Heart re-transplantation in Eurotransplant

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation

El trabajo de la fuerza de fricción en libros de texto universitarios

Considerando una revisión de la literatura relacionada con la enseñanza de la física, estamos desarrollando una investigación que analiza cómo se presenta el trabajo de las fuerzas de roce y sus relaciones con el teorema de trabajo y energía, en libros de texto de nivel universitario básico. Si bien algunos artículos ampliamente citados destacan aspectos relevantes que deberían ser considerados en el tratamiento del tema y han sido publicados hace más de dos décadas, encontramos textos que no se han hecho eco de los mismos, otros que introducen modificaciones parciales y pocos que reflejan explícitamente los cambios sugeridos. Las tendencias mencionadas se ilustran considerando tres textos de uso muy difundido en nuestro ámbito

El trabajo de la fuerza de fricción en libros de texto universitarios

Considerando una revisión de la literatura relacionada con la enseñanza de la física, estamos desarrollando una investigación que analiza cómo se presenta el trabajo de las fuerzas de roce y sus relaciones con el teorema de trabajo y energía, en libros de texto de nivel universitario básico. Si bien algunos artículos ampliamente citados destacan aspectos relevantes que deberían ser considerados en el tratamiento del tema y han sido publicados hace más de dos décadas, encontramos textos que no se han hecho eco de los mismos, otros que introducen modificaciones parciales y pocos que reflejan explícitamente los cambios sugeridos. Las tendencias mencionadas se ilustran considerando tres textos de uso muy difundido en nuestro ámbito

Can Non-lytic CD8+T Cells Drive HIV-1 Escape?

The CD8+ T cell effector mechanisms that mediate control of HIV-1 and SIV infections remain poorly understood. Recent work suggests that the mechanism may be primarily non-lytic. This is in apparent conflict with the observation that SIV and HIV-1 variants that escape CD8+ T cell surveillance are frequently selected. Whilst it is clear that a variant that has escaped a lytic response can have a fitness advantage compared to the wild-type, it is less obvious that this holds in the face of non-lytic control where both wild-type and variant infected cells would be affected by soluble factors. In particular, the high motility of T cells in lymphoid tissue would be expected to rapidly destroy local effects making selection of escape variants by non-lytic responses unlikely. The observation of frequent HIV-1 and SIV escape poses a number of questions. Most importantly, is the consistent observation of viral escape proof that HIV-1- and SIV-specific CD8+ T cells lyse infected cells or can this also be the result of non-lytic control? Additionally, the rate at which a variant strain escapes a lytic CD8+ T cell response is related to the strength of the response. Is the same relationship true for a non-lytic response? Finally, the potential anti-viral control mediated by non-lytic mechanisms compared to lytic mechanisms is unknown. These questions cannot be addressed with current experimental techniques nor with the standard mathematical models. Instead we have developed a 3D cellular automaton model of HIV-1 which captures spatial and temporal dynamics. The model reproduces in vivo HIV-1 dynamics at the cellular and population level. Using this model we demonstrate that non-lytic effector mechanisms can select for escape variants but that outgrowth of the variant is slower and less frequent than from a lytic response so that non-lytic responses can potentially offer more durable control

Clinical and research implications of the findings of the Tanzania 2022 Population and Housing Census for the development and suitability of neuropsychological tests for older adults in Tanzania

\ua9 The Author(s) 2025.Background: The identification of dementia using valid and reliable neuropsychological tests is crucial for the development of effective preventive interventions, treatments, and care plans. Methods: We analysed the 2022 Population and Housing Census data in Tanzania to determine the age-adjusted prevalence of subjective memory, hearing, and visual complaints and explore factors that may influence the development and suitability of neuropsychological assessment batteries among adults aged 60 and older. Age-adjusted prevalence estimates were calculated using the WHO Direct Method. Logistic regression models were performed to examine the factors associated with memory complaints. Mediation analysis was conducted using path analysis, and the significance of the indirect effects was tested using bootstrapping procedures. Results: Adults aged 60 + constituted 5.7% of the population. The median (IQR) age was 68 (60–97) years. Literacy and numeracy rates were 59.7% and 67.7% respectively. The age-adjusted prevalence of subjective memory, hearing, and visual complaints, were 7.3% (95%CI: 7.2–7.4), 7.5% (95%CI: 7.4–7.6), and 16.3% (95%CI: 16.2– 16.4). Being married (AOR 0.83; 95%CI: 0.74–0.93; p = 0.002) and having a seven-year education or more (p ≤ 0.001) reduced the odds of memory complaints, while hearing (AOR = 4.62; 95%CI: 4.37–4.88; p ≤ 0.001) and visual (AOR 7.12; 95%CI: 6.78–7.47; p ≤ 0.001) complaints increased the likelihood of memory complaints. Age (p ≤ 0.001) and female sex (p ≤ 0.001) accounted for 21% and 7% of the effects of sex and education on subjective memory complaints respectively. Conclusion: Literacy and numeracy decrease with age in adults aged 60 and older in Tanzania. Hearing and visual complaints are common among seniors; they are more prevalent in rural areas and increase the risk of memory complaints. Our findings may inform the development and suitability of neuropsychological tests for seniors and highlight the need for policymakers to develop dementia prevention interventions and improve access to vision and hearing services for this group. Clinical trial number: Not applicable

Delayed Care and Mortality Among Women and Men with Myocardial Infarction

Background-Women with ST-segment-elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex-related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women. Methods and Results-We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time-delay cohorts. We estimated the 30-day risk of all-cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30-day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of (odds ratio: 0.77; 95% confidence interval, 0.29-2.02). Conclusions-Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia

The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens

A persistent goal of vaccine development is the enhancement of the immunogenicity of antigens while maintaining safety. One strategy involves alteration of the presentation of the antigen by combining antigens with a multimeric scaffold. Multi-antigen vaccines are under development, and there are presently far more candidate antigens than antigen scaffolding strategies. This is potentially problematic, since prior immunity to a scaffold may inhibit immune responses to the antigen-scaffold combination. In this study, a series of domains from S. aureus which have been shown to crystallise into multimeric structures have been examined for their scaffolding potential. Of these domains, SAR1376, a 62 amino acid member of the 4-oxalocrotonate tautomerase (4-OT) family, was pro-immunogenic in mice when fused to a range of pathogen antigens from both S. aureus and P. falciparum, and delivered by either DNA vaccination, viral vector vaccines or as protein-in-adjuvant formulations. The adjuvant effect did not depend on enzymatic activity, but was abrogated by mutations disrupting the hexameric structure of the protein. We therefore propose that SAR1376, and perhaps other members of the 4-OT protein family, represent very small domains which can be fused to a wide range of antigens, enhancing immune responses against them

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.