Citations

ABSTRACT Extracellular vesicles (EVs) are membrane‐enclosed nanoparticles that mediate intercellular communication by transferring proteins, nucleic acids, and lipids. Within the hematopoietic system, EVs orchestrate critical signaling between bone marrow (BM) niche cells and hematopoietic stem and progenitor cells (HSPCs) to regulate quiescence, proliferation, and lineage commitment. During aging, senescence and telomere attrition drive a profound remodeling of EV biogenesis and cargo. Aged EVs, particularly those released from senescent mesenchymal stromal cells (MSCs) and osteoblasts, exhibit altered microRNA profiles and reduced protective antioxidants. These changes perpetuate niche dysfunction, induce senescence in recipient cells, and promote myeloid‐biased hematopoiesis. Importantly, this communication is a selective process governed by vesicle‐intrinsic surface signatures, such as tetraspanins and integrins, which interact with specific receptors on distinct hematopoietic subsets to regulate signaling fidelity. Conversely, EVs from young or pluripotent stem cells deliver rejuvenating signals that can restore aged HSPC function and attenuate inflammaging. Elucidating these mechanisms of selective targeting and stress‐responsive cargo remodeling provides vital insights for developing EV‐based diagnostic tools and rejuvenation strategies to prevent age‐related immune imbalances and hematologic malignancies.

Abstract Background Identification of individuals at increased risk for synucleinopathies is becoming more feasible with advances in biomarkers. However, the ethical and practical aspects of communicating disease risk remain unresolved, particularly across diagnostic groups and cultural contexts. Objectives We aimed to evaluate attitudes toward disclosure of future synucleinopathy risk among individuals with isolated/idiopathic REM sleep behavior disorder (iRBD), as well as in individuals who developed Parkinson's disease (PD), or multiple system atrophy (MSA), in a large non‐Western registry. Methods This nationwide survey study included participants from 28 movement disorders and sleep centers across Türkiye. Questionnaires assessing attitudes toward risk disclosure, additional testing, and clinical trial participation were administered face‐to‐face. Responses were analyzed using contingency tables and regression models. Results are reported following the Consensus‐Based Checklist for Reporting of Survey Studies (CROSS) guideline. Results Among 1385 participants (1039 PD, 107 MSA, 239 iRBD), individuals with iRBD showed the highest support for risk disclosure (88.3%), exceeding PD (64.4%) and MSA (51.9%). Approval declined modestly (3–8%) when framed within the absence of disease‐modifying treatment. iRBD participants were more willing for additional testing but less willing to join clinical trials (31.8%) than PD (45.3%) or MSA (48%). MSA patients expressed the greatest concern about psychological impact. Male sex had more favorable views on disclosure and trial participation, while younger and better‐educated participants favored additional testing. Conclusions Attitudes toward risk disclosure differ markedly across the synucleinopathy spectrum and demographic characteristics. Culturally informed and diagnosis‐specific disclosure strategies will be essential for trial recruitment and patient‐centered care.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder, characterized by recurrent upper airway obstruction during sleep, resulting in intermittent hypoxia, increased sympathetic activation, and sleep deficiency. Over the past 2 decades, there has been a robust body of evidence to support a strong link between OSA and cardiometabolic diseases. Obesity is an important risk factor for OSA. Observational studies indicate that OSA is a strong risk factor for the development of hypertension and diabetes. Moreover, clinical and experimental studies support a causal role of OSA in hypertension and impairments in glucose metabolism, beyond excess weight. Notably, OSA is particularly underdiagnosed and undertreated in women, which may heighten the cardiometabolic risk. OSA is often overlooked during pregnancy and has been linked to adverse cardiometabolic outcomes in observational studies. In randomized clinical trials, treatment of OSA with continuous positive airway pressure reduces blood pressure in individuals with hypertension, but the beneficial effects of continuous positive airway pressure on glycemic outcomes are less convincing. Inconsistent cardiometabolic response to OSA treatment can be partly explained by failure to consider heterogeneity in OSA and variable continuous positive airway pressure adherence among diverse populations. In this review, we summarize the relationships between OSA and cardiometabolic conditions with a particular focus on obesity, hypertension, and diabetes. We review the current knowledge on the heterogeneity in OSA and discuss potential underlying mechanisms for impairments in blood pressure and glucose metabolism in OSA. We also provide a clinical perspective for OSA management considering current research gaps and emerging approaches for the prevention and treatment of cardiometabolic disease.

Background Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks. Methods We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%–74% agreement. Results A total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research. Conclusions We achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care.

Background There is heterogeneity in the names and anatomical descriptions of regional anesthetic techniques. This may have adverse consequences on education, research, and implementation into clinical practice. We aimed to produce standardized nomenclature for abdominal wall, paraspinal, and chest wall regional anesthetic techniques. Methods We conducted an international consensus study involving experts using a three-round Delphi method to produce a list of names and corresponding descriptions of anatomical targets. After long-list formulation by a Steering Committee, the first and second rounds involved anonymous electronic voting and commenting, with the third round involving a virtual round table discussion aiming to achieve consensus on items that had yet to achieve it. Novel names were presented where required for anatomical clarity and harmonization. Strong consensus was defined as ≥75% agreement and weak consensus as 50% to 74% agreement. Results Sixty expert Collaborators participated in this study. After three rounds and clarification, harmonization, and introduction of novel nomenclature, strong consensus was achieved for the names of 16 block names and weak consensus for four names. For anatomical descriptions, strong consensus was achieved for 19 blocks and weak consensus was achieved for one approach. Several areas requiring further research were identified. Conclusions Harmonization and standardization of nomenclature may improve education, research, and ultimately patient care. We present the first international consensus on nomenclature and anatomical descriptions of blocks of the abdominal wall, chest wall, and paraspinal blocks. We recommend using the consensus results in academic and clinical practice.

Abstract Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) are anatomically different bariatric operations. RYGB achieves greater weight loss compared with LAGB. Changes in the gut microbiome have been documented after RYGB, but not LAGB, and the microbial contribution to sustainable surgical weight loss warrants further evaluation. We hypothesized that RYGB imposes greater changes on the microbiota and its metabolism than LAGB, and that the altered microbiota may contribute to greater weight loss. Using multi-omic approaches, we analyzed fecal microbial community structure and metabolites of pre-bariatric surgery morbidly obese (PreB-Ob), normal weight (NW), post-RYGB, and post-LAGB participants. RYGB microbiomes were significantly different from those from NW, LAGB and PreB-Ob. Microbiome differences between RYGB and PreB-Ob populations were mirrored in their metabolomes. Diversity was higher in RYGB compared with LAGB, possibly because of an increase in the abundance of facultative anaerobic, bile-tolerant and acid-sensible microorganisms in the former. Possibly because of lower gastric acid exposure, phylotypes from the oral cavity, such as Escherichia, Veillonella and Streptococcus, were in greater abundance in the RYGB group, and their abundances positively correlated with percent excess weight loss. Many of these post-RYGB microorganisms are capable of amino-acid fermentation. Amino-acid and carbohydrate fermentation products—isovalerate, isobutyrate, butyrate and propionate—were prevalent in RYGB participants, but not in LAGB participants. RYGB resulted in greater alteration of the gut microbiome and metabolome than LAGB, and RYGB group exhibited unique microbiome composed of many amino-acid fermenters, compared with nonsurgical controls.

The purpose of this descriptive comparative study is to compare the levels of decisional involvement of staff nurses between one Midwestern health care system in the United States with a nongovernmental University hospital in Turkey. The Decisional Involvement Scale was used for data collection. U.S. ( n = 163) and Turkey ( n = 50) staff nurses were included in the study. Both samples preferred more decisional involvement than they currently experienced. However, Turkish nurses experienced and preferred lower levels of decisional involvement than the U.S. sample. Shared governance structures may be a strategy used to enhance staff nurse decisional involvement.

AbstractTNFRSF13B, which encodes TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor), is mutated in 10% of patients with common variable immune deficiency (CVID). One of the 2 most common TACI mutations in CVID, A181E, introduces a negative charge into the transmembrane domain. To define the consequence of the A181E mutation on TACI function, we studied the effect of its murine equivalent, mTACI A144E, on TACI signaling in transfected cells and on TACI function in transgenic mice. The mTACI A144E mutant, like its human TACI A181E counterpart, was expressed on the surface of 293T transfectants and was able to bind ligand, but exhibited impaired constitutive and ligand-induced NFκB signaling. In addition, constitutive and ligand-induced clustering of the intracellular domain was deficient for A144E as measured by fluorescence resonance energy transfer. Transgenic mice expressing the A144E mutant on TACI−/− background had low serum IgA levels and significantly impaired antibody responses to the type II T-independent antigen TNP-Ficoll. B cells from A144E transgenic mice were impaired in their capacity to proliferate and secrete IgG1 and IgA in response to TACI ligation. These results suggest that mTACI A144E mutation and its human counterpart, A181E, disrupt TACI signaling and impair TACI-dependent B-cell functions.