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Assessing congestion is challenging but important to patients with chronic heart failure (CHF). However, there are limited data regarding the association between estimated plasma volume status (ePVS) determined using hemoglobin/hematocrit data and outcomes in patients with stable CHF. We prospectively analyzed 231 patients; the median follow-up period was 35.6 months. We calculated ePVS at admission using the Duarte and Strauss formula, derived from hemoglobin and hematocrit ratios and divided patients into three groups. The primary outcome was a composite of all-cause mortality or heart failure rehospitalization. Among 274 patients (61.98 years of age, 2.3% male), the mean ePVS was 3.98±0.90 dL/g. The third ePVS tertile had a higher proportion of primary outcome (71.4%) than the first or second tertile (48.1% and 59.7%, respectively; p=0.013). On multivariable Cox analysis, after adjusting for potential confounders, higher ePVS remained significantly associated with increased rate of primary outcome (adjusted HR 1.567, 95% CI 1.267 to 1.936; p less then 0.001). Kaplan-Meier survival analyses showed that the occurrence of primary outcome, all-cause mortality and rehospitalization increased progressively from first to third tertiles (p=0.006, 0.014 and 0.001; respectively). In receiver operating characteristic analysis, the area under the curve of ePVS for primary outcome was 0.645. ePVS determined using hemoglobin and hematocrit was independently associated with clinical outcomes for patients with stable CHF. Our study thus further strengthens the evidence that ePVS has important prognostic value in patients with stable CHF. Trial registration number ChiCTR-ONC-14004463.Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) reduce blood pressure (BP) in obese patients with hypertension (HTN). We compared the effect of RYGB and SG on BP in obese patients with HTN at a large-volume, private bariatric surgery center using a propensity score analysis. The measurement and management of BP were exclusively left to the patient's provider without any involvement of Tulane investigators. At month 1, RYGB and SG equally decreased (1) mean body weight 12.7 vs 13.2 kg (p=not significant (NS)) (2) systolic/diastolic BP 8.5/5.3 vs 8.0/4.2 mm Hg (p=NS) and (3) average number of antihypertensive medications from 1.5 to 0.8 and from 1.6 to 0.6 per patient (p=NS). From month 1 to 12, BP remained unchanged after RYGB but tended to increase from month 6 to 12 after SG. Remission of HTN occurred in 52% and 44% of patients after RYGB and SG. In contrast to the full effect of RYGB and SG on BP at 1 month, body weight decreases steadily over 12 months after RYGB and SG. In conclusion, early after surgery, RYGB and SG equally reduce BP in obese patients with HTN. Thereafter, RYGB has a more sustained effect on BP than SG.Heterogeneity among naive adaptive lymphocytes determines their individual functions and fate decisions during an immune response. NK cells are innate lymphocytes capable of generating "adaptive" responses during infectious challenges. However, the factors that govern various NK cell functions are not fully understood. In this study, we use a reporter mouse model to permanently "time stamp" NK cells and type 1 innate lymphoid cells (ILC1s) to characterize the dynamics of their homeostatic turnover. We found that the homeostatic turnover of tissue-resident ILC1s is much slower than that of circulating NK cells. NK cell homeostatic turnover is further accelerated without the transcription factor Eomes. Finally, heterogeneity in NK cell age diversifies NK cell function, with "older" NK cells exhibiting more potent IFN-γ production to activating stimuli and more robust adaptive responses during CMV infection. These results provide insight into how the functional response of an NK cell varies over its lifespan.Permanent hypoparathyroidism is an endocrine disease that is mostly associated with the disruption of the parathyroid glands during surgery. Allotransplantation is the most promising approach for treatment particularly for its cost-effective and exact curative potential. Herein our aim was to evaluate human leukocyte antigen (HLA)-A allele matching effect on clinical improvement and graft survival after parathyroid transplantation. We performed parathyroid transplantation between ABO/Rh compatible recipient and an unrelated donor who has chronic kidney disease. Preoperative immunological tests include panel reactive antibody, T-flow cytometry crossmatch, B-flow cytometry crossmatch, autoflow cytometry crossmatch, and complement-dependent cytotoxicity crossmatch tests were performed. After histopathological evaluation, half of the resected parathyroid gland cells were isolated and transplanted to the omentum surface by laparoscopy. The transplantation outcome was followed up throughout 382 days. The recipient discharged 2 days after transplantation without any complication. read more During follow-up, calcium and vitamin D supplementation reduced to a one-third dose; even the intact PTH levels remained low. However, clinical improvement was observed by serum calcium levels. The recipient still continues with low-dose supplementation after 382 days of post-transplantation. Parathyroid cell transplantation to the omental tissue is the most promising option even with only one allele matching for patients with using lifelong high-dose supplementation. Clinical improvements and long-term effect of HLA-A allele matching should be evaluated with more studies and in larger cohorts as well.Meckel's diverticulum (MD) is a well-defined diagnosis in children presenting with either bleeding or obstruction. Although anecdotally adult patients may present with complications from MD, their presentation seems to be different, with a reported predominance of non-bleed-related presentations. Reports in this population, however, are limited, and little is known of the epidemiology of MD in older patients. We performed a retrospective analysis of the Agency of Healthcare Research and Quality National Inpatient Sample of all US hospital discharges from 2012 to 2016. We identified patients with a primary discharge diagnosis of MD. Data were abstracted as raw numbers and population weighted rates of discharge with age group, income level, length of stay (LOS) and hospital charges as additional information. On average, 2030 individuals were discharged annually; most (71.1%) were adults (>18 years). Although MD was predominant in males in all age groups, the gender ratio decreased with older age categories from 3.51.0 (1-17 years) to 1.61.0 (65-84 years). LOS averaged 5.3 days with no clear relationship to other parameters. Median income category, however, closely correlated (R2=0.9996) with diagnosis in older age categories. MD may be significantly more prevalent in adult patients than was previously understood. Differences in gender preponderance suggest that gender may influence the pattern of presentation. Diagnosis in older individuals is closely associated with income or socioeconomic status but not hospital charges or LOS.The Pediatric Emergency Care Applied Research Network (PECARN) Head Injury/Trauma Algorithm is a well-validated decision rule used to identify patients at low risk of clinically important traumatic brain injuries who may not need head CT. In adult patients with mild head trauma, elevated serum glucose and white cell count (WCC) have been associated with abnormal head CT findings. link2 Currently, glucose or WCC is not considered in pediatric patients. The objective of this study was to determine if elevations in glucose or WCC could be used as additional tools to risk-stratify pediatric trauma patients for intracranial injury (ICI). Data were abstracted from the Maryland Trauma Registry and from electronic medical records for patients at the Johns Hopkins Children's Center from 2017 to 2020. We evaluated 145 encounters that met the inclusion criteria. There were 33 cases of ICI on CT. In addition to higher median glucose and WCC, we found that patients with ICI had a younger median age and were less likely to have other clinically significant injuries than patients without ICI. Following multiple logistic regression analysis, WCC (OR 1.113, 95% CI 1.02 to 1.21), younger age (OR 0.89, 95% CI 0.8 to 0.98), and absence of other injuries (OR 0.41, 95% CI 0.23 to 0.73) were found to be associated with risk of ICI. The area under the curve for our model was 0.79. When used with the PECARN algorithm, our model could help determine which patients may avoid head CT or undergo a shorter observation period.High-altitude environments, characterized by low oxygen levels and low ambient temperatures, have been repeatedly colonized by small altricial mammals. These species inhabit mountainous regions year-round, enduring chronic cold and hypoxia. The adaptations that allow small mammals to thrive at altitude have been well studied in non-reproducing adults; however, our knowledge of adaptations specific to earlier life stages and reproductive females is extremely limited. In lowland natives, chronic hypoxia during gestation affects maternal physiology and placental function, ultimately limiting fetal growth. During post-natal development, hypoxia and cold further limit growth both directly by acting on neonatal physiology and indirectly via impacts on maternal milk production and care. Although lowland natives can survive brief sojourns to even extreme high altitude as adults, reproductive success in these environments is very low, and lowland young rarely survive to sexual maturity in chronic cold and hypoxia. Here, we review the limits to maternal and offspring physiology - both pre-natal and post-natal - that highland-adapted species have overcome, with a focus on recent studies on high-altitude populations of the North American deer mouse (Peromyscus maniculatus). link3 We conclude that a combination of maternal and developmental adaptations were likely to have been critical steps in the evolutionary history of high-altitude native mammals.

FSGS caused by mutations in

is characterized by a podocytopathy with mistrafficked nephrin, an essential component of the slit diaphragm. Because INF2 is a formin-type actin nucleator, research has focused on its actin-regulating function, providing an important but incomplete insight into how these mutations lead to podocytopathy. A yeast two-hybridization screen identified the interaction between INF2 and the dynein transport complex, suggesting a newly recognized role of INF2 in regulating dynein-mediated vesicular trafficking in podocytes.

Live cell and quantitative imaging, fluorescent and surface biotinylation-based trafficking assays in cultured podocytes, and a new puromycin aminoglycoside nephropathy model of

transgenic mice were used to demonstrate altered dynein-mediated trafficking of nephrin in INF2 associated podocytopathy.

Pathogenic

mutations disrupt an interaction of INF2 with dynein light chain 1, a key dynein component. The best-studied mutation, R218Q, diverts dynein-mediated postendocytic sorting of nephrin from recycling endosomes to lysosomes for degradation. Antagonizing dynein-mediated transport can rescue this effect. Augmented dynein-mediated trafficking and degradation of nephrin underlies puromycin aminoglycoside-induced podocytopathy and FSGS

.

mutations enhance dynein-mediated trafficking of nephrin to proteolytic pathways, diminishing its recycling required for maintaining slit diaphragm integrity. The recognition that dysregulated dynein-mediated transport of nephrin in R218Q knockin podocytes opens an avenue for developing targeted therapy for INF2-mediated FSGS.

INF2 mutations enhance dynein-mediated trafficking of nephrin to proteolytic pathways, diminishing its recycling required for maintaining slit diaphragm integrity. The recognition that dysregulated dynein-mediated transport of nephrin in R218Q knockin podocytes opens an avenue for developing targeted therapy for INF2-mediated FSGS.

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