Association analysis between the human interleukin 1beta (-511) gene polymorphism and susceptibility to febrile convulsions

This study was designed to examine whether anxious personality, i.e. trait anxiety, influences the autonomic nervous functions in humans without manipulation of experimental stressors. The degrees of state and trait anxiety, blood pressure, heart rate, pupillary light reflex (PLR), and body temperature were measured at the same hour on four different days in 14 healthy college students. A multiple regression analysis showed that trait anxiety predominantly influenced state anxiety and the PLR parameters. A single regression analysis showed that trait anxiety positively correlated to the initial pupillary diameter and the constricted diameter of PLR and negatively to the amplitude of PLR. It was concluded that trait anxiety predicts state anxiety and a smaller amplitude of PLR in humans at rest.     

“Handedness” of spiral fractures of the tibia

Handedness is a basic property of spirals. In many cases it is possible to determine whether spiral fractures are right or left handed by analysis of radiographs. Spiral fractures of the tibia show striking bilateral symmetry, with right-handed spirals predominating on the left side of the body, and left-handed spirals on the right.     

Trends and Outcomes in Simultaneous Liver and Kidney Transplantation in Australia and New Zealand

AimRates of simultaneous liver and kidney transplantation (SLKT) have increased, but indications for SLKT remain poorly defined. Additional data are needed to determine which patients benefit from SLKT to best direct use of scarce donor kidneys.MethodsData were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) database for all SLKT performed until the end of 2017. Patients were divided by pretransplant dialysis status into no dialysis before SLKT (preemptive kidney transplant) and any dialysis before SLKT (nonpreemptive). Baseline characteristics and outcomes were compared.ResultsBetween 1989 and 2017, inclusive, 84 SLKT procedures were performed in Australia, of which 24% were preemptive. Preemptive and nonpreemptive SLKT recipients did not significantly differ in age (P = .267), sex (P = .526), or ethnicity (P = .870). Over a median follow-up time of 4.5 years, preemptively transplanted patients had a statistically equivalent risk of kidney graft failure (hazard ratio (HR) 1.83, 95% confidence interval [CI]: 0.36-12.86, P = .474) and all-cause mortality (HR 1.69, 95% CI: 0.51-5.6, P = .226) compared to nonpreemptive patients. Overall, 1- and 5-year survival rates for all SLKTs were 92% (95% CI: 86-96) and 60% (95% CI: 45-75), respectively.ConclusionKidney graft and overall patient survival were similar between patients with preemptive kidney transplant and those who were dialysis dependent.     

Glutamine Metabolism in Osteoprogenitors Is Required for Bone Mass Accrual and PTH-Induced Bone Anabolism in Male Mice

Skeletal homeostasis critically depends on the proper anabolic functioning of osteolineage cells. Proliferation and matrix synthesis are highly demanding in terms of biosynthesis and bioenergetics, but the nutritional requirements that support these processes in bone-forming cells are not fully understood. Here, we show that glutamine metabolism is a major determinant of osteoprogenitor function during bone mass accrual. Genetic inactivation of the rate-limiting enzyme glutaminase 1 (GLS1) results in decreased postnatal bone mass, caused by impaired biosynthesis and cell survival. Mechanistically, we uncovered that GLS1-mediated glutamine catabolism supports nucleotide and amino acid synthesis, required for proliferation and matrix production. In addition, glutamine-derived glutathione prevents accumulation of reactive oxygen species and thereby safeguards cell viability. The pro-anabolic role of glutamine metabolism was further underscored in a model of parathyroid hormone (PTH)-induced bone formation. PTH administration increases glutamine uptake and catabolism, and GLS1 deletion fully blunts the PTH-induced osteoanabolic response. Taken together, our findings indicate that glutamine metabolism in osteoprogenitors is indispensable for bone formation. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.     

Sex Differences in Voyeuristic and Exhibitionistic Interests: Exploring the Mediating Roles of Sociosexuality and Sexual Compulsivity from an Evolutionary Perspective

Sociosexuality and sexual compulsivity predict sex differences in voyeuristic interest in the population. In this study, we used a sample of 1113 participants from the UK (46% men) to consider whether sociosexuality and sexual compulsivity interacted to explain these sex differences and whether this relationship extended to the related domain of exhibitionism. In doing so, we tested novel predictions derived from an evolutionary perspective which views voyeuristic and exhibitionistic interest as manifestations of a short-term mating strategy. Participants reported their levels of repulsion toward voyeurism and exhibitionism and their interest in performing such acts under different levels of risk. There were clear sex differences in voyeuristic and exhibitionistic repulsion that were partially mediated by the serial combination of sociosexuality and sexual compulsivity. Examining the sexes separately revealed qualitatively different relationships between sociosexuality and sexual compulsivity when predicting exhibitionistic, but not voyeuristic, repulsion. Combined, sociosexuality and sexual compulsivity also mediated the sex difference in willingness to commit acts of voyeurism, but not exhibitionism, which was equally low for both sexes. The results highlight the role sociosexuality plays in voyeuristic and exhibitionistic interest, which coupled with an evolutionary perspective, may have implications for how we view courtship disorders.

     

Methimazole as a protectant against cisplatin-induced nephrotoxicity using the dog as a model

Dexniguldipine-HCl (DNIG) — a prospective clinical modulator of p170-glycoprotein (pgp170)-mediated multidrug resistance (MRD) — was evaluated in a drug-accumulation assay in MDR murine leukemia cell strain F4-6RADR expressing pgp170. The compound elevated low accumulation of either doxorubicin (DOX), daunorubicin (DNR), or mitoxantrone (MITO) in resistant F4-6RADR cells to the very levels observed in drug-sensitive F4-6 precursor cells. In parallel with the increase in DNR content (F4-6RADR, solvent: 303±27 pmol/mg protein; DNIG (3.3 mol/l): 1,067±174 pmol/mg protein; F4-6P, solvent: 948±110 pmol/mg protein;n=8–9, SEM), the amount of DNR tightly bound to the acid precipitate pellet obtained from F4-6RADR (i.e., protein, DNA, RNA) increased 3.9-times to the levels observed in sensitive F4-6 cells. The main pyridine metabolite of DNIG displayed similar activity. Concentration-response analysis revealed that DNIG and R,S-verapamil (VER) induced 100% reversal of the DNR accumulation shortage associated with the MDR phenotype but DNIG was 8 times more potent than VER (50% inhibitory concentration (IC₅₀), 0.73 vs 5.4 mol/l). In keeping with the accumulation assay, DNIG was about 10 times more potent than VER in sensitizing F4-6RADR cells to the cytostatic and cytotoxic effects of DNR in proliferation assays. In conclusion, DNIG is a potent in vitro modulator, improving (a) the accumulation of anthracycline-like cytostatics, (B) drug access to cellular binding sites, and (c) the cytostatic action of DNR in F4-6RADR leukemia cells of the MDR phenotype.Abbreviations DOX doxorubicin - CSA cyclosporin A - DMSO dimethylsulfoxide - DNIG dexniguldipine-HCl - DNR daunorubicin - MDR multidrug resistance - MITO mitoxantrone - pgp170 permease glycoprotein 170 - VER R.S.-verapamil Dexniguldipine-HCl is the proposed INN for compound B859-35, the R-enantiomer of niguldipine. Segments of this work have been reported in the abstract form