Interdisciplinary Transgender Veteran Care: Development of a Core Curriculum for VHA Providers

Purpose: The Veteran\u27s Health Administration (VHA) has created a training program for interdisciplinary teams of providers on the unique treatment needs of transgender veterans. An overview of this program\u27s structure and content is described along with an evaluation of each session and the program overall. Methods: A specialty care team delivered 14 didactic courses supplemented with case consultation twice per month over the course of 7 months through video teleconferencing to 16 teams of learners. Each team, consisting of at least one mental health provider (e.g., social worker, psychologist, or psychiatrist) and one medical provider (e.g., physician, nurse, physician assistant, advanced practice nurse, or pharmacist), received training and consultation on transgender veteran care. Results: In the first three waves of learners, 111 providers across a variety of disciplines attended the sessions and received training. Didactic topics included hormone therapy initiation and adjustments, primary care issues, advocacy within the system, and psychotherapy issues. Responses were provided to 39 veteran-specific consult questions to augment learning. Learners reported an increase in knowledge plus an increase in team cohesion and functioning. As a result, learners anticipated treating more transgender veterans in the future. Conclusion: VHA providers are learning about the unique healthcare needs of transgender veterans and benefitting from the training opportunity offered through the Transgender Specialty Care Access Network-Extension of Community Healthcare Outcomes program. The success of this program in training interdisciplinary teams of providers suggests that it might serve as a model for other large healthcare systems. In addition, it provides a path forward for individual learners (both within VHA and in the community) who wish to increase their knowledge

Epithelial NAD+ depletion drives mitochondrial dysfunction and contributes to intestinal inflammation

IntroductionWe have previously demonstrated that a pathologic downregulation of peroxisome proliferator-activated receptor–gamma coactivator 1-alpha (PGC1α) within the intestinal epithelium contributes to the pathogenesis of inflammatory bowel disease (IBD). However, the mechanism underlying downregulation of PGC1α expression and activity during IBD is not yet clear.MethodsMice (male; C57Bl/6, Villincre/+;Pgc1afl/fl mice, and Pgc1afl/fl) were subjected to experimental colitis and treated with nicotinamide riboside. Western blot, high-resolution respirometry, nicotinamide adenine dinucleotide (NAD+) quantification, and immunoprecipitation were used to in this study.ResultsWe demonstrate a significant depletion in the NAD+ levels within the intestinal epithelium of mice undergoing experimental colitis, as well as humans with ulcerative colitis. While we found no decrease in the levels of NAD+-synthesizing enzymes within the intestinal epithelium of mice undergoing experimental colitis, we did find an increase in the mRNA level, as well as the enzymatic activity, of the NAD+-consuming enzyme poly(ADP-ribose) polymerase-1 (PARP1). Treatment of mice undergoing experimental colitis with an NAD+ precursor reduced the severity of colitis, restored mitochondrial function, and increased active PGC1α levels; however, NAD+ repletion did not benefit transgenic mice that lack PGC1α within the intestinal epithelium, suggesting that the therapeutic effects require an intact PGC1α axis.DiscussionOur results emphasize the importance of PGC1α expression to both mitochondrial health and homeostasis within the intestinal epithelium and suggest a novel therapeutic approach for disease management. These findings also provide a mechanistic basis for clinical trials of nicotinamide riboside in IBD patients

Arrhythmogenic mechanisms in the isolated perfused hypokalaemic murine heart

AIM: Hypokalaemia is associated with a lethal form of ventricular tachycardia (VT), torsade de pointes, through pathophysiological mechanisms requiring clarification. METHODS: Left ventricular endocardial and epicardial monophasic action potentials were compared in isolated mouse hearts paced from the right ventricular epicardium perfused with hypokalaemic (3 and 4 mm [K(+)](o)) solutions. Corresponding K(+) currents were compared in whole-cell patch-clamped epicardial and endocardial myocytes. RESULTS: Hypokalaemia prolonged epicardial action potential durations (APD) from mean APD(90)s of 37.2 ± 1.7 ms (n = 7) to 58.4 ± 4.1 ms (n =7) and 66.7 ± 2.1 ms (n = 11) at 5.2, 4 and 3 mm [K(+)](o) respectively. Endocardial APD(90)s correspondingly increased from 51.6 ± 1.9 ms (n = 7) to 62.8 ± 2.8 ms (n = 7) and 62.9 ± 5.9 ms (n = 11) giving reductions in endocardial–epicardial differences, ΔAPD(90), from 14.4 ± 2.6 to 4.4 ± 5.0 and −3.4 ± 6.0 ms respectively. Early afterdepolarizations (EADs) occurred in epicardia in three of seven spontaneously beating hearts at 4 mm [K(+)](o) with triggered beats followed by episodes of non-sustained VT in nine of 11 preparations at 3 mm. Programmed electrical stimulation never induced arrhythmic events in preparations perfused with normokalemic solutions yet induced VT in two of seven and nine of 11 preparations at 4 and 3 mm [K(+)](o) respectively. Early outward K(+) current correspondingly fell from 73.46 ± 8.45 to 61.16±6.14 pA/pF in isolated epicardial but not endocardial myocytes (n = 9) (3 mm [K(+)](o)). CONCLUSIONS: Hypokalaemic mouse hearts recapitulate the clinical arrhythmogenic phenotype, demonstrating EADs and triggered beats that might initiate VT on the one hand and reduced transmural dispersion of repolarization reflected in ΔAPD(90) suggesting arrhythmogenic substrate on the other

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Problemy geodezyjnej obsługi budowy przęsła mostu wznoszonego w technologii nawisowej

W artykule przedstawiono analizę metod realizacji zadań geodezyjnych w ramach obsługi budowy przęsła obiektu mostowego wznoszonego w technologii nawisowej. W przypadku budowy obiektu w tej technologii konieczna jest m.in. skomplikowana geodezyjna koordynacja montażu wózka rusztowaniowego oraz deskowania kolejnych segmentów przęsła. Podstawę opracowania stanowiły pomiary geodezyjne wykonywane w trakcie budowy mostu przez Wisłokę w miejscowości Łabuzie, prowadzonej w ramach modernizacji drogi krajowej nr 4 na odcinku Machowa – Łańcut.This article presents an analysis of surveying methods employed during the construction of a bridge span erected using the cantilever method. With this specific technique used for construction of a structure, a complex geodetic coordination of scaffolding trolley and formwork assembly for consecutive segments of the span is required. This work was prepared based on the surveys conducted during the construction of a bridge across the Wisłoka river in Łabuzie, implemented as part of the modernization of the national road No. 4 between Machowa and Łańcut

Consumer preferences and behaviors in the natural cosmetics market

Głównym celem pracy było zbadanie preferencji i zachowań na rynku kosmetyków naturalnych oraz wskazanie, jak te zachowania i preferencje zmieniły się na przestrzeni dwóch lat. Drugim celem było zidentyfikowanie przyczyn braku zainteresowania zakupem tego produktu wśród osób, które nie kupują kosmetyków naturalnych. Dodatkowym celem była identyfikacja marek kosmetyków naturalnych znanych respondentom. Badanie przeprowadzono metodą CAWI, w ankiecie wzięło udział 299 respondentów, w tym 91,5% to użytkownicy kosmetyków naturalnych. Sformułowano pięć hipotez, spośród których część została potwierdzona, część odrzucona. Bazując na wynikach, stwierdzono m.in., że główne motywy zakupu kosmetyków naturalnych (skład i zdrowie) nie uległy zmianie, a Internet jest nadal głównym miejscem ich zakupu. Grono konsumentów tego produktu powiększyło się – wciąż są to młode kobiety, ale już nie tylko z dużych miast. Nie potwierdzono jednak, że użytkownicy kosmetyków naturalnych charakteryzują się wysokim poziomem wiedzy na temat tych produktów. Brak wiedzy był również barierą najczęściej wskazywaną przez osoby, które nie kupują kosmetyków naturalnych

Problemy związane z kwalifikacją wybranych budowli przemysłowych w aspekcie naliczania podatku od nieruchomości

W artykule przedstawiono kryteria kwalifikacji wybranych budowlanych obiektów przemysłowych – magazynów, zbiorników, zasobników, fundamentów oraz konstrukcji wsporczych – pod kątem naliczania podatku od nieruchomości. Zagadnienie to jest szczególnie skomplikowane ze względu na liczbę i zróżnicowanie pod względem konstrukcyjnym i funkcjonalnym wymienionych obiektów, znajdujących się w dużych zakładach przemysłowych. Kwalifikacja składników majątku związanych z prowadzeniem działalności gospodarczej do kategorii „budowle”, w rozumieniu przepisów ustawy Prawo budowlane, skutkuje ich opodatkowaniem podatkiem od nieruchomości. Wyspecyfikowane na podstawie przyjętych kryteriów kategorie obiektów zostały zilustrowane przykładami z dużych zakładów przemysłowych.This article presents a criteria for qualifying selected industrial structures: warehouses, storage tanks, reservoirs, foundations and supporting structures, in terms of charging property tax. This issue is particularly complicated due to the number of the above-mentioned structures located at large industrial plants, as well as because of their diversification in terms of structure and function. Qualifying assets used for running a business activity to the category “structures”, within the meaning of the Construction Law, results in them being subject to property tax. The categories of objects, specified on the basis of the adopted criteria, have been illustrated with examples from large industrial plants

Selected methods of data mining and machine learning in risk analysis for developments located in mining areas

W referacie przedstawiono metodykę oraz wyniki badań wpływu oddziaływań eksploatacji górniczej na zabudowę powierzchni, które zostały przeprowadzone w ostatnich latach w Katedrze Geodezji Inżynieryjnej i Budownictwa AGH. Obejmowały one modelowanie przebiegu zużycia technicznego budynków metodami uczenia maszynowego oraz analizę zakresu i intensywności ich uszkodzeń z zastosowaniem metod eksploracji danych. Uzyskane wyniki potwierdzają przydatność zastosowanych metod do rozwiązywania zagadnień związanych z budownictwem na terenach górniczych.This paper presents the methodology and results of the studies on the influence of mining impacts on developments located in mining areas, which have been performed in recent years at the Department of Engineering Surveying and Civil Engineering of AGH University of Science and Technology. The studies included modeling the course of technical wear of buildings, by the methods of machine learning, as well as the analysis of the scope and intensity of their damage with the methods of data mining. The obtained results confirm the usefulness of the methods to solve the issues related to construction in mining areas