Detection and Mapping of Quantitative Trait Loci that Determine Responsiveness

Exposure to 70% N2O evokes a robust antinociceptive effect in C57BL/6 (B6) but not in DBA/2 (D2) inbred mice. This study was conducted to identify quantitative trait loci (QTL) in the mouse genome that might determine responsiveness to N2O. Offspring from the F2 generation bred from B6 and D2 progenitors exhibited a broad range of responsiveness to N2O antinociception as determined by the acetic acid-induced abdominal constriction test. QTL analysis was then used to dissect this continuous trait distribution into component loci, and to map them to broad chromosomal regions. To this end, 24 spleens were collected from each of the following four groups: male and female F2 mice responding to 70% N2O in oxygen with 100% response (high-responders); and male and female F2 mice responding with 0% response (low-responders). Genomic DNA was extracted from the spleens and genotyped with simple sequence length polymorphism MapPairs markers. Findings were combined with findings from the earlier QTL analysis from BXD recombinant inbred mice [Brain Res 725 (1996) 23]. Combined results revealed two significant QTL that influence responsiveness to nitrous oxide on proximal chromosome 2 and distal chromosome 5, and one suggestive QTL on midchromosome 18. The chromosome 2 QTL was evident only in males. A significant interaction was found between a locus on chromosome 6 and another on chromosome 13 with a substantial effect on N2O antinociception

Measuring Urinary Sensation with Current Perception Threshold: A Comparison between Method of Limits and Method of Levels

Purpose. To determine the association between the two methods of obtaining current perception thresholds (CPTs) in the lower urinary tract (LUT). Materials and Methods. Twenty-one women undergoing pelvic surgery underwent CPT determinations of the urethra. CPTs were measured at 2,000, 250, and 5 Hz (corresponding to A-β, A-δ, and C fibers, resp.) both pre- and postoperatively. Threshold values were obtained in all patients by using the method of limits and the method of levels. Results. CPT values obtained by using the method of levels and the methods of limits were highly correlated at all frequencies before and after surgery (ρ = 0.93–0.99, P < 0.0001). The mean threshold values obtained by the method of levels were significantly lower at all frequencies compared with those obtained by the method of limits. Conclusions. Our findings suggest that the method of levels is more sensitive for the detection of CPTs compared to the method of limits

The Role of Reference Points in Machine-Learned Atomistic Simulation Models

This paper introduces the Chemical Environment Modeling Theory (CEMT), a novel, generalized framework designed to overcome the limitations inherent in traditional atom-centered Machine Learning Force Field (MLFF) models, widely used in atomistic simulations of chemical systems. CEMT demonstrated enhanced flexibility and adaptability by allowing reference points to exist anywhere within the modeled domain and thus, enabling the study of various model architectures. Utilizing Gaussian Multipole (GMP) featurization functions, several models with different reference point sets, including finite difference grid-centered and bond-centered models, were tested to analyze the variance in capabilities intrinsic to models built on distinct reference points. The results underscore the potential of non-atom-centered reference points in force training, revealing variations in prediction accuracy, inference speed and learning efficiency. Finally, a unique connection between CEMT and real-space orbital-free finite element Density Functional Theory (FE-DFT) is established, and the implications include the enhancement of data efficiency and robustness. It allows the leveraging of spatially-resolved energy densities and charge densities from FE-DFT calculations, as well as serving as a pivotal step towards integrating known quantum-mechanical laws into the architecture of ML models

IL-10 is necessary and sufficient for autoimmune diabetes in conjunction with NOD MHC homozygosity.

Contrary to expectations based on in vitro experiments, we previously found that pancreatic IL-10 did not inhibit autoimmune diabetes but accelerated it in an MHC-dependent manner. Therefore, the ability of IL-10 to overcome the absence of all non-MHC diabetes susceptibility (Idd) alleles was studied in transgenic mice expressing pancreatic IL-10 backcrossed to B10.H2g7 congenic mice, which have no Idd alleles other than NOD MHC (H2g7). IL-10 transgenic backcross 1 (BC1) mice with H2g7/g7 haplotype developed clear-cut insulitis and diabetes, but neither transgenic mice with the H2g/b haplotype nor nontransgenic BC1 mice did so. Further implicating IL-10 in autoimmune diabetes, anti-IL-10 antibody treatment inhibited the development of insulitis in NOD mice. These results suggest that IL-10 may be necessary and sufficient for producing autoimmune diabetes in conjunction with NOD MHC homozygosity and that some Idd genes may be related to the regulation of IL-10

Septic arthritis of the shoulder due to Ureaplasma urealyticum after emergency caesarean section: a case report

Ureaplasma urealyticum is an intra-cellular bacterium frequently found colonizing the genital tract. Known complications include localized infections, which can result in premature deliveries. Septic arthritis due to U. urealyticum in healthy patients is exceptionally rare, although opportunistic septic arthritis in agammaglobulinemic patients have been reported. However, there are no reports of septic arthritis due to U. urealyticum following caesarean section or in the post-partum period. A 38-year-old immunocompetent woman presented with severe right shoulder pain, 1 month following emergency caesarean section at 26 weeks of gestation for pre-eclampsia and spontaneous placental disruption with an uncomplicated post-operative recovery. Our suspicion of septic arthritis was confirmed with abundant pus following arthrotomy by a delto-pectoral approach. Awaiting culture results, empirical antibiotic treatment with intravenous amoxicilline and clavulanic acid was initiated. In spite of sterile cultures, clinical evolution was unfavorable with persistent pain, inflammation and purulent drainage, requiring two additional surgical débridement and lavage procedures. The 16S ribosomal RNA PCR of the purulent liquid was positive for U. urealyticum at 2.95 × 10 &lt;sup&gt;6&lt;/sup&gt; copies/ml, specific cultures inoculated a posteriori were positive for U. urealyticum. Levofloxacin and azithromycine antibiotherapy was initiated. Susceptibility testing showed an intermediate sensibility to ciprofloxacin and clarithromycin. The strain was susceptible to doxycycline. Following cessation of breastfeeding, we started antibiotic treatment with doxycycline for 4 weeks. The subsequent course was favorable with an excellent functional and biological outcome. We report the first case of septic arthritis due to U. urealyticum after caesarean section. We hypothesize that the breach of the genital mucosal barrier during the caesarean section led to hematogenous spread resulting in purulent septic arthritis. The initial beta-lactam based antibiotic treatment, initiated for a purulent arthritis, did not provide coverage for cell wall deficient organisms. Detection of 16S rRNA allowed for a correct microbiological diagnosis in a patient with an unexpected clinical course

The prevention of lower urinary tract symptoms (PLUS) research consortium: A transdisciplinary approach toward promoting bladder health and preventing lower urinary tract symptoms in women across the life course

Lower urinary tract symptoms (LUTS) are highly prevalent in women, and are expected to impose a growing burden to individuals and society as the population ages. The predominance of research related to LUTS has focused on underlying pathology, disease mechanisms, or the efficacy of treatments for women with LUTS. Although this research has been vital for helping to reduce or ameliorate LUTS conditions, it has done little to prevent the onset of LUTS. Health promotion and prevention require an expansion of scientific inquiry beyond the traditional paradigm of studying disease mechanisms and treatment to the creation of an evidence base to support recommendations for bladder health promotion and, in turn, prevention of LUTS. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) introduced the concept of prevention as an important priority for women's urologic research as a prelude to supporting the formation of the Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium. In this article, we introduce the PLUS research consortium to the scientific community; share the innovative paradigms by which the consortium operates; and describe its unique research mission: to identify factors that promote bladder health across the life course and prevent the onset of LUTS in girls and women