Vision Foundation Models(VFMs) have achieved remarkable success in various computer vision tasks. However, their application to semantic segmentation is hindered by two significant challenges: (1) the disparity in data scale, as segmentation datasets are typically much smaller than those used for VFM pre-training, and (2) domain distribution shifts, where real-world segmentation scenarios are diverse and often underrepresented during pre-training. To overcome these limitations, we present Rein++, an efficient VFM-based segmentation framework that demonstrates superior generalization from limited data and enables effective adaptation to diverse unlabeled scenarios. Specifically, Rein++ comprises a domain generalization solution Rein G and a domain adaptation solution Rein-A. Rein-G introduces a set of trainable, instance-aware tokens that effectively refine the VFM's features for the segmentation task. This parameter efficient approach fine-tunes less than 1% of the backbone's parameters, enabling robust generalization. Building on the Rein-G, Rein-A performs unsupervised domain adaptation at both the instance and logit levels to mitigate domain shifts. In addition, it incorporates a semantic transfer module that leverages the class-agnostic capabilities of the segment anything model to enhance boundary details in the target domain. The integrated Rein++ pipeline first learns a generalizable model on a source domain (e.g., daytime scenes) and subsequently adapts it to diverse target domains (e.g., nighttime scenes) without any target labels. Comprehensive experiments demonstrate that Rein++ significantly outperforms state-of-the-art methods with efficient training, underscoring its roles an efficient, generalizable, and adaptive segmentation solution for VFMs, even for large models with billions of parameters. The code is available at https://github.com/wloves/Rein.
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Emerging evidence has linked high dietary fructose intake with adverse health outcomes, yet its role in colitis-associated colorectal cancer (CAC) remains underexplored. Here, we demonstrate that high fructose consumption aggravates intestinal inflammation and significantly promotes tumorigenesis in an AOM/DSS-induced CAC model via activation of the EREG-EGFR signaling axis. We first developed the Food∩TCM database, which encompasses 112 medicine and food homologous TCM, along with their chemical compositions. Using the network-based pharmacological intelligence platform, we identified Laminaria japonica (kelp) and its bioactive components-fucoidan and dieckol-as promising dietary interventions. Dieckol was found to target the RNA/DNA-binding protein CNBP, which has traditionally been regarded as a positive regulator of pro-inflammatory gene expression, but here was shown to enhance its nuclear localization under inflammatory conditions and thereby repress Ereg transcription. Notably, fructose promoted O-GlcNAcylation-mediated stabilization and secretion of EREG in inflammatory fibroblasts, contributing to tumor progression. Together, these findings reveal the tumor-promoting effects of dietary fructose in CAC and highlight CNBP as a key regulator restraining Ereg expression. Our findings underscore the significance of integrating food-based strategies into chronic disease prevention, and support the development of Laminaria japonica-derived compounds as safe, long-term dietary agents for managing colitis-associated colorectal cancer.
Real-world practices for managing anemia and iron deficiency in chronic kidney disease appear heterogeneous and sometimes controversial. This study aimed to describe the prescribing preferences and habits of French nephrologists in this area. All nephrologists seeing patients at one of the 40 centers participating in the Chronic Kidney Disease – Renal Epidemiology and Information Network (CKD-REIN) cohort were invited to participate in two waves (2015–2016 and 2019–2020) of a practice survey. The self-administered questionnaires collected information on nephrologists’ characteristics and their management strategies for anemia and iron deficiency in patients with stage 4–5 CKD. A total of 137 nephrologists participated in the first wave and 60 in the second wave. Most reported initiating treatment with erythropoiesis-stimulating agents (ESAs) when hemoglobin levels were between 9.5 and 10.5 g/dL (85% in the first wave and 96% in the second). In patients with anemia and iron deficiency, the thresholds for initiating iron therapy varied widely: for oral iron, transferrin saturation (TSAT) ranged from 10% to more than 35% and ferritin from 50 to 500 μg/L; for intravenous iron, TSAT ranged from 10 to 30% and ferritin from 50 to 500 μg/L. Between 2015–2016 and 2019–2020, French nephrologists’ practices for ESA management were relatively homogeneous and in line with current recommendations. In contrast, approaches to iron deficiency varied greatly among practitioners. Les pratiques de prise en charge de l’anémie et de la carence martiale (CM) dans la maladie rénale chronique (MRC) apparaissent hétérogènes et controversées. Cette étude visait à décrire les préférences et habitudes de prescription des néphrologues français dans ce domaine. Tous les néphrologues consultant dans un des 40 centres participants à la cohorte Chronic Kidney Disease – Renal Epidemiology and Information Network (CKD-REIN) ont été invités à répondre à deux vagues (2015-2016 et 2019-2020) d’une enquête de pratique. Les auto-questionnaires comprenaient des informations sur les caractéristiques des néphrologues, et leurs habitudes de prise en charge de l’anémie et de la CM chez les patients présentant une MRC de stade 4/5. Le nombre de néphrologues participants était de 137 pour la première vague et 60 pour la seconde. La majorité des néphrologues (85 % pour la première vague et 96 % pour la deuxième) déclaraient débuter un traitement par agents stimulant l’érythropoïèse (ASE) pour un niveau d’hémoglobine se situant entre 9,5 et 10,5 g/dL. En cas de CM et d’anémie, les seuils pour initier un traitement martial variaient fortement : pour la voie orale, de 10 % à plus de 35 % de coefficient de saturation (CS) et de 50 à 500 μg/L de ferritine ; pour la voie intraveineuse, de 10 à 30 % de CS et de 50 à 500 μg/L de ferritine. En 2015-2016 et 2019-2020, les pratiques des néphrologues français, concernant la gestion des ASE, étaient relativement homogènes et en cohérence avec les recommandations en vigueur. Au contraire, la gestion de la CM était hétérogène.
Military jet pilots are exposed to extreme +Gz, imposing strain on the cervical musculoskeletal system. Neck pain prevalence is well documented, but the acute effects of real flight on cervical muscles and kinematics remain unclear. This study assessed acute effects in Eurofighter pilots vs. non-pilot controls. It was hypothesized that acute high +Gz exposure during a real flight affects cervical 3D kinematics, muscle mechanical properties, and pilot-reported pain scores compared to a nonexposed control group and effects of acute high +Gz exposure persist 24 h postflight, resulting in altered cervical 3D kinematics, modified muscle mechanical properties, and increased subjective pain compared to the nonexposed control group. A controlled, longitudinal study compared 20 Eurofighter pilots with 20 matched controls. Cervical 3D kinematics, subjective neck pain, and cervical muscle stiffness were assessed preflight, immediately postflight, and 24 h postflight. Pilots executed high +Gz maneuvers during real flight following a scripted mission. Primary outcomes were group-by-time differences. Statistics included repeated-measures of variance. In pilots, cervical extension range of motion decreased postflight from 56.4 ± 6.5° to 52.4 ± 7.8°, and at 24 h to 53.3 ± 6.4°. Subjective neck pain increased postflight and persisted at 24 h [pain 0.0-10.0; medians from 0.0 (0.0)-2.1 (3.0), then 1.8 (2.9)]. Right trapezius muscle stiffness decreased postflight (241.0 ± 20.3-227.8 ± 20.7 N · m-1) and after 24 h at 234.1 ± 20.1 N · m-1. High +Gz exposure and extreme head postures reduce range of motion and increase neck pain in fighter pilots. The stiffness decrease suggests a muscular mechanical overload. Findings support the need for targeted neck conditioning and real-time monitoring to mitigate injury risk to sustain operational readiness. Lingscheid R, Nuesse R, Rein R, Goell F, Albracht K, Braunstein B. High +Gz flight reduces cervical 3D kinematics and increases neck pain in fighter pilots. Aerosp Med Hum Perform. 2026; 97(3):151-159.
President Trump came into office with an agenda to rein in government programs and regulations. The Trump administration has focused on making government smaller and nearly eliminating humanitarian foreign health aid, while eschewing conclusions drawn by the mainstream scientific community, particularly regarding vaccination policy. Specific actions have included cuts to both health personnel and budgets, efforts to remove vaccine mandates, attempts to end diversity efforts, and the essentially shuttering of the United States Agency for International Development program. Reforms also include allowing the expiration of enhanced federal premium subsidies for the individual insurance marketplaces beginning in 2026 and a substantial reduction in federal payments to state Medicaid programs beginning in 2027. Downstream impacts will include collecting less health data, moving away from research on communicable diseases, promoting vaccine hesitancy, and reducing access to, and possibly the quality of, care. Cutting humanitarian foreign health aid may have an even larger impact, as access to vaccinations and medications has already been curtailed, especially in Africa. Cuts to global health have endangered lives in many of the world's poorest countries, while the destabilization of global trade has limited the scope for European countries to fill the gap. Millions of Americans will lose their health insurance coverage, while people in many countries - especially Africa - will have their lives endangered. Vaccination rates, particularly among young children, will decline, exposing more Americans to communicable diseases. Scientific research output is likely to decline as universities face increasing financial pressures.
Older patients on dialysis have a complex regimen of drugs to manage their chronic kidney disease (CKD), associated complications, and co-morbidities. Our aim was to describe drug use in the year before and after dialysis initiation in the older population. We included all patients aged ≥ 65 years initiating chronic dialysis in France between 2010 and 2019 identified from the national kidney replacement therapy registry and matched with the national health data system. Drug use prevalence was described by pharmacotherapeutic classes, based on anatomical therapeutic chemical codes, and estimated quarterly for patients with ≥ 1 drug dispensing in the year before and after the initiation of dialysis. Analysis was stratified according to dialysis modality, sex, and age at dialysis initiation. Among 55,238 patients included, hyper-polypharmacy (≥ 10 drugs) rose to 76% at dialysis initiation, and slightly decreasing afterwards. Non-CKD-related drugs, including insulins, psychotropic, analgesic and non-antihypertensive cardiovascular drugs, showed stable prevalence, except for proton pump inhibitors (PPI) use which rose sharply before dialysis (40.8% to 54.8%) and then stabilized. Conversely, CKD-related drugs varied. At dialysis initiation, antihypertensives (except diuretics), potassium binders, and hypouricemic agents use declined, while calcium supplementation rose then stabilized. Vitamin D and phosphate binder use increased steadily. Trends in drug use patterns were similar across dialysis modality, sex and age. Prescription changes occur at dialysis initiation, particularly for CKD-related drugs. Hyperpolypharmacy was highly prevalent, yet much of it is likely appropriate given the complex clinical profile of older dialysis patients. Further work is needed to explain the high prevalence of PPI. The online version contains supplementary material available at 10.1186/s12877-026-07113-6. - This nationwide study of older French patients shows that dialysis initiation is accompanied by many changes mainly in CKD-related drugs and that hyper-polypharmacy remains high. - Proton pump inhibitor use rises sharply before dialysis and remains high afterwards. - Trends are consistent across dialysis modality, sex, and age groups. - These findings reinforce the need to support patients in their medication management, particularly at the time of dialysis initiation. - Further studies are needed to better understand the persistent hyper-polypharmacy and especially the increase in PPI use and to investigate the appropriate or inappropriate use of the drugs used. The online version contains supplementary material available at 10.1186/s12877-026-07113-6.
Many European countries have experienced a decrease in the incidence of kidney replacement therapy (KRT), from as far back as 2008 for some. However, in France, the incidence increased by +0.8% annually from 2005 to 2014. This study aimed to examine the recent trend in incidence of KRT in France and variations in different subgroups to understand the possible mechanisms involved. To estimate the trend in KRT incidence for the French population, we used data from the Renal Epidemiology Information Network (REIN) registry, which has been available and comprehensive since 2012 for all of France. We estimated time trends from 2012 to 2023 by using a Joinpoint regression model that provides the annual percentage change and its confidence interval. We also analyzed the data by patient subgroups (age, comorbidities, etc.) or treatment conditions (emergency initiation, preemptive kidney transplantation, etc.). From 2012 to 2017, the number of new patients starting KRT increased annually by +2.7% in France, but the standardized incidence was stable. Since 2017, the number of new patients has been stable and the age- and sex-standardized incidence rate has decreased annually by 2.2%, likely due to the aging of the population. The reversal of the trend was particularly noticeable among older people and people with diabetes. Early mortality in people aged ≥75 years decreased significantly, which suggests that the most comorbid patients are now referred for conservative treatment. Even before the flat-rate payment system was introduced in 2019, more comprehensive and multidisciplinary care may have been developed for patients with stage 4-5 disease. In France, since 2017, the age- and sex-standardized KRT incidence rate decreased probably due to the combination of factors relating to changes in practices, the arrival of new treatments and changes in the general population.
Cognitive impairment (CI) affects self-management in chronic diseases, leading to poor decision-making, delayed care, and increased mortality. The specific impact of CI on adverse outcomes in chronic kidney disease (CKD) remains poorly explored. The French CKD - Renal Epidemiology and Information Network (CKD-REIN) cohort included 3033 patients with CKD stage 2 to 5 and 5 years of follow-up. CI was assessed using the Mini-Mental State Examination (MMSE), and estimated glomerular filtration rate (eGFR) was estimated using the CKD Epidemiology Collaboration creatinine equation. Cox models evaluated the risks of all-cause mortality, kidney replacement therapy (KRT) initiation, and major adverse cardiovascular (CV) events (MACEs). A total of 3004 patients were included in the analysis (mean age: 67 years, mean eGFR: 34 ml/min per 1.73 m2), and 64%, 23%, and 13%, respectively had MMSE scores > 26, from 24 to 26, and < 24 at baseline. During the follow-up period (mean: 3.87 years), 21.5% of patients initiated KRT, 13.4% died, and 15.3% experienced a MACE before KRT or non-CV death. In adjusted Cox models, patients with a MMSE < 24 had a higher risk of clinical adverse outcome, relative to those with a MMSE > 26: hazard ratio (HR) [95% confidence interval] was 1.42 [1.12-1.81], 1.57 [1.19-2.07], and 1.32 [1.02-1.70] for KRT initiation, all-cause mortality, and MACE, respectively. In addition, CI was associated with all-cause mortality in the MMSE of 24 to 26 group (HR: 1.45, 95% confidence interval: 1.15-1.83). In CKD, a baseline MMSE score < 24 predicts higher overall-death, KRT initiation, and MACEs, relative to a baseline score > 26. These results highlight CI's prognostic value, and suggest that earlier detection could better personalize management, particularly for kidney and CV complications.
Monogenic causes of nephrolithiasis and nephrocalcinosis are relatively common but underdiagnosed. Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease that causes progressive ectopic calcium phosphate deposits throughout the body. PXE results from homozygous mutations in the ATP-binding cassette subfamily C member 6 (ABCC6) gene, which encodes an ATP transporter that is predominantly expressed in the liver but also expressed in the kidney proximal tubule. ABCC6 transports ATP extracellularly, where ectonucleotide pyrophosphatase/phosphodiesterase 1 metabolizes ATP into AMP and pyrophosphate (PPi), an inhibitor of calcium crystallization. Loss-of-function mutations in ABCC6 are associated with low serum PPi levels, leading to ectopic calcifications. PXE is associated with an increased risk of nephrolithiasis, but it is currently unknown if heterozygotes are also at risk. Herein, we presented 3 patients with recurrent nephrolithiasis who had relatively unremarkable risk factors but were found to have heterozygous mutations in ABCC6-patient 1 c.1685T>C (p.Met562Thr); patient 2 c.933C>A (p.Phe311Leu); and patient 3 c.3413G>A (p.Arg1138Gln). We proposed that heterozygous ABCC6 mutations are an unrecognized risk factor for nephrolithiasis. Development of a clinical assay to measure urinary PPi may help identify people at risk of nephrolithiasis, elucidate the underlying mechanisms of recurrent nephrolithiasis, and potentially identify a therapeutic target to reduce stone burden.
Sea turtles are among the many wildlife species adversely affected by Florida red tide, Karenia brevis. This marine dinoflagellate blooms almost annually along Florida's west coast and produces brevetoxins, a suite of potent neurotoxins. Brevetoxins can reach carnivorous loggerhead and Kemp's ridley sea turtles via aerosols and marine food webs, leading to multi-system physiological effects. Sea turtles stranded during red tide can be rescued, transported to rehabilitation facilities, and given palliative care with the goal of return to the wild. However, there are no definitive diagnostic criteria for brevetoxicosis other than stranding in association with red tide. Often sea turtles experience delayed exposure due to the long temporal scale of trophic transfer of toxins. To identify exposure biomarkers and to better understand the mechanism of toxicity of brevetoxins, plasma samples from red-tide exposed and healthy loggerhead and Kemp's ridley sea turtles were analyzed via bottom-up TMT-labeled quantitative liquid chromatography tandem mass spectrometry-based proteomics. Multiple sea turtle plasma protein abundances were significantly altered in red tide exposed turtles, including several immune system proteins like serum amyloid A5 (SAA-5; loggerheads) and CD160 antigen (Kemp's ridley). Pro-inflammatory markers serum amyloid A (SAA) and myeloid-related protein 126 (MRP-126) were measured independently in plasma of loggerhead turtles, with significant increases in these markers with red tide toxin exposure. The two species also differed in their proteomic response to red tide, indicating distinct biomarker candidates. Amid intensifying red tide events and the endangered status of these species, our findings provide a foundation for biomarker-based diagnosis of brevetoxicosis in sea turtles.
Nutritional management after kidney transplantation remains heterogeneous despite major metabolic, cardiovascular, and immunological implications related to immunosuppressive therapy. To describe current dietary practices and nutritional strategies implemented after kidney transplantation in France, Belgium, and Luxembourg. A cross-sectional online survey was conducted from June to July 2023 among members of the Association de diététique et nutrition en néphrologie (ADNN) and the Groupe des diététicien(ne)s de néphrologie (GDN, Belgium). The 43-item questionnaire explored consultation modalities, interprofessional coordination, adherence to nutritional recommendations, dietary prescription practices, and participation in therapeutic education programs. The survey was self-administered, and descriptive analyses were expressed as frequencies and percentages. Forty-seven dietitians responded (51% from France, 47% from Belgium, 2% from Luxembourg). Most worked in dialysis (80.8%), nephrology (46.8%), or transplantation units (30%). Dietary follow-up of kidney transplant recipients was reported mainly during hospitalization (86.7%), particularly at the time of transplantation, and in outpatient consultations (73.3%) during subsequent weeks or months. Most dietitians reported following fewer than 20 transplant patients per year. Weight changes (94%), post-transplant diabetes (41%), and digestive disorders (14%) were the leading consultation motives. Balanced diets (69%), sodium restriction (56%), and reduced sugar intake (28%) were the main strategies. In the early postoperative phase, a light, then high-protein (67%) and low-microbial (53%) diet was usually prescribed. Strict food safety measures were applied in >90% of centers, typically for six months. Coordination between teams remained limited, with one third reporting no formalized protocol. The survey highlights the variability of dietary management after kidney transplantation and the need for standardized nutritional protocols, specific professional training, and improved inter-team coordination. La prise en soin nutritionnelle après transplantation rénale reste hétérogène malgré les implications métaboliques, cardiovasculaires et immunologiques majeures liées aux traitements immunosuppresseurs. Il s’agit de décrire les pratiques diététiques et les stratégies nutritionnelles mises en œuvre après transplantation rénale en France, Belgique et Luxembourg. Une enquête transversale en ligne a été menée de juin à juillet 2023 auprès des membres de l’Association de diététique et nutrition en néphrologie (ADNN) et du Groupe des diététicien(ne)s de néphrologie (GDN, Belgique). Le questionnaire, composé de 43 items, explorait les modalités de consultation, la coordination interprofessionnelle, l’appropriation des recommandations nutritionnelles, les pratiques de prescription diététique et la participation à des programmes d’éducation thérapeutique. L’enquête était auto-administrée, et les analyses descriptives ont été exprimées en effectifs et pourcentages. Quarante-sept diététiciens ont répondu (51 % France, 47 % Belgique, 2 % Luxembourg). La majorité exerçait en dialyse (80,8 %), en néphrologie (46,8 %) ou en transplantation (30 %). Le suivi diététique des patients transplantés s’effectuait principalement lors d’une hospitalisation (86,7 %), en particulier au moment de la transplantation, et en consultation externe (73,3 %) dans les semaines ou mois suivants, la plupart suivant moins de 20 patients transplantés par an. Les principaux motifs de consultation concernaient la prise ou la perte de poids (94 %), le diabète post-transplantation (41 %) et les troubles digestifs (14 %). Les stratégies diététiques les plus fréquentes reposaient sur une alimentation équilibrée (69 %), réduite en sel (56 %) et en sucres (28 %). En phase post-opératoire, une alimentation légère puis hyperprotidique (67 %) et pauvre en germes (53 %) était proposée. Des mesures strictes d’hygiène alimentaire étaient appliquées dans plus de 90 % des centres, le plus souvent pendant six mois. La coordination entre services restait limitée, un tiers signalant l’absence de protocole formalisé. Cette enquête met en évidence une hétérogénéité des pratiques diététiques après transplantation rénale ainsi que des différences organisationnelles entre diététiciens de transplantation et ceux exerçant en néphrologie ou en dialyse, notamment en termes de volume de patients suivis et de modalités de suivi. Les résultats soulignent également des limites dans la transmission des informations entre ces équipes, alors que le suivi nutritionnel au long cours est souvent assuré en dehors des centres de transplantation. Ces observations mettent en évidence la nécessité de renforcer la coordination interprofessionnelle, de développer des outils de transmission adaptés et de proposer des formations spécifiques pour les diététiciens impliqués dans la prise en soin des patients transplantés.
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This study investigated the effects of donepezil and a combination of donepezil and mefloquine (THN201) on cognitive function and electroencephalography (EEG) parameters during a scopolamine challenge in healthy participants. Scopolamine, which is known to induce cognitive impairment, was used to model transient cognitive deficits similar to those observed in Alzheimer's disease. The study involved 152 healthy male participants, who were subjected to various cognitive tests and EEG recordings to assess the impact of the treatments on attention and memory processes. The results showed significant temporal effects on cognitive performance and positive component around 300 milliseconds EEG parameters, indicating that scopolamine-induced notable changes in cognitive functions and brain activity. However, this study did not find significant overall group differences or interactions between time and group for most cognitive and EEG measures. The combination of donepezil and mefloquine (THN201) did not show a clear protective or restorative effect against scopolamine-induced impairments, highlighting the role of the cholinergic system in cognitive processes and the potential of EEG parameters as markers for cognitive impairment. This study underscores the complexity of cholinergic modulation in attention and memory, suggesting a need for more targeted approaches in future research. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Fibromyalgia is characterized by chronic widespread pain that is often exacerbated by movement that interferes with daily activities. Development of effective treatments for movement-evoked pain is essential for improving function for individuals with fibromyalgia. To evaluate whether the addition of transcutaneous electrical nerve stimulation (TENS) to outpatient physical therapy improves fibromyalgia-associated movement-evoked pain. The Fibromyalgia TENS in Physical Therapy (FM-TIPS) study was a cluster-randomized clinical trial of participants with fibromyalgia at 28 outpatient PT clinics from 6 health care systems. Between February 1, 2021, and September 31, 2024, 958 participants were screened, 459 participants enrolled, and 384 completed baseline data collection, with final data collected in March 2025. Clinics were randomized to PT plus TENS (PT-TENS) and PT-only groups. Data were captured on days 1, 30, 60 (primary end point, randomized phase), 90, and 180. Participants in the PT-only group received TENS after day 60 (extension phase). TENS was applied to the upper and lower back with instructions to use 2 hours daily with parameters of modulating frequency of 2 to 125 Hz for 100 to 180 microseconds at a strong but comfortable intensity. The primary outcome was a change in movement-evoked pain (scale of 0-10, with 0 indicating no pain and 10 indicating worst pain imaginable) from baseline to day 60 rated during a 5-times sit-and-stand task using a linear mixed-effects model. In addition, patient-reported improvement based on the Patient Global Impression of Change score and patient-reported adverse events were assessed. A total of 384 FM-TIPS participants (mean [SD] age, 53 [15] years; 351 [91%] female) completed baseline data collection (modified intention-to-treat), with 191 individuals in PT-TENS group and 193 in PT-only group. Movement-evoked pain at day 60 during TENS treatment was significantly lower in the PT-TENS group compared with the PT-only group (group mean difference, -1.2; 95 CI, -1.6 to -0.7; d = 0.46). A dose-response effect for TENS was observed, with more participants in the PT-TENS group reporting improvement on the Patient Global Impression of Change (120 [72%] vs 86 [51%], P = .001) and a 30% or greater reduction in movement-evoked pain in responder analysis (66 of 161 [41%] vs 22 of 169 [13%]; P < .001). At day 180, 217 respondents (81%) found TENS helpful and 147 (55%) used TENS daily. There were no serious adverse events, and 109 of 358 (30%) experienced minor adverse events during the entire 6 months of the study. In this cluster randomized clinical trial of TENS in fibromyalgia, TENS meaningfully reduced movement-evoked pain and remained effective for 6 months. This study's results suggest that TENS is a safe, inexpensive, and readily available treatment for fibromyalgia. ClinicalTrials.gov Identifier: NCT04683042.
Dialysate composition is crucial for managing secondary hyperparathyroidism (SHPT) in patients on hemodialysis. Acetate-based dialysates elevate serum acetate and trigger adverse effects, while citrate and hydrochloric acid formulations might offer distinct clinical benefits. In this longitudinal observational real-life study, 876 adult patients on hemodialysis were classified by acid component of the dialysate (acetic acid, citric acid, or hydrochloric acid). Monthly pre-dialysis parathyroid hormone (PTH) and bone-mineral biomarkers were measured. A linear mixed model (LMM), adjusted for baseline PTH, demographics, and clinical covariates, evaluated PTH trajectories over two years. The significance of the main effect of dialysate and its interaction with time was assessed using likelihood-ratio tests (LRT). At baseline, serum PTH was significantly higher in the acetate group. The LMM confirmed significant influence of dialysate type (p < 0.001) and its interaction with time (p = 0.048) on PTH trajectories. Over two years, acetate showed a modest, non-significant PTH reduction of 2.9% (95% CI: -8.8% to +3.4%), whereas hydrochloric acid resulted in a significant cumulative PTH reduction of 10.9% (95% CI: -15.7% to -0.2%), with a significantly different yearly slope versus acetate (p = 0.044). Citrate showed a modest, non-significant change compared to acetate (-2.3%; 95% CI: -6.7% to +8.4%). Baseline PTH, phosphate, prior hypercalcemia, and dialysate calcium concentration were major predictors in the model. In adjusted longitudinal analyses, hydrochloric acid-based bicarbonate dialysate was associated with a steeper decline in pre-dialysis PTH over two years compared with acetate, while citrate did not differ from acetate. Prospective studies are needed to confirm whether buffer composition influences PTH control under standardized calcium-bath strategies.
Thiamine (vitamin B1) deficiency is a reversible, yet potentially fatal condition that affects both the central and peripheral nervous systems. Although commonly linked to chronic alcoholism, non-alcoholic causes, including malabsorption syndromes, are increasingly being recognized. We report the case of a 22-year-old woman who presented with progressive lower limb weakness, gait disturbances, and confusional symptoms, following a history of intermittent diarrhea and vomiting. Neurological examination revealed ascending motor deficits, areflexia, cerebellar syndrome, and internuclear ophthalmoplegia. Brain magnetic resonance imaging (MRI) showed bilateral symmetrical lesions in the caudate nuclei and periaqueductal area, suggesting Gayet-Wernicke encephalopathy (GWE). The electroneuromyography (ENMG) revealed axonal sensorimotor polyneuropathy. Cerebrospinal fluid (CSF) analysis showed mild hyperproteinorachia mimicking acute inflammatory demyelinating polyneuropathy (AIDP). A profound thiamine deficiency (22.4 nmol/L) was identified alongside duodenal lymphocytosis without villous atrophy or celiac-specific antibodies. High-dose intravenous (IV) thiamine therapy led to rapid improvement in neuropsychiatric symptoms, with partial motor recovery over two months and near-complete resolution on follow-up MRI at six months. This case highlights the diagnostic complexity of non-alcoholic thiamine deficiency, in which Gayet-Wernicke encephalopathy and dry beriberi may present atypically. MRI findings and clinical response to thiamine are key to early diagnosis. Duodenal lymphocytosis may suggest an underlying malabsorption process even in the absence of definitive celiac disease. Clinicians must maintain a high index of suspicion for thiamine deficiency in patients with neurological and gastrointestinal (GI) symptoms regardless of alcohol use. Prompt thiamine supplementation is crucial to prevent irreversible neurological damage.
Plastics are hydrophobic carbon polymers with a half-life of approximately 500 years. The widespread production and environmental accumulation of plastics pose significant toxicity concerns. Humans are routinely exposed to micro- and nanoplastics (MNPs), which can enter rate the bloodstream and reach various organs, including the kidneys. Here, we review research on nephrotoxic effects of plastics and the underlying mechanisms. The results of several studies of kidneys in mammals and kidney cells from humans suggest that MNPs induce renal toxicity. Although the underlying mechanisms remain to be characterized in detail, the current body of evidence suggests that MNPs promote the production of reactive oxygen species and thus trigger local (renal) and systemic inflammatory responses. These processes enhance cytotoxicity and may drive MNP-induced kidney damage. This toxicity results in histopathological changes in renal tissues (including glomerular and tubular damage and fibrosis) and modifications in key biomarkers of renal function (such as the glomerular filtration rate, albuminuria, and the blood urea nitrogen level). Moreover, MNPs have been shown to induce cardiovascular damage, which may contribute to the progression of chronic kidney disease (CKD) - potentially via the activation of aryl hydrocarbon receptors. Notably, the nephrotoxic effects of MNPs appear to be exacerbated by co-exposure to other environmental contaminants and uremic toxins. CKD can impair the kidneys' ability to eliminate MNP. Furthermore, dialyzed patients are substantially exposed to MNPs during dialysis sessions, which potentially compounds their vulnerability. With a view to better understanding the effects of MNPs on renal health and the impact of CKD and dialysis on levels of exposure to plastics, further studies are essential.
To investigate drug delivery in cancer therapy, we integrate fluorescence lifetime measurements, microspectrometry, and confocal laser scanning microscopy to track the uptake of inorganic-organic hybrid nanoparticles (IOH-NPs) by breast cancer cells over incubation periods ranging from 2 to 24 h. Non-radiative energy transfer (FRET) from the LysoTracker Green to the IOH-NPs confirms their lysosomal localization and possibly improves their optical excitation. Beyond the resolution limits of light and electron microscopy, fluorescence lifetime kinetics-including FRET-can thus reveal the nanoscale cellular localization of IOH-NPs and guide the optimization of fluorescence excitation. Here, we extend optical microscopy into a fifth dimension-picosecond fluorescence decay times-complementing 3D spatial and spectral information, establishing lifetime measurements as a versatile tool to study nanoparticle uptake in cancer therapy.