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The sodium/hydrogen exchanger 6 (NHE6) localizes to recycling endosomes, where it mediates endosomal alkalinization through K+/H+ exchange. Mutations in the SLC9A6 gene encoding NHE6 cause severe X-linked mental retardation, epilepsy, autism and corticobasal degeneration in humans. Patients with SLC9A6 mutations exhibit skeletal malformations, and a previous study suggested a key role of NHE6 in osteoblast-mediated mineralization. The goal of this study was to explore the role of NHE6 in bone homeostasis. To this end, we studied the bone phenotype of NHE6 knock-out mice by microcomputed tomography, quantitative histomorphometry and complementary ex vivo and in vitro studies. We detected NHE6 transcript and protein in both differentiated osteoclasts and mineralizing osteoblasts. In vitro studies with osteoclasts and osteoblasts derived from NHE6 knock-out mice demonstrated normal osteoclast differentiation and osteoblast proliferation without an impairment in mineralization capacity. Microcomputed tomography and bone histomorphometry studies showed a significantly reduced bone volume and trabecular number as well as an increased trabecular space at lumbar vertebrae of 6 months old NHE6 knock-out mice. The bone degradation marker c-terminal telopeptides of type I collagen was unaltered in NHE6 knock-out mice. However, we observed a reduction of the bone formation marker procollagen type 1 N-terminal propeptide, and increased circulating sclerostin levels in NHE6 knock-out mice. Subsequent studies revealed a significant upregulation of sclerostin transcript expression in both primary calvarial cultures and femora derived from NHE6 knock-out mice. Thus, loss of NHE6 in mice causes an increase of sclerostin expression associated with reduced bone formation and low bone volume.

Differences have been reported in incidence rates of fractures in the pediatric population, between countries and over time. The aim of this study was to evaluate the incidence and characteristics of fractures over 20 years among Israeli children.

Incidence rates of fractures were derived from the electronic database of Meuhedet Health Services, a health maintenance organization providing healthcare services to 1.2 million people in Israel. Demographic and clinical data were extracted of all the fractures in individuals aged <18 years during 2000-2019. Fracture sites were determined according to ICD9 definitions. Fracture data were analyzed by age, sex, season and sector (general Jewish population, ultra-orthodox Jews and Arabs).

During the study period 188,283 fractures occurred in 142,049 individuals. The most common were fractures of the upper limb (65%), followed by fractures of the lower limb [20%]. The overall fracture rate was 251 per 10,000 person- years (PY), and was higher for boys than girons for targeted prevention strategies.Alzheimer's disease (AD) includes a long asymptomatic stage, which precedes the formal diagnosis of dementia. AD biomarker models provide a framework for precision medicine approaches during this stage. However, such approaches have ignored the possible influence of sex on cognition and brain health, despite female sex noted as a major risk factor. Since AD-related changes may emerge in midlife, intervention efforts are being redirected around this period. Midlife coincides with several endocrinological changes, such as the menopausal transition experienced by women. In this narrative review, we discuss evidence for sex-differences in AD neuropathological burden and outline key endocrinological mechanisms for both sexes, focussing on hormonal events throughout the lifespan that may influence female susceptibility to AD neuropathology and dementia onset. We further consider common non-modifiable (genetic) and modifiable (lifestyle and health) risk factors, highlighting possible sex-dependent differential effects for the AD disease course. Finally, we evaluate the studies selected for this review demonstrating sex-differences in cognitive, pathological and health factors, summarising the state of sex differences in AD risk factors. We further provide recommendations for targeted research on female-specific risk factors, to inform personalised strategies for AD-prevention and the promotion of female brain health.Unpredictable environmental changes displace individuals from homeostasis and elicit a stress response. In vertebrates, the stress response is mediated mainly by glucocorticoids (GCs) which initiate physiological changes while minimizing allostatic overload. Individuals and species vary consistently in baseline and stress-induced GC levels and the speed with which GC levels can be upregulated or downregulated, but the extent to which variation in hormone regulation influences baseline and stress-induced GC levels is unclear. Using mathematical modeling, we tested how GC regulation rate, frequencies and durations of acute stressors, fitness functions, and allostatic overload affect GC levels during control and acute stress periods. As GC regulation rate slows, baseline and acute stress-induced GC levels become more similar. When the speed of up- and downregulation decreased, hormone levels became more linked to anticipated future conditions to avoid fitness costs of mismatching a new environmental state. More frequent acute stressors caused baseline and acute stress-induced GC levels to converge. When fitness was more tightly linked to hormone levels during acute stress periods than during control states, the speed of upregulation influenced optimal hormone levels more than the downregulation rate. selleckchem With allostatic overload costs included, predicted GC levels were lower and more dependent on the frequency of past acute stressors. Our results show the value of optimality modeling to study the hormonal response to stressors and suggest GC levels depend on past and anticipated future environmental states as well as individual differences in hormone regulation.

Vascularized lymph node transfer (VLNT) is an increasingly popular technique for treating lymphedema. However, while many studies have been performed, its efficacy to increase patients' quality of life and reduce lymphedema in the affected body part are still controversial. In this systematic review we summarize the evidence on VLNT for treating breast cancer related lymphedema (BCRL).

MEDLINE, EMBASE and Cochrane CENTRAL were searched for studies including patients with BCRL who received VLNT. Methodology was assessed by the MINORS tool. Primary outcomes were change in volume difference between arms and quality of life. Secondary outcomes were skin infections, complications and discontinuation of compression garment use.

17 Studies were included for qualitative synthesis and eight studies for meta-analysis. The average reduction rate between the healthy and affected arm for studies included in the meta-analysis was 40.31%. Five studies evaluated QoL and in all of these studies QoL was significantly incsage while coinciding with a low complication rate.

Venous thromboembolism (VTE) is a well-known complication associated with surgical procedures. The implementation of thromboprophylaxis in this population has become a vital aspect of peri-operative care to decrease VTE-associated morbidity and mortality risk. However, data assessing the role of thromboprophylaxis for patients undergoing vascular surgery is sparse.

Assessing the role of thromboprophylaxis by low molecular weight heparin (LMWH) or unfractionated heparin (UFH) in vascular surgery.

We searched MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception until December 2020, for randomized controlled trials (RCTs) assessing the role of thromboprophylaxis in vascular surgery.

Eight RCTs met inclusion criteria, including 3,130 patients, with a mean age of 55.35 years and 45% were females. Compared to placebo, anticoagulant use was associated with a reduction of deep venous thrombosis (DVT) (RR 0.34; 95% CI 0.11-1.05; P=0.06 I

=68%) and pulmonary embord reduced incidence of VTE when compared to placebo, though not statistically significant. Bleeding outcomes were comparable between both treatment groups.

In the present study, we evaluated the technical and clinical outcomes after endovascular inferior vena cava (IVC) reconstruction in patients with nonmalignant obstruction.

The preoperative, procedural, and follow-up medical records and imaging studies were retrospectively reviewed for 59 consecutive patients who had undergone endovascular IVC reconstruction for nonmalignant obstruction from February 2014 to January 2019. The patients were classified into three groups according to the quality of their infrainguinal inflow vessels. The outcomes measured were the primary, primary-assisted, and secondary patency rates, reintervention rates, and symptomatic resolution.

The indications for treatment were post-thrombotic syndrome (n= 41), acute deep vein thrombosis (n= 12), and retroperitoneal fibrosis (n= 6). The median patient age was 37years, 11months, 71.2% were men, and 32.2% had a diagnosis of thrombophilia, with no significant difference in these demographics between the three inflow groups. The mediane was 2.8 at 1year and 0 at 2years. In the patients with retroperitoneal fibrosis, the Venous Insufficiency Epidemiological and Economic Study Quality of Life score had improved from a mean of 25.3 at baseline to 44 at 6months.

Endovascular IVC reconstruction for nonmalignant obstruction can achieve good patency and clinical improvement, although the outcomes were poorer for patients with post-thrombotic disease of the femoral and deep femoral veins.

Endovascular IVC reconstruction for nonmalignant obstruction can achieve good patency and clinical improvement, although the outcomes were poorer for patients with post-thrombotic disease of the femoral and deep femoral veins.Snakebite envenomation caused by the Western and Eastern Russell's Vipers (Daboia russelii and Daboia siamensis) may potentially induce capillary leak syndrome (CLS), while the use of antivenom in treating this has not been well examined. This study investigated the CLS-inducing toxicity of Russell's Viper venoms from various sources and examined the neutralization activity of regionally available antivenoms, using a newly devised mouse model. D. russelii venoms demonstrated a more consistent vascular leakage activity (76,000-86,000 CLS unit of vascular leak index, a function of the diameter and intensity of Evans Blue dye extravasation into dermis) than D. siamensis venoms (33,000-88,000 CLS unit). Both species venoms increased hematocrits markedly (53-67%), indicating hemoconcentration. Regional antivenoms (DsMAV-Thailand, DsMAV-Taiwan, VPAV-India) preincubated with the venoms effectively neutralized the CLS effect to different extents. When the antivenoms were administered intravenously post-envenomation (challenge-rescue model), the neutralization was less effective, implying that CLS has a rapid onset that preceded the neutralizing activity of antivenom, and/or the antivenom has limited biodistribution to the venom's inoculation site. In conclusion, Russell's Viper venoms of both species from various locales induced CLS in mice. Antivenoms generally had limited efficacy in neutralizing the CLS effect. Innovative treatment for venom-induced CLS is needed.