Hydrogen sulfide (H
2
S) has emerged as a signalling molecule capable of regulating several important physiological functions such as blood pressure, neurotransmission and inflammation. The ...mechanisms behind these effects are still largely elusive and oxidative posttranslational modification of cysteine residues (protein persulfidation or
S
-sulfhydration) has been proposed as the main pathway for H
2
S-induced biological and pharmacological effects. As a signalling mechanism, persulfidation has to be controlled. Using an improved tag-switch assay for persulfide detection we show here that protein persulfide levels are controlled by the thioredoxin system. Recombinant thioredoxin showed an almost 10-fold higher reactivity towards cysteine persulfide than towards cystine and readily cleaved protein persulfides as well. This reaction resulted in H
2
S release suggesting that thioredoxin could be an important regulator of H
2
S levels from persulfide pools. Inhibition of the thioredoxin system caused an increase in intracellular persulfides, highlighting thioredoxin as a major protein depersulfidase that controls H
2
S signalling. Finally, using plasma from HIV-1 patients that have higher circulatory levels of thioredoxin, we could prove depersulfidase role
in vivo
.
H
2
S signals
via
protein persulfidation. To be regulatory the modification will have to be reversible. Using a new method for persulfide detection, we discover this missing link and show that thioredoxin system acts as depersulfidase
in vivo
.
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IJS, KILJ, NUK, UL, UM, UPUK
The speed of sound greatly exceeds typical flow velocities in many stellar and planetary interiors. To follow the slow evolution of subsonic motions, various sound-proof models attempt to remove fast ...acoustic waves while retaining stratified convection and buoyancy dynamics. In astrophysics, anelastic models typically receive the most attention in the class of sound-filtered stratified models. Generally, anelastic models remain valid in nearly adiabatically stratified regions like stellar convection zones, but may break down in strongly sub-adiabatic, stably stratified layers common in stellar radiative zones. However, studying stellar rotation, circulation, and dynamos requires understanding the complex coupling between convection and radiative zones, and this requires robust equations valid in both regimes. Here we extend the analysis of equation sets begun in Brown et al., which studied anelastic models, to two types of pseudo-incompressible models. This class of models has received attention in atmospheric applications, and more recently in studies of white-dwarf supernova progenitors. We demonstrate that one model conserves energy but the other does not. We use Lagrangian variational methods to extend the energy conserving model to a general equation of state, and dub the resulting equation set the generalized pseudo-incompressible (GPI) model. We show that the GPI equations suitably capture low-frequency phenomena in both convection and radiative zones in stars and other stratified systems, and we provide recommendations for converting low-Mach number codes to this equation set.
The objective of our study was to determine the accuracy of imaging-guided percutaneous renal mass biopsy and its impact on clinical management.
With institutional review board approval, we ...retrospectively reviewed imaging-guided renal biopsies performed by radiologists at our institution between February 1999 and July 2005. Patient records, pathology reports, and imaging studies were reviewed. Concordance of biopsy diagnosis and follow-up data was assessed. Significant impact on clinical management was determined in collaboration with two experienced urologists and was defined as a change from no therapy to therapy, including surgery, tumor ablation, chemotherapy, or radiation.
Two hundred seventy-six renal biopsies were performed during the study period. Of these, 123 were random biopsies and fine-needle technique was used for one; these 124 were excluded. One hundred fifty-two renal mass biopsies were performed using coaxial 18-gauge core needle technique in 125 patients (55 women, 70 men; average age, 60 years; range, 28-90 years). There were two (1.3%) postprocedural hematomas (one 0.7% requiring blood transfusion) and one (0.7%) delayed renal pseudoaneurysm attributed to biopsy. No tumor seeding was identified. In 85 biopsies (56%), malignant neoplasm was found, 61 biopsies (40%) yielded benign findings, and six (4%) were nondiagnostic. The sensitivity for malignancy was 97.7%; specificity, 100%; positive predictive value, 100%; and negative predictive value, 100%. At least 92 (60.5%) biopsy results significantly impacted clinical management.
Imaging-guided percutaneous core needle biopsy of renal masses is safe and highly accurate. Tissue diagnosis alters clinical decision making in a majority of the cases and may allow a number of unnecessary nephrectomies to be avoided.
Sarcoidosis is a multisystem disease that can affect any region of the body. Rarely, sarcoid involvement may even involve the male genitourinary tract, including the testicles. Testicular sarcoidosis ...causes spontaneous and severe effects on male fertility due to obstructive azoospermia. The case presented offers an insight into successful fertility treatment in a patient with obstructive testicular sarcoidosis. The patient and his partner presented to the clinic two years post successful natural conception of their first child with subsequent infertility. Within this period, the male partner was diagnosed with sarcoidosis and was on a treatment plan consisting of methotrexate and glucocorticoids. Complete azoospermia was confirmed via two separate semen analyses six weeks apart. The patient’s testosterone (free and total), thyroid stimulating hormone (TSH), prolactin, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were all within normal limits. With approval of pulmonology, methotrexate was discontinued for three months; however, subsequent semen analysis revealed no improvement. The patient was referred to urology, who confirmed the presence a palpable testicular nodule. Treatment of infertility was eventually achieved via testicular sperm aspiration (TESA) followed by in vitro fertilization (IVF) using intracytoplasmic sperm injection (ICSI). This treatment was successful in achieving one blastocyst and one morula, which were replaced via fresh transfer, resulting in a successful term singleton pregnancy. The possibility of obstructive azoospermia should be considered in males diagnosed with sarcoidosis who are seeking to preserve their reproductive potential.
Recurrent pregnancy loss (RPL) can be a devastating experience for individuals trying to have children. Various potential causes contribute to the multifactorial pathogenesis of RPL, including ...chromosomal anomalies, endocrine conditions, autoimmunity, thrombophilias, and infectious agents. Antinuclear antibodies (ANAs) offer an unspecific clue to the underlying autoimmune pathogenic etiology of RPL. This case details a 40-year-old female with a history of RPL, fibromyalgia, and ANA positivity, who spontaneously developed lupus anticoagulant antibodies during her second trimester of pregnancy. Although the recommended American Society of Reproductive Medicine (ASRM) diagnostic criteria for initiating a thrombophilia evaluation was not formally met, the patient's maintenance of low-molecular-weight heparin (LMWH) throughout her pregnancy may have contributed to the success of the pregnancy. When treating a patient with RPL, consideration of the comprehensive clinical picture should precede the need to strictly adhere to published criteria for using non-proven clinical interventions. A risk-benefit analysis ought to be considered when offering patients additional medications that may come with some risks but could significantly improve the chances of a successful clinical outcome, such as live birth. We aim to provide evidence to promote greater flexibility in guidelines so that a patient's unique autoimmune etiologies of RPL are not overlooked.
Anti-ovarian antibodies (AOAs) have been linked to autoimmune premature ovarian insufficiency (POI). This report details a case in which a patient experienced transient POI after a COVID-19 infection ...and tested positive for AOA. After treatment with oral contraceptives and subsequent high-dose oral corticosteroids, the patient underwent fertility treatment with in vitro fertilization (IVF). A total of 23 oocytes were retrieved. Two euploid blastocysts and three untested blastocysts were successfully created. This report hypothesizes the connection between autoimmune POI, AOA, and COVID-19. Conflicting data have been reported linking COVID-19 and ovarian injury. However, it is suggested that COVID-19 transiently impacts the menstrual cycle and anti-Mullerian hormone (AMH) levels. Treatment to overcome poor ovarian response due to AOA has not been adequately determined; however, similar autoimmune conditions have been successfully treated with corticosteroids.
Background
Hemodialysis (HD) guidelines recommend permanent vascular access (PVA) in children unlikely to receive kidney transplant within 1 year of starting HD. We aimed to determine predictors of ...primary and secondary patency of PVA in pediatric HD patients.
Methods
Retrospective chart reviews were performed for first PVAs in 20 participating centers. Variables collected included patient demographics, complications, interventions, and final outcome.
Results
There were 103 arterio-venous fistulae (AVF) and 14 AV grafts (AVG). AVF demonstrated superior primary (
p
= 0.0391) and secondary patency (
p
= 0.0227) compared to AVG. Primary failure occurred in 16 PVA (13.6%) and secondary failure in 14 PVA (12.2%). AVF were more likely to have primary failure (odds ratio (OR) = 2.10) and AVG had more secondary failure (OR = 3.33). No demographic, clinical, or laboratory variable predicted primary failure of PVA. Anatomical location of PVA was predictive of secondary failure, with radial having the lowest risk compared to brachial (OR = 12.425) or femoral PVA (OR = 118.618). Intervention-free survival was predictive of secondary patency for all PVA (
p
= 0.0252) and directly correlated with overall survival of AVF (
p
= 0.0197) but not AVG. Study center demonstrated statistically significant effect only on intervention-free AVF survival (
p
= 0.0082), but not number of complications or interventions, or outcomes.
Conclusions
In this multi-center pediatric HD cohort, AVF demonstrated primary and secondary patency advantages over AVG. Radial PVA was least likely to develop secondary failure. Intervention-free survival was the only predictor of secondary patency for AVF and directly correlated with overall access survival. The study center effect on intervention-free survival of AVF deserves further investigation.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Curcumin is a commonly used herbal supplement purported for its antioxidant, anti-inflammatory, and antineoplastic properties. The effects of curcumin supplementation on endometrial lining have been ...proposed; however, endometrial preparation in the case of frozen-thawed embryo transfer (FET) has not been established. This case series references two scenarios where turmeric was ingested by the patient, and endometrial thickness was subsequently reduced disrupting the FET cycle. Throughout this case series, curcumin's possible interactions with the uterine lining are summarized. Additionally, these cases highlight the importance of physicians' awareness of taking a full history of any herbal remedies or supplements in addition to prescription or over-the-counter medications taken when undergoing treatment for controlled FET cycles or in-vitro fertilization (IVF). To our knowledge, no studies to date have investigated this relationship.
The original version of this article unfortunately contained a mistake. The name of Vimal Chadha was presented incorrectly. The corrected author list is given above.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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