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Objective: To assess the usefulness of establishing a routine gravimetric as quality assurance after the development of parenteral nutrition (PN) with a gravimetric error less than ± 5%. Material and methods: Prospective study in which 5 to 8 large volume PN were weighed daily during 2 months and for 4 months all small volume PN, considering this the real weight. The theoretical weight was calculated taking into account the densities, volumes of all products used in processing and the weight of the bags used. The gravimetric error was calculated as a percentage compared to the theoretical weight. Results: 168 large volume PN and 42 small volume were weighed, gravimetric errors measures were 1,42% (SD = 1,31) and 1,26% (SD = 0,64), with a gravimetric error less than 5% in 98,8% and 100% respectively. Conclusion: Establishing a routine gravimetric control is an useful strategy that can help to guarantee the quality of the PN development. [ABSTRACT FROM AUTHOR]

Outbreaks of acute respiratory disease caused by adenovirus are rarely documented in civilian populations, and adenovirus 35 is an uncommon serotype best recognized as a cause of serious disease in immunocompromised patients. An outbreak of adenovirus 35 pneumonia among residents and staff of a chronic care psychiatric facility was investigated. Fourteen (26%) of 53 residents and 4 (2%) of approximately 200 staff had radiographically confirmed pneumonia. Thirteen (93%) of 14 residents with pneumonia were hospitalized, 5 (36%) required mechanical ventilation, and 1 (7%) died. One staff member was hospitalized. Adenovirus infection was diagnosed in 17 (94%) persons with pneumonia by culture or serology and was confirmed as adenovirus 35 infection in 8 persons. Residents with pneumonia had resided at the facility longer than other residents. Chronic illness was not a risk factor for severe disease. Crowding and poor hygienic behaviors probably facilitated transmission among residents. [ABSTRACT FROM AUTHOR]

The slowdown in economic development caused by traffic accidents in Spain, together with the disparity in the risk of death or injury due to traffic accidents in its provinces, makes it necessary to evaluate their road safety performance. Therefore, the objectives of the present research are, on the one hand, to find out the level of road safety efficiency of Spanish provinces in the period 2014-2018. On the other hand, it is also aimed to determine to what extent the annual efficiency change is originated by pure changes in efficiency or by technological changes. To achieve both objectives, the nonparametric technique of Data Envelopment Analysis and the Malmquist Index have been used based on the consideration of the Safety Performance Indicators (SPI) as the inputs of the process. The research findings show changes in the level of road safety efficiency in each of the years of the study period. Thus, it is possible to identify a geographical delimitation of the causes that generate changes in efficiency in recent years. A contraction in efficiency and technological progress is identified in part of the Spanish provinces in the north, northeast, and south of Spain., Competing Interests: Declaration of Conflicting InterestsThe author(s) declare(s) that there is no conflict of interest with respect to the research, authorship, and/or publication of this article.

Solitary intradural plasmacytomas are extremely rare. We present a case of a patient with headache and diagnosis of meningiomatosis. Onset symptoms were abrupt neurological deterioration and paraparesis. The patient underwent surgery by craniotomy and tumor resection, with final pathological findings of solitary extramedullary plasmacytoma without evidence of multiple myeloma. Of note is the great similarity of this infrequent pathology with meningiomas and the need to differentiate it from the dural involvement of multiple myeloma. Treatment always includes tumor resection surgery and postoperative radiotherapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Brain Circulation.)

Aim: To evaluate the association between the frequency and severity of dental fluorosis and Molar Incisor Hypomineralization (MIH) in 8-12-year-old schoolchildren living in an area with a high concentration of fluoride in the drinking water., Methods: The present cross‑sectional study was conducted on Mexican children (n = 573) selected from one community presenting a drinking water fluoride concentration of 1.39 ppm/F. The prevalence of dental fluorosis was ascertained using the Thylstrup and Fejerskov Index (TFI). The presence and severity of MIH was evaluated using the European Academy of Pediatric Dentistry (EAPD) criteria. A multinomial regression model was used to estimate the odds ratio (OR) and the 95% confidence intervals (CI), using the severity of MIH as the result., Results: The prevalence of MIH was 37.7% and, by severity, was 16.1% mild, 14.3% moderate, and 7.3% severe. The prevalence of dental fluorosis in permanent dentition was 70.9% (TFI ≥1) and, by severity, was 29.2% (TFI = 0), 45.6% (TFI 1-3) and 25.3% (TFI ≥4), while 54.5% of subjects were found to have poor oral hygiene. Schoolchildren with fluorosis (TFI ≥4) were 49% less likely [OR = 0.51; p = 0.025] to present mild MIH than children with fluorosis (TFI <4). Similarly, children with fluorosis (TFI ≥4) were 53% [OR = 0.47; p = 0.019] and 62% [OR = 0.38; p = 0.036] less likely to present moderate and severe MIH than children with fluorosis (TFI <4)., Conclusion: An inverse relationship between the presence of fluorosis and MIH was found. The results obtained by the present study may contribute to both the early identification of disorders affecting the enamel and the creation and implementation of long-term oral health prevention, promotion, and intervention programs in the affected population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Medina Varela 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.)

Merkel cell carcinoma is a very aggressive primary skin tumour with a high risk of local recurrences and lymphatic and distant metastases. The frequent association between this carcinoma and other skin tumour and lymphoid malignancies, its similar cellular morphology with leukocytes, and limited infiltration in bone marrow constituted a challenging diagnosis. We report an unusual case of an 82-year-old male who simultaneously presented Merkel cell carcinoma and acute myeloid lymphoma. The diagnosis was established through flow cytometry, immunohistochemical studies and next generation sequencing (NGS) analysis. Flow cytometry allowed for the differentiation of the two cell populations in bone marrow aspirate, which was crucial to the diagnosis of Merkel cell carcinoma and acute myeloid leukaemia (AML), after confirmed by immunohistochemistry. AML could be classified based on NGS results. Following diagnosis, the patient received palliative care and died 50 days later. immunophenotypic analysis by flow cytometry and Immunohistochemical study was crucial to establish the diagnosis of simultaneous affection of Merkel cell carcinoma and hematologic disorder., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lafora disease is a rare and fatal form of progressive myoclonic epilepsy typically occurring early in adolescence. The disease results from mutations in the EPM2A gene, encoding laforin, or the EPM2B gene, encoding malin. Laforin and malin work together in a complex to control glycogen synthesis and prevent the toxicity produced by misfolded proteins via the ubiquitin-proteasome system. Disruptions in either protein cause alterations in this complex, leading to the formation of Lafora bodies containing abnormal, insoluble, and hyperphosphorylated forms of glycogen. We used the Epm2a -/- knockout mouse model of Lafora disease to apply gene therapy by administering intracerebroventricular injections of a recombinant adeno-associated virus carrying the human EPM2A gene. We evaluated the effects of this treatment through neuropathological studies, behavioral tests, video-electroencephalography, electrophysiological recordings, and proteomic/phosphoproteomic analysis. Gene therapy ameliorated neurological and histopathological alterations, reduced epileptic activity and neuronal hyperexcitability, and decreased the formation of Lafora bodies. Moreover, differential quantitative proteomics and phosphoproteomics revealed beneficial changes in various molecular pathways altered in Lafora disease. Our results represent proof of principle for gene therapy with the coding region of the human EPM2A gene as a treatment for EPM2A-related Lafora disease., Competing Interests: Declaration of interests The authors report no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

MADS-domain transcription factors play pivotal roles in numerous developmental processes in Arabidopsis thaliana. While their involvement in flowering transition and floral development has been extensively examined, their functions in root development remain relatively unexplored. Here, we explored the function and genetic interaction of three MADS-box genes ( XAL2 , SOC1 and AGL24 ) in primary root development. By analyzing loss-of-function and overexpression lines, we found that SOC1 and AGL24 , both critical components in flowering transition, redundantly act as repressors of primary root growth as the loss of function of either SOC1 or AGL24 partially recovers the primary root growth, meristem cell number, cell production rate, and the length of fully elongated cells of the short-root mutant xal2-2 . Furthermore, we observed that the simultaneous overexpression of AGL24 and SOC1 leads to short-root phenotypes, affecting meristem cell number and fully elongated cell size, whereas SOC1 overexpression is sufficient to affect columella stem cell differentiation. Additionally, qPCR analyses revealed that these genes exhibit distinct modes of transcriptional regulation in roots compared to what has been previously reported for aerial tissues. We identified 100 differentially expressed genes in xal2-2 roots by RNA-seq. Moreover, our findings revealed that the expression of certain genes involved in cell differentiation, as well as stress responses, which are either upregulated or downregulated in the xal2-2 mutant, reverted to WT levels in the absence of SOC1 or AGL24 ., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Castañón-Suárez, Arrizubieta, Castelán-Muñoz, Sánchez-Rodríguez, Caballero-Cordero, Zluhan-Martínez, Patiño-Olvera, Arciniega-González, García-Ponce, Sánchez, Álvarez-Buylla and Garay-Arroyo.)

Lafora disease is a rare and fatal form of progressive myoclonic epilepsy with onset during early adolescence. The disease is caused by mutations in EPM2A, encoding laforin, or EPM2B, encoding malin. Both proteins have functions that affect glycogen metabolism, including glycogen dephosphorylation by laforin and ubiquitination of enzymes involved in glycogen metabolism by malin. Lack of function of laforin or malin results in the accumulation of polyglucosan that forms Lafora bodies in the central nervous system and other tissues. Enzyme replacement therapy through intravenous administration of alglucosidase alfa (Myozyme®) has shown beneficial effects removing polyglucosan aggregates in Pompe disease. We evaluated the effectiveness of intracerebroventricular administration of alglucosidase alfa in the Epm2a -/- knock-out and Epm2a R240X knock-in mouse models of Lafora disease. Seven days after a single intracerebroventricular injection of alglucosidase alfa in 12-month-old Epm2a -/- and Epm2a R240X mice, the number of Lafora bodies was not reduced. Additionally, a prolonged infusion of alglucosidase alfa for 2 or 4 weeks in 6- and 9-month-old Epm2a -/- mice did not result in a reduction in the number of LBs or the amount of glycogen in the brain. These findings hold particular significance in guiding a rational approach to the utilization of novel therapies in Lafora disease., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Global egg production is mainly based on cage systems, which have been associated with negative effects on the welfare of birds. Stress factors in restrictive production systems can lead to changes in gene transcription and protein synthesis, ultimately impacting the quality of poultry products. The liver serves various metabolic functions, such as glycogen storage, and plays a crucial role in animals' adaptation to environmental changes. Consequently, both internal and external conditions can influence liver functions. The aim of this study was to evaluate the gene expression of AGP , CRP , NOX4 , SOD1 , CAT , GPX1 , SREBF1 , and FXR in the liver of laying hens under two different production systems. Liver tissues from Hy-Line Brown hens housed in conventional cage and cage-free egg production systems at 60 and 80 weeks of production were used. mRNA transcript levels were determined by qPCR using the relative quantification method and ACTB as the reference gene. AGP , SOD1 , and SREBF1 gene expressions were significantly higher in the conventional cage group at the 60 weeks of production. Furthermore, the mRNA levels of transcripts related to oxidative stress and lipid metabolism were higher in the group of laying hens housed in conventional cages compared to those in cage-free systems. These results suggest differential gene expression of genes related to oxidative stress in liver tissues from hens housed in conventional cages compared to cage-free systems. The conditions of the egg production system can impact the gene expression of oxidative stress and lipid synthesis genes, potentially leading to changes in the metabolism and performance of hens, including egg quality., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 María Paula Herrera-Sánchez et al.)

Background: Molar-incisor hypomineralisation (MIH) is the most common developmental abnormality observed in teeth. Being a relatively new condition, its treatment can present a challenge for the dentist. There is currently no study available that has evaluated the knowledge of Mexican dental personnel. This study aimed to evaluate the knowledge, experience, and perceptions of dental surgeons regarding the detection, assessment, and treatment of MIH in the metropolitan area of Mexico City., Methods: A cross-sectional study was designed. Dentists from Mexico City and its metropolitan area were invited through social networks to answer a questionnaire of 30 questions related to MIH. Participants were classified into general practice dentists, paediatric dentists, and other speciality dentists. Pearson's chi-square test was used for data analysis., Results: The questionnaire was answered by 391 dentists. A total of 86% (338 out of 391) of them identified MIH lesions, while 84% of them reported having observed MIH lesions in their practice. The most frequently observed lesions were yellow-brown opacities which accounted for 47% of the lesions, 46% were white opacities, while only 7% were observed as post-eruptive fractures in the enamel as part of the manifestations of MIH. The most frequently reported problem in the management of teeth with MIH was insufficient training for treating children with MIH. A total of 84% of dentists stated that they would like more information on the treatment of MIH lesions., Conclusions: Most of the surveyed dentists recognised MIH and reported having observed MIH lesions in their practice. Most of the dentists indicated that the main problem for the management of the MIH is the lack of training., (© 2023. The Author(s).)

Background: Dyspareunia is defined as the occurrence of pain during or after sexual intercourse, which directly affects physical, sexual, and mental health. This condition can lead to depression, anxiety, and low self-esteem in women who experience it., Objectives: The aim of this research was to evaluate the effectiveness of physical therapy interventions for the treatment of female dyspareunia., Design: A systematic review and meta-analysis was conducted., Method: Search of publications was conducted in Scopus, Medline, Pubmed, Cinahl and Web of Science. Treatment effects were defined as standardized mean difference and their 95% confidence intervals. Statistical heterogeneity was assessed using Crohan's Q test and quantified using the I 2 index., Results: Of the 19 articles selected, six applied multimodal physiotherapy treatments; five, electrotherapy; three, Thiele's massage; two, interdisciplinary interventions or pelvic floor muscle training; and one, extracorporeal shockwave therapy. The meta-analysis showed significant results for the variables pain and quality of life with the interventions based on electrotherapy and electrotherapy combined with pelvic floor muscle training. These interventions did not show significant results for the improvement of sexual function., Conclusions: Physiotherapy techniques are effective and procedures have been identified with reliable results in improving pain and quality of life in patients with dyspareunia. One of the most important aspects is the strengthening of the perineal musculature and the application of Transcutaneous Electrical Nerve Stimulation. Furthermore, manual trigger point release therapy and Thiele massage, optimize and guarantee the reduction of pain intensity., Prospero Registration: CRD42021236155., (© 2023. The Author(s).)

Objective: To evaluate the efficacy of percutaneous electrolysis for the treatment of patients with tendinopathies., Data Sources: A systematic search of publications was conducted in Pubmed, Cinahl, Medline, Scopus and Web of Science., Methods: The Oxford 2011 Levels of Evidence and the Jadad scale were used to assess the quality of studies. The mean and standard deviation were obtained for each study group and used to calculate the effect size. The DerSimonian and Laird method was used to develop a random-effects model., Results: Of the 14 articles, four applied percutaneous electrolysis to the knee, three to the shoulder, three to the elbow, two to the hip and two to the ankle and foot. A meta-analysis on intensity of pain (evaluated with algometer and the Visual Analogue Scale) was performed on studies comparing percutaneous electrolysis with a control group, indicating that the groups treated with percutaneous electrolysis had better results ( p  = 0.01). Although percutaneous electrolysis did not overcome the analgesic effect achieved by corticosteroid injections., Conclusions: The percutaneous electrolysis is effective for the treatment of tendinopathies. The combination of this technique with eccentric training has proven to be one of the most effective treatments to date for improving pain. PROSPERO Registration: CRD42021230005.

Lafora disease is a rare recessive form of progressive myoclonic epilepsy, usually diagnosed during adolescence. Patients present with myoclonus, neurological deterioration, and generalized tonic-clonic, myoclonic, or absence seizures. Symptoms worsen until death, usually within the first ten years of clinical onset. The primary histopathological hallmark is the formation of aberrant polyglucosan aggregates called Lafora bodies in the brain and other tissues. Lafora disease is caused by mutations in either the EPM2A gene, encoding laforin, or the EPM2B gene, coding for malin. The most frequent EPM2A mutation is R241X, which is also the most prevalent in Spain. The Epm2a -/- and Epm2b -/- mouse models of Lafora disease show neuropathological and behavioral abnormalities similar to those seen in patients, although with a milder phenotype. To obtain a more accurate animal model, we generated the Epm2a R240X knock-in mouse line with the R240X mutation in the Epm2a gene, using genetic engineering based on CRISPR-Cas9 technology. Epm2a R240X mice exhibit most of the alterations reported in patients, including the presence of LBs, neurodegeneration, neuroinflammation, interictal spikes, neuronal hyperexcitability, and cognitive decline, despite the absence of motor impairments. The Epm2a R240X knock-in mouse displays some symptoms that are more severe that those observed in the Epm2a -/- knock-out, including earlier and more pronounced memory loss, increased levels of neuroinflammation, more interictal spikes and increased neuronal hyperexcitability, symptoms that more precisely resemble those observed in patients. This new mouse model can therefore be specifically used to evaluate how new therapies affects these features with greater precision., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare that are relevant to the content of this article. We affirm that we have read the Journal's position on issues related to ethical publication and state that this report is consistent with those guidelines., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with COVID-19 have a high incidence of acute kidney injury (AKI), which is associated with mortality. The objective of the study was to determine the factors associated with AKI in patients with COVID-19., Methodology: A retrospective cohort was established in two university hospitals in Bogotá, Colombia. Adults hospitalized for more than 48 h from March 6, 2020, to March 31, 2021, with confirmed COVID-19 were included. The main outcome was to determine the factors associated with AKI in patients with COVID-19 and the secondary outcome was estimate the incidence of AKI during the 28 days following hospital admission., Results: A total of 1584 patients were included: 60.4% were men, 738 (46.5%) developed AKI, 23.6% were classified as KDIGO 3, and 11.1% had renal replacement therapy. The risk factors for developing AKI during hospitalization were male sex (OR 2.28, 95% CI 1.73-2.99), age (OR 1.02, 95% CI 1.01-1.03), history of chronic kidney disease (CKD) (OR 3.61, 95% CI 2.03-6.42), High Blood Pressure (HBP) (OR 6.51, 95% CI 2.10-20.2), higher qSOFA score to the admission (OR 1.4, 95% CI 1.14-1.71), the use of vancomycin (OR 1.57, 95% CI 1.05-2.37), piperacillin/tazobactam (OR 1.67, 95% CI 1.2-2.31), and vasopressor support (CI 2.39, 95% CI 1.53-3.74). The gross hospital mortality for AKI was 45.5% versus 11.7% without AKI., Conclusions: This cohort showed that male sex, age, history of HBP and CKD, presentation with elevated qSOFA, in-hospital use of nephrotoxic drugs and the requirement for vasopressor support were the main risk factors for developing AKI in patients hospitalized for COVID-19., (© 2023. The Author(s).)

Salmonellosis is a common infectious disease in humans caused by Salmonella spp., which in recent years has shown an increase in its incidence, with products of avian origin being a common source of transmission. To present a successful infective cycle, there are molecular mechanisms such as virulence factors that provide characteristics that facilitate survival, colonization, and damage to the host. According to this, the study aims to characterize the virulence factors of Salmonella spp. strains isolated from broilers ( n  = 39) and humans ( n  = 10). The presence of 24 virulence genes was evaluated using end-point PCR. All the strains of Salmonella spp. isolated from broiler chickens revealed presence of 7/24 (29, 16%) virulence genes ( lpfA , csgA , sitC , sipB , sopB , sopE , and sivH ). Regarding the strains isolated from cases of gastroenteritis in humans, all strains contained (14/24, 58, 33%) virulence genes ( lpfA , csgA , pagC , msgA , spiA , sitC , iroN , sipB , orgA , hilA , sopB , sifA , avrA , and sivH ). In summary, the presence of virulence genes in different strains of Salmonella isolated from broilers and humans could be described as bacteria with potential pathogenicity due to the type and number of virulence genes detected. These findings are beneficial for the pathogenic monitoring of Salmonella in Colombia., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Kelly Johanna Lozano-Villegas et al.)

Background and Aim: Heat shock proteins are highly conserved proteins that work as molecular chaperones expressed in response to thermal stress. This study aimed to determine the expression profile of genes related to the heat stress response in whole blood obtained from the Romosinuano creole breed., Materials and Methods: Real-time polymerase chain reaction was performed to analyze the transcript of hsp90 , hsp70 , hsp60 , and hsf1 in the whole blood of Romosinuano under different temperature-humidity indices (THIs)., Results: The expression levels of the hsp70 and hsf1 genes at the high-THI level were higher (p = 0.0011 and p = 0.0003, respectively) than those at the low-THI level. In addition, no differences in the expression levels of the hsp60 and hsP90 genes were detected between the two THIs., Conclusion: The overexpression of hsf1 and hsp70 genes play an important role in protecting cells from damage induced by heat stress., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Taborda-Charris, et al.)

Background: The liver and spleen play a pivotal role in metabolism and immune response. During stress, neuroendocrine response induces changes in gene expression, and its assessment demands the validation of the stability of the reference genes to perform relative gene expression experiments., Aim: The objective of this study was to determine the expression stability of four reference genes ( GAPDH, ACTB, RNA18S , and HMBS ) in the liver and spleen tissues from laying hens housed in a conventional cage (CC) and cage-free (CF) egg production systems., Methods: Liver and spleen from Hy-Line Brown hens housed in CC and CF egg production systems were used. mRNA transcript levels were determined by quantitative polymerase chain reaction (qPCR), and the gene expression stability was evaluated using geNorm, BestKeeper, and NormFinder algorithms., Results: The most stable gene from liver tissue was ACTB in CC, CF, and CC-CF groups (overall data). In the spleen, the most stable genes were GAPDH (CC), HMBS (CF), and ACTB (CC-CF)., Conclusion: The ACTB gene was the most stable gene in the liver, and GAPDH and HMBS genes were stable in spleen tissues that could be used for the normalization in qPCR experiments performed in liver and spleen tissues of laying hens housed CC and CF production systems., Competing Interests: The authors declare that they have no conflicts of interest.

Background: Serial clinical observation of asymptomatic newborns at risk of early-onset sepsis is an alternative option for which there is limited scientific evidence., Aims: To evaluate the rate of protocol compliance, the impact on blood tests, percentage of hospitalizations and subsequent procedures, and course of diagnosed early-onset sepsis cases of a protocol based on serial clinical observation., Methods: Retrospective observational study comparing an 18-month period under this protocol against a previous protocol based on laboratory tests., Subjects: 6895 asymptomatic newborns with over 35 weeks of gestation., Outcome Measures: number of evaluations performed on each subject at risk, percentage of patients undergoing blood draws and hospitalization rates., Results: Some of the evaluations included in the protocol were omitted in 51.6 % of the newborns undergoing the physical examinations. The implementation of this new approach was associated with a decrease in the percentage of patients undergoing blood draws from 16.8 % to 0.7 % (p < 0.001) with no differences in the progression of the five cases of sepsis studied in each period. The serial clinical observation protocol was associated with a significant increase in hospitalizations for suspected infection, although with no difference in the rate of lumbar punctures performed or antibiotic treatments administered., Conclusion: Compliance with the serial clinical observation protocol can be difficult. This approach often detects newborns with abnormal clinical data that are not explained by early-onset sepsis. Clinical observation is a safe option that minimizes the rate of blood draws., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lafora disease is a fatal form of progressive myoclonic epilepsy caused by mutations in the EPM2A or NHLRC1/EPM2B genes that usually appears during adolescence. The Epm2a -/- and Epm2b -/- knock-out mouse models of the disease develop behavioral and neurological alterations similar to those observed in patients. The aim of this work is to analyze whether early treatment with metformin (from conception to adulthood) ameliorates the formation of Lafora bodies and improves the behavioral and neurological outcomes observed with late treatment (during 2 months at 10 months of age). We also evaluated the benefits of metformin in patients with Lafora disease. To assess neurological improvements due to metformin administration in the two mouse models, we evaluated the effects on pentylenetetrazol sensitivity, posturing, motor coordination and activity, and memory. We also analyzed the effects on Lafora bodies, neurodegeneration, and astrogliosis. Furthermore, we conducted a follow-up study of an initial cohort of 18 patients with Lafora disease, 8 treated with metformin and 10 untreated. Our results indicate that early metformin was more effective than late metformin in Lafora disease mouse models improving neurological alterations of both models such as neuronal hyperexcitability, motor and memory alterations, neurodegeneration, and astrogliosis and decreasing the formation of Lafora bodies. Moreover, patients receiving metformin had a slower progression of the disease. Overall, early treatment improves the outcome seen with late metformin treatment in the two knock-out mouse models of Lafora disease. Metformin-treated patients exhibited an ameliorated course of the disease with slower deterioration of their daily living activities., (© 2022. The American Society for Experimental Neurotherapeutics, Inc.)

Aquaporins ( AQPs ) are proteins with various functions related to proper cell function and early development in mammals. The aim of this study was to evaluate the presence of AQPs and determine their mRNA levels in the cumulus oocyte complex (COC) of four bovine breeds and in blastocysts of five bovine crosses. Grade I, II and III COCs were collected by ovum pick up from non-lactating heifers of the Brahaman, Holstein, Gir and Romosinuano breeds. Embryos were produced in vitro up to the blastocyst stage of the bovine ♀Gir × ♂Holstein, ♀Holstein × ♂Gir, ♀Brahman × ♂Holstein, ♀Holstein × ♂Brahman, and ♀Romosinuano × ♂Holstein crosses. mRNA expression of AQP1 - AQP12b was estimated in COC and embryos by real-time-PCR. The presence of the twelve AQPs in the COCs and bovine embryos was established. Additionally, significant differences were determined in the expression of AQP6 and AQP12b in COCs, as well as in transcripts levels of AQP4 , AQP8 and AQP9 from bovine embryos. Gene expression of AQPs in COCs and bovine embryos is consistent with the previously described biological functions. This is the first report of AQPs in COC of Gir, Brahman, Holstein and Romosinuano and embryos of five crossbreeds between Bos indicus and B. taurus .

Salmonella enterica is a pathogen capable of colonizing various environments, including the intestinal tract of different animals such as mammals, birds, and reptiles, which can act as carriers. S. enterica infection induces different clinical diseases, gastroenteritis being the most common, which in some cases, can evolve to septicemia and meningitis. Reptiles and amphibians have been reported as a reservoir of Salmonella , and transmission of the pathogen to humans has been documented. This study aimed to determine the presence of virulence genes and characterize the genotypic antibiotic resistance profile in Salmonella strains isolated from Caiman crocodilus fuscus obtained in situ (natural habitat) in Prado, Tolima, Colombia in a previous study and stored in a strain bank in our laboratory. Fifteen Salmonella strains were evaluated through endpoint PCR to determine the presence of resistance genes and virulence genes. The genes bla TEM , strB , and sul1 were detected in all the strains that confer resistance to ampicillin, streptomycin, and sulfamethoxazole, as well as the virulence genes invA , pefA , prgH , spaN , tolC , sipB , sitC , pagC , msgA , spiA , sopB , sifA , lpfA , csgA , hilA , orgA , iroN , avrA , and sivH , indicating the possible role of babilla ( Caiman crocodilus fuscus ) as a carrier of multidrug-resistant bacteria.

Genome-wide association studies (GWAS) have allowed the identification of different loci associated with primary root (PR) growth, and Arabidopsis is an excellent model for these studies. The PR length is controlled by cell proliferation, elongation, and differentiation; however, the specific contribution of proliferation and differentiation in the control of PR growth is still poorly studied. To this end, we analyzed 124 accessions and used a GWAS approach to identify potential causal genomic regions related to four traits: PR length, growth rate, cell proliferation and cell differentiation. Twenty-three genes and five statistically significant SNPs were identified. The SNP with the highest score mapped to the fifth exon of NAC048 and this change makes a missense variant in only 33.3% of the accessions with a large PR, compared with the accessions with a short PR length. Moreover, we detected five more SNPs in this gene and in NAC3 that allow us to discover closely related accessions according to the phylogenetic tree analysis. We also found that the association between genetic variants among the 18 genes with the highest scores in our GWAS and the phenotypic classes into which we divided our accessions are not straightforward and likely follow historical patterns.

Background: Appropriate patient/caregiver training and continuity of care after hospital discharge are key factors for the success of home enteral nutrition (HEN). This study aims to assess the effects of a specific patient support program (PSP) on the nutrition status, health-related quality of life (HRQoL), and healthcare resource utilization and associated costs of patients with HEN., Methods: Observational study of adult patients with HEN enrolled in a PSP. Sociodemographic variables (baseline), HRQoL (NutriQoL) and nutrition status (Mini Nutritional Assessment [MNA]) (baseline, 6 months after PSP enrollment), and use of unplanned HEN-related healthcare resources (6 months prior to or after PSP enrollment) were recorded. HEN-related resource cost was estimated from total resources used (all patients) and each resource cost. Data were analyzed with Stata program (v. 14), considering P < 0.05 as significant., Results: Forty-three patients were included in the study (mean age, 72 years [SD = 21]; 54% women; mean HEN duration, 4 years [SD = 5]). A total of 401 calls were recorded in the PSP, 7% made proactively by the patient. HRQoL and nutrition status remained stable during the study period (NutriQoL baseline, 64; 6-months, 66; P = 0.3737; MNA baseline, 10; 6-months, 10; P = 0.0675). Unplanned resources amounted to €6229 (US $5563) and €4711 (US $4207) before and after PSP enrollment, respectively. Cost savings, representing €1518 (US $1356), were related to fewer emergency visits., Conclusions: Health advice provided through a PSP and close patient monitoring in the hospital can help to maintain patients' nutrition status and HRQoL and to reduce the use of certain unplanned HEN-related resources, leading to cost savings., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Congenital heart defects have been associated with adverse neurodevelopmental outcomes due to factors that result in a hypoxic-ischemic cerebral cumulative effect. We present a pair of fraternal twins: the first twin was healthy, and the second was born with a complex congenital heart defect (CCHD). They were followed for growth and neurodevelopmental outcomes to determine the comparative effect of exposure to a CCHD. Results show that exposure to a CCHD could be related to a persistent motor deficiency with hypotonia and concurrent height for age delay. CCHD requires a comprehensive neurodevelopmental approach; the pathophysiology and the surrounding stimuli are influential.

The hypomethylating agents, decitabine (DEC) and azacitidine (AZA), allowed more elderly acute myeloid leukemia (AML) patients to be treated. However, there are little direct comparative data on AZA and DEC. This multicenter retrospective study compared the outcomes of AZA and DEC in terms of response and overall survival (OS). Potential predictors associated with response and OS were also evaluated. A total of 626 AML patients were included (487 treated with AZA and 139 with DEC). Response rates were similar in both groups: CR was 18% with AZA vs. 23% with DEC (p = 0.20), CR/CRi was 20.5% vs. 25% (p = 0.27) and ORR was 32% vs. 39.5% (p = 0.12), respectively. Patients with leukocytes < 10 × 109/L, bone marrow blasts < 50% and ECOG ≥ 2 had higher ORR with DEC than with AZA. OS was similar in both groups: 10.4 months (95% CI: 9.2−11.7) vs. 8.8 months (95% CI: 6.7−11.0, p = 0.455), for AZA and DEC, respectively. Age (≥80 years), leukocytes (≥ 10 × 109/L), platelet count (<20 × 109/L) and eGFR (≥45 mL/min/1.73 m2) were associated with higher OS with AZA compared to DEC. In conclusion, we found no differences in response and OS rates in AML patients treated with AZA or DEC.

Background: Lymphedema, secondary to breast cancer (BCRL), is the abnormal accumulation of protein-rich fluid in the interstitium caused by a malfunction of the lymphatic system. It causes swelling, deficiencies in upper limb functions and structures, sensory pain and emotional alterations, which have a chronic course and affect the upper limb's functionality. This study aims to verify the efficacy and efficiency in the upper limb´s functionality of a protocolized experimental approach based on occupational therapy, TAPA (activity-oriented proprioceptive antiedema therapy), in the rehabilitation of BCRL in stages I and II, comparing it with the conservative treatment considered as the standard, complex decongestive therapy (CDT), through a multicenter randomized clinical trial., Methods: a randomized and prospective clinical trial was conducted with experimental and control groups. Women diagnosed with BCRL belonging to institutions in Córdoba and Aragon (Spain) participated. Sociodemographic variables and those related to the functionality of the affected upper limb were evaluated before and after the intervention., Results: The results showed statistically significant differences in the analysis of covariance performed for the variable joint balance of the shoulder´s external rotation ( p = 0.045) that could be attributed to the intervention performed; however, the effect size was minimal (η 2 ≤ 0.080). In the rest of the variables, no significant differences were found., Conclusions: TAPA may be an alternative to the conservative treatment of women with BCRL. It was shown to be just as effective for volume reduction and activity performance as CDT but more effective in improving external rotation in shoulder joint balance.

Background: Alterations derived from lymphedema in the upper-limb secondary to breast cancer-related lymphedema (BCRL) decrease the health-related quality of life (HRQoL), but there is limited evidence of the impact of the different interventions on it. The aim of this research was to compare the effect of conventional treatment with another treatment based on Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) on HRQoL in women diagnosed with BCRL., Methods: A prospective clinical study was designed with two parallel arms. The study population consisted of women diagnosed with BCRL in stage I and II, belonging to different institutions in Córdoba and Aragon, Spain. Sociodemographic and HRQoL-related variables, pain, tightness, heaviness and functionality were obtained before and after treatments., Results: 51 women participated in the study, 25 received the conventional treatment and 26 the TAPA, with a mean age of 59.24 ± 9.55 years. HRQoL was significantly related to upper-limb function and pain on the participants' affected side. In addition, covariance analysis (ANCOVA) showed that the TAPA treatment interfered less in the performance of activities of daily life and produced significant improvements in the social dimension of HRQoL., Conclusions: the non-use of compressive elements in the rehabilitative treatment of the BCRL that is proposed with TAPA improves aspects such as self-image and participation in social and recreational activities.

Arabidopsis (Arabidopsis thaliana) primary and lateral roots (LRs) are well suited for 3D and 4D microscopy, and their development provides an ideal system for studying morphogenesis and cell proliferation dynamics. With fast-advancing microscopy techniques used for live-imaging, whole tissue data are increasingly available, yet present the great challenge of analyzing complex interactions within cell populations. We developed a plugin "Live Plant Cell Tracking" (LiPlaCeT) coupled to the publicly available ImageJ image analysis program and generated a pipeline that allows, with the aid of LiPlaCeT, 4D cell tracking and lineage analysis of populations of dividing and growing cells. The LiPlaCeT plugin contains ad hoc ergonomic curating tools, making it very simple to use for manual cell tracking, especially when the signal-to-noise ratio of images is low or variable in time or 3D space and when automated methods may fail. Performing time-lapse experiments and using cell-tracking data extracted with the assistance of LiPlaCeT, we accomplished deep analyses of cell proliferation and clonal relations in the whole developing LR primordia and constructed genealogical trees. We also used cell-tracking data for endodermis cells of the root apical meristem (RAM) and performed automated analyses of cell population dynamics using ParaView software (also publicly available). Using the RAM as an example, we also showed how LiPlaCeT can be used to generate information at the whole-tissue level regarding cell length, cell position, cell growth rate, cell displacement rate, and proliferation activity. The pipeline will be useful in live-imaging studies of roots and other plant organs to understand complex interactions within proliferating and growing cell populations. The plugin includes a step-by-step user manual and a dataset example that are available at https://www.ibt.unam.mx/documentos/diversos/LiPlaCeT.zip., (© American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Myelin basic protein (MBP) is one of the most important structural components of the myelin sheaths in both central and peripheral nervous systems. MBP has several functions including organization of the myelin membranes, reorganization of the cytoskeleton during the myelination process, and interaction with the SH3 domain in signaling pathways. Likewise, MBP has been proposed as a marker of demyelination in traumatic brain injury and chemical exposure., Methods: The aim of this study was to molecularly characterize the myelin basic protein a (mbpa) gene from the Colombian native fish, red-bellied pacu, Piaractus brachypomus. Bioinformatic tools were used to identify the phylogenetic relationships, physicochemical characteristics, exons, intrinsically disordered regions, and conserved domains of the protein. Gene expression was assessed by qPCR in three models corresponding to sublethal chlorpyrifos exposure, acute brain injury, and anesthesia experiments., Results: mbpa complete open reading frame was identified with 414 nucleotides distributed in 7 exons that encode 137 amino acids. MBPa was recognized as belonging to the myelin basic protein family, closely related with orthologous proteins, and two intrinsically disordered regions were established within the sequence. Gene expression of mbpa was upregulated in the optic chiasm of the chlorpyrifos exposed fish in contrast to the control group., Conclusions: The physicochemical computed features agree with the biological functions of MBP, and basal gene expression was according to the anatomical distribution in the tissues analyzed. This study is the first molecular characterization of mbpa from the native species Piaractus brachypomus., (© 2022. The Author(s).)

This is the first pilot study on alternative conceptions and obstacles pertaining to pneumonia in adolescents of different school vulnerability indexes. Countries with low socioeconomic levels are disproportionately affected, with Latin America and the Caribbean (LAC) being the second-most affected area in the world, after sub-Saharan Africa. In spite of this fact, pneumonia is not included as an important component within the contents of the microbiology curriculum unit in the natural science school program. Therefore, we wanted to study how students knew about this topic by putting One Health into action by building and validating qualitative and quantitative questionnaires, put together by different experts in pedagogy, didactics, microbiology, and veterinary to find out what students knew about pneumonia and their misconceptions about it. A total of 148 students (in 8th and 9th grade) participated in this survey. The results reveal that no statistically significant differences between the different scholar grades ( p = 0.3360 Pearson chi ∧ 2) or genders ( p = 0.8000 Fisher's exact test) presented higher or lower School Vulnerability Index (SVI). Regardless of the social stratum or the level of vulnerability of the students, they have heard about this disease primarily through their family/relatives, maintaining a superficial notion of the disease, learning wrong ideas about microorganisms and treatments that can contribute to the risk to public health., 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. The handling editor is currently organizing a Research Topic with one of the authors DF., (Copyright © 2021 Marchant, Sánchez, Duprat, Mena, Sjöberg-Herrera, Cabal and Figueroa.)

American bison ( Bison bison ) is listed as near-threatened and in danger of extinction in Mexico. Recent studies have demonstrated the presence of several emerging pathogens at the Janos Biosphere Reserve (JBR), inhabited by one wild herd of American bison. Blood samples were collected from 26 American bison in the JBR. We tested for the presence of Anaplasma marginale , Babesia bigemina , B. bovis , Borrelia burgdorferi sensu lato , and Rickettsia rickettsii DNA using nested and semi-nested PCR protocols performing duplicates in two different laboratories. Results showed three animals (11.5%) positive for B. burgdorferi s. l. , three more (11.5%) for Rickettsia rickettsii, and four (19.2%) for B. bovis . Two individuals were co-infected with B. burgdorferi s. l. and B. bovis . We found no animals positive for A. marginale and B. bigemina . This is the first report in America of R. rickettsii in American bison. American bison has been described as an important reservoir for pathogens of zoonotic and veterinary importance; thus, the presence of tick-borne pathogen DNA in the JBR American bison indicates the importance of continuous wildlife health surveys.

Background: Heart failure is one of the most pressing current public health concerns. However, in Spain there is a lack of population data. We aimed to examine thirteen-year nationwide trends in heart failure hospitalization, in-hospital mortality and 30-day readmission rates in Spain., Methods: We conducted a retrospective observational study of patients discharged with the principal diagnosis of heart failure from The National Health System' acute hospitals during 2003-2015. The source of the data was the Minimum Basic Data Set. Temporal trends were modelled using Poisson regression analysis. The risk-standardized in-hospital mortality ratio was calculated using a multilevel risk adjustment logistic regression model., Results: A total of 1 254 830 episodes of heart failure were selected. Throughout 2003-2015, the number of hospital discharges with principal diagnosis of heart failure increased by 61%. Discharge rates weighted by age and sex increased during the period [incidence rate ratio (IRR): 1.03; 95% confidence interval (95% CI): 1.03-1.03; P < .001)], although this increase was motivated by the increase in older age groups (≥75 years old). The crude mortality rate diminished (IRR: 0.99; 95% CI: 0.98-1, P < .001), but 30-day readmission rate increased (IRR: 1.05; 95% CI: 1.04-1.06; P < .001). The risk-standardized in-hospital mortality ratio did not change throughout the study period (IRR: 0.997; 95% CI: 0.992-1; P = .32)., Conclusions: From 2003 to 2015, heart failure admission rates increased significantly in Spain as a consequence of the sustained increase of hospitalization in the population ≥75 years. 30-day readmission rates increased, but the risk-standardized in-hospital mortality ratio did not significantly change for the same period., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Real-time PCR is widely used to study the relative abundance of mRNA due to its specificity, sensitivity, and repeatability quantification. However, relative quantification requires a reference gene, which should be stable in its expression, showing lower variation by experimental conditions or tissues. The aim of this study was to evaluate the stability of the expression of five commonly used reference genes (actb , ywhaz , b2m , sdha , and 18s rRNA ) at different physiological stages (alert and emergency) in three different cattle breeds. In this study, five genes ( actb , ywhaz , b2m , sdha , and 18s rRNA ) were selected as candidate reference genes for expression studies in the whole blood from three cattle breeds (Romosinuano, Gyr, and Brahman) under heat stress conditions. The transcription stability of the candidate reference genes was evaluated using geNorm and NormFinder. The results showed that actb , 18SrRNA , and b2m expression were the most stable reference genes for whole blood of Gyr and Brahman breeds under two states of livestock weather safety (alert and emergency). Meanwhile, actb , b2m , and ywhaz were the most stable reference genes for the Romosinuano breed.

Background and Aim: Salmonella is one of the most common foodborne pathogens, the emergence of antibiotic-resistant strains of which is increasing. The aim of this study was to phenotypically and genotypically characterize the fluoroquinolone resistance of Salmonella isolates from broiler and humans in two regions of Colombia., Materials and Methods: Salmonella strains (n = 49) were evaluated. The phenotype of antibiotic resistance was assessed by an automated method and agar diffusion method, as well as the presence of the quinolone resistance genes qnrA , qnrB , qnrC , qnrD , qnrS , and aac(6')-Ib as determined by polymerase chain reaction., Results: Strains were resistant to ciprofloxacin (75%), levofloxacin (57.1%), and enrofloxacin (38.8%). Molecular identification showed that 24 out of 49 strains possessed the qnrB gene (48.9%), while only one isolate from the Santander region possessed the aac(6')-Ib gene. Regarding Class 1 integron, it was present in 11 out of the 49 strains (22.44%)., Conclusion: This study reports the presence of the gene qnrB as well the presence of Class 1 integrons in broiler Salmonella isolates, which may contribute to the resistance to fluoroquinolones., (Copyright: © Herrera-Sánchez, et al.)

Background: Options to treat elderly patients (≥65 years old) newly diagnosed with acute myeloid leukemia (AML) include intensive and attenuated chemotherapy, hypomethylating agents with or without venetoclax, and supportive care. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of a fludarabine, cytarabine, and filgrastim (FLUGA) regimen in comparison with azacitidine (AZA)., Methods: Patients (n = 283) were randomized 1:1 to FLUGA (n = 141) or AZA (n = 142). Response was evaluated after cycles 1, 3, 6, and 9. Measurable residual disease (MRD) was assessed after cycle 9. When MRD was ≥0.01%, patients continued with the treatment until relapse or progressive disease. Patients with MRD < 0.01% suspended treatment to enter the follow-up phase., Results: The complete remission (CR) rate after 3 cycles was significantly better in the FLUGA arm (18% vs 9%; P = .04), but the CR/CR with incomplete recovery rate at 9 months was similar (33% vs 29%; P = .41). There were no significant differences between arms in early mortality at 30 or 60 days. Hematologic toxicities were more frequent with FLUGA, especially during induction. The 1-year overall survival (OS) rate and the median OS were superior with AZA versus FLUGA: 47% versus 27% and 9.8 months (95% confidence interval [CI], 5.6-14 months) versus 4.1 months (95% CI, 2.7-5.5 months; P = .005), respectively. The median event-free survival was 4.9 months (95% CI, 2.8-7 months) with AZA and 3 months (95% CI, 2.5-3.5 months) with FLUGA (P = .001)., Conclusions: FLUGA achieved more remissions after 3 cycles, but the 1-year OS rate was superior with AZA. However, long-term outcomes were disappointing in both arms (3-year OS rate, 10% vs 5%). This study supports the use of an AZA backbone for future combinations in elderly patients with AML., (© 2021 American Cancer Society.)