Conectar
This study aimed to systematically delineate the clinical characteristics and identify the key risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) infections in burn patients, thereby informing targeted preventive measures and therapeutic strategies. This retrospective study included 270 burn patients with Staphylococcus aureus (S. aureus) infections at a Chinese centre (2019–2022), comprising 127 MRSA and 143 methicillin-susceptible S. aureus (MSSA) cases. Clinical data were analysed to assess infection profiles, resistance patterns and MRSA risk factors. Amongst the infections, 68.1% (184/270) were caused by multi-drug resistant S. aureus, specifically 47.0% (127/270) by MRSA and 21.1% (57/270) by MSSA. The predominant resistance pattern (penicillin, oxacillin, gentamicin, clindamycin, erythromycin, ciprofloxacin, levofloxacin, tetracycline) accounted for 23.9% (44/184) of multidrug-resistant cases. The overall MRSA detection rate was 47.0% (127/270). Univariate analysis identified multiple factors significantly associated with MRSA infection (p < 0.05). Multivariate analysis identified the use of ≥ 3 types of antibiotics as an independent risk factor for MRSA infection in burn wounds. The detection rate of multi-drug resistant S. aureus (including MRSA) infections in burn wounds is relatively high. A number of variables are the influencing factors for MRSA infections. Medical personnel should adopt infection control measures to block the transmission of multi-drug resistant bacteria (including MRSA).
by Abdulmujeeb Opeyemi Muhammad-Olodo, Laura Asher
IntroductionHuman papillomavirus (HPV) vaccine prevents over 90% of cervical cancers. In October 2023, Nigeria launched a free HPV vaccination campaign targeting girls aged 9–14 years. Despite removing cost barriers, misinformation about fertility impacts and population control contributed to variable uptake across states. Understanding caregiver decision-making is crucial for improving coverage. This study aimed to explore factors influencing caregivers’ HPV vaccination decisions during Nigeria’s 2023 campaign in Ilorin East Local Government Area, Kwara State.
MethodsA qualitative study using focus group discussions (FGDs) was conducted using purposive and snowball sampling. We recruited 41 caregivers (mean age 47 years; 71% female) of eligible girls from urban and rural communities. Five FGDs were conducted: four with vaccine acceptors (n = 35) and one with decliners (n = 6). Discussions were conducted in Yoruba, audio-recorded, transcribed verbatim, and analysed using Braun and Clarke’s reflexive thematic analysis. Ethical approval was obtained from two institutional review boards.
ResultsFour themes emerged from the analysis. Trust operated at multiple levels: institutional (government programmes), interpersonal (healthcare worker competence), and community (religious/traditional leader endorsement). Historical medical mistrust, intensified by COVID-19 experiences, may have manifested as fertility and population control fears. Personal cancer experiences strongly motivated acceptance, whilst concerns about childhood sexuality influenced timing preferences. Despite free provision, barriers included geographic inequities (remote Fulani-Hausa communities were excluded), language barriers (no Hausa translators), school-based delivery gaps, and indirect costs (transport, time). Caregivers recommended house-to-house campaigns, multilingual services, traditional leader engagement, and permanent vaccination centres.
ConclusionFree vaccine provision is necessary but not sufficient to ensure uptake. Successful HPV vaccination requires rebuilding trust through community engagement, addressing historical medical exploitation concerns, and ensuring equitable access. Integrating these findings into Nigeria’s National Programme on Immunisation could improve coverage from current estimates of 54% to targeted 90%, protecting more girls from cervical cancer whilst respecting community values.
by Ying Fei, Ming-Yi Gao, Nan Qiao, Jia Hu, Ling He, Jiao-Li Zhou, Ning-Ning Zheng, Ting-Ting Liu
BackgroundThe effect of fecal microbiota transplantation (FMT) in treating irritable bowel syndrome (IBS) may be attributed to the modulation of CD8 + T cells. This study aims to identify FMT-mediated key genes to explore the underlying mechanism.
MethodsTranscriptomic datasets GSE138297 (colonic biopsies from 8 IBS patients pre- and post-FMT) and GSE134649 (single-cell data from 3 healthy colon tissues) were obtained from GEO during December 2023–December 2024. Key genes were identified by intersecting differentially expressed genes (DEGs) and the most relevant co-expression module derived from weighted correlation network analysis. Functional enrichment, gene set enrichment analysis, immune infiltration profiling via TIMER 2.0, single-cell annotation using PanglaoDB and Seurat, and drug–gene interaction screening from DrugBank were conducted to decipher the regulatory mechanisms.
ResultsTen key genes were identified through integration of DEGs and the MEgreen module. Functional analyses revealed significant involvement in the positive regulation of CD8 + T cells activation. Immune infiltration assessment demonstrated a marked increase in CD8 + T cells abundance post-FMT. Single-cell data indicated predominant expression of LILRB1, P2RY13, CLEC10A, and CLEC12A in dendritic cells, and LILRB1, PIPOX, and CLEC11A were annotated within CD8 + T cells clusters in healthy colonic tissue. Nine (database-derived and speculative) drugs targeting seven key genes were identified, most implicated in the management of IBS symptoms or immunomodulation.
ConclusionAn association between key gene regulation and CD8 + T cell-related immunoregulation is correlated with the therapeutic effect of FMT in IBS.
by Su-jin Kim, Jinhee Kim
BackgroundPost-Acute Sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is characterized by persistent and heterogeneous symptoms that impair health-related quality of life (HRQoL). Although several studies have identified symptom subgroups in Western populations using person-centered approaches, data on Asian populations remain limited.
ObjectivesIn this study, we aimed to classify the symptom profiles of Korean adults with PASC using latent profile analysis (LPA) and examine the differences in HRQoL and associated factors between the identified profiles.
MethodsWe conducted an online survey of 629 adults in Korea who experienced persistent symptoms ≥12 weeks after coronavirus disease (COVID-19) diagnosis. Symptom burden was assessed using the Long COVID Symptom Tool (26 items), and HRQoL was measured using the SF-36 v2®. LPA was performed to identify the symptom subgroups. One-way analysis of variance (ANOVA) and multiple linear regression were used to compare HRQoL across profiles and explore predictors.
ResultsA four-class model provided the best fit: Class 1 (Low symptom, 23.3%), Class 2 (Moderate multisystem, 44.1%), Class 3 (Fatigue/post-exertional malaise dominant, 15.9%), and Class 4 (High multisystem burden, 16.7%). HRQoL differed significantly between classes (p Conclusions
Korean adults with PASC exhibit heterogeneous symptom patterns that substantially affect their HRQoL. The identification of distinct symptom profiles supports the need for tailored interventions, including rehabilitation, cognitive training, and psychological support. Our findings provide crucial evidence for developing Korean population-specific screening tools and management guidelines for PASC.
by Gunnhild Helmsdal, Marnar Fríðheim Kristiansen, Eyðbjørg Klemmentsen Gaard, Barbara Joensen Eysturoy, Pál Weihe, Eina Hansen Eliasen, Maria Skaalum Petersen
BackgroundSix years since the emergence of SARS-CoV-2, the newer variants of the virus continue to have long-term health effects.
ObjectivesThe aim of the study was to investigate persistent symptoms, cognitive impairment, and clinical and paraclinical predictors of long COVID in individuals infected during the Omicron wave.
MethodsWe conducted a clinical case-control study including participants with persistent symptoms up to 13 months after confirmed SARS-CoV-2 Omicron infection (long COVID or LC group) and antibody-verified never-infected controls (NI group).
ResultsA total symptom score based on a 24-item questionnaire was strongly associated with increased odds of long COVID (adjusted odds ratio (aOR) 1.21, 95% CI 1.13–1.30, p Conclusions
One year after Omicron infection, a subset of people continue to experience a substantial symptom burden, particularly fatigue, cognitive impairment, and mental well-being, and a higher frequency of intercurrent infections.
by Sneha Vidyasagar, Kanakamani Jeyaraman, Syeda Farah Zahir, Paul Varghese
ObjectiveThis retrospective study evaluated calcitonin as an adjunct therapy for reducing phantom limb pain (PLP) following lower limb amputation.
MethodThe study included 35 patients who received at least 3 days of calcitonin treatment between January 1, 2017, and December 31, 2023. We collected demographic data and pain ratings (intensity, distress, and interference with activity) before and after calcitonin treatment. Descriptive statistics and paired t-tests analysed the data, with a two-way repeated measures ANOVA used to compare outcomes between patients with and without diabetes. Raw and Standardized mean differences (Cohen’s d) are presented for each measure.
ResultsThe average age of participants was 57.09 years (SD = 13.66), with 40% female. Amputation types were below-knee (65.7%), above-knee (25.7%), and other (8.6%). The main causes of amputation included diabetic foot infection (25.7%), peripheral vascular disease (34.3%), trauma (25.7%), and other (14.3%). Ten participants had diabetes, and 20% had depression.Calcitonin was associated with significant reductions in pain outcomes from pre- to post-intervention (Day 0 to Day 7), with calcitonin given from day 1–3. Mean pain intensity decreased from 6.41 to 5.24 (Cohen’s d = 0.66); p = 0.02), and pain-related distress decreased from 5.85 to 4.81 (Cohen’s d = 0.71; p = 0.014). Perceived pain relief scores increased from 33.69 to 58.21, indicating greater patient-reported pain relief following treatment (Cohen’s d = 0.53; p = 0.035). No significant differences in pain intensity or distress were observed between patients with and without diabetes. Additionally, there was no significant change in the Oral Morphine Equivalent Daily Dose (p = 0.94).
ConclusionIn conclusion, calcitonin significantly reduced perceived pain intensity and pain-related distress scores while increasing perceived pain relief scores (i.e., patients’ reported degree of pain reduction), with similar effects observed in both patients with and without diabetes.
by Agatha Ribeiro Kalthof, Nikolas Dresch Ferreira, Caio Mateus Silva, Iuri Cordeiro Valadão, Iguaracy Pinheiro de Sousa, Ester Riserio Matos Bertoldi, Vanessa Morais Lima, Lauro Thiago Turaca, Ana Beatriz Ruiz Afonso Barbosa, Miriam Helena Fonseca-Alaniz, Jean-Paul Concordet, Elida Adalgisa Neri, Jose E. Krieger
Generating mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) remains a major obstacle to accurate disease modeling and cardiac repair. As the transcription factor Irx3 is a key determinant of ventricular conduction system fate in mice, we hypothesized that suppressing IRX3 expression accelerates human working cardiomyocyte differentiation. Here, we demonstrate that depleting IRX3 enhances hiPSC-CM differentiation. IRX3-knockout (KO) hiPSCs generated a greater number of cardiomyocytes with elevated expression of TNNI1 and CX43. Notably, IRX3-KO cardiomyocytes exhibited improved electrophysiological properties, more uniform mitochondrial distribution, better sarcomere organization, and enhanced intercellular connectivity. We observed that IRX3 expression peaks during the early stages of cardiomyocyte differentiation, whereas IRX3-KO cardiac progenitors have increased expression of GATA4, NKX2–5, and TBX5, as well as enhanced cell proliferation. These integrative analyses indicate that IRX3 influences cardiomyocyte differentiation by modulating the gene regulatory networks driven by GATA4, NKX2–5, and TBX5, providing functional evidence linking gene regulatory networks to the structural and electrophysiological development of cardiomyocytes. Collectively, these findings identify IRX3 as a key regulator of early cardiac commitment and highlight the potential of IRX3 suppression to enhance the molecular and functional phenotype of hiPSC-derived cardiomyocytes.To develop predictive models for early and overall tuberculosis (TB) deaths for prospective use at TB diagnosis in resource-constrained TB programme settings.
Statewide cohort study using routinely captured secondary data.
With the majority of TB deaths being early (within 2 months), India’s TB programme’s information management system (Ni-kshay)-dependent death prediction models (using age, gender, TB site, previous treatment, microbiological confirmation, HIV, diabetes and bank account availability) are not feasible for prospective use, as few variables are captured at diagnosis. Utilising routinely captured triage variables for severe illness at diagnosis (body mass index, pedal oedema, respiratory rate, oxygen saturation and ability to stand without support) from an ongoing statewide and state-specific differentiated TB care initiative to reduce TB deaths in Tamil Nadu state (southern India, 80 million population with 0.1 million annual notifications), robust models for prospective use were developed.
Adults (aged ≥15 years) with TB (not known to be drug-resistant at diagnosis) that were notified from public facilities of Tamil Nadu from July 2022 to June 2023.
Early and overall (within 12 months of notification) TB deaths. Area under the receiver operating characteristic curve (AUC) was used to assess accuracy of models built using modified Poisson regression.
Among 55 971 adults, the overall death rate was 7.4%, and 67.9% of the deaths were early. In predicting overall deaths, accuracy of the model using all Ni-kshay variables (AUC 0.716 (95% CI 0.707 to 0.725)) was as good as the model using triage variables for severe illness only (AUC 0.701 (95% CI 0.691 to 0.711)). To the latter, adding potentially capturable Ni-kshay variables at diagnosis (age, gender, TB site, previous treatment and microbiological confirmation) significantly improved model accuracy (AUC 0.754 (95% CI 0.745 to 0.763)). Further addition of remaining Ni-kshay variables did not improve accuracy significantly. Death prediction equations were generated for these models.
Simple and easily measurable triage variables for severe illness should be routinely captured at TB diagnosis. A death prediction calculator (http://44.208.93.99/) based on these variables (specifically triage variables for severe illness combined with age, gender, TB site, previous treatment and microbiological confirmation) may be used by Indian states and high TB burden countries seeking scalable, data-driven interventions to reduce TB deaths.
Acute febrile illness is a major cause of morbidity and healthcare seeking in sub-Saharan Africa, including Mozambique. However, few studies have explored the perceptions and practices related to clinical management of acute febrile illness. Our aim was to understand the perceptions, knowledge and practices of healthcare professionals and community members regarding the management of acute febrile illness.
A qualitative study was conducted using a thematic analysis approach. Eight focus group discussions (FGDs) and three in-depth interviews (IDIs) were conducted in two Mozambican provinces across four healthcare facilities. Purposive sampling was used to select participants, comprising both healthcare professionals and community members. Data were analysed thematically through manual coding, applying inductive and deductive approaches, in line with established qualitative analytical frameworks.
The study included a total of 60 participants, 28 healthcare professionals who participated in FGDs (25) and IDIs (3) and 32 community members who participated in FGDs. Major causes of fever, according to healthcare professionals, were upper and lower respiratory infections, malaria, diarrhoeal diseases and COVID-19. The diagnostic approach for febrile patients primarily included screening, malaria testing and other non-specific investigations depending on availability at health facilities. Antibiotics and antipyretics were the most commonly prescribed treatments. The healthcare professionals reported a decrease in prescribing antimalarials due to extensive training on malaria case management. In contrast, community members reported relying primarily on home-based and traditional practices to treat acute febrile illness before seeking care at health facilities. These practices are related to sociocultural habits, such as the use of traditional medicine and self-medication. The main barriers to seeking care at health facilities were the perception of poor quality of care, long waiting times, cultural beliefs and lack of medicines.
Proper management of non-malarial febrile illness remains a major challenge for both healthcare professionals and communities. Training, adherence to case management protocols and efforts to change behaviours to mitigate harmful sociocultural practices are urgently necessary to improve febrile illness management.
by Daniel H. Nguyen, Debottama Das, Ali Bilgin, Dianne Patterson, Matthew Hook, Chris Butson, Alberto Cacciola, Vinod Kumar Jangir, Manojkumar Saranathan
Leveraging diffusion tractography, connectivity-based parcellation (CBP) is one of the oldest methods for thalamic nuclei segmentation. The goal of this work was to reassess CBP using higher spatial resolution diffusion MRI data and reconstruction algorithms, and to compare it with recent state-of-the-art methods for thalamic nuclei segmentation. Furthermore, these methods were systematically evaluated against three histological atlases and one functional MRI–based atlas to examine their relative anatomical similarities and differences. High resolution diffusion and T1-weighted MRI data from 67 healthy individuals in the Human Connectome Project Young Adult database were analyzed. CBP was performed using probabilistic tractography with cortical targets derived from combining labels of the Human Connectome Project Multi-Modal Parcellation 1.0 atlas into 8, 11, and 23 regions. Results were compared against three recent methods: orientation distribution function clustering (ODF), track density imaging (TDI), and structural MRI-based segmentation. Group level analyses were conducted in the Montreal Neurological Institute space, and Dice overlap coefficients were calculated using four atlases (three histological, one functional). CBP results using newer data and methods were still remarkably similar to the original CBP parcellation results. Across atlases, a consistent hierarchy was observed: HIPS-THOMAS performed best, followed by TDI, ODF, and CBP (Kendall’s W = 1.00, p = 0.007). Histological atlases showed strong mutual agreement (Pearson r = 0.71–0.85), whereas the Zhang atlas demonstrated lower concordance (Pearson r = 0.51–0.63). Despite methodological advances, CBP remains constrained in its ability to delineate thalamic nuclei with histological accuracy. By contrast, structural and diffusion microstructural approaches provided better nuclear localization. These findings highlight the need for hybrid workflows that integrate structural and diffusion-based information to enable more reliable thalamic segmentation for neuroscience research.by Yi-De Tai, Joel Villalobos, Nima Wickramasinghe, Bryce Widdicombe, Ranjith R. Unnithan, David B. Grayden, Sam E. John
BackgroundEndovascular neural interfaces (ENIs) offer a minimally invasive approach for neural stimulation and recording without the need for open brain surgery. However, current generation devices have long transvascular wires from the implant site to the chest. Eliminating these wires will unlock clinical usability, including lowering infection risk from transvascular wires, reducing the risk of thrombosis from altered hemodynamics, and improving mechanical reliability. However, removing these transvascular wires would require efficient power transfer across the skull and tissue while meeting specific absorption rate (SAR) limits, which is a significant challenge in the field.
ObjectiveThis work designed and evaluated endovascular receiver (Rx) and transmitter (Tx) coils within endovascular geometric and biological constraints to maximize wireless power transfer.
MethodsThis study evaluated the optimal operating frequencies, quantified coupling, coil quality factors, power transfer efficiency, and SAR using computational modeling, benchtop, and in-vivo testing. The study also assessed the tolerance to coil misalignment and load mismatch. We evaluated each case with and without ferrites with measurements in air, sheep tissue, and in vivo in sheep.
ResultsThe results showed that inductive power transfer delivered power to endovascular geometry devices at clinically relevant depths. The maximum power transfer efficiency (PTE) reached 11% at 15 mm and 2% at 30 mm, with up to 72 mW delivered at 30 mm under SAR safety limits. The rectangular planar coil pair performed best at ≤15 mm, whereas the ferrite-core flux-pipe Tx with a helical Rx outperformed beyond ~20 mm and was more tolerant to misalignment.
ConclusionThis study demonstrated the feasibility of wirelessly powering multichannel ENIs using coils that can be placed inside a blood vessel and powered inductively. Making an endovascular neural interface fully wireless has the potential to transform the technology by improving both safety and reliability.
by Atala Jongo, Edwin Lugazia, Salehe Mrutu, Amina Abillah Omari, Hassani Msanga, Ansbert Sweetbert Ndebea, Felix Paul Amani
BackgroundSepsis continues to pose a significant global health challenge, particularly in low- and middle-income countries, which face a disproportionate burden of sepsis and sepsis-related deaths. The estimated prevalence of sepsis and sepsis-related mortality is higher in intensive care units than in hospitals overall. The burden can be higher in tertiary referral centers that receive patients from different regions.This study aimed to determine the prevalence of sepsis, its outcomes, and the factors associated with these outcomes among adult patients admitted to the Intensive Care Unit (ICU) of the Muhimbili National Hospital (MNH) in Tanzania.
MethodologyThis prospective cohort study was conducted over a period of six months from May 16 to November 16, 2023, at MNH. A total of 248 patients were admitted during the study period and screened for sepsis on admission or for the development of sepsis during their ICU stay. Sepsis was defined according to the Sepsis-3 criteria as a suspected infection with a Sequential Organ Failure Assessment (SOFA) score ≥2 within 24 h of ICU admission. Proportions were used for descriptive statistics, and modified Poisson regression analysis was used to identify independent predictors of mortality at a 95% confidence interval, with P Results
The prevalence of sepsis was 41.5%. The respiratory system was the most common source of infection (32%), and 22.3% of patients had more than one infection site. The ICU mortality rate was 55.3%, with 35% of patients developing systemic complications during their ICU stay.Factors independently associated with mortality included multiple comorbidities (aPR 3.35, 95% confidence interval [CI], 1.20–9.32; p = 0.021) and a higher SOFA score (aPR 7.08, 95% CI 3.48–14.4; p Conclusion
This study revealed a high prevalence of sepsis and sepsis-related mortality in the ICU. A high SOFA score and multiple complications were independent predictors of mortality. Early initiation of antibiotic therapy was an independent predictor of survival. This underscores the importance of early treatment, close monitoring, and aggressive management in patients with predictors of poor outcome.
by Linda Furness, Janani Pinidiyapathirage, Matthew French, James Ware, Liam Weber, Brendan Carrigan
IntroductionIn rural generalist clinical settings, medical trainees routinely assess patients and discuss their findings with supervisors to plan ongoing care. These interactions termed ‘learning conversations’, serve as important opportunities for workplace-based learning and clinical decision making. However, preliminary evidence and stakeholder feedback indicate a lack of shared understanding regarding how these conversations should be structured, facilitated, and optimised. This study aims to observe current practices, identify supervisor and trainee learning needs, and co-design a model of learning conversations that enhances educational value and supports safe, effective patient care.
Methods and analysisThis study will use an exploratory sequential mixed methods design structured around the 3Cs of co-design (Co-define, Co-design, Co-refine). Phase 1 (co-define) will involve qualitative observation and audio-recording of learning conversations across two rural hospitals to characterise current practice and inform a protype model. In Phase 2 (co-design), supervisor and trainee focus groups will explore perceived needs, expectations, and feedback on the prototype model. A national online survey of rural supervisors and trainees will further inform model refinement. Phase 3 (co-refine) will incorporate national stakeholder input through a workshop, followed by feasibility testing of the refined model during a pilot simulation at a Rural Clinical School. Outcome data will focus on model usability, perceived relevance, applicability across contexts, and users’ experiences of employing the model during simulated learning conversations.
DiscussionThis study will produce a stakeholder-informed model that responds to the specific learning and clinical needs of rural generalist practice. By embedding co-design throughout the research process, the resulting model is expected to strengthen learning conversations, optimise trainee learning, and enhance the quality and safety of patient care. The findings have potential applicability across broader health professional training contexts and can support workforce development in rural healthcare settings.
by Taotao Peng, Yu Li, Yukun Ren, Mi Yang, Zonghong Long, Dukun Zuo, Lu Huang, Huawei Liu, Zhenxin Duan, Hong Li
Pulmonary complications in non-pulmonary sepsis (PC-NPS) are the leading cause of morbidity and mortality in the intensive care unit. Early prevention and monitoring are paramount since the prevention strategies remain limited yet. Magnesium, an essential electrolyte involved in inflammation and vascular regulation, may influence the development of such complications. This retrospective cohort study used data from the MIMIC-IV database to explore the relationship between baseline serum magnesium levels and PC-NPS among 4,836 patients with non-pulmonary sepsis. Survival analysis demonstrated that patients who developed PC-NPS had significantly higher 90-day mortality compared with those without lung injury. When stratified by baseline serum magnesium quartiles, patients in the highest quartile (>2.1 mg/dL) showed the poorest survival. Multivariable logistic regression confirmed that elevated magnesium was independently associated with increased risk of PC-NPS, and restricted cubic spline modeling revealed a U-shaped, nonlinear association between baseline magnesium concentration and PC-NPS risk. Inflection points at 1.26 and 1.91 mg/dL identified a range of relatively lower risk. These findings suggest that baseline serum magnesium levels exhibit a U-shaped relationship with the risk of PC-NPS. Evaluating these levels may aid in clinical prognostication and the exploration of underlying mechanisms.by Sven Göbel, Lennart Jacobtorweihe, Max-Leopold Rössig, Frauke Braatz, Fabien Perugi, Yvonne Genzel, Udo Reichl
Building on the established use of enveloped viral vectors, like lentivirus and vesicular stomatitis virus, we investigated the stability of the oncolytic Newcastle disease virus LaSota strain and the chimeric construct of a Zika vaccine candidate YF ZIKprM/E. These vectors are currently being developed for the treatment of solid tumors, such as melanoma and glioblastoma, and for vaccine initiatives, respectively. Virus stability is a critical attribute during cell culture-based virus production and also relevant for downstream processing, storage of the produced material, final vaccine storage and shelf life. Therefore, temperature and pH stability were tested as important parameters during upstream processing and freeze-thaw cycles were tested in context of laboratory-analytics. In this study, both viruses exhibited strong stability of the infectious virus titer when subjected to repeated freeze-thaw cycles. However, exposure to temperatures above 22°C substantially reduced the infectious titers, indicating sensitivity to elevated temperatures. To improve viral stability during storage, we investigated the use of sucrose as a stabilizing excipient. While this did not result in significant improvements for YF-ZIKV, an extended half-life for NDV at room temperature was observed. The observed half-life values of upstream material from NDV of 2.6 h and 2.8 h for YF-ZIKV at 37°C demand consideration of changes to the process design, such as the implementation of a perfusion process to enable continuous, cooled virus harvesting.by Hui-Ying Luk, Casey R. Appell, Fangyuan Zhang, Jarrod Blinch, K. Sreekumaran Nair, Chwan-Li Shen, Danielle E. Levitt
IntroductionGlycemic dysregulation is a hallmark of type 2 diabetes (T2D) and contributes to skeletal muscle (SKM) loss and frailty risk, especially in older adults. Glycemic control and physical function are supported by SKM capillarization and mitochondrial function, and their impairment contributes to T2D development. While high-intensity interval training (HIIT) is a promising intervention, adherence and effectiveness remain concerns for prescribing HIIT among older adults at risk for T2D. Local heat therapy (LHT) may be a more practical initial strategy to improve SKM architectural factors and precondition SKM, enhancing physiological adaptations to exercise in this population.
Methods and analysisHeat and Exercise in Aging as Therapy (HEAT) is a two-phase, randomized, sham-controlled clinical trial investigating the efficacy of LHT to improve glycemic control and decrease frailty risk via improved SKM architecture among older adults with prediabetes. LHT is tested as a standalone intervention and as a means to precondition SKM for subsequent HIIT, improving exercise adaptations. In Phase 1, LHT and sham (CON) groups apply heat pads for 90 minutes/day, 6 days/week, for 12 weeks. A separate HIIT group completes 4x4-minute cycling intervals at 90–95% VO₂peak, 3 days/week. In Phase 2, LHT and CON groups begin HIIT. Participants (≥50 years) have impaired fasting glucose (100–125 mg/dL) and/or HbA1c (5.7–6.4%). Biospecimen collection and clinical assessments occur at baseline (T1), after Phase 1 (T2), and Phase 2 (T3). To our knowledge, this is the first study to determine the use of local heat pad on pre-diabetic older population. If successful, LHT may be a practical, scalable, non-invasive intervention to improve glycemic control and reduce frailty risk in older adults with prediabetes, preventing progression to T2D.
by Julian Kylies, Fabian Haas, Anna Duprée, Tobias B. Huber, Karl-Heinz Frosch, Matthias Priemel, Dominik Kylies
BackgroundLiposarcomas (LS) of the extremities and trunk are aggressive soft-tissue sarcomas and surgical resection combined with multimodal therapy represents the cornerstone of curative treatment. Despite advances in surgical and medical management patients are still at risk of developing medical complications that negatively affect morbidity and mortality. Kidney dysfunction, sarcopenia and progressive loss of visceral adipose tissue have emerged as prognostically relevant and potentially treatable complications in surgical oncology. However, despite their growing relevance, little is known about their frequency and impact on survival and morbidity in the context of LS.
MethodsWe conducted a retrospective study of 47 adult patients with localized LS of the extremities and trunk who underwent curative-intent surgery. Kidney function, CT morphometry of muscle (skeletal muscle index, SMI) and visceral adipose tissue (VAT) as well as clinical assessments including ECOG score were recorded at diagnosis (t1) and after a median follow-up (t2) of 11 months. Kidney dysfunction, defined as a decrease in eGFR of ≥ 25% between time points, was analyzed in relation to survival, sequentially assessed CT-morphometry of muscle and adipose tissue as well as functional status assessed by ECOG scores.
ResultsAll patients underwent curative-intent surgical treatment with or without additional multimodal treatment (surgery only: 51.1%, additional radiation: 31.9%, additional chemotherapy: 38.3%). Kidney dysfunction was frequent in our cohort (53.2% of all patients) and significantly associated reduced overall survival in Kaplan–Meier, uni- and multivariate Cox proportional hazards regression models (multivariate hazard ratio: 6.7; p = 0.03). In addition, patients with kidney dysfunction experienced a significantly accelerated loss of SMI (p Conclusions
To our knowledge, this is among the first studies to investigate kidney dysfunction and its consequences in adult LS patients. In our cohort of surgically treated adult patients with LS of the extremities and trunk, kidney dysfunction was a frequent and clinically impactful complication. It was significantly associated with decreased overall survival, loss of muscle and adipose tissue in sequential CT morphometry assessments and progressive functional decline. Off note, CT-morphometry enabled objective, high-resolution tracking of body composition decline and may serve as a promising additional tool for risk stratification. Nonetheless, given the limited cohort size and retrospective single-center design, the generalizability of our findings is limited and the results should therefore be interpreted with caution. Despite these limitations, our findings call for future prospective studies and an awareness for heightened renal surveillance and integrated body composition assessments in the multimodal management of sarcoma patients.
To evaluate the effectiveness of multidisciplinary offloading versus standard care on one-year diabetic foot ulcer recurrence, amputation, mortality, and functional recovery. In this prospective cohort study, 232 patients with healed diabetic foot ulcers were stratified into a control group (76 patients) or an intervention group (156 patients) receiving offloading modalities ranging from felt padding to custom-made therapeutic footwear. Assignment was based on shared decision-making considering biomechanical needs and economic feasibility. Primary outcomes included recurrence, amputation, and mortality. Secondary outcomes assessed quality of life, working ability, and ankle function. The intervention group demonstrated significantly lower recurrence (10.9% vs. 25.0%; p = 0.007) and mortality (3.2% vs. 14.5%; p = 0.004). Multivariable analysis identified offloading as independently protective against recurrence (odds ratio 0.35) and mortality (odds ratio 0.24). Amputation rates did not differ significantly after adjustment. Functionally, the intervention group achieved superior recovery in quality of life, working ability, and ankle scores (p < 0.001). Subgroup analysis indicated that customized therapeutic footwear yielded the lowest complication rates and highest patient satisfaction. Multidisciplinary offloading significantly reduces recurrence and mortality while restoring physical function. Although financial barriers influence device selection, customized therapeutic footwear offers the optimal balance of biomechanical protection and functional outcomes.
FreshRSS 