Primary cilia as a targetable node between biliary injury, senescence and regeneration in liver transplantation.

BACKGROUND & AIMS: Biliary complications are a major cause of morbidity and mortality in liver transplantation. Up to 25% of patients that develop biliary complications require additional surgical procedures, re-transplantation or die in the absence of a suitable regraft. Here, we investigate the role of the primary cilium, a highly-specialised sensory organelle, in biliary injury leading to post-transplant biliary complications. METHODS: Human biopsies were used to study the structure and function of primary cilia in liver transplant recipients that develop biliary complications (N=7) in comparison with recipients without biliary complications (N=12). To study the biological effects of the primary cilia during transplantation, we generated murine models that recapitulate liver procurement and cold storage, and assessed the elimination of the primary cilia in biliary epithelial cells in the K19CreERTKif3aflox/flox mouse model. To explore the molecular mechanisms responsible for the observed phenotypes we used in vitro models of ischemia, cellular senescence and primary cilia ablation. Finally, we used pharmacological and genetic approaches to target cellular senescence and the primary cilia, both in mouse models and discarded human donor livers. RESULTS: Prolonged ischemic periods before transplantation result in ciliary shortening and cellular senescence, an irreversible cell cycle arrest that blocks regeneration. Our results indicate that primary cilia damage results in biliary injury and a loss of regenerative potential. Senescence negatively impacts primary cilia structure and triggers a negative feedback loop that further impairs regeneration. Finally, we explore how targeted interventions for cellular senescence and/or the stabilisation of the primary cilia improve biliary regeneration following ischemic injury. CONCLUSIONS: Primary cilia play an essential role in biliary regeneration and we demonstrate that senolytics and cilia-stabilising treatments provide a potential therapeutic opportunity to reduce the rate of biliary complications and improve clinical outcomes in liver transplantation. IMPACT AND IMPLICATIONS: Up to 25% of liver transplants result in biliary complications, leading to additional surgery, retransplants, or death. We found that the incidence of biliary complications is increased by damage to the primary cilium, an antenna that protrudes from the cell and is key to regeneration. Here, we show that treatments that preserve the primary cilia during the transplant process provide a potential solution to reduce the rates of biliary complications.

Neuronal Ceroid Lipofuscinosis in a Mixed-Breed Dog with a Splice Site Variant in CLN6.

A 23-month-old neutered male dog of unknown ancestry presented with a history of progressive neurological signs that included anxiety, cognitive impairment, tremors, seizure activity, ataxia, and pronounced visual impairment. The clinical signs were accompanied by global brain atrophy. Due to progression in the severity of disease signs, the dog was euthanized at 26 months of age. An examination of the tissues collected at necropsy revealed dramatic intracellular accumulations of autofluorescent inclusions in the brain, retina, and cardiac muscle. The inclusions were immunopositive for subunit c of mitochondrial ATP synthase, and their ultrastructural appearances were similar to those of lysosomal storage bodies that accumulate in some neuronal ceroid lipofuscinosis (NCL) diseases. The dog also exhibited widespread neuroinflammation. Based on these findings, the dog was deemed likely to have suffered from a form of NCL. A whole genome sequence analysis of the proband's DNA revealed a homozygous C to T substitution that altered the intron 3-exon 4 splice site of CLN6. Other mutations in CLN6 cause NCL diseases in humans and animals, including dogs. The CLN6 protein was undetectable with immunolabeling in the tissues of the proband. Based on the clinical history, fluorescence and electron-microscopy, immunohistochemistry, and molecular genetic findings, the disorder in this dog was classified as an NCL resulting from the absence of the CLN6 protein. Screening the dog's genome for a panel of breed-specific polymorphisms indicated that its ancestry included numerous breeds, with no single breed predominating. This suggests that the CLN6 disease variant is likely to be present in other mixed-breed dogs and at least some ancestral breeds, although it is likely to be rare since other cases have not been reported to date.

Closing the computational biology 'knowledge gap': Spanish Wikipedia as a case study.

MOTIVATION: Wikipedia is a vital open educational resource in computational biology. The quality of computational biology coverage in English-language Wikipedia has improved steadily in recent years. However, there is an increasingly large 'knowledge gap' between computational biology resources in English-language Wikipedia, and Wikipedias in non-English languages. Reducing this knowledge gap by providing educational resources in non-English languages would reduce language barriers which disadvantage non-native English speaking learners across multiple dimensions in computational biology. RESULTS: Here, we provide a comprehensive assessment of computational biology coverage in Spanish-language Wikipedia, the second most accessed Wikipedia worldwide. Using Spanish-language Wikipedia as a case study, we generate quantitative and qualitative data before and after a targeted educational event, specifically, a Spanish-focused student editing competition. Our data demonstrates how such events and activities can narrow the knowledge gap between English and non-English educational resources, by improving existing articles and creating new articles. Finally, based on our analysis, we suggest ways to prioritize future initiatives to improve open educational resources in other languages. AVAILABILITY AND IMPLEMENTATION: Scripts for data analysis are available at: https://github.com/ISCBWikiTeam/spanish.

Plant Protease Inhibitors as Emerging Antimicrobial Peptide Agents: A Comprehensive Review.

Antimicrobial peptides (AMPs) are important mediator molecules of the innate defense mechanisms in a wide range of living organisms, including bacteria, mammals, and plants. Among them, peptide protease inhibitors (PPIs) from plants play a central role in their defense mechanisms by directly attacking pathogens or by modulating the plant's defense response. The growing prevalence of microbial resistance to currently available antibiotics has intensified the interest concerning these molecules as novel antimicrobial agents. In this scenario, PPIs isolated from a variety of plants have shown potential in inhibiting the growth of pathogenic bacteria, protozoans, and fungal strains, either by interfering with essential biochemical or physiological processes or by altering the permeability of biological membranes of invading organisms. Moreover, these molecules are active inhibitors of a range of proteases, including aspartic, serine, and cysteine types, with some showing particular efficacy as trypsin and chymotrypsin inhibitors. In this review, we provide a comprehensive analysis of the potential of plant-derived PPIs as novel antimicrobial molecules, highlighting their broad-spectrum antimicrobial efficacy, specificity, and minimal toxicity. These natural compounds exhibit diverse mechanisms of action and often multifunctionality, positioning them as promising molecular scaffolds for developing new therapeutic antibacterial agents.

Higher adherence to the Mediterranean Diet is associated with better academic achievement in Spanish university students: A multicenter cross-sectional study.

The objective was to assess the association of the overall score and different items of the Mediterranean Diet Adherence Screener (MEDAS) questionnaire with academic achievement in Spanish university students. We hypothesized that university students with greater adherence to the Mediterranean Diet (MedDiet) would have better academic achievement. A cross-sectional study was performed involving 266 first-year students from the University of Castilla-La Mancha, Spain, during the 2017-2018 academic year. Adherence to the Mediterranean diet was evaluated with the 14-item MEDAS questionnaire. As an indicator variable for academic achievement, the average marks of the examinations required for access to Spanish universities were used. A total of 63 participants (23.6%) adhered to MedDiet recommendations. Analysis of covariance models showed that participants with higher adherence to the MedDiet had significantly higher scores on academic achievement than their peers with low adherence (P < .001) after controlling for potential confounders. Additionally, the evaluation of each item of the MEDAS questionnaire showed that a diet rich in olive oil, vegetables, fruits, legumes, fish and shellfish, and a low consumption of sweets and carbonated beverages were positively associated with academic achievement; nevertheless, wine intake was inversely associated. This study showed that Spanish university students had a low prevalence of good adherence to the MedDiet. Additionally, our results suggested that higher adherence to the MedDiet is associated with better academic achievement in Spanish university students. From a public health perspective and because of low adherence, it is important to continue to focus on promoting adherence to the MedDiet as part of a healthy lifestyle pattern to improve the academic performance of young university students.

Are artificial intelligence chatbots a reliable source of information about contact lenses?

INTRODUCTION: Artificial Intelligence (AI) chatbots are able to explain complex concepts using plain language. The aim of this study was to assess the accuracy of three AI chatbots answering common questions related to contact lens (CL) wear. METHODS: Three open access AI chatbots were compared: Perplexity, Open Assistant and ChatGPT 3.5. Ten general CL questions were asked to all AI chatbots on the same day in two different countries, with the questions asked in Spanish from Spain and in English from the U.K. Two independent optometrists with experience working in each country assessed the accuracy of the answers provided. Also, the AI chatbots' responses were assessed if their outputs showed any bias towards (or against) any eye care professional (ECP). RESULTS: The answers obtained by the same AI chatbots were different in Spain and the U.K. Also, statistically significant differences were found between the AI chatbots for accuracy. In the U.K., ChatGPT 3.5 was the most and Open Assistant least accurate (p < 0.01). In Spain, Perplexity and ChatGPT were statistically more accurate than Open Assistant (p < 0.01). All the AI chatbots presented bias, except ChatGPT 3.5 in Spain. CONCLUSIONS: AI chatbots do not always consider local CL legislation, and their accuracy seems to be dependent on the language used to interact with them. Hence, at this time, although some AI chatbots might be a good source of information for general CL related questions, they cannot replace an ECP.

Host space, not energy or symbiont size, constrains feather mite abundance across passerine bird species.

Comprehending symbiont abundance among host species is a major ecological endeavour, and the metabolic theory of ecology has been proposed to understand what constrains symbiont populations. We parameterized metabolic theory equations to investigate how bird species' body size and the body size of their feather mites relate to mite abundance according to four potential energy (uropygial gland size) and space constraints (wing area, total length of barbs and number of feather barbs). Predictions were compared with the empirical scaling of feather mite abundance across 106 passerine bird species (26,604 individual birds sampled), using phylogenetic modelling and quantile regression. Feather mite abundance was strongly constrained by host space (number of feather barbs) but not by energy. Moreover, feather mite species' body size was unrelated to the body size of their host species. We discuss the implications of our results for our understanding of the bird-feather mite system and for symbiont abundance in general.

Funcionamiento, Discapacidad, Rehabilitación, Inclusión y Desempeño. Terminología Universal y Comunicación Efectiva, un Desafío de la Fisioterapia/Kinesiología

La comunicación efectiva en las intervenciones de fisioterapia/kinesiología tiene un impacto directo en los resultados y en la experiencia de los usuarios. Además, promover un lenguaje y una terminología universal en nuestra disciplina facilita la colaboración y la investigación nacional e internacional. El enfoque centrado en la Convención de las Naciones Unidas sobre los Derechos de las Personas con Discapacidad adoptado por la Confederación Mundial de Fisioterapia nos compromete a alinearnos con definiciones de conceptos acordados internacionalmente, lo que fortalece la profesión y promueve el profesionalismo en las acciones terapéuticas. Avanzar hacia reflexión y consensos en la comunidad de fisioterapia/kinesiología en torno a conceptos claves como discapacidad, rehabilitación, inclusión y desempeño, con la impronta del funcionamiento humano, optimizan la praxis profesional y su impacto en las intervenciones a lo largo del curso de vida en todos los niveles asistenciales.

Results of the transition from posterolateral to anterior minimally invasive approach for total hip arthroplasty.

BACKGROUND: The anterior minimally invasive (AMI) approach reduces soft tissue damage, risk of dislocation and enhances recovery, but it is associated with certain complications. The aim of this study is to compare the outcomes of patients who underwent total hip arthroplasty (THA) through posterolateral (PL) and AMI approaches performed by the same surgeon, in order to determine the learning curve associated with this new approach. METHODS: This retrospective cohort study included patients who underwent THA via PL and AMI approach between 2017 and 2022, with a minimum follow-up of 1 year. Hip fracture and oncologic patients were excluded. Demographic variables, functional scores and perioperative complications were assessed. A bivariate analysis was performed to identify differences between groups. RESULTS: Data of 124 AMI and 120 PL patients were analyzed. Demographic characteristics among groups were homogeneous. Functional outcomes at 3 months were superior for AMI (Oxford: 43 vs. 38; p < 0.05), no dislocations were identified (0% vs. 4.2%; p < 0.05) and no differences in the transfusion rate were found (6.5% AMI vs. 6.7% PL; p = 0.996). Infection rate was 4% for AMI and 3.4% for PL (p = 0.572). Surgical time was shorter for the PL approach, but the median surgical time of the last 25 AMI cases was shorter. CONCLUSIONS: The AMI approach is an excellent alternative for patients requiring THA. Although surgical time and perioperative bleeding were greater during the learning curve, this approach offers improved functional outcomes and a lower dislocation rate, without significant differences in transfusion and infection outcomes, demonstrating that responsible innovation and safe implementation of new techniques is possible.

Bilateral Variation of the Vertebral Artery: Report of a Case and its Clinical Implication / Variación Bilateral de la Arteria Vertebral; Reporte de un Caso y su Implicancia Clínica

SUMMARY: There are many reports on anatomical variations of the vertebral arteries, which may be related to origin, trajectory, caliber, and side. Bilateral variations are less frequent, however, and less common are bilateral variants that differ from each other. The aim of this work was to report the presence of a bilateral variation of the vertebral artery and its functional and clinical implications. Dissection of a female cadaver, fixed in 10 % buffered formaldehyde, which had not undergone any previous surgeries in the study area and had anatomical variations in both vertebral arteries. In each one, follow-up was done from its origin to its end, determining its trajectory, diameters, branching, and anatomical relations. A left vertebral artery was found, starting in the aortic arch and making a sinuous trajectory of 4 curvatures to enter the transverse foramen of C4. The right vertebral artery began as the first branch of the subclavian artery. Its initial trajectory was rectilinear, followed by a right concave curve, a 360° loop that included a second ascending curve, and ended straight before entering the transverse foramen of C6. The coexistence of bilateral variations in the vertebral arteries is possible. This atypical situation can potentially generate vascular and neurological pathologies, but with different symptoms and causes. Knowing these variations and deliberately searching for them will enable the specialist to make a suitable differential diagnosis.

Existen múltiples reportes sobre variaciones anatómicas de las arterias vertebrales, las que se pueden relacionar con origen, trayecto, calibre y lateralidad. Sin embargo, las variaciones bilaterales son menos frecuentes, y menos común es que las variantes bilaterales sean diferentes entre ellas. El objetivo de este trabajo fue reportar la presencia de una variación bilateral de la arteria vertebral y su implicancia funcional y clínica. Disección en un cadáver de sexo femenino, fijado en formaldehido tamponado al 10 %, el cual no presentaba intervenciones quirúrgicas previas en la región de estudio y que tenía variaciones anatómicas en ambas arterias vertebrales. En cada una se realizó seguimiento desde su origen hasta su terminación, pudiendo determinar su trayecto, diámetros, ramificaciones y relaciones anatómicas. Se encontró una arteria vertebral izquierda originada en el arco aórtico, que realizaba un trayecto sinuoso de 4 curvaturas e ingresaba al foramen transverso de C4. La arteria vertebral derecha se originaba como primera rama de la arteria subclavia. Su trayecto inicial era rectilíneo seguido por una curva de concavidad derecha, un loop (giro) de 360° que incluía una segunda curva ascendente y terminaba en dirección recta antes de ingresar al foramen transverso de C6. La coexistencia de variaciones bilaterales en las arterias vertebrales es posible. Esta situación atípica, potencialmente puede generar en la persona patologías neurológicas de origen vascular, pero con sintomatología y causas diferentes. Conocer estas variaciones y realizar una búsqueda intencionada de ellas permitirá el especialista realizar un adecuado diagnóstico diferencial.

Mediterranean Dietary Pattern and Psychosocial Health Problems in Spanish Adolescents: The EHDLA Study.

The aims of the present study were twofold: to determine the association between adherence to the Mediterranean diet (MedDiet) and psychological problems and to assess the relationship between different food groups of the MedDiet and different patterns of psychosocial health problems in a sample of Spanish adolescents from the Valle de Ricote (Region of Murcia, Spain). This cross-sectional study included a representative sample of 700 adolescents (57% girls) between 12 and 17 years of age. Adherence to the MedDiet was assessed by the Mediterranean Diet Quality Index for Children and Teenagers (KIDMED). Psychosocial health problems were measured by the 25-item self-report version of the Strengths and Difficulties Questionnaire (SDQ). ANCOVA models were used to test the mean differences in psychosocial health problems (SDQ subscales) by adherence to MedDiet categories (low, medium, and high). Multiple linear regression was used to determine the association between different food groups of the MedDiet and psychosocial health problems. Adolescents with low adherence to the MedDiet had significantly higher scores in SDQ total difficulties, conduct problems, and hyperactivity problems and lower scores in pro-social behavior (p < 0.05) than their peers with medium and high adherence to the MedDiet. In relation to specific MedDiet food groups, fruit, nut, and legume intake were associated with higher psychosocial health. However, sweets, skipping breakfast, or high consumption of pasta or rice (≥5 weeks) were associated to higher psychosocial health problems. Our results show that adolescents with higher adherence to the MedDiet could benefit from greater psychosocial health. Individually, some patterns of MedDiet, such as fruit, nut, and legume intake, may reduce psychosocial health problems. These cross-sectional results should be confirmed in longitudinal and intervention studies.

25OHVitamin D Levels in a Canarian Pediatric Population with and without Type 1 Diabetes: The Role of Acidosis.

The role of Vitamin D in the development of type 1 diabetes (T1D) is controversial. The Canary Islands have the highest incidence of childhood-onset T1D in Spain and one of the highest in Europe. We aimed to evaluate 25OHVitamin D concentrations in a Canarian pediatric population, to assess the existence of seasonal variation, to study their association with T1D, and to evaluate the role of acidosis in its levels. In a retrospective, case-control study, we obtained data from 146 T1D patients (<15 years of age) and 346 control children; 25OHVitamin D concentrations were assessed in serum by automatic ChemiLuminescence ImmunoAssay technology. We found significantly higher 25OHVitamin D levels in the summer and autumn months and an inverse correlation between T1D and age; 25OHVitamin D sufficiency was similar in both groups (44.5% vs. 45.1%), with significant differences in the percentage of patients presenting vitamin D deficiency (11.6% (T1D) vs. 16.4% (controls)). When stratified according to the presence of ketoacidosis at sampling, only patients with acidosis showed lower 25OHVitamin D concentrations than controls. Despite its subtropical geographic location, Vitamin D deficiency is frequent in children in Gran Canaria, and 25OHVitamin D concentrations show seasonal variation. After adjusting for acidosis, no differences were found between children with and without T1D.

MDRD is the eGFR equation most strongly associated with 4-year mortality among patients with diabetes in Colombia.

INTRODUCTION: We compared the association of glomerular filtration rate (GFR) estimated with the Cockcroft-Gault, Modification of Diet in Renal Disease study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), or the new CKD-EPI without race (CKD-EPI-NR) equations, with 4-year all-cause mortality in patients with diabetes. RESEARCH DESIGN AND METHODS: We analyzed a nationwide, centralized database of all adults diagnosed with diabetes assisted by the Colombian Health System between July 1, 2015, and June 30, 2019. Plasma creatinine was used to calculate baseline estimated glomerular filtration rate (eGFR) and classify each patient in a chronic kidney disease (CKD) stage, by each of the four equations. We used multivariate logistic regression to compare the association between CKD stage and mortality, and receiver operating characteristic (ROC) analyses to assess the overall association of eGFR by each equation and mortality. RESULTS: The study included 758,219 patients (58% female, 7.2% black race, mean age 62.3, Glycated hemoglobin A1c [HbA1c] 7.4%). There were 35,296 deaths over the study follow-up. Considering eGFR by each equation as a continuous variable, the odds of death decreased by 1.1%-1.5% for each additional mL/min. Compared with CKD stage 1 of each equation, being placed in CKD stages 3a, 3b, or 4 by MDRD or CKD-EPI-NR was associated with greater odds of death than being categorized in the same stages by CKD-EPI. Among patients of black race, the adjusted OR of mortality for CKD stage 4 relative to stage 1 was 4.63 (95% CI 3.39 to 6.35) for MDRD, 3.66 (2.85 to 4.69) for CKD-EPI-NR, 3.01 (2.38 to 3.81) for CKD-EPI, and 2.82 (2.29 to 3.49) for Cockcroft-Gault. The area under the ROC curve to discriminate by survival status was greatest for MDRD, followed by CKD-EPI-NR, CKD-EPI, and Cockcroft-Gault, in that order (p<0.001 for all differences). CONCLUSIONS: Compared with other eGFR equations, MDRD showed the strongest association with all-cause mortality in a sample of Latin-American patients with diabetes. This difference was most pronounced among patients of black race.

Combining Heart Rate Variability and Oximetry to Improve Apneic Event Screening in Non-Desaturating Patients.

In this paper, we thoroughly analyze the detection of sleep apnea events in the context of Obstructive Sleep Apnea (OSA), which is considered a public health problem because of its high prevalence and serious health implications. We especially evaluate patients who do not always show desaturations during apneic episodes (non-desaturating patients). For this purpose, we use a database (HuGCDN2014-OXI) that includes desaturating and non-desaturating patients, and we use the widely used Physionet Apnea Dataset for a meaningful comparison with prior work. Our system combines features extracted from the Heart-Rate Variability (HRV) and SpO2, and it explores their potential to characterize desaturating and non-desaturating events. The HRV-based features include spectral, cepstral, and nonlinear information (Detrended Fluctuation Analysis (DFA) and Recurrence Quantification Analysis (RQA)). SpO2-based features include temporal (variance) and spectral information. The features feed a Linear Discriminant Analysis (LDA) classifier. The goal is to evaluate the effect of using these features either individually or in combination, especially in non-desaturating patients. The main results for the detection of apneic events are: (a) Physionet success rate of 96.19%, sensitivity of 95.74% and specificity of 95.25% (Area Under Curve (AUC): 0.99); (b) HuGCDN2014-OXI of 87.32%, 83.81% and 88.55% (AUC: 0.934), respectively. The best results for the global diagnosis of OSA patients (HuGCDN2014-OXI) are: success rate of 95.74%, sensitivity of 100%, and specificity of 89.47%. We conclude that combining both features is the most accurate option, especially when there are non-desaturating patterns among the recordings under study.

Clinical outcomes in patients with solid tumors living in rural and urban areas followed via telemedicine: experience in a highly complex latin american hospital.

BACKGROUND: Difficulties in cancer services access increase the burden of disease and mortality in rural areas, and telehealth can be a useful tool to address these inequalities. OBJECTIVE: We aimed to describe the outcomes of patients in rural and urban areas with solid tumors managed by oncologists through telemedicine. METHODS: We conducted a retrospective cohort study of patients with solid tumors from March to December 2020. A total of 1270 subjects with solid tumors were included, 704 living in urban areas and 566 in rural areas. RESULTS: The most frequent tumors were breast (51.8%) and prostate (12.4%). The trend of telemedicine care was similar for both populations; in-person care was more frequent in the urban population. There were no differences in referral to the emergency room, need for hospitalization, and mortality for both groups. CONCLUSION: Telemedicine is a care modality that reduces barriers in the care of patients with solid tumors, evidencing similar outcomes regardless of living in rural or urban areas.

Strong Negative Association of non-HDL Cholesterol Goal Achievement With Incident CKD Among Adults With Diabetes.

Context: The relative importance of the control of different metabolic risk factors for the prevention of chronic kidney disease among patients with diabetes in real life conditions is insufficiently understood. Objective: We evaluated the effect of the achievement of glycated hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDLc) or non-high-density lipoprotein cholesterol (non-HDLc) goals (ABC goals) on the development of incident chronic kidney disease (iCKD) among patients with diabetes. Methods: In a nationwide registry of all individuals diagnosed with diabetes assisted by the health system in Colombia, we analyzed the association between baseline or sustained goal achievement and development of iCKD over a 4-year follow-up. iCKD was defined as a new occurrence of an estimated glomerular filtration rate less than 60 mL/min/1.73 m2, hemodialysis, peritoneal dialysis, or kidney transplant. Results: The study included 998 790 adults with diabetes (56% female, mean age 59). There were 125 626 cases of iCKD. After adjustment for multiple confounders, a baseline SBP less than 130 mm Hg (odds ratio [OR] 0.79 [0.78-0.80]) and a baseline HbA1c less than 7.0% (OR 0.86 [0.85-0.87]) were negatively associated with iCKD. Sustained achievement showed stronger negative associations with iCKD than just baseline achievement. Considering each goal separately, sustained non-HDLc less than 130 mg/dL had the strongest negative association with iCKD (OR 0.67 [0.65-0.69]). Patients who maintained the triple ABC goal over the entire follow-up had 32% (29-34) lower odds of developing CKD, 38% (34-42) if they additionally kept a normal body mass index (BMI). Sustained ABC control including a normal BMI was more strongly associated with a lower incidence of CKD in patients of Black race (OR 0.72 vs 0.89; P for interaction = .002). Conclusion: At the country level, sustained achievement of ABC goals and most especially non-HDLc were associated with substantial reductions in iCKD.

Functional Brain Connectivity Prior to the COVID-19 Outbreak Moderates the Effects of Coping and Perceived Stress on Mental Health Changes: A First Year of COVID-19 Pandemic Follow-up Study.

BACKGROUND: The COVID-19 pandemic provides a unique opportunity to investigate the psychological impact of a global major adverse situation. Our aim was to examine, in a longitudinal prospective study, the demographic, psychological, and neurobiological factors associated with interindividual differences in resilience to the mental health impact of the pandemic. METHODS: We included 2023 healthy participants (age: 54.32 ± 7.18 years, 65.69% female) from the Barcelona Brain Health Initiative cohort. A linear mixed model was used to characterize the change in anxiety and depression symptoms based on data collected both pre-pandemic and during the pandemic. During the pandemic, psychological variables assessing individual differences in perceived stress and coping strategies were obtained. In addition, in a subsample (n = 433, age 53.02 ± 7.04 years, 46.88% female) with pre-pandemic resting-state functional magnetic resonance imaging available, the system segregation of networks was calculated. Multivariate linear models were fitted to test associations between COVID-19-related changes in mental health and demographics, psychological features, and brain network status. RESULTS: The whole sample showed a general increase in anxiety and depressive symptoms after the pandemic onset, and both age and sex were independent predictors. Coping strategies attenuated the impact of perceived stress on mental health. The system segregation of the frontoparietal control and default mode networks were found to modulate the impact of perceived stress on mental health. CONCLUSIONS: Preventive strategies targeting the promotion of mental health at the individual level during similar adverse events in the future should consider intervening on sociodemographic and psychological factors as well as their interplay with neurobiological substrates.

Senolytic treatment preserves biliary regenerative capacity lost through cellular senescence during cold storage.

Liver transplantation is the only curative option for patients with end-stage liver disease. Despite improvements in surgical techniques, nonanastomotic strictures (characterized by the progressive loss of biliary tract architecture) continue to occur after liver transplantation, negatively affecting liver function and frequently leading to graft loss and retransplantation. To study the biological effects of organ preservation before liver transplantation, we generated murine models that recapitulate liver procurement and static cold storage. In these models, we explored the response of cholangiocytes and hepatocytes to cold storage, focusing on responses that affect liver regeneration, including DNA damage, apoptosis, and cellular senescence. We show that biliary senescence was induced during organ retrieval and exacerbated during static cold storage, resulting in impaired biliary regeneration. We identified decoy receptor 2 (DCR2)-dependent responses in cholangiocytes and hepatocytes, which differentially affected the outcome of those populations during cold storage. Moreover, CRISPR-mediated DCR2 knockdown in vitro increased cholangiocyte proliferation and decreased cellular senescence but had the opposite effect in hepatocytes. Using the p21KO model to inhibit senescence onset, we showed that biliary tract architecture was better preserved during cold storage. Similar results were achieved by administering senolytic ABT737 to mice before procurement. Last, we perfused senolytics into discarded human donor livers and showed that biliary architecture and regenerative capacities were better preserved. Our results indicate that cholangiocytes are susceptible to senescence and identify the use of senolytics and the combination of senotherapies and machine-perfusion preservation to prevent this phenotype and reduce the incidence of biliary injury after transplantation.

The Role of Angiopoietins in Neovascular Diabetes-Related Retinal Diseases.

Diabetic retinopathy is a devastating and frequent complication of poorly controlled diabetes, whose pathogenesis is still only partially understood. Advances in basic research over the last two decades have led to the discovery of angiopoietins, proteins that strongly influence the growth and integrity of blood vessels in many vascular beds, with particular importance in the retina. Angiopoietin 1 (Ang1), produced mostly by pericytes and platelets, and angiopoietin 2 (Ang2), produced mainly by endothelial cells, bind to the same receptor (Tie2), but exert opposing effects on target cells. Ang1 maintains the stability of the mature vasculature, while Ang2 promotes vessel wall destabilization and disruption of the connections between endothelial cells and pericytes. Human retinal endothelial cells exposed to Ang2 show reduced membrane expression of the adhesion molecule VE-cadherin, and patients with proliferative diabetic retinopathy or diabetic macular edema have markedly increased vitreal concentrations of Ang2. Faricimab, a bi-specific antibody simultaneously directed against Ang2 and VEGF, has shown promising results in clinical trials among patients with diabetic retinopathy, and other agents targeting the angiopoietin system are currently in development.

Posterior hamstring harvest improves aesthetic satisfaction and decreases sensory complications as compared to the classic anterior approach in anterior cruciate ligament reconstruction surgery.

PURPOSE: The use of the posterior approach for harvesting hamstring grafts has recently become popular thanks to new all-inside techniques and retrograde drills. This study aims to compare the classic anterior approach with the posterior approach in the popliteal fossa. METHODS: Retrospective comparative study of 100 consecutive cases of primary ligamentoplasty performed using ipsilateral semitendinosus autograft with at least one year of follow-up. 50 patients with anterior approach (group A) and 50 patients with posterior approach (P). Ratio men/women: 9/1. Mean age: 32 ± 13 years. Mean operative time: 64.88 ± 12.28 min. STUDY VARIABLES: Graft harvest time; intraoperative complications (semitendinous [ST] tendon cut); postoperative neurological complications (allodynia, paresthesia, pain) or hematoma in the donor area; atrophy of the operated thigh compared to the contralateral thigh, postoperative VAS score, aesthetic satisfaction and overall satisfaction. RESULTS: Graft harvest time of 9.5 min in group A versus 5.25 min in group P (p < 0.05). Sensory complications: 16% in group A versus 2% in group P (p < 0.05). Regarding the patient's evaluation of the aesthetic result of the surgery, 80% in group A and 92% in group P were very satisfied, 16% in group A and 8% in group P were satisfied and 4% in group A and no patients in group P not very satisfied (p < 0.05). No significant differences were found in terms of total operative time, postoperative joint movement, atrophy of the operated thigh, postoperative VAS, or overall patient satisfaction. CONCLUSIONS: The posterior approach to harvesting the ipsilateral hamstring graft obtained better results than the anterior approach in terms of aesthetic satisfaction of the patient, lower rate of neurological complications (allodynia, paresthesias and hypoesthesia in the anterior region of the knee and leg) and shorter hamstring harvest time. LEVEL OF EVIDENCE: IV.