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Background Current human retina studies predominantly utilize post-mortem tissue, and the sample accessibility constraints make the characterization of the living human retina at single-cell resolution a challenge. Although single-nucleus RNA-seq expands the utility of frozen samples, it provides a nuclear-centric view, potentially missing key cytoplasmic information and transient biological processes. Thus, it is important to generate resources directly from living human retinal tissue to complement existing datasets. Methods We profiled 106,829 single cells from nine unfrozen human retina samples. Living samples were collected within 10 min of therapeutic enucleation and four postmortem samples were collected within 6 h. After standardized dissociation, single-cell transcriptomes were generated using 10x Genomics 3’ RNA-seq and applied scVI to generate batch-corrected integrated atlas. Major cell types and subtypes were annotated through iterative Leiden clustering, canonical markers. Subsequent analyses included differential expression comparisons between cell states and regulon activity profiling to further characterize cellular identities and regulatory networks. Transcriptional dynamics were assessed using RNA velocity, and cell-cell signaling pathways were inferred with CellChat. Key findings were validated in independent samples from two additional donors (four samples) using the identical workflow. Results We contribute to establishing a reference for retinal cell type proportions and cellular states. Our analysis revealed ELF1-mlCone, a distinct cluster of mlCone photoreceptors identified by distinct transcriptional features. The presence and transcriptional features of this cluster were validated in independent samples. Additionally, by comparing living and post-mortem samples, our study highlights differences in transcriptional dynamics: living tissue preserved coherent RNA velocity streams, enabling clear dynamic state transitions, while post-mortem tissue exhibited disorganized patterns. These findings suggest that using living tissue can improve the capture of active cellular states and transitions. Conclusions Our atlas provides a single-cell reference contrasting living versus early postmortem human retina, integrating cell type composition, transcriptional diversity, and functional insights. It may serve as a useful resource for retinal research and for understanding aspects of human retinal biology, particularly given its inclusion of living tissue and diverse pathological states.

In Canada, organ donation from deceased donors is a common practice that saves or improves the lives of more than nearly 2000 Canadians every year, accounting for more than 3 of 4 of all transplanted organs. Deceased donation is permitted after either neurologic or circulatory determination of death, with the latter accounting for 25% of all organs donated in Canada in 2017.1 The current Canadian guideline recommendations for donation after circulatory determination of death, published in 2006, address the conventional scenario of an unconscious, incapable, critically ill patient not expected to survive the withdrawal of life-sustaining measures. The target audience of this guidance consists of clinicians, organ donation organizations, end-of-life care experts, medical assistance in dying providers and policy-makers. This document is intended to inform policies related to offering organ and tissue donation to patients who have made a decision that will lead to imminent death.

Background Policy decisions about opt-in and opt-out consent for organ donation are based on limited evidence. To fill this gap we investigated the difference between deceased and living organ donation rates in opt-in and opt-out consent systems across a 13 year period. We controlled for extensive covariates and estimated the causal effect of consent with instrumental variables analysis. Method This panel study used secondary data analysis to compare organ donor and transplant rates in 48 countries that had either opt-in or opt-out consent. Organ donation data were obtained over a 13-year period between 2000 and 2012. The main outcome measures were the number of donors, number of transplants per organ and total number (deceased plus living) of kidneys and livers transplanted. The role of consent on donor and transplant rates was assessed using multilevel modeling and the causal effect estimated with instrumental variables analysis. Results Deceased donor rates (per-million population) were higher in opt-out ( M  = 14.24) than opt-in consent countries ( M  = 9.98; χ  = -4.27, 95% confidence interval (CI) = -8.08, -0.45, P  = .029). However, the number of living donors was higher in opt-in ( M  = 9.36) than opt-out countries ( M  = 5.49; B  = 3.86, 95% CI = 1.16, 6.56, P  = .006). Importantly, the total number of kidneys transplanted (deceased plus living) was higher in opt-out ( M  = 28.32) than opt-in countries ( M  = 22.43; B  = -5.89, 95% CI = -11.60, -0.17, P  = .044). Similarly, the total number of livers transplanted was higher in opt-out ( M  = 11.26) than opt-in countries ( M  = 7.53; B  = -3.73, 95% CI = -7.47, 0.01, P  = .051). Instrumental variables analysis suggested that the effect of opt-in versus opt-out consent on the difference between deceased and living donor rates is causal. Conclusions While the number of deceased donors is higher than the number of living donors, opt-out consent leads to a relative increase in the total number of livers and kidneys transplanted.

Purpose The purpose of this paper is to provide a method for determining the numerical solutions of the thermal damage of cylindrical living tissues using hyperbolic bioheat model. Due to the complex governing equation, the finite element approach has been adopted to solve these problems. To approve the accuracy of the numerical solution, the numerical outcomes obtained by the finite element approach are compared with the existing experimental study. In addition, the comparisons between the numerical outcomes and the existing experimental data displays that the present mathematical models are efficient tools to evaluate the bioheat transfer in the cylindrical living tissue. Numerical computations for temperatures and thermal damage are presented graphically. Design/methodology/approach In this section, the complex equation of bioheat transfer based upon one relaxation time in cylindrical living tissue is summarized by using the finite element method. This method has been used here to get the solution of equation (8) with initial conditions (9) and boundary conditions (10). The finite element technique is a strong method originally advanced for numerical solutions of complex problems in many fields, and it is the approach of choice for complex systems. Another advantage of this method is that it makes it possible to visualize and quantify the physical effects independently of the experimental limits. Abbas and his colleagues [26-34] have solved several problems under generalized thermoelastic theories. Findings In this study, the different values of blood perfusion and thermal relaxation time of the dermal part of cylindrical living tissue are used. To verify the accuracy of the numerical solutions, the numerical outcomes obtained by the finite element procedure and the existing experimental study have been compared. This comparison displays that the present mathematical model is an effective tool to evaluate the bioheat transfer in the living tissue. Originality/value The validation of the obtained results by using experimental data the numerical solution of hyperbolic bioheat equation is presented. Due to the nonlinearity of the basic equation, the finite element approach is adopted. The effects of thermal relaxation times on the thermal damage and temperature are studied.

In 2021, the International Society of Physical and Rehabilitation Medicine (ISPRM) special interest group on sarcopenia included the quadriceps thickness assessed with ultrasound image as an indicator of muscle mass in the diagnosis criteria of sarcopenia. If quadriceps echo intensity of older inpatients is to be a strong predictor of quadriceps thickness, muscle quality of the quadriceps may be estimated by the muscle mass when diagnosing sarcopenia using the criteria of ISPRM. This study aimed to examine the association between muscle mass and fraction of intramuscular adipose tissue of the quadriceps in older inpatients. This cross-sectional study included 399 inpatients aged ≥ 65 years. Primary outcomes were muscle mass and fraction of intramuscular adipose tissue of the quadriceps. Images were acquired using a B-mode ultrasound. Muscle mass and fraction of intramuscular adipose tissue of the quadriceps were assessed based on the muscle thickness and echo intensity, respectively. A multiple regression analysis (forced entry method) was performed to confirm whether quadriceps echo intensity was related to quadriceps thickness even after adjusting for other factors. In the multiple regression analyses for both male and female models, quadriceps echo intensity (male: β = - 0.537, p < 0.001; female: β = - 0.438, p < 0.001), Geriatric Nutritional Risk Index (male: β = 0.236, p < 0.001; female: β = 0.213, p < 0.001), and subcutaneous fat thickness of the thigh (male: β = 0.197, p < 0.001; female: β = 0.248, p < 0.001) were independently and significantly associated with quadriceps thickness. Our results show that there is a negative and significant association between muscle mass and fraction of intramuscular adipose tissue in older inpatients. Muscle quality of the quadriceps in older inpatients may be estimated to some extent by the muscle mass.

Background: Use of lungs donated after circulatory death (DCD) has expanded, but changes in donor/recipient characteristics and comparison to brain dead donors (DBD) has not been studied. We examined the evolution of the use of DCD lungs for transplantation and compare outcomes to DBD lungs. Methods: The SRTR database was used to construct three 5-year intervals. Perioperative variables and survival were compared by era and for DCD vs. DBD. Geographic variation was estimated using recipient permanent address. Results: 728 DCD and 27,205 DBD lung transplants were identified. DCD volume increased from Era 1 ( n = 73) to Era 3 ( n = 528), representing 1.1% and 4.2% of lung transplants. Proportionally more DCD recipients were in ICU or on ECMO pre-transplant, and had shorter waitlist times. DCD donors were older, had lower PaO2/FiO2 ratios compared to DBD, more likely to be bilateral, had longer ischemic time, length of stay, post-op dialysis, and increased use of lung perfusion. There was no difference in overall survival. Geographically, use was heterogeneous. Conclusion: DCD utilization is low but increasing. Despite increasing ischemic time and transplantation into sicker patients, survival is similar, which supports further DCD use in lung transplantation. DCD lung transplantation presents an opportunity to continue to expand the donor pool.

Background Frailty is a multidimensional syndrome characterized by loss of physiologic and cognitive reserve that heightens vulnerability. Frailty has been well described among elderly patients (i.e., 65 years of age or older), but few studies have evaluated frailty in nonelderly patients with critical illness. We aimed to describe the prevalence, correlates, and outcomes associated with frailty among younger critically ill patients. Methods We conducted a prospective cohort study of 197 consecutive critically ill patients aged 50–64.9 years admitted to intensive care units (ICUs) at six hospitals across Alberta, Canada. Frailty was defined as a score ≥5 on the Clinical Frailty Scale before hospitalization. Multivariable analyses were used to evaluate factors independently associated with frailty before ICU admission and the independent association between frailty and outcome. Results In the 197 patients in the study, mean (SD) age was 58.5 (4.1) years, 37 % were female, 73 % had three or more comorbid illnesses, and 28 % ( n  = 55; 95 % CI 22–35) were frail. Factors independently associated with frailty included not being completely independent (adjusted OR [aOR] 4.4, 95 % CI 1.8–11.1), connective tissue disease (aOR 6.0, 95 % CI 2.1–17.0), and hospitalization within the preceding year (aOR 3.3, 95 % CI 1.3–8.1). There were no significant differences between frail and nonfrail patients in reason for admission, Acute Physiology and Chronic Health Evaluation II score, preference for life support, or treatment intensity. Younger frail patients did not have significantly longer (median [interquartile range]) hospital stay (26 [9–68] days vs. 19 [10–43] days; p  = 0.4), but they had greater 1-year rehospitalization rates (61 % vs. 40 %; p  = 0.02) and higher 1-year mortality (33 % vs. 20 %; adjusted HR 1.8, 95 % CI 1.0–3.3; p  = 0.039). Conclusions Prehospital frailty is common among younger critically ill patients, and in this study it was associated with higher rates of mortality at 1 year and with rehospitalization. Our data suggest that frailty should be considered in younger adults admitted to the ICU, not just in the elderly. Additional research is needed to further characterize frailty in younger critically ill patients, along with the ideal instruments for identification.

This multicenter trial showed that, despite immunologic challenges, recipients of kidney transplants from HLA-incompatible live donors had a survival benefit as compared with controls who remained on the waiting list or received transplants from deceased donors. More than 32,000 patients awaiting kidney transplantation in the United States have anti-HLA antibodies. 1 The presence of anti-HLA antibodies makes it very difficult to find a match with a compatible donor, and these “sensitized” patients can remain on the waiting list for a kidney transplant for years without a suitable donor ever being identified. 2 , 3 Those fortunate enough to have a willing but incompatible live donor can either participate in paired kidney donation, for which the chance of a compatible match is also limited, 4 – 9 or undergo desensitization and subsequent transplantation with a kidney from an incompatible live donor. 10 – . . .

The immune system of laboratory mice raised in an ultra-hygienic environment resembles that ofnewborn humans, but can be induced to resemble the immune system of adult humans or 'dirty' mice by co-housing with pet store-bought mice. Do 'dirty' mice make better immunological models? The laboratory mouse is by far the dominant model organism for in vivo immunological research which — particularly in the light of disappointing results obtained with some recent transfers of disease treatments from laboratory to clinic — raises the question of how accurately the model reflects the human immune system. These authors compare the immune status of laboratory mice with that of feral mice and with mice bought commercially as pets. They find that the immune system of the ubiquitous laboratory 'specific pathogen free' mouse approximates that of human neonates, rather than human adults. Co-housing laboratory mice with 'pet store' mice leads to maturation of the immune system, making it more similar to that of the human adult, and resulting in increased resistance in several models of infection. The use of such 'dirty' mice could supplement current models to either increase translational potential to human disease or to better inform the efficacy of preclinical prophylactic and therapeutic modalities. Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 . Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice—like newborn, but not adult, humans—lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

This study aimed to examine whether intramuscular adipose tissue of the quadriceps at admission is related to the recovery of swallowing ability during a hospital stay in older inpatients. This prospective study included 344 inpatients ages ≥ 65 y. Those who had stroke that was the obvious cause of dysphagia were excluded. Recovery of swallowing ability was assessed using Food Intake Level Scale (FILS) score at discharge and FILS change. Ultrasound images were acquired at admission. Intramuscular adipose tissue and muscle mass of the quadriceps were assessed based on echo intensity and muscle thickness, respectively. Multiple regression analysis was performed to examine whether quadriceps echo intensity is independently associated with FILS score at discharge and FILS change. The independent variables were quadriceps echo intensity and thickness, subcutaneous fat thickness of the thigh, Barthel Index score at admission, age, sex, number of medications, C-reactive protein, updated Charlson Comorbidity Index, FILS score at admission, Geriatric Nutritional Risk Index, days from disease onset, length of hospital stay, and units of rehabilitation therapy. Quadriceps echo intensity was independently and significantly associated with FILS score at discharge (β = −0.15, P < 0.01) and FILS change (β = −0.19, P < 0.01). Quadriceps thickness was not independently and significantly associated with FILS score at discharge or FILS change. The present study revealed that intramuscular adipose tissue of the quadriceps in older inpatients is more strongly related to recovery of swallowing ability than is muscle mass. •We examined the relationship between intramuscular adipose tissue of the quadriceps at admission and recovery of swallowing ability in older inpatients.•Increased intramuscular adipose tissue was more strongly related to worse recovery of swallowing ability than was loss of muscle mass.•Assessing intramuscular adipose tissue of the quadriceps is important for predicting recovery of swallowing ability.•Intervention for intramuscular adipose tissue may be important for improving swallowing ability in older inpatients.