiences of Zika virus (ZIKV) test and outcome-related communication during the ZIKV pandemic. We used thematic analysis to analyze the in-depth interviews. Participants in Brazil and Colombia reported that the healthcare system's lack of preparation and organization in communicating ZIKV test results and associated adverse outcomes led to their feeling abandoned and alone in confronting the challenges of a ZIKV-affected pregnancy. In contrast, participants in Puerto Rico reported that the regular testing schedules and clear, well-planned communication between the care team and between providers and pregnant women helped them to feel they could prepare for a ZIKV-affected pregnancy. Communication of the risk associated with an emerging pathogen suspected to affect pregnancy and developmental outcomes is a fraught issue. Public health authorities and healthcare providers should work together in the interpandemic period to understand families' preferences for risk communication during pregnancy in the presence of uncertainty and develop a community-informed plan for risk communication., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Montoya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study aimed to compare the insertion torque (IT), flexural strength (FS) and surface alterations between stainless steel (SS-MIs) and titanium alloy (Ti-MIs) orthodontic mini-implants., Methods: Twenty-four MIs (2 x 10 mm; SS-MIs, n = 12; Ti-MIs, n = 12) were inserted on artificial bone blocks of 20 lb/ft3 (20 PCF) and 40 lb/ft3 (40 PCF) density. The maximum IT was recorded using a digital torque meter. FS was evaluated at 2, 3 and 4 mm-deflection. Surface topography and chemical composition of MIs were assessed by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). General linear and mixed models were used to assess the effect of the MI type, bone density and deflection on the evaluated outcomes., Results: The IT of Ti-MIs was 1.1 Ncm greater than that obtained for the SS-MIs (p= 0.018). The IT for MIs inserted in 40 PCF test blocks was 5.4 Ncm greater than that for those inserted in 20 PCF test blocks (p < 0.001). SS-MIs inserted in higher density bone (40 PCF) had significantly higher flexural strength than the other groups, at 2 mm (98.7 ± 5.1 Ncm), 3 mm (112.0 ± 3.9 Ncm) and 4 mm (120.0 ± 3.4 Ncm) of deflection (p< 0.001). SEM evidenced fractures in the Ti-MIs. EDS revealed incorporation of 18% of C and 2.06% of O in the loaded SS-MIs, and 3.91% of C in the loaded Ti-MIs., Conclusions: Based on the findings of this in vitro study, it seems that SS-MIs offer sufficient stability and exhibit greater mechanical strength, compared to Ti-MIs when inserted into higher density bone.

COVID-19 is a devastating disease and imbalanced matrix metalloproteinase (MMP) activity may contribute to its pathophysiology. This exploratory study examined whether increased circulating concentrations of MMP-2 and MMP-9, and their endogenous inhibitors, the tissue inhibitors of MMP (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4 are persistently found in patients 2 weeks after their recovery from severe or critical COVID-19 as compared with those in healthy controls. Subjects who had severe (n = 26) or critical (n = 25) PCR-confirmed COVID-19 and healthy controls (n = 21) had blood samples drawn 2 weeks after recovery and serum MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were determined using two Human Luminex® Discovery Assays. Circulating MMP activity was also determined by gel zymography. Patients who had severe or critical COVID-19 had increased circulating MMP-9 and MMP-2 concentrations, with increased MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios indicating increased MMP activity, confirmed by gel zymography (all p < 0.05). Higher circulating MMP-9 (but not MMP-2) concentrations were found in critical versus severe COVID-19 (p < 0.05). We found increased circulating MMP-9 and MMP-2 concentrations and activity many days after recovery from the acute disease, with MMP-9 levels associated with disease severity. These biochemical alterations suggest that MMP-2 and MMP-9 may be important pharmacological targets in COVID-19., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Aims: Evaluate the existing evidence of osteoradionecrosis (ORN) treatment in adults with head and neck cancer, the methodological quality and the evidence grade within systematic reviews (SRs)., Methods: An extensive systematic literature search of SRs that addressed ORN in head and neck cancer patients was conducted with screening of eligible studies, data extraction, methodological (AMSTAR 2) and evidence quality assessment (GRADE) of the SRs by independent and calibrated authors., Results: A total of six SRs were enrolled. Based primarily on studies from the 1990s, there is critically low- or moderate-quality evidence that hyperbaric oxygen therapy (HBO) improves ORN healing. From 2005 onward, evidence has been discovered in relation to treatment with pentoxifylline and tocopherol (PENTO). The SRs indicate that the management of ORN with PENTO appears to be promising. The greatest rates of healing are seen in mild and moderate stages of ORN. However, the quality of evidence regarding PENTO, surgery and other treatments remains critically low., Conclusion: There is no standardized protocol to treat ORN. PENTO appears to be the most promising conservative treatment; however, the current level of evidence regarding PENTO is still critically low. More robust clinical studies are needed to establish the best treatment for ORN., (© 2023 Special Care Dentistry Association and Wiley Periodicals LLC.)

Recently, a classification with four types of septal longitudinal strain patterns was described using echocardiography, suggesting a pathophysiological continuum of left bundle branch block (LBBB)-induced left ventricle (LV) remodeling. The aim of this study was to assess the feasibility of classifying these strain patterns using cardiovascular magnetic resonance (CMR), and to evaluate their association with LV remodeling and myocardial scar. Single center registry included LBBB patients with septal flash (SF) referred to CMR to assess the cause of LV systolic dysfunction. Semi-automated feature-tracking cardiac resonance (FT-CMR) was used to quantify myocardial strain and detect the four strain patterns. A total of 115 patients were studied (age 66 ± 11 years, 57% men, 28% with ischemic heart disease). In longitudinal strain analysis, 23 patients (20%) were classified in stage LBBB-1, 37 (32.1%) in LBBB-2, 25 (21.7%) in LBBB-3, and 30 (26%) in LBBB-4. Patients at higher stages had more prominent septal flash, higher LV volumes, lower LV ejection fraction, and lower absolute strain values (p < 0.05 for all). Late gadolinium enhancement (LGE) was found in 55% of the patients (n = 63). No differences were found between the strain patterns regarding the presence, distribution or location of LGE. Among patients with LBBB, there was a good association between strain patterns assessed by FT-CMR analysis and the degree of LV remodeling and LV dysfunction. This association seems to be independent from the presence and distribution of LGE., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: This study aimed to evaluate silver nanoparticles (AgNPs) obtained by a 'green' route associated or not to tyrosol (TYR) against Streptococcus mutans and Candida albicans in planktonic and biofilms states., Methods: AgNPs were obtained by a 'green' route using pomegranate extract. The minimum inhibitory concentration (MIC) against S. mutans and C. albicans was determined for AgNPs and TYR combined and alone, and fractional inhibitory concentration index (FICI) was calculated. Single biofilms of C. albicans and S. mutans were cultivated for 24 h and then treated with drugs alone or in combination for 24 h., Results: AgNPs and TYR were effective against C. albicans and S. mutans considering planktonic cells alone and combined. The MIC values obtained for C. albicans was 312.5 µg/mL (AgNPs) and 50 mM (TYR) and for S. mutans was 78.1 µg/mL (AgNPs) and 90 mM (TYR). The combination of these antimicrobial agents was also effective against both microorganisms: 2.44 µg/mL/0.08 mM (AgNPs/TYR) for C. albicans and 39.05 µg/mL /1.25 mM (AgNPs/TYR) for S. mutans. However, synergism was observed only for C. albicans (FICI 0.008). When biofilm was evaluated, a reduction of 4.62 log 10 was observed for S. mutans biofilm cells treated with AgNPs (p < 0.05, Tukey test). However, the addition of TYR to AgNPs did not improve their action against biofilm cells (p > 0.05). AgNPs combined with TYR demonstrated a synergistic effect against C. albicans biofilms., Conclusions: These findings suggest the potential use of AgNPs with or without TYR against C. albicans and S. mutans, important oral pathogens., Clinical Significance: AgNPs obtained by a 'green' route combined or not with TYR can be an alternative to develop several types of oral antimicrobial therapies and biomaterials., 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 © 2024. Published by Elsevier Ltd.)

Bladder carcinoma (BC) is the tenth most frequent malignancy worldwide, with high morbidity and mortality rates. Despite recent treatment advances, high-grade BC and muscle-invasive BC present with significant progression and recurrence rates, urging the need for alternative treatments. The microRNA-21 (miR-21) has superexpression in many malignancies and is associated with cellular invasion and progression. One of its mechanisms of action is the regulation of RECK, a tumor suppressor gene responsible for inhibiting metalloproteinases, including MMP9. In a high-grade urothelial cancer cell line, we aimed to assess if miR-21 downregulation would promote RECK expression and decrease MMP9 expression. We also evaluated cellular migration and proliferation potential by inhibition of this pathway. In a T24 cell line, we inhibited miR-21 expression by transfection of a specific microRNA inhibitor (anti-miR-21). There were also control and scramble groups, the last with a negative microRNA transfected. After the procedure, we performed a genetic expression analysis of miR-21, RECK, and MMP9 through qPCR. Migration, proliferation, and protein expression were evaluated via wound healing assay, colony formation assay, flow cytometry, and immunofluorescence.After anti-miR-21 transfection, miR-21 expression decreased with RECK upregulation and MMP9 downregulation. The immunofluorescence assay showed a significant increase in RECK protein expression (p < 0.0001) and a decrease in MMP9 protein expression (p = 0.0101). The anti-miR-21 transfection significantly reduced cellular migration in the wound healing assay (p < 0.0001). Furthermore, in the colony formation assay, the anti-miR-21 group demonstrated reduced cellular proliferation (p = 0.0008), also revealed in the cell cycle analysis by flow cytometry (p = 0.0038). Our results corroborate the hypothesis that miR-21 is associated with BC cellular migration and proliferation, revealing its potential as a new effective treatment for this pathology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: There are no conflicts of interest.

Microcephaly presents heterogeneous genetic etiology linked to several neurodevelopmental disorders (NDD). Copy number variants (CNVs) are a causal mechanism of microcephaly whose investigation is a crucial step for unraveling its molecular basis. Our purpose was to investigate the burden of rare CNVs in microcephalic individuals and to review genes and CNV syndromes associated with microcephaly. We performed chromosomal microarray analysis (CMA) in 185 Brazilian patients with microcephaly and evaluated microcephalic patients carrying < 200 kb CNVs documented in the DECIPHER database. Additionally, we reviewed known genes and CNV syndromes causally linked to microcephaly through the PubMed, OMIM, DECIPHER, and ClinGen databases. Rare clinically relevant CNVs were detected in 39 out of the 185 Brazilian patients investigated by CMA (21%). In 31 among the 60 DECIPHER patients carrying < 200 kb CNVs, at least one known microcephaly gene was observed. Overall, four gene sets implicated in microcephaly were disclosed: known microcephaly genes; genes with supporting evidence of association with microcephaly; known macrocephaly genes; and novel candidates, including OTUD7A, BBC3, CNTN6, and NAA15. In the review, we compiled 957 known microcephaly genes and 58 genomic CNV loci, comprising 13 duplications and 50 deletions, which have already been associated with clinical findings including microcephaly. We reviewed genes and CNV syndromes previously associated with microcephaly, reinforced the high CMA diagnostic yield for this condition, pinpointed novel candidate loci linked to microcephaly deserving further evaluation, and provided a useful resource for future research on the field of neurodevelopment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this study was to investigate the association between maternal and paternal licit and illicit drug use, smoking and drinking and autism spectrum disorder (ASD). We conducted a case-control study with children and adolescents diagnosed with ASD and neurotypical individuals. The data were collected using a semi-structured questionnaire administered during interviews with the children's mothers or guardians. The following variables were analyzed: child sex and age; maternal and parental age; use of medicines before and during pregnancy; classes of medicines used during pregnancy; maternal and paternal smoking; maternal and paternal drinking; maternal and paternal illicit drug use. The data were analyzed using logistic regression and crude and adjusted odds ratios (OR). After adjustment, the results showed an association between maternal use of antipyretics/pain killers during pregnancy (OR = 2.26; 95%CI 1.29-3.95; p < 0.040) and ASD. No association was found between maternal and paternal smoking, drinking and illicit drug use before and during pregnancy and ASD. The findings suggest that the development of ASD is influenced by environmental factors.

Objectives: To evaluate the anti-demineralizing effect of a mouthwash comprising pomegranate peel extract (PPE 3%), sodium trimetaphosphate (TMP 0.3%), and fluoride (F 225 ppm) in an in situ study, and to assess its irritation potential in an ex vivo study., Methods: This double-blind crossover study was conducted in four phases with 7 days each. Twelve volunteers used palatal appliances containing enamel blocks, which were subjected to cariogenic challenges. The ETF formulation (PPE + TMP + F, pH 7.0), TF formulation (TMP + F, pH 7.0), deionized water (W, pH 7.0), and essential oil commercial mouthwash (CM, 220 ppm F, pH 4.3) were dropped onto the enamel twice daily. The percentage of surface hardness loss, integrated loss of subsurface hardness, calcium, phosphorus, and fluoride in enamel and biofilms were determined. In addition, alkali-soluble extracellular polysaccharide concentrations were analyzed in the biofilms. The irritation potential was evaluated using the hen's egg chorioallantoic membrane test through the vascular effect produced during 300-s of exposure., Results: ETF was the most efficacious in preventing demineralization. It also showed the highest concentrations of calcium and phosphorus in the enamel and in the biofilm, as well as the lowest amount of extracellular polysaccharides in the biofilm. In the eggs, ETF produced light reddening, whereas CM led to hyperemia and hemorrhage., Conclusions: The addition of PPE to formulations containing TMP and F increased its anti-demineralizing property, and this formulation presented a lower irritation potential than the CM., Clinical Relevance: ETF can be a promising alternative alcohol-free mouthwash in patients at high risk of caries., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study evaluated the independent and combined environmental impacts of the consumption of beef and ultra-processed foods in Brazil., Design: Cross-sectional study., Setting: Brazil., Participants: We used food purchases data from a national household budget survey conducted between July 2017 and July 2018, representing all Brazilian households. Food purchases were converted into energy, carbon footprints and water footprints. Multiple linear regression models were used to assess the association between quintiles of beef and ultra-processed foods in total energy purchases and the environmental footprints, controlling for sociodemographic variables., Results: Both beef and ultra-processed foods had a significant linear association with carbon and water footprints ( P < 0·01) in crude and adjusted models. In the crude upper quintile of beef purchases, carbon and water footprints were 47·7 % and 30·8 % higher, respectively, compared to the lower quintile. The upper quintile of ultra-processed food purchases showed carbon and water footprints 14·4 % and 22·8 % higher, respectively, than the lower quintile. The greatest reduction in environmental footprints would occur when both beef and ultra-processed food purchases are decreased, resulting in a 21·1 % reduction in carbon footprint and a 20·0 % reduction in water footprint., Conclusions: Although the environmental footprints associated with beef consumption are higher, dietary patterns with lower consumption of beef and ultra-processed foods combined showed the greatest reduction in carbon and water footprints in Brazil. The high consumption of beef and ultra-processed foods is harmful to human health, as well as to the environment; thus, their reduction is beneficial to both.

Objective. to develop an optimization and training pipeline for a classification model based on principal component analysis and logistic regression using neuroimages from PET with 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG PET) for the diagnosis of Alzheimer's disease (AD). Approach. as training data, 200 FDG PET neuroimages were used, 100 from the group of patients with AD and 100 from the group of cognitively normal subjects (CN), downloaded from the repository of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Regularization methods L1 and L2 were tested and their respective strength varied by the hyperparameter C. Once the best combination of hyperparameters was determined, it was used to train the final classification model, which was then applied to test data, consisting of 192 FDG PET neuroimages, 100 from subjects with no evidence of AD (nAD) and 92 from the AD group, obtained at the Centro de Diagnóstico por Imagem (CDI). Main results. the best combination of hyperparameters was L1 regularization and C ≈ 0.316. The final results on test data were accuracy = 88.54%, recall = 90.22%, precision = 86.46% and AUC = 94.75%, indicating that there was a good generalization to neuroimages outside the training set. Adjusting each principal component by its respective weight, an interpretable image was obtained that represents the regions of greater or lesser probability for AD given high voxel intensities. The resulting image matches what is expected by the pathophysiology of AD. Significance. our classification model was trained on publicly available and robust data and tested, with good results, on clinical routine data. Our study shows that it serves as a powerful and interpretable tool capable of assisting in the diagnosis of AD in the possession of FDG PET neuroimages. The relationship between classification model output scores and AD progression can and should be explored in future studies., (© 2024 Institute of Physics and Engineering in Medicine.)

The Zika virus (ZIKV) epidemic had a sanitary, psychosocial, and economic impact on individuals of reproductive age. The primary concern revolved around infection during pregnancy due to possible vertical transmission and its association with adverse fetal and infant outcomes, known as Congenital Zika Syndrome (CZS). This qualitative study employs phenomenology and grounded theory. This study includes interviews with 98 women, some pregnant during the ZIKV epidemic in Brazil, Colombia, and Puerto Rico, who had children with CZS or without diagnosed neurological impairment. Additionally, the study included a group of women who were pregnant during the COVID-19 pandemic in these same countries. In both groups, interviewees had varying levels of knowledge about ZIKV. The study found that messages conveyed through the media tended to be alarmist, in contrast to the information provided by healthcare professionals, which was considered more trustworthy. Pregnant women during the ZIKV epidemic reported receiving their ZIKV and CSZ infection diagnoses late, either during or after childbirth. The study underscores the needs of pregnant women in high-risk scenarios, the importance of health education processes, and the necessity to reinforce communication and continuing education.

Background: Insulin (INS) resistance and hypoinsulinemia commonly observed in cancer-carrying, can contribute to cachexia. However, the effects of INS and INS sensitizers, such as pioglitazone (PIO), particularly when used in combination therapy, on cancer cachexia have not been evaluated sufficiently. We investigated the effects of INS and PIO, at various doses, either isolated or combined, on cachexia in Walker-256 tumor-bearing rats (TB rats)., Methods: INS or INS + PIO were administered in TB rats, for 6 or 12 days, starting from the day of tumor cells inoculation., Results: INS at 18 or 27 U/kg (12-days treatment), but not 9 U/kg, reduced fat loss and slightly prevented weight loss. However, INS 18 U/kg + PIO 5, 10, 20, or 40 mg/kg (6 or 12-day treatment) reduced fat loss and markedly prevented weight loss but did not affect muscle wasting. While TB rats lost weight (37.9% in 12 days), TB rats treated with INS 18 U/kg + PIO 5 mg/kg showed pronounced weight gain (73.7%), which was greater than the sum (synergism) of the weight gains promoted by isolated treatments with INS 18 U/kg (14.7%) or PIO 5 mg/kg (13.1%). The beneficial effect of the INS 18 U/kg + PIO 5 mg/kg on weight loss was associated with improved INS sensitivity, as indicated by the higher blood glucose clearance constant (kITT), decreased levels of free fatty acids and triacylglycerols (INS resistance-inducing factors) in the blood, and increased expression of p-Akt (INS signaling pathway protein) in adipose tissue., Conclusions: The combined treatment with INS 18 U/kg + PIO 5 mg/kg was more effective in preventing advanced cachexia in TB rats than each treatment alone, emerging as the best approach, considering the lower dosage and higher efficacy. This combination completely preserved adipose mass and markedly reduced weight loss through a synergistic mechanism linked to improved insulin sensitivity. These findings provide new insights into the importance of drug combinations in effectively combating fat loss in advanced cachexia., (© 2023. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Rothmund-Thomson syndrome (RTS) is a rare, heterogeneous autosomal recessive genodermatosis, with poikiloderma as its hallmark. It is classified into two types: type I, with biallelic variants in ANAPC1 and juvenile cataracts, and type II, with biallelic variants in RECQL4 , increased cancer risk and no cataracts. We report on six Brazilian probands and two siblings of Swiss/Portuguese ancestry presenting with severe short stature, widespread poikiloderma and congenital ocular anomalies. Genomic and functional analysis revealed compound heterozygosis for a deep intronic splicing variant in trans with loss of function variants in DNA2 , with reduction of the protein levels and impaired DNA double-strand break repair. The intronic variant is shared by all patients, as well as the Portuguese father of the European siblings, indicating a probable founder effect. Biallelic variants in DNA2 were previously associated with microcephalic osteodysplastic primordial dwarfism. Although the individuals reported here present a similar growth pattern, the presence of poikiloderma and ocular anomalies is unique. Thus, we have broadened the phenotypical spectrum of DNA2 mutations, incorporating clinical characteristics of RTS. Although a clear genotype-phenotype correlation cannot be definitively established at this moment, we speculate that the residual activity of the splicing variant allele could be responsible for the distinct manifestations of DNA2 -related syndromes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

There is an increasing need for developing a strategy to analyze the penetration of pesticides in cultures during postharvest control with minimal or no sample preparation. This study explores the combined use of laser ablation electrospray ionization mass spectrometry imaging (LAESI imaging) and tissue spray ionization mass spectrometry (TSI-MS) to investigate the penetration of thiabendazole (TBZ) in fruits, simulating a postharvest procedure. Slices of guava and apple were prepared, and an infrared laser beam was used, resulting in the ablation of TBZ directly ionized by electrospray and analyzed by mass spectrometry. The experiments were conducted for 5 days of fruit storage after TBZ administration to simulate a postharvest treatment. During postharvest treatment, TBZ is applied directly to the fruit peel after harvesting. Consequently, TBZ residues may remain on the peel if the consumer does not wash the fruit properly before its consumption. To evaluate the effectiveness of household washing procedures, TSI-MS was employed as a rapid and straightforward technique to monitor the remaining amount of TBZ in guava and apple peels following fruit washing. This study highlights the advantages of LAESI imaging for evaluating TBZ penetration in fruits. Moreover, the powerful capabilities of TSI-MS are demonstrated in monitoring and estimating TBZ residues after pesticide application, enabling the comprehensive unveiling of pesticide contaminants in fruits.

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients' treatment options and has been progressively incorporated into diagnostic laboratories. Here, we assessed the performance of an in-house HRD testing system deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDM TM HRD Solution and AmoyDx ® (HRD Focus Panel)) with the reference assay from Myriad MyChoice ® (CDx). A total of 85 ovarian cancer samples were subject to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R = 0.87, p -value = 3.39 × 10 -19 ). The comparison of the assigned HRD status to the reference Myriad's test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA's test, while AmoyDx's test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data shows that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, making it an ideal alternative to offer to a broader number of patients while maintaining high-quality standards at more accessible price tiers.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations., Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity., Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status., Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients., Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication., Clinical Trial Number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701., Competing Interests: GN, SV, AK, TS, NK, DA, JA, JA, ZB, NB, TB, BB, SB, MB, PB, SB, BB, HB, CC, HC, JD, AD, NE, LF, DF, CF, MG, CG, PG, SG, MH, HH, DH, CH, CJ, SJ, MJ, VK, EK, NK, VK, AK, DK, CL, PL, KL, ML, XL, GL, GL, DM, AM, MM, SM, RM, IM, VM, RN, SN, RN, TN, TO, OP, KP, JP, KP, JP, HP, MP, YR, PR, SR, JR, DR, MR, SR, AR, LS, PS, MS, LS, MS, DS, MS, LT, MT, ST, LW, GW, MW, EW, SM, BF, JW, ML, MA, DS No competing interests declared

Background: During the aging process, cognitive functions and performance of the muscular and neural system show signs of decline, thus making the elderly more susceptible to disease and death. These alterations, which occur with advanced age, affect functional performance in both the lower and upper members, and consequently human motor functions. Objective measurements are important tools to help understand and characterize the dysfunctions and limitations that occur due to neuromuscular changes related to advancing age. Therefore, the objective of this study is to attest to the difference between groups of young and old individuals through manual movements and whether the combination of features can produce a linear correlation concerning the different age groups., Methods: This study counted on 99 participants, these were divided into 8 groups, which were grouped by age. The data collection was performed using inertial sensors (positioned on the back of the hand and on the back of the forearm). Firstly, the participants were divided into groups of young and elderly to verify if the groups could be distinguished through the features alone. Following this, the features were combined using the linear discriminant analysis (LDA), which gave rise to a singular feature called the LDA-value that aided in verifying the correlation between the different age ranges and the LDA-value., Results: The results demonstrated that 125 features are able to distinguish the difference between the groups of young and elderly individuals. The use of the LDA-value allows for the obtaining of a linear model of the changes that occur with aging in the performance of tasks in line with advancing age, the correlation obtained, using Pearson's coefficient, was 0.86., Conclusion: When we compare only the young and elderly groups, the results indicate that there is a difference in the way tasks are performed between young and elderly individuals. When the 8 groups were analyzed, the linear correlation obtained was strong, with the LDA-value being effective in obtaining a linear correlation of the eight groups, demonstrating that although the features alone do not demonstrate gradual changes as a function of age, their combination established these changes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: This study evaluated  the effects of advanced platelet-rich fibrin (A-PRF +) on the healing of upper third molar post-extraction sockets., Methods: Sixteen patients who underwent extractions of the upper third molars (18 and 28) were included in this randomized split-mouth study. The alveoli on the test side were filled with A-PRF + , while the control side was maintained with blood clot. The side that received treatment was randomly defined. Alveolar bone regeneration was evaluated by CBCT scans to assess healing stage, bone density, and fractal analysis 1 week and 90 days post-extraction. Additionally, pain, edema, bleeding, and soft tissue alveolar repair were evaluated by clinical analyses 3, 7, 14, 30, and 90 days after the surgical procedure using a visual analog scale., Results: There were no clinical differences regarding treatments in any experimental period. In the tomographic evaluation, at 7 days, the alveoli treated with A-PRF + presented a suggestive sign of higher bone density than the control alveoli, which was not confirmed 90 days after the surgical procedure., Conclusion: Thus, the use of A-PRF + does not demonstrate a clinical advantage in the repair of post-extraction sockets of upper third molars., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pembrolizumab is FDA approved for tumors with tumor mutational burden (TMB) of ≥10 mutations/megabase (mut/Mb). However, the response to immune checkpoint inhibitors (ICI) varies significantly among cancer histologies. We describe the landscape of frameshift mutations (FSs) and evaluated their role as a predictive biomarker to ICI in a clinical cohort of patients., Methods: Comprehensive genomic profiling was performed on a cohort of solid tumor samples examining at least 324 genes. The clinical cohort included patients with metastatic solid malignancies who received ICI monotherapy and had tumor sequencing. Progression-free survival (PFS), overall survival, and objective response rates (ORR) were compared between the groups., Results: We analyzed 246,252 microsatellite stable (MSS) and 4561 samples with microsatellite instability across solid tumors. Histologies were divided into groups according to TMB and FS. MSS distribution: TMB-L (<10 mut/Mb)/FS-A (absent FS) (N=111,065, 45%), TMB-H (≥10 mut/Mb)/FS-A (N=15,313, 6%), TMB-L/FS-P (present ≥1 FS) (N=98,389, 40%) and TMB-H/FS-P (N=21,485, 9%). FSs were predominantly identified in the p53 pathway. In the clinical cohort, 212 patients were included. Groups: TMB-L/FS-A (N=80, 38%), TMB-H/FS-A (N=36, 17%), TMB-L/FS-P (N=57, 27%), TMB-H/FS-P (N=39, 18%). FSs were associated with a higher ORR to ICI, 23.8% vs 12.8% (p=0.02). TMB-L/FS-P had superior median PFS (5.1 months) vs TMB-L/FS-A (3.6 months, p<0.01). The 12-month PFS probability was 34% for TMB-L/FS-P vs 17.1% for TMB-L/FS-A., Conclusions: FSs are found in 47% of patients with MSS/TMB-L solid tumors in a pan-cancer cohort. FS may complement TMB in predicting immunotherapy responses, particularly for tumors with low TMB., Competing Interests: Competing interests: VF consultant or advisory role Deciphera, Incyte. AM has patent applications related to the use of cytokines to enhance macrophage immunotherapy. ESS and GF are employees of Foundation Medicine and Shareholders in Roche. HPS consultant or advisory role Ipsen, AstraZeneca, ITM, Novartis, TerSera. SP consultant or advisory role IntegrityCE, Dava Oncology. US consultant or advisory role Astellas, Exelixis, Seattle Genetics, Imvax, Sanofi, and AstraZeneca. WP consultant or advisory role Astellas. IG-L consultant or advisory role SOTIO, Kanaph, Jazz, OncXer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute lymphoblastic leukemia (ALL) can be classified into different subgroups based on recurrent genetic alterations. Here, targeted RNA sequencing was used to identify the novel subgroups of ALL in 144 B-other and 40 "classical" ALL samples. The classical TCF3-PBX1, ETV6-RUNX1, KMT2A-rearranged, and BCR-ABL1, and novel P2RY8-CRLF2, ABL-, JAK2-, ZNF384-, MEF2D-, and NUTM1-fusions were easily identified by fusion transcript analysis. IGH-CRLF2 and IGH-EPOR were found by abnormally high levels of expression of CRLF2 or EPOR. DUX4-rearranged was identified by the unusual expression of DUX4 genes and an alternative exon of ERG, or by clustering analysis of gene expression. PAX5-driven ALL, including fusions, intragenic amplifications, and mutations were identified by single-nucleotide variant analysis and manual inspection using the IGV software. Exon junction analysis allowed detection of some intragenic ERG and IKZF1 deletions. CRLF2-high associated with initial white blood cell (WBC) counts of ≥50 × 103/μL and GATA3 risk alleles (rs3781093 and rs3824662), whereas ABL/JAK2/EPOR-fusions associated with high WBC counts, National Cancer Institute's high-risk classification, and IKZF1del. ZNF384-fusions associated with CALLA-negativity and NUTM1-fusions in infants. In conclusion, targeted RNA sequencing further classified 66.7% (96 of 144) B-other ALL cases. All BCP-ALL subgroups, except for iAMP21, hyperdiploid and hypodiploid cases, were identified. Curiously, we observed higher frequencies of females within B-rest ALLs and males in PAX5-driven cases., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

This study aimed to evaluate the effects of the repeated administration of tramadol subcutaneously on postoperative analgesia, liver, kidneys, and oxidative status in the postoperative period of cats undergoing ovariohysterectomy. Thirty-seven cats were randomly assigned to 5 groups, according to the postoperative analgesic treatment: NaCl 0.9%, GC; tramadol at 2 mg/kg, T2B (q12h) and T2T (q8h); or 4 mg/kg, T4B (q12h) and T4T (q8h). Oxidative status was assessed at baseline, 12 hours and 24 hours after the final administration of tramadol by the activity of superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), butyrylcholinesterase (BuChE), and lipoperoxidation (MDA). Total blood count, serum biochemistry and urinalysis were compared between baseline and 12 hours posttramadol. Postoperative pain was evaluated by applying the Glasgow Feline Composite Measure Pain Scale at baseline, 3 (T3), 6 (T6), 8 (T8), 12 (T12), 24 (T24) e 36 (T36) hours after extubation. No side effects were observed. Tramadol increased SOD activity while CAT varied among groups in all time points but not over time. MDA levels increased from baseline to 12 hours in all groups but T4T. MPO activity decreased from baseline to 24 hours in some groups, including GC. Creatinine and phosphatase alkaline decreased in T2T, T4B, and T4T at 12 hours. Higher pain scores were observed from T3 to T8, except for GC. Rescue analgesia was administered only at T3. No difference in pain scores was observed from T8 onwards. Based on the findings, it is suggested that tramadol at 2 mg/kg every 8 hours is recommended for postoperative analgesia of cats undergoing ovariohysterectomy., Competing Interests: Declaration of Competing Interest None of the authors of this article has a financial or personal relationship with other people or organizations that may influence the content of the article, declaring any potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The clinical progression of Leishmania (Leishmania) amazonensis infection depends on multiple factors, including immunological status of the host and their genotypic interaction. Several immunological processes depend directly on minerals for an efficient performance. Therefore, this study used an experimental model to investigate the alterations of trace metals in L. amazonensis infection associate with clinical outcome, parasite load, and histopathological lesions, and the effect of CD4 + T cells depletion on these parameters., Methods: A total of 28 BALB/c mice were divided into 4 groups: 1-non-infected; 2-treated with anti-CD4 antibody; 3-infected with L. amazonensis; and 4-treated with anti-CD4 antibody and infected with L. amazonensis. After 24 weeks post-infection, levels of calcium (Ca), iron (Fe), magnesium (Mg), manganese (Mn), Cu, and Zn were determined by inductively coupled plasma optical emission spectroscopy using tissue samples of the spleen, liver, and kidneys. Additionally, parasite burdens were determined in the infected footpad (inoculation site) and samples of inguinal lymph node, spleen, liver, and kidneys were submitted to histopathological analysis., Results: Despite no significant difference was observed between groups 3 and 4, L. amazonensis-infected mice had a significant reduction of Zn (65.68-68.32%) and Mn (65.98 to 82.17%) levels. Presence of L. amazonensis amastigotes was also detected in the inguinal lymph node, spleen, and liver samples in all infected animals., Conclusion: The results showed that significant alterations in micro-elements levels occur in BALB/c mice experimentally infected with L. amazonensis and may increase the susceptibility of individuals to the infection., (© 2023. The Author(s) under exclusive licence to Witold Stefański Institute of Parasitology, Polish Academy of Sciences.)

Bauhinia forficata Link. is a native South American plant, which possesses volatile compounds with pharmaceutical and medicinal properties such as antidiabetic and anti-inflammatory effects. However, the conservation and propagation of this plant are complicated by its recalcitrant seeds and delayed flowering transition. Hence, tissue culture is employed for the safe and efficient propagation of B. forficata . However, the optimal conditions for the in vitro cultivation of B. forficata remain unknown. Thus, this study aimed to characterize the volatile profile of adult B. forficata field plants and evaluate the effects of different light intensities (43 and 70 μmol m -2  s -1 ), gas exchange rates (14 and 25 µL L -1  s -1 ), and exogenous sucrose concentrations (0, 20, and 30 g L -1 ) on their in vitro development. The results showed that β-caryophyllene is the major volatile compound produced by B. forficata . Moreover, culturing in a medium containing 30 g L -1 of sucrose and flasks with membranes that allow CO 2 exchange at the rate of 25 µL L -1  s -1 produced vigorous and hardened plants with high survival rates independent of irradiance. This study is the first to report the optimal in vitro culture conditions for B. forficata as a reference for future studies on micropropagation and secondary metabolite production using this species., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03634-8., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© King Abdulaziz City for Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objectives: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis., Methods: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed., Results: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003)., Conclusion: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples., Competing Interests: The authors report no conflicts of interest.

Background: Congenital syphilis (CS) is a major and avoidable cause of neonatal death worldwide. In this study, we aimed to estimate excess all-cause mortality in children under 5 years with CS compared to those without CS., Methods and Findings: In this population-based cohort study, we used linked, routinely collected data from Brazil from January 2011 to December 2017. Cox survival models were adjusted for maternal region of residence, maternal age, education, material status, self-declared race and newborn sex, and year of birth and stratified according to maternal treatment status, non-treponemal titers and presence of signs and symptoms at birth. Over 7 years, a total of 20 057 013 live-born children followed up (through linkage) to 5 years of age, 93 525 were registered with CS, and 2 476 died. The all-cause mortality rate in the CS group was 7·84/1 000 person-years compared with 2·92/1 000 person-years in children without CS, crude hazard ratio (HR) = 2·41 (95% CI 2·31 to 2·50). In the fully adjusted model, the highest under-five mortality risk was observed among children with CS from untreated mothers HR = 2·82 (95% CI 2·63 to 3·02), infants with non-treponemal titer higher than 1:64 HR = 8·87 (95% CI 7·70 to 10·22), and children with signs and symptoms at birth HR = 7·10 (95% CI 6·60 to 7·63). Among children registered with CS, CS was recorded as the underlying cause of death in 33% (495/1 496) of neonatal, 11% (85/770) of postneonatal, and 2·9% (6/210) of children 1 year of age. The main limitations of this study were the use of a secondary database without additional clinical information and the potential misclassification of exposure status., Conclusions: This study showed an increased mortality risk among children with CS that goes beyond the first year of life. It also reinforces the importance of maternal treatment that infant non-treponemal titers and the presence of signs and symptoms of CS at birth are strongly associated with subsequent mortality., Trial Registration: Observational study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Paixao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)