TGFβ1 orchestrates renal fibrosis following Escherichia coli pyelonephritis

Renal scarring after pyelonephritis is linked to long-term health risks for hypertension and chronic kidney disease. Androgen exposure increases susceptibility to, and severity of, uropathogenic Escherichia coli (UPEC) pyelonephritis and resultant scarring in both male and female mice, while anti-androgen therapy is protective against severe urinary tract infection (UTI) in these models. This work employed androgenized female C57BL/6 mice to elucidate the molecular mechanisms of post-infectious renal fibrosis and to determine how these pathways are altered by the presence of androgens. We found that elevated circulating testosterone levels primed the kidney for fibrosis by increasing local production of TGFβ1 before the initiation of UTI, altering the ratio of transcription factors Smad2 and Smad3 and increasing the presence of mesenchymal stem cell (MSC)-like cells and Gli1 + activated myofibroblasts, the cells primarily responsible for deposition of scar components. Increased production of TGFβ1 and aberrations in Smad2:Smad3 were maintained throughout the course of infection in the presence of androgen, correlating with renal scarring that was not observed in non-androgenized female mice. Pharmacologic inhibition of TGFβ1 signaling blunted myofibroblast activation. We conclude that renal fibrosis after pyelonephritis is exacerbated by the presence of androgens and involves activation of the TGFβ1 signaling cascade, leading to increases in cortical populations of MSC-like cells and the Gli1 + activated myofibroblasts that are responsible for scarring

Senators treat female Supreme Court nominees differently. Here’s the evidence.

Over the weekend, President Trump nominated Judge Amy Coney Barrett to fill the Supreme Court seat left empty by Justice Ruth Bader Ginsburg’s death. Senate Majority Leader Mitch McConnell (R-Ky.) has promised to move the nomination swiftly through to confirmation. As a result, the nation’s attention will soon turn to Barrett’s confirmation hearings in the Senate Judiciary Committee. Based on our empirical examinations of every question asked and every answer given at the hearings since the first in 1939, here is what to expect

Implementing the Five-A Model of technical refinement: Key roles of the sport psychologist

There is increasing evidence for the significant contribution provided by sport psychologists within applied coaching environments. However, this rarely considers their skills/knowledge being applied when refining athletes’ already learned and well-established motor skills. Therefore, this paper focuses on how a sport psychologist might assist a coach and athlete to implement long-term permanent and pressure proof refinements. It highlights key contributions at each stage of the Five-A Model—designed to deliver these important outcomes—providing both psychomotor and psychosocial input to the support delivery. By employing these recommendations, sport psychologists can make multiple positive contributions to completion of this challenging task

Assessing the efficacy of medetomidine and tiletamine-zolazepam for remote immobilisation of feral horses (Equus caballus)

Context The study of any wild animal's home range requires the collection of spatiotemporal data, obtained independently of climatic conditions or time of day. This can be achieved by the attachment of global positioning system (GPS) data loggers, which, in large species, is best achieved by remote immobilisation. Feral horses (Equus caballus) usually occupy remote areas of Australia; however, a considerable population increase has been observed in a close proximity to metropolitan areas of the Australian east coast, creating increasing conflict with human interests. Aim The aim of the present study was to investigate the efficacy of remote chemical immobilisation of feral horses with medetomidine combined with tiletamine-zolazepam to facilitate placement of satellite GPS collars. Methods Nine feral horses were darted from the ground with 60mg (i.m.) medetomidine and 1500mg (i.m.) tiletamine-zolazepam. The effects of medetomidine were reversed with 50-100mg (i.m. or i.v.) atipamezole 30-40min after induction (IV/IM). Physiological variables monitored during anaesthesia were heart rate, respiratory rate, temperature and oxygen haemoglobin saturation (Spo2). Key results All horses were successfully immobilised with between one and three darts (n≤9). The mean (± s.e.m.) dose of medetomidine was 0.15±0.01mg kg-1, whereas that of tiletamine-zolazepam was 3.61±0.16mg kg-1. Mean time from darting to lateral recumbency was 13.3±2.7min and mean recumbency time was 54±13min. Vital signs for all anaesthetised animals remained within the normal range during anaesthesia, with the exception of one animal exhibiting a transient drop in Spo2. There were no deaths. Key conclusions The combination of medetomidine and tiletamine-zolazepam provided adequate anaesthesia in feral horses in the field for application of GPS collars. Implications Although a limited number of horses was immobilised, the present study shows that the combination of medetomidine and tiletamine-zolazepam provides effective short-term anaesthesia for feral horses, affording a practical and field-accessible capture technique. This method could also be applied to other management actions requiring the safe and humane capture of feral horses

Outcomes of a Pharmacist-Managed Clinic for Underserved Persons with Unmanaged Type 2 Diabetes Mellitus

Background A multidisciplinary approach is recommended for the management of type 2 diabetes mellitus (DM). Aim To evaluate the impact of a pharmacist intervention on haemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), and diabetes-related hospitalisations in an underserved cohort with unmanaged type 2 DM. Methods This analysis was a retrospective cohort study. Criteria for inclusion were persons with unmanaged type 2 DM defined as HbA1c values ≥8% at time of enrolment, ≥18 years old, and enrolment in a pharmacist-managed clinic for ≥12 months. Pre- and post-intervention differences in HbA1c, SBP and DBP values were assessed using repeated measures analysis of variance (ANOVA). The risk of diabetes-related hospitalisations was estimated during the 12 months prior and during the 12 months post-intervention, and the relative risk (RR) was calculated. Results Mean HbA1c values at 3, 6 and 12 months post-intervention were lower than baseline values (p \u3c 0.05). There was no significant difference in mean HbA1c values at 6 or 12 months compared to 3 months post intervention. Mean SBP values at 3, 6 and 12 months were lower than baseline (p \u3c 0.05). Likewise, mean DBP values at 6 and 12 months were lower than baseline (p \u3c 0.05). The estimated RR of diabetes-related hospitalisations was 0.40 (95% CI: 0.20–0.83; p = 0.013). Conclusion Enrolment in a pharmacist-managed diabetes program was associated with a significant reduction in HbA1c, SBP and DBP and reduction in risk of diabetes-related hospitalisations in an underserved cohort of patients with diabetes over a 12-month period

Head Removal Enhances Planarian Electrotaxis

Certain animal species utilize electric fields for communication, hunting and spatial orientation. Freshwater planarians move toward the cathode in a static electric field (cathodic electrotaxis). This planarian behavior was first described by Raymond Pearl more than a century ago. However, planarian electrotaxis has received little attention since, and the underlying mechanisms and evolutionary significance remain unknown. To close this knowledge gap, we developed an apparatus and scoring metrics for automated quantitative and mechanistic studies of planarian behavior upon exposure to a static electric field. Using this automated setup, we characterized electrotaxis in the planarian Dugesia japonica and found that this species responds to voltage instead of current, in contrast to results from previous studies using other planarian species. Surprisingly, we found differences in electrotaxis ability between small (shorter) and large (longer) planarians. To determine the cause of these differences, we took advantage of the regenerative abilities of planarians and compared electrotaxis in head, tail and trunk fragments of various lengths. We found that tail and trunk fragments electrotaxed, whereas head fragments did not, regardless of size. Based on these data, we hypothesized that signals from the head may interfere with electrotaxis when the head area/body area reached a critical threshold. In support of this hypothesis, we found that (1) smaller intact planarians that cannot electrotax have a relatively larger head-to-body-ratio than large planarians that can electrotax, and (2) the electrotaxis behavior of cut head fragments was negatively correlated with the head-to-body ratio of the fragments. Moreover, we could restore cathodic electrotaxis in head fragments via decapitation, directly demonstrating inhibition of electrotaxis by the head

The development of parental monitoring during adolescence : A meta-analysis

As adolescents grow up, one of the important developmental tasks is to individuate themselves and to become more autonomous from parents. This requires a realignment of the parent-adolescent communication. The current meta-analytic study aims at identifying developmental changes in parent-adolescent communication, conceptualized within the parental monitoring framework, as entailing parental solicitation, control and knowledge, and adolescent’s disclosure and secrecy. Thirty-one longitudinal studies published between 2000 and 2015 were identified and included in the current meta-analysis. Informants, age at assessment and study duration were tested as moderators. Results showed a low to medium normative decline in parental control (Cohen’s d = −.395, 95% CI [−.541, −.249]), knowledge (d = −.245,95% CI [−.331, −.160] and adolescence disclosure (d = −.147, 95% CI [−.204, −.090]), and an increase in adolescent’s secrecy (d = .194, CI [031, .356]). Parental solicitation decreased based on parents’ (d = −.242, 95% CI[−.376, −.109]) but not on adolescents’ reports (d = .038, 95% CI[−.099, .175]). Another significant moderator was the duration of the study, with studies longer than 2 years being able to detect a more pronounced change in parental control than studies lasting less than 2 years (≤2 years, d = −.139 vs. duration > 2 years, d = −.581). Limitations of the current knowledge and new directions of studies are discussed.Peer reviewe

Saving Bones: a direct comparison of FTIR-ATR, whole bone percent nitrogen, and NIR

89th Annual Meeting of the American-Association-of-Physical-Anthropologists (AAPA), Los Angeles, CA, APR 15-18, 202