Short and long-arm fiberglass cast immobilization for displaced distal forearm fractures in children: a randomized controlled trial

PURPOSE The aim of this study was to investigate whether short-arm fiberglass cast (SAC) immobilization provides fracture stabilization comparable to that of long-arm cast (LAC) treatment of displaced distal forearm fractures after closed reduction in paediatric patients. METHODS A prospective, randomized, controlled trial of children aged four to 16 years (mean 9.9 years) was designed with a sample of 120 children, whose size was set a priori, with 60 treated with SAC and 60 with LAC. The primary outcome was fracture stability and rate of loss of reduction. The secondary outcome analysis evaluated duration of analgesic therapy, restriction in activities of daily life, and the duration until patients regained normal range of motion in the elbow. RESULTS No statistically significant differences were found between the two groups in loss of reduction or duration of analgesic therapy. In contrast, the duration until normal range of motion in the elbow was regained was significantly longer in the LAC group (median 4.5 days, P < 0.001). Restriction in activities of daily life did not differ significantly between the two groups except for the item "help needed with showering in the first days after trauma" (SAC 60%, LAC 87%, P = 0.001). CONCLUSION Fracture immobilization with short-arm fiberglass cast in reduced distal forearm fractures is not inferior to long-arm casts in children four years and older, excluding completely displaced fractures. Furthermore, short-arm casting reduces the need for assistance during showering. TRIAL REGISTRATION NCT03297047, September 29, 2017

Rgg Regulates Growth Phase-Dependent Expression of Proteins Associated with Secondary Metabolism and Stress in Streptococcus pyogenes

The transcriptional regulatory protein Rgg coordinates amino acid catabolism and virulence factor expression in Streptococcus pyogenes. We used a proteomic approach to compare cytoplasmic proteins isolated from S. pyogenes wild-type strain NZ131 (serotype M49) to proteins isolated from an rgg mutant strain during the exponential and stationary phases of growth. Proteins were separated by two-dimensional gel electrophoresis, and 125 protein spots of interest were identified by tandem mass spectrometry. Comparative analysis of proteins isolated from the isogenic strains revealed that growth phase-associated regulation of enzymes involved in the metabolism of arginine (ArcABC), histidine (HutI), and serine (SdhA) was abrogated in the rgg mutant strain, which synthesized the proteins in the exponential phase of growth. In contrast, the enzymes were detected only among wild-type proteins isolated from organisms in the stationary phase of growth. The differences in protein composition were correlated with previously described metabolic changes. In addition, proteins associated with thermal and oxidative stress responses, including ClpE and ClpL, were present in samples isolated from the rgg mutant strain but not in samples isolated from the wild-type strain. The rgg mutant strain was more tolerant to elevated temperature and puromycin than the wild-type strain; however, the mutant was less tolerant to paraquat. We concluded that Rgg is a global regulatory factor that contributes to growth phase-dependent synthesis of proteins associated with secondary metabolism and oxidative and thermal stress responses

The cost and cost-effectiveness of gender-responsive interventions for HIV: a systematic review.

INTRODUCTION: Harmful gender norms and inequalities, including gender-based violence, are important structural barriers to effective HIV programming. We assess current evidence on what forms of gender-responsive intervention may enhance the effectiveness of basic HIV programmes and be cost-effective. METHODS: Effective intervention models were identified from an existing evidence review ("what works for women"). Based on this, we conducted a systematic review of published and grey literature on the costs and cost-effectiveness of each intervention identified. Where possible, we compared incremental costs and effects. RESULTS: Our effectiveness search identified 36 publications, reporting on the effectiveness of 22 HIV interventions with a gender focus. Of these, 11 types of interventions had a corresponding/comparable costing or cost-effectiveness study. The findings suggest that couple counselling for the prevention of vertical transmission; gender empowerment, community mobilization, and female condom promotion for female sex workers; expanded female condom distribution for the general population; and post-exposure HIV prophylaxis for rape survivors are cost-effective HIV interventions. Cash transfers for schoolgirls and school support for orphan girls may also be cost-effective in generalized epidemic settings. CONCLUSIONS: There has been limited research to assess the cost-effectiveness of interventions that seek to address women's needs and transform harmful gender norms. Our review identified several promising, cost-effective interventions that merit consideration as critical enablers in HIV investment approaches, as well as highlight that broader gender and development interventions can have positive HIV impacts. By no means an exhaustive package, these represent a first set of interventions to be included in the investment framework

Isolation of 8 ß -hydroxy-goyazensanolide from Eremanthus argenteus and the complete and unequivocal 1H and 13C NMR data assignment for this sesquiterpene lactone

This work describes the first isolation of 8 ß-hydroxy-goyazensanolide from Eremanthus argenteus and the complete and unequivocal 1H and 13C NMR assignments for this compound. The assignments were carried out in the means of spectroscopic data from 1H NMR, 13C{1H} NMR, gCOSY, gHMQC, gHMBC and J-resolved experiments. All hydrogen homonuclear coupling constants were measured, and all hydrogen signals multiplicities were clarified. This is the first report of 13C NMR data for this sesquiterpene lactone to our knowledge

Living kidney donors with HIV: experience and outcomes from a case series by the HOPE in Action Consortium.

BACKGROUND: Living kidney donation is possible for people living with HIV (PLWH) in the United States within research studies under the HIV Organ Policy Equity (HOPE) Act. There are concerns that donor nephrectomy may have an increased risk of end-stage renal disease (ESRD) in PLWH due to HIV-associated kidney disease and antiretroviral therapy (ART) nephrotoxicity. Here we report the first 3 cases of living kidney donors with HIV under the HOPE Act in the United States. METHODS: Within the HOPE in Action Multicenter Consortium, we conducted a prospective study of living kidney donors with HIV. Pre-donation, we estimated the 9-year cumulative incidence of ESRD, performed genetic testing of apolipoprotein L1 (APOL1), excluding individuals with high-risk variants, and performed pre-donation kidney biopsies (HOPE Act requirement). The primary endpoint was ≥grade 3 nephrectomy-related adverse events (AEs) in year one. Post-donation, we monitored glomerular filtration rate (measured by iohexol/Tc-99m DTPA [mGFR] or estimated with serum creatinine [eGFR]), HIV RNA, CD4 count, and ART. FINDINGS: There were three donors with two-four years of follow-up: a 35 year-old female, a 52 year-old male, and a 47 year-old male. Pre-donation 9-year estimated cumulative incidence of ESRD was 3.01, 8.01, and 7.76 per 10,000 persons, respectively. In two donors with APOL1 testing, no high-risk variants were detected. Biopsies from all three donors showed no kidney disease. Post-donation, two donors developed nephrectomy-related&nbsp;≥grade 3 AEs: a medically-managed ileus and a laparoscopically-repaired incisional hernia. GFR declined from 103 to 84&nbsp;mL/min/1.73&nbsp;m2&nbsp;at four years (mGFR) in donor 1, from 77 to 52&nbsp;mL/min/1.73&nbsp;m2&nbsp;at three years (eGFR) in donor 2, and from 65 to 39&nbsp;mL/min/1.73&nbsp;m2&nbsp;at two years (eGFR) in donor 3. HIV RNA remained &lt;20 copies/mL and CD4 count remained stable in all donors. INTERPRETATION: The first three living kidney donors with HIV under the HOPE Act in the United States have had promising outcomes at two-four years, providing proof-of-concept to support living donation from PLWH to recipients with HIV. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health

Rhabdomyosarcoma Associated with Core Myopathy/Malignant Hyperthermia: Combined Effect of Germline Variants in RYR1 and ASPSCR1 May Play a Role

Rhabdomyosarcomas have been described in association with thyroid disease, dermatomyositis, Duchenne muscular dystrophy, and in muscular dystrophy models but not in patients with ryanodine receptor-1 gene (RYR1) pathogenic variants. We described here an 18-year-old male who reported a cervical nodule. Magnetic resonance images revealed a mass in the ethmoidal sinus corresponding to rhabdomyosarcoma. As his father died from malignant hyperthermia (MH), an in vitro contracture test was conducted and was positive for MH susceptibility. Muscle histopathological analysis in the biopsy showed the presence of cores. Molecular analysis using NGS sequencing identified germline variants in the RYR1 and ASPSCR1 (alveolar soft part sarcoma) genes. This report expands the spectrum of diseases associated with rhabdomyosarcomas and a possible differential diagnosis of soft tissue tumors in patients with RYR1 variants.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)0012021_06180-

National Landscape of Human Immunodeficiency Virus-Positive Deceased Organ Donors in the United States.

BackgroundOrgan transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety.MethodsWe performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors.ResultsBetween March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL &lt;400 copies/mL. The median CD4 T-cell count (interquartile range) was 194/µL (77-331/µL), and the median CD4 T-cell percentage was 27.0% (16.8%-36.1%). Major HIV DRMs were detected in 42%, including nonnucleoside reverse-transcriptase inhibitors (33%), integrase strand transfer inhibitors (4%), and multiclass (13%). Serum ART was detected in 46% and matched ART by history.ConclusionThe use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor-based regimens is rare, which is reassuring regarding safety