The reduced number of animals in most wild felid populations implies a loss of genetic diversity. The death of juveniles, prior to the production of mature sperm, represents a loss of potential ...genetic contribution to future populations. Since 2011 mouse testicular organ culture has introduced an alternative mechanism to produce sperm in vitro from immature tissue. However, extension of this technology to other species has remained limited. We have used the domestic cat (Felis catus) as a model for wild felids to investigate spermatogenesis initiation and regulation, with the mouse serving as a control species. Testicular tissue fragments were cultured in control medium or medium supplemented with knockout serum replacement (KSR), AlbuMax, beta-estradiol or AlbuMax plus beta-estradiol. Contrary to expectations, and unlike results obtained in mouse controls, no germ cell differentiation could be detected. The only germ cells observed after six weeks of culture were spermatogonia regardless of the initial stage of tubule development in the donor tissue. Moreover, the number of spermatogonia decreased with time in culture in all media tested, especially in the medium supplemented with KSR, while AlbuMax had a slight protective effect. The combination of AlbuMax and beta-estradiol led to an increase in the area occupied by seminiferous tubules, and thus to an increase in total number of spermatogonial cells. Considering all the media combinations tested the stimulus for felid germ cell differentiation in this type of system seems to be different from the mouse. Studies using other triggers of differentiation and tissue survival factors should be performed to pursue this technology for the genetic diversity preservation in wild felids.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Statin treatment in association with physical exercise practice can substantially reduce cardiovascular mortality risk of dyslipidemic individuals, but this practice is associated with myopathic ...event exacerbation. This study aimed to present the most recent results of specific literature about the effects of statins and its association with physical exercise on skeletal musculature. Thus, a literature review was performed using PubMed and SciELO databases, through the combination of the keywords "statin" AND "exercise" AND "muscle", restricting the selection to original studies published between January 1990 and November 2013. Sixteen studies evaluating the effects of statins in association with acute or chronic exercises on skeletal muscle were analyzed. Study results indicate that athletes using statins can experience deleterious effects on skeletal muscle, as the exacerbation of skeletal muscle injuries are more frequent with intense training or acute eccentric and strenuous exercises. Moderate physical training, in turn, when associated to statins does not increase creatine kinase levels or pain reports, but improves muscle and metabolic functions as a consequence of training. Therefore, it is suggested that dyslipidemic patients undergoing statin treatment should be exposed to moderate aerobic training in combination to resistance exercises three times a week, and the provision of physical training prior to drug administration is desirable, whenever possible.
Kidney transplant is the optimal treatment for end-stage kidney disease as it offers significant survival and quality of life advantages over dialysis. While recent advances have significantly ...improved early graft outcomes, long-term overall graft survival has remained largely unchanged for the last 20 years. Due to the young age at which children receive their first transplant, most children will require multiple transplants during their lifetime. Each subsequent transplant becomes more difficult because of the development of
de novo
donor specific HLA antibodies (dnDSA), thereby limiting the donor pool and increasing mortality and morbidity due to longer time on dialysis awaiting re-transplantation. Secondary prevention of dnDSA through increased post-transplant immunosuppression in children is constrained by a significant risk for viral and oncologic complications. There are currently no FDA-approved therapies that can meaningfully reduce dnDSA burden or improve long-term allograft outcomes. Therefore, primary prevention strategies aimed at reducing the risk of dnDSA formation would allow for the best possible long-term allograft outcomes without the adverse complications associated with over-immunosuppression. Epitope matching, which provides a more nuanced assessment of immunological compatibility between donor and recipient, offers the potential for improved donor selection. Although epitope matching is promising, it has not yet been readily applied in the clinical setting. Our review will describe current strengths and limitations of epitope matching software, the evidence for and against improved outcomes with epitope matching, discussion of eplet load vs. variable immunogenicity, and conclude with a discussion of the delicate balance of improving matching without disadvantaging certain populations.
ABSTRACT
Introduction
In this study we investigated the effects of high‐intensity resistance training (RT) on dexamethasone (DEX)‐induced muscle atrophy in flexor hallucis longus (FHL), tibialis ...anterior (TA), and soleus (SOL) muscles. Methods: Rats underwent either high‐intensity RT or were kept sedentary. In the last 10 days they received either DEX (0.5 mg/kg/day, intraperitoneally) or saline. Results: DEX reduced body weight (−21%), food intake (−28%), FHL and TA muscle mass (−20% and −18%, respectively), and increased muscle‐specific ring finger 1 (MuRF‐1) protein level (+37% and +45.5%). RT attenuated FHL muscle atrophy through a combination of low increase in MuRF‐1 protein level (−3.5%) and significant increases in mammalian target of rapamycin (mTOR) (+63%) and p70S6K (+46% and +49% for control and DEX, respectively) protein levels. Conclusion: RT attenuated DEX‐induced muscle atrophy through a combination of increases in mTOR and p70S6K protein levels and a low increase in MuRF‐1 protein level. Muscle Nerve 53: 779–788, 2016
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In 2007, the Emory Transplant Center (ETC) kidney transplant program implemented a required educational session for ESRD patients referred for renal transplant evaluation to increase patient ...awareness and decrease loss to follow-up. The purpose of this study was to evaluate the association of the ETC education program on completion of the transplant evaluation process.
Incident, adult ESRD patients referred from 2005 to 2008 were included. Patient data were abstracted from medical records and linked with data from the United States Renal Data System. Evaluation completion was compared by pre- and posteducational intervention groups in binomial regression models accounting for temporal confounding.
A total of 1126 adult ESRD patients were examined in two transplant evaluation eras (75% pre- and 25% postintervention). One-year evaluation completion was higher in the post- versus preintervention group (80.4% versus 44.7%, P<0.0001). In adjusted analyses controlling for time trends, the adjusted probability of evaluation completion at 1 year was higher among the intervention versus nonintervention group (risk ratio=1.38, 95% confidence interval=1.12-1.71). The effect of the intervention was stronger among black patients and those patients living in poor neighborhoods (likelihood ratio test for interaction, P<0.05).
Standardizing transplant education may help reduce some of the racial and socioeconomic disparities observed in kidney transplantation.
Structured Problem Solving (SPS) is a patient-centered approach to promoting behavior change that relies on productive collaboration between coaches and participants and reinforces participant ...autonomy. We aimed to describe the design, implementation, and assessment of SPS in the multicenter Prevention of Urinary Stones with Hydration (PUSH) randomized trial.
In the PUSH trial, individuals with a history of urinary stone disease and low urine output were randomized to control versus a multicomponent intervention including SPS that was designed to promote fluid consumption and thereby prevent recurrent stones. We provide details specifically about training and fidelity assessment of the SPS coaches. We report on implementation experiences related to SPS during the initial conduct of the trial.
With training and fidelity assessment, coaches in the PUSH trial applied SPS to help participants overcome barriers to fluid consumption. In some cases, coaches faced implementation barriers such as variable participant engagement that required tailoring their work with specific participants. The coaches also faced challenges including balancing rapport with problem solving, and role clarity for the coaches.
We adapted SPS to the setting of kidney stone prevention and overcame challenges in implementation, such as variable patient engagement. Tools from the PUSH trial may be useful to apply to other health behavior change settings in nephrology and other areas of clinical care.
ClinicalTrials.gov Identifier NCT03244189.
The modified Blalock-Taussig-Thomas shunt is the gold standard palliation for securing pulmonary blood flow in infants with ductal-dependent pulmonary blood flow. Recently, the ductus arteriosus ...stent (DAS) has become a viable alternative.
This was a retrospective multicenter study of neonates ≤30 days undergoing DAS or Blalock-Taussig-Thomas shunt placement between January 1, 2017 and December 31, 2020 at hospitals reporting to the Pediatric Health Information Systems database. We performed generalized linear mixed-effects modeling to evaluate trends in intervention and intercenter variation, propensity score adjustment and inverse probability weighting with linear mixed-effects modeling to analyze length of stay and cost of hospitalization, and generalized linear mixed modeling to analyze differences in 30-day outcomes. There were 1874 subjects (58% male, 61% White) from 45 centers (29% DAS). Odds of DAS increased with time (odds ratio OR 1.23, annually,
<0.01 95% CI, 1.10-1.38) with significant intercenter variation (median OR, 3.81 95% CI, 2.74-5.91). DAS was associated with shorter hospital length of stay (ratio of geometric means, 0.76 95% CI, 0.63-0.91), shorter intensive care unit length of stay (ratio of geometric means, 0.77 95% CI, 0.61-0.97), and less expensive hospitalization (ratio of geometric means, 0.70 95% CI, 0.56-0.87). Intervention was not significantly associated with odds of 30-day transplant-free survival (OR,1.18 95% CI, 0.70-1.99) or freedom from catheter reintervention (OR, 1.02 95% CI, 0.65-1.58), but DAS was associated with 30-day freedom from composite adverse outcome (OR, 1.51 95% CI, 1.11-2.05).
Use of DAS is increasing, but there is variability across centers. Though odds of transplant-free survival and reintervention were not significantly different after DAS, and DAS was associated with shorter length of stay and lower in-hospital costs.
A multigram synthesis of the repeating unit of GATG (gallic acid-triethylene glycol) dendrimers is described through an efficient and cost-effective route. These conditions overcome major problems ...precluding scaling up and afford product in excellent overall yield and purity. Special attention has been paid in this process to green chemistry principles: atom economy, safety, and waste reduction. This scheme could be easily adapted for the preparation of similar dendritic systems.
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IJS, KILJ, NUK, PNG, UL, UM
Dexamethasone (DEX) causes rarefaction. In contrast, training (T) prevents rarefaction and stimulates angiogenesis. This study investigated the mechanisms responsible for the preventive role of T in ...DEX-induced rarefaction. Rats underwent T or were kept sedentary (8 weeks) and were treated with DEX or saline during the following 14 days. Tibialis anterior muscle was used for measurements of capillary density (CD), capillary-to-fiber ratio (C:F ratio), superoxide dismutase CuZn (SOD-1), superoxide dismutase MnSOD (SOD-2), catalase (CAT) mRNA as well as SOD-1, SOD-2, CAT, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGF-R2), cyclooxygenase-2 (COX-2), B-cell lymphoma 2 (Bcl-2), Bd-2-like protein 4 (Bax), p-Bax, and caspase-3 cleaved protein levels. DEX decreased CD (-38.1%), C:F ratio (-30.0%), VEGF (-19.0%), VEGFR-2 (-20.1%), COX-2 (-22.8%), Bcl-2 (-20.5%), Bcl-2/Bax ratio (-13.7%), p-Bax/Bax (-20.0%) and increased SOD-2 (+41.6%) and caspase-3 cleaved (+24.1%). Conversely, T prevented reductions in CD (+54.2%), C:F ratio (+32.9%), VEGF (+25.3%), VEGFR-2 (+22.2%), COX-2 (+31.5%), Bcl-2 (+35.5%), Bcl-2/Bax ratio (+19.9%), p-Bax/Bax (+32.1%), and caspase-3 cleaved increase (-7.8%). T increased CAT mRNA (+21.5%) in the DEX-treated group. In conclusion, T prevented the DEX-induced rarefaction by increasing antioxidant enzymes resulting in a better balance between apoptotic and anti-apoptotic protein levels.
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