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Canine parvovirus type 2 (CPV-2) is one of the main etiologies of viral gastroenteritis in dogs across the globe. This disease is mainly characterized by the presence of diarrhea, abdominal pain, vomiting, anorexia, and dehydration. This virus is responsible for high mortality and morbidity rates in unvaccinated dogs and those younger than three months. The monitoring of viral variants in our region has demonstrated that in the last seven years, variant CPV-2c has been circulating exclusively, which is unusual if we consider that in the rest of the world, at least two variants co-circulate among dog populations. To the best of our knowledge, no studies in Mexico have reported genomic sequences of CPV-2, which are relevant for population comparisons at the genetic level. Therefore, the present study aimed to sequence genomes associated with CPV-2c. To meet this objective, rectal swab samples were collected from dogs with suspected CPV-2 infection. Five positive cases diagnosed by lateral flow testing and polymerase chain reaction were selected for viral genome sequencing. Comparative analyses illustrated that the obtained genome sequences were > 99% homologous to those reported for CPV-2 in the GenBank. On the other hand, 52 nucleotide mutations were identified in the vp1/vp2 gene, out of which three impacted amino acid transition (T226S, F267Y, and A440T). Phylogenetic analysis of the vp1/vp2 gene demonstrated that the five sequences clustered in a clade called "III", pertaining to sequences from USA and Uruguay. To our knowledge, this was the first report of genomic sequences associated with CPV-2 in Mexico, which is of great relevance for the epidemiological-molecular understanding and evolution of the virus. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a prevalent and significant health problem worldwide, especially in developed countries. The aim of this study was to evaluate the CRC mortality rate in Chile in the last 25 years. An ecological descriptive study was carried out using public mortality data from 1997 to 2022, which included a total of 50,944 deaths. The results revealed that colon cancer represented the majority of cases (72.15%) where the sigmoid colon was the most affected site. The average mortality rate was 11.19 per 100,000 individuals, showing a significant increase over time. The analysis by age showed a greater burden of mortality in individuals from 75 to 90 years. Gender disparities were observed, with a predominance of female deaths until 2019. The analysis of the rate configured by region revealed non-significant differences in mortality rates, with Valparaíso and Magallanes and Antártica Chilena being the regions with the highest rates for colon and rectal cancer, respectively. These findings contribute to our understanding of the epidemiology of CRC in Chile and emphasize the need for specific interventions in primary prevention and screening to reduce mortality from this disease. [ABSTRACT FROM AUTHOR]

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Introduction: Despite the recommendations of the clinical guidelines, the percentage of central venous catheters (CVC) continues to be above the recommended standards. We do not know whether the increasing use of catheters is due to unavoidable or avoidable factors and, in the latter case, it would be in our power to modify these results. The aim of this study was to analyze the causes that condition the use of CVC in a prevalent hemodialysis (HD) population in order to identify those modifiable factors on which to act in order to achieve the objectives of the guidelines., Methods: Retrospective, descriptive and observational study in all prevalent patients on chronic hemodialysis belonging to 7 hemodialysis centers in Madrid, Castilla-León and Galicia in a cross-sectional study carried out in June 2021 (637 patients). The following were analyzed: age, sex, nationality, etiology of CKD, the vascular access with which they started hemodialysis, the number of previous failed arteriovenous fistulas (AVF), time since the start of HD, time since the placement of the CVC for the first time, the situation with respect to surgery and the causes of being a CVC carrier. In patients whose cause was refusal to undergo AVF, patients were asked about the cause of the refusal by directed questioning., Results: Of the 637 patients studied, 255 (40%) had a CVC, 346 had an AVF (54.3%) and 36 (5.7%) had a prosthesis. Of the 255 patients with CVC, 20.4% (52 p) were awaiting vascular access (AVF/prosthesis), 10.2% (26 p) had an AVF but could not be used and 69.4% (177 p) were not considered candidates for surgery (due to vascular surgery (16.9%; 43 pac), nephrology (16.5%, 42 pac) and patient refusal (36%; 92 pac). The most frequent cause for refusal of AVF was fear and patient preference. One of the most important factors associated with CVC use in prevalent patients was having started hemodialysis with a CVC. The greatest use of CVC at the start of HD was significantly associated with having more than one AVF performed, or starting HD urgently and not having been followed up and evaluated in the ACKD consultation., Conclusions: There is a high percentage of patients with a central venous catheter due to modifiable causes, which makes it necessary to systematically evaluate the process of creating AVF in order to enhance the planning, creation and maintenance of vascular access from the ACKD clinic, and to achieve the objective of the guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Objective: To determine the branching patterns of the inferior mesenteric artery (IMA) and to describe the clinical applicability of computed tomography (CT) angiography in the evaluation of these vessels to facilitate the planning of colorectal cancer surgery., Materials and Methods: We included 100 patients who underwent CT angiography of the abdomen and pelvis. The branching patterns of the IMA were examined and classified as type 1 (bifurcated), including 1A (sigmoid and left colic arteries arising from a common trunk), 1B (sigmoid and superior rectal arteries arising from a common trunk) and 1C (sigmoid arteries arising from both trunks); type 2 (trifurcated); and type 3 (no left colic branch)., Results: Among the 100 patients evaluated, we found the variant to be type 1A in 9%, type 1B in 47%, type 1C in 24%, type 2 in 16%, and type 3 in 4%., Conclusion: Preoperative CT angiography for evaluating the IMA branching pattern could inform decisions regarding the surgical approach to colorectal cancer.

Background: Endoscopic skull base surgery is constantly evolving and its scope has expanded. The acquisition of surgical skills involves a long learning curve with significant risks for the patient. Therefore, training in the laboratory has become essential to achieve appropriate proficiency and reduce the morbidity and mortality associated with these procedures. The objective of our work is to develop and validate a cost-effective and easily replicable simulator for endonasal endoscopy training using a swine cadaveric model., Methods: We used fresh Pietrain swine heads. Training exercises of increasing complexity were performed. A Specific Technical Skills and Knowledge Scale was created considering the objectives to be assessed in each task. After the simulation, the trainees were required to answer a satisfaction survey., Results: Ten participants were recruited (5 neurosurgery residents and 5 neurosurgeons). The simulator assessment showed statistically significant differences between groups. Performance was better among the group with endoscopic surgery experience. Face validity was assessed through a postsimulation questionnaire showing an overall mean score of 28.7 out of 30, indicating a highly positive overall assessment of the simulator. Furthermore, 100% of the trainees believe that including endoscopy training in their education would be beneficial., Conclusions: The endonasal endoscopy training simulator using a swine cadaveric model is a useful and accessible tool for enhancing surgical skills in this field. It provides an opportunity for training outside the operating room, reducing the potential risks associated with patient practice, and improving the training of residents., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Vomocytosis is a process that occurs when internalized fungal pathogens escape from phagocytes without compromising the viability of the pathogen and the host cell. Manual quantification of time-lapse microscopy videos is currently used as the standard to study pathogen behavior and vomocytosis incidence. However, human-driven quantification of vomocytosis (and the closely related phenomenon, exocytosis) is incredibly burdensome, especially when a large volume of cells and interactions needs to be analyzed. In this study, we designed a MATLAB algorithm that measures the extent of colocalization between the phagocyte and fungal cell ( Cryptococcus neoformans ; CN) and rapidly reports the occurrence of vomocytosis in a high throughput manner. Our code processes multichannel, time-lapse microscopy videos of cocultured CN and immune cells that have each been fluorescently stained with unique dyes and provides quantitative readouts of the spatiotemporally dynamic process that is vomocytosis. This study also explored metrics, such as the rate of change of pathogen colocalization with the host cell, that could potentially be used to predict vomocytosis occurrence based on the quantitative data collected. Ultimately, the algorithm quantifies vomocytosis events and reduces the time for video analysis from over 1 h to just 10 min, a reduction in labor of 83%, while simultaneously minimizing human error. This tool significantly minimizes the vomocytosis analysis pipeline, accelerates our ability to elucidate unstudied aspects of this phenomenon, and expedites our ability to characterize CN strains for the study of their epidemiology and virulence., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Co-published by Nanjing University and American Chemical Society.)

Cancer is a genomic disease, with driver mutations contributing to tumorigenesis. These potentially heritable variants influence risk and underlie familial breast cancer (BC). This study evaluated associations between BC risk and 13 SNPs in driver genes MAP3K1 , SF3B1 , SMAD4 , ARID2 , ATR , KMT2C , MAP3K13 , NCOR1 , and TBX3 , in BRCA1/2 -negative Chilean families. SNPs were genotyped using TaqMan Assay in 492 cases and 1285 controls. There were no associations between rs75704921:C>T ( ARID2 ); rs2229032:A>C ( ATR ); rs3735156:C>G ( KMT2C ); rs2276738:G>C, rs2293906:C>T, rs4075943T:>A, rs13091808:C>T ( MAP3K13 ); rs178831:G>A ( NCOR1 ); or rs3759173:C>A ( TBX3 ) and risk. The MAP3K1 rs832583 A allele (C/A+A/A) showed a protective effect in families with moderate BC history (OR = 0.7 [95% CI 0.5-0.9] p = 0.01). SF3B1 rs16865677-T (G/T+T/T) increased risk in sporadic early-onset BC (OR = 1.4 [95% CI 1.0-2.0] p = 0.01). SMAD4 rs3819122-C (A/C+C/C) increased risk in cases with moderate family history (OR = 2.0 [95% CI 1.3-2.9] p ≤ 0.0001) and sporadic cases diagnosed ≤50 years (OR = 1.6 [95% CI 1.1-2.2] p = 0.006). SMAD4 rs12456284:A>G increased BC risk in G-allele carriers (A/G + G/G) in cases with ≥2 BC/OC cases and early-onset cases (OR = 1.2 [95% CI 1.0-1.6] p = 0.04 and OR = 1.4 [95% CI 1.0-1.9] p = 0.03, respectively). Our study suggests that specific germline variants in driver genes MAP3K1 , SF3B1 , and SMAD4 contribute to BC risk in Chilean population.

Introduction: There is a growing interest in vegetarian and vegan diets, but both can potentially affect tissue fatty acids (FA) composition. We aimed to evaluate the effect of vegetarian diets on plasma, erythrocytes, and sperm n-3 polyunsaturated fatty acids (n-3 PUFA) status in healthy young men., Methods: Four groups were studied: i) men consuming a regular omnivore diet (OMV-1, n = 35); ii) men consuming an omnivore diet but excluding fish and seafood (OMV-2, n = 34); iii) men consuming a pescetarian diet (including dairy, eggs, fish, and seafood) (PESC, n = 36); and iv) men following a strict vegan diet (VEG, n = 35). Participants in each group should follow their diet for at least the previous 12 months. Diet evaluation used a structured validated food frequency questionnaire. FA composition was measured in plasma, erythrocyte phospho-lipids, and spermatozoa by gas-liquid chromatography, expressed as a mole percentage of the total FA content., Results: Main findings showed higher alpha-linolenic fatty acid (ALA) and total n-3 PUFA dietary intake in the VEG group. In plasma, arachidonic and eicosapentaenoic acids were higher in OMV and PESC groups, whereas docosahexaenoic acid (DHA) level was lower in VEG. Higher ALA, but reduced DHA and total n-3 PUFA levels were found in erythrocytes and spermatozoa in the VEG group., Conclusion: Higher dietary ALA intake was found in pescetarians and vegan men. However, the higher ALA intake was not reflected in higher DHA content in the evaluated tissues. PUFA assessment, with particular emphasis in DHA, are necessary to improve PUFA status in vegan men., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Venous thromboembolism (VTE) and major bleeding (MB) are common in cancer patients. Reduced-doses of antithrombotics as secondary prophylaxis have limited data. This work aims to describe and to compare treatments and outcomes for cancer-associated VTE., Research Design and Methods: Retrospective study. Adults with cancer-associated VTE were included. After 3-6 months of full-doses of anticoagulants, three strategies were considered: A) lowering the doses; B) maintaining full-doses; C) stopping treatment. The strategy and medication used were shown in a descriptive analysis and the rate of bleeding and VTE-recurrence between those in a comparative analysis., Results: A total of 420 patients were included, 56.2% received DOACs, 43.8% enoxaparin. Strategy was defined in 257 patients: A (50.2%), B (46.3%), and C (3.5%). Forty-one (9.8%) had VTE-recurrence and 15 (3.6%) had MB or clinically relevant non-major bleeding (CRNMB).According to strategy, recurrent-VTE was 8.5% (A), 4.2% (B), and 11.1 (C) ( p  = 0.22), MB or CRNMB was 0.8% (A), 1.7% (B), and 0% (C) ( p  = 0.64)., Conclusions: DOACs and strategy A were the most frequently used agent and strategy, respectively. There were no differences between medications or strategies used. The results must be interpreted with caution, and it is a retrospective single-center study, probably with information and selection bias.

Cancer cells use acetate to support the higher demand for energy and lipid biosynthesis during uncontrolled cell proliferation, as well as for acetylation of regulatory proteins. Acyl-CoA thioesterase 12 (Acot12) is the enzyme that hydrolyzes acetyl-CoA to acetate in liver cytosol and is downregulated in hepatocellular carcinoma (HCC). A mechanistic role for Acot12 in hepatocarcinogenesis was assessed in mice in response to treatment with diethylnitrosamine(DEN)/carbon tetrachloride (CCl 4 ) administration or prolonged feeding of a diet that promotes non-alcoholic steatohepatitis (NASH). Relative to controls, Acot12 -/- mice exhibited accelerated liver tumor formation that was characterized by the hepatic accumulation of glycerolipids, including lysophosphatidic acid (LPA), and that was associated with reduced Hippo signaling and increased yes-associated protein (YAP)-mediated transcriptional activity. In Acot12 -/- mice, restoration of hepatic Acot12 expression inhibited hepatocarcinogenesis and YAP activation, as did knockdown of hepatic YAP expression. Excess LPA produced due to deletion of Acot12 signaled through LPA receptors (LPARs) coupled to Gα12/13 subunits to suppress YAP phosphorylation, thereby promoting its nuclear localization and transcriptional activity. These findings identify a protective role for Acot12 in suppressing hepatocarcinogenesis by limiting biosynthesis of glycerolipids including LPA, which preserves Hippo signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Cryptococcus neoformans (CN) cells survive within the acidic phagolysosome of macrophages (MΦ) for extended times, then escape without impacting the viability of the host cell via a phenomenon that has been coined 'vomocytosis'. Through this mechanism, CN disseminate throughout the body, sometimes resulting in a potentially fatal condition-Cryptococcal Meningitis (CM). Justifiably, vomocytosis studies have focused primarily on MΦ, as alveolar MΦ within the lung act as first responders that ultimately expel this fungal pathogen. Herein, we hypothesize that dendritic cells (DCs), an innate immune cell with attributes that include phagocytosis and antigen presentation, can also act as 'vomocytes'. Presciently, this report shows that vomocytosis of CN indeed occurs from murine, bone marrow-derived DCs. Primarily through time-lapse microscopy imaging, we show that rates of vomocytosis events from DCs are comparable to those seen from MΦ and further, are independent of the presence of the CN capsule and infection ratios. Moreover, the phagosome-altering drug bafilomycin A inhibits this phenomenon from DCs. Although DC immunophenotype does not affect the total number of vomocytic events, we observed differences in the numbers of CN per phagosome and expulsion times. Interestingly, these observations were similar in murine, bone marrow-derived MΦ. This work not only demonstrates the vomocytic ability of DCs, but also investigates the complexity of vomocytosis regulation in this cell type and MΦ under multiple modulatory conditions. Understanding the vomocytic behavior of different phagocytes and their phenotypic subtypes is needed to help elucidate the full picture of the dynamic interplay between CN and the immune system. Critically, deeper insight into vomocytosis could reveal novel approaches to treat CM, as well as other immune-related conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pacifici 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.)

Roosts are vital for the survival of many species, and how individuals choose one site over another is affected by various factors. In bats, for example, species may use stiff roosts such as caves or compliant ones such as leaves; each type requires not only specific morphological adaptations but also different landing manoeuvres. Selecting a suitable roost within those broad categories may increase landing performance, reducing accidents and decreasing exposure time to predators. We addressed whether bats select specific roost sites based on the availability of a suitable landing surface, which could increase landing performance. Our study focused on Spix's disc-winged bats (Thyroptera tricolor), a species known to roost within developing tubular leaves. As previous studies show that this species relies on the leaves' apex for safe landing and rapid post-landing settlement, we predicted that bats would prefer to roost in tubular structures with a longer apex and that landing would be consistently more effective on those leaves. Field observations showed that T. tricolor predominantly used two species for roosting, Heliconia imbricata and Calathea lutea, but they preferred roosting in the former. The main difference between these two plant species was the length of the leaf's apex (longer in H. imbricata). Experiments in a flight cage also showed that bats used more consistent approach and landing tactics when accessing leaves with a longer apex. Our results suggest that landing mechanics may strongly influence resource selection, especially when complex manoeuvres are needed to acquire those resources., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

The coronavirus pandemic has transformed the way we communicate. Telehealth has gained relevance and has become a priority issue on the innovation agenda of health systems. Clinical attention of the adolescent population has some unique characteristics that set it apart from others. The objective of this document is to generate a guide of good practices that is useful in the virtual consultation with the adolescent patient. This guide is presented as a support tool for health professionals, understanding that it must be reviewed and updated in successive versions., Competing Interests: None., (Sociedad Argentina de Pediatría.)

During the second European Joint Action on Antimicrobial Resistance (AMR) and Healthcare-Associated Infections (HCI) (EU-JAMRAI) annual meeting, the Evaluation Team elicited stakeholders' opinions regarding the implementation of the National Strategies and Action Plans to fight AMR and HCI, the One Health integration and the EU-JAMRAI support to the national and EU authorities in two Focus Groups. This qualitative exercise contributed to identify criticalities and possible improvements in aspects such as political priorities, legislation/legal requirements, human and financial resources, and supervision in many health sectors to ensure effective implementation of the action plans. Stakeholders pointed out at the different speed of EU member states, in particular concerning the One Health integration in the plans. Finally, the Stakeholders strongly asked the EU-JAMRAI to reinforce the integration and dissemination of the best practices and results, to help policymakers at national and European levels in defining and implementing harmonized policies and actions against AMR and HCI.

Microfluidic-assisted particle fabrication provides a route to circumvent the disadvantages associated with traditional methods of polymeric particle generation, such as low drug loading efficiency, challenges in controlling encapsulated drug release rates, batch-to-batch variability in particle physical properties and formulation instability. However, this approach primarily produces particles with nanometer size dimensions, which limits drug delivery modalities. Herein, we systematically studied parameters for the generation of micron-sized poly(lactic-co-glycolic) acid (PLGA) particles using a microfluidic system, the NanoAssemblr benchtop. Initially, we used two organic solvents that have been reported suitable for the fabrication of PLGA nanoparticles - acetone and acetonitrile. Subsequently, we methodically manipulated polymer concentration, organic: aqueous flow rate ratios, total flow rate, organic phase composition, and surfactant concentration to develop a route for the fabrication of micron-sized PLGA particles. Further, we incorporated hydroxychloroquine (HCQ), a clinically approved drug for malaria and lymphoma, and measured how its incorporation impacted particle physicochemical properties. Briefly, altering the organic phase composition by including ethyl acetate (less polar solvent), resulted in micron-scale particles, as well as increased polydispersity indexes (PDIs). Adjusting the surfactant concentration of poly vinyl alcohol (PVA) after the addition of these solvent mixtures rendered large particles with lower PDI variability. Moreover, encapsulation of HCQ influenced particle hydrodynamic diameter and PDI in a PVA concentration dependent manner. Finally, we demonstrated that unloaded and HCQ-loaded microparticles did not affect the viability of RAW 264.7 macrophages. This study provides an itinerary for fabricating biocompatible, drug-loaded, micron-sized polymeric particles, particularly when the drug of interest is not readily soluble in conventional organic solvents., (© 2022 Wiley Periodicals LLC.)

Background: Central nervous system (CNS) infection has been an ongoing concern in paediatrics. The FilmArray® Meningoencephalitis (FAME) panel has greater sensitivity in identifying the aetiology of CNS infections. This study's objective was to compare the aetiological identification and hospitalization costs among patients with suspected CNS infection before and after the use of FAME., Methods: An analytical observational study was carried out using a retrospective cohort for the pre-intervention (pre-FAME use) period and a prospective cohort for the post-intervention (post-FAME use) period in children with suspected CNS infection., Results: A total of 409 CSF samples were analysed, 297 pre-intervention and 112 post-intervention. In the pre-intervention period, a total of 85.5% of patients required hospitalization, and in the post-intervention period 92.7% required hospitalization (p < 0.05). Median of ICU days was significantly lower in the post-intervention period than it was in the pre-intervention period. The overall positivity was 9.4 and 26.8%, respectively (p < 0.001). At ages 6 months and below, we found an increase in overall positivity from 2.6 to 28.1%, along with an increased detection of viral agents, S. agalactiae, S. pneumoniae, and N. meningitidis. The use of this diagnostic technology saved between $2916 and $12,240 USD in the cost of ICU bed-days. FAME use provided the opportunity for more accurate aetiological diagnosis of the infections and thus the provision of adequate appropriate treatment., Conclusions: The cost/benefit ratio between FAME cost and ICU bed-day cost savings is favourable. Implementation of FAME in Chilean public hospitals saves public resources and improves the accuracy of aetiological diagnosis., (© 2022. The Author(s).)

The urinary tract infection (UTI) is one of the most common bacterial infections in childhood. An adequate diagnosis is essential to be able to carry out a rational, efficient and effective treatment, however, there great heterogeneity in diagnostic methods, specifically in the study of antimicrobial susceptibility. The aim of these recommendations is to provide tools to homogenize the diagnosis criteria, susceptibility study and antimicrobial treatment of urinary tract infection in the pediatric population, with a rational use of antibiotics approach. In the first part, the recommendations regarding diagnosis are presented, such as sampling and cut-off points, as well as microbiological considerations for susceptibility study and management of UTI in pediatrics. The second part details the management of complications, UTI in special situations, and pharmacokinetic and pharmacodynamic considerations of antimicrobials to be prescribed in UTI.

The urinary tract infection (UTI) is one of the most common bacterial infections in childhood. An adequate diagnosis is essential to be able to carry out a rational, efficient and effective treatment, however, there is great heterogeneity in diagnostic methods, specifically in the study of antimicrobial susceptibility. The aim of these recommendations is to provide tools to homogenize the diagnosis criteria, susceptibility study and antimicrobial treatment of urinary tract infection in the pediatric population, with a rational use of antibiotics approach. In the first part, the recommendations regarding diagnosis were presented, such as sampling and cut-off points, as well as microbiological considerations for susceptibility study and management of UTI in pediatrics. This second part details the management of complications, UTI in special situations, and pharmacokinetic and pharmacodynamic considerations of antimicrobials to be prescribed in UTI.

HIV-1 genetic diversity and resistance profile might change according to the risky sexual behavior of the host. To show this, we recruited 134 individuals between the years 2015 and 2017 identified as transgender women sex workers (TWSW, n  = 73) and Heterosexual Military Officers (HET-MO, n  = 61). After obtaining informed consent, we collected a blood sample to perform the HIV genotyping, CD4 cell count, and viral load. We used bioinformatics approaches for detecting resistance mutations and recombination events. Epidemiological data showed that both groups reported sexually transmitted diseases and they were widespread among TWSW, especially syphilis and herpes virus (35.6%). Illegal drugs consumption was higher among TWSW (71.2%), whereas condom use was inconsistent for both HET-MO (57.4%) and TWSW (74.0%). TWSW showed the shortest time exposition to antiretroviral therapy (ART) (3.5 years) and the lowest access to ART (34.2%) that conducted treatment failure (>4 logs). HIV-1 sequences from TWSW and HET-MO were analyzed to determine the genetic diversity and antiretroviral drug resistance. Phylogeny analysis revealed 125 (93%) cases of subtype B, 01 subtype A (0.76%), 07 (5.30%) BF recombinants, and 01 (0.76%) AG recombinant. Also, TWSW showed a higher recombination index (9.5%, 7/73) than HET-MO (1.5%, 1/68). HET-MO only showed acquired resistance (26.23%, 16/61), whereas TWSW showed both acquired as transmitted resistance (9.59% for each). In conclusion, TWSW and HET-MO showed significant differences considering the epidemiological characteristics, genetic diversity, recombination events, and HIV resistance profile.

Niemann-Pick type A (NPA) disease is a fatal lysosomal neurodegenerative disorder caused by the deficiency in acid sphingomyelinase (ASM) activity. NPA patients present severe and progressive neurodegeneration starting at an early age. Currently, there is no effective treatment for this disease and NPA patients die between 2 and 3 years of age. NPA is characterized by an accumulation of sphingomyelin in lysosomes and dysfunction in the autophagy-lysosomal pathway. Recent studies show that c-Abl tyrosine kinase activity downregulates autophagy and the lysosomal pathway. Interestingly, this kinase is also activated in other lysosomal neurodegenerative disorders. Here, we describe that c-Abl activation contributes to the mechanisms of neuronal damage and death in NPA disease. Our data demonstrate that: 1) c-Abl is activated in-vitro as well as in-vivo NPA models; 2) imatinib, a clinical c-Abl inhibitor, reduces autophagy-lysosomal pathway alterations, restores autophagy flux, and lowers sphingomyelin accumulation in NPA patient fibroblasts and NPA neuronal models and 3) chronic treatment with nilotinib and neurotinib, two c-Abl inhibitors with differences in blood-brain barrier penetrance and target binding mode, show further benefits. While nilotinib treatment reduces neuronal death in the cerebellum and improves locomotor functions, neurotinib decreases glial activation, neuronal disorganization, and loss in hippocampus and cortex, as well as the cognitive decline of NPA mice. Our results support the participation of c-Abl signaling in NPA neurodegeneration and autophagy-lysosomal alterations, supporting the potential use of c-Abl inhibitors for the clinical treatment of NPA patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marín, Dulcey, Campos, de la Fuente, Acuña, Castro, Pinto, Yañez, Cortez, McGrath, Sáez, Gorshkov, Zheng, Southall, Carmo-Fonseca, Marugán, Alvarez and Zanlungo.)

One of the main microvascular complications presented in the Mexican population is diabetic retinopathy which affects 27.50% of individuals with type 2 diabetes. Therefore, the purpose of this study is to construct a predictive model to find out the risk factors of this complication. The dataset contained a total of 298 subjects, including clinical and paraclinical features. An analysis was constructed using machine learning techniques including Boruta as a feature selection method, and random forest as classification algorithm. The model was evaluated through a statistical test based on sensitivity, specificity, area under the curve (AUC), and receiving operating characteristic (ROC) curve. The results present significant values obtained by the model obtaining 69% of AUC. Moreover, a risk evaluation was incorporated to evaluate the impact of the predictors. The proposed method identifies creatinine, lipid treatment, glomerular filtration rate, waist hip ratio, total cholesterol, and high density lipoprotein as risk factors in Mexican subjects. The odds ratio increases by 3.5916 times for control patients which have high levels of cholesterol. It is possible to conclude that this proposed methodology is a preliminary computer-aided diagnosis tool for clinical decision-helping to identify the diagnosis of DR.

Thyroid hormone (TH) action is essential for hepatic lipid synthesis and oxidation. Analysis of hepatocyte-specific thyroid receptor β1 (TRβ1) knockout mice confirmed a role for TH in stimulating de novo lipogenesis and fatty acid oxidation through its nuclear receptor. Specifically, TRβ1 and its principal corepressor NCoR1 in hepatocytes repressed de novo lipogenesis, whereas the TH-mediated induction of lipogenic genes depended on the transcription factor ChREBP. Mice with a hepatocyte-specific deficiency in ChREBP lost TH-mediated stimulation of the lipogenic program, which, in turn, impaired the regulation of fatty acid oxidation. TH regulated ChREBP activation and recruitment to DNA, revealing a mechanism by which TH regulates specific signaling pathways. Regulation of the lipogenic pathway by TH through ChREBP was conserved in hepatocytes derived from human induced pluripotent stem cells. These results demonstrate that TH signaling in the liver acts simultaneously to enhance both lipogenesis and fatty acid oxidation.