In vitro metabolism of carotenoids, ß carotene and lutein into retinoids in amphibians

Carotenoids are a family of over 600 natural lipid-soluble pigments that are produced within microalgae, phytoplankton, and higher plants. Of these only 50 have provitamin A activity, with the capacity to be transformed into retinol and dehydroretinol. Animals are unable to synthesise carotenoids de novo. As animals lack the ability to synthesize vitamin A, they are dependent on   dietary intake to provide adequate levels of vitamin A. Vitamin A (retinol) and its naturally occurring and synthetic derivatives are collectively referred to as retinoids. Retinoids are important metabolites of carotenoids that have at least one non-hydroxylated ring system of the β-type, e.g. carotenes (β-carotene, α-carotene, and γ-carotene) and xanthophyls (β-cryptoxanthin and echinenone).  The pigmentation and colouration in amphibian occur owing to the deposition of carotenoids from their metabolism by consuming the carotenoids through foods from their habitat or through conversion of these carotenoids into different metabolites during development. The status of the retinoids formed through conversion of carotenoids was examined from the lipid extracts of the carotenoid administered tadpoles of Duttaphrynus melanostictus and Haplobactrachus tigerinus. The extracts were subjected to UV –VIS spectrophotometer for tentative analysis of the retinoids formed and then by the HPLC procedures for final results. The findings show that larval forms of amphibians of both the species Duttaphrynus melanostictus and Haplobactrachus tigerinus can convert β–carotene to retinol and lutein to dehydroretinol. The conversion of carotenoids into different retinoids is explained through the mode of cleavage of the carotenoids molecules

Fingernails - foreign objects in root canal: a case report

Foreign objects in the pulp chamber or root canal are not unusual findings in patients undergoing root canal treatments in which canals have been left open for drainage. Detailed case history, clinical and radiographic examinations are necessary to come to a conclusion about the nature, size, location of the foreign body and difficulty involved in its retrieval. This kind of situation is more likely to occur in children due to their habit of placing foreign objects in the mouth. The foreign objects may act as a potential source of infection and may later lead to a painful condition. Reported here is an unusual case of metallic pin along with multiple nail pieces retrieved from root canal of a patient with nail biting habit

Intersectoral (in)activity: Towards an understanding of public sector department links between water, sanitation and hygiene (WASH) and childhood undernutrition in South Africa

Associations between different forms of malnutrition and environmental conditions, including water, sanitation and hygiene (WASH), contribute to poor child health, nutritional status and physical growth. The primary responsibility for the provision of water and sanitation, as a basic service and human right, lies with the State, as such, a number of stakeholders are involved. Despite relatively high levels of WASH infrastructure coverage in South Africa, enteric infections and stunting remain high for a middle-income country. The aim of this study is to elucidate the landscape of WASH in South Africa in relation to nutritional status of children under the age of 5 years in the South African, Gauteng and City of Johannesburg contexts. The authors detailed the national and provincial public sector departments and through purposive sampling proceeded to map the various departments and associated policies that are responsible for the provision of WASH facilities, as well the nutritional status of children

Enhanced Synthetic Access to Tris-CF₃-Substituted Corroles

Separate focus on the oligomerization and oxidative cyclization steps required for the synthesis of 5,10,15-tris(trifluoromethyl)corrole revealed [bis(trifluoroacetoxy)iodo]benzene (PIFA) as a superior alternative oxidant. Under optimized conditions, the pure free-base corrole was obtained with a 6-fold increase in chemical yield and an 11-fold rise in isolated material per synthesis. The corresponding gallium(III) and manganese(III) complexes were isolated by adding the appropriate metal salt prior to corrole purification

Growth attributes of malt barley (Hordeum vulgare) as influenced by fertility levels and liquid biofertilizers

The experiments were conducted during winter (rabi) seasons of 2020–21 and 2021–22 at Rajasthan College of Agriculture, Maharana Pratap University of Agriculture and Technology, Udaipur, Rajasthan to study the effect of fertility levels and biofertilizers on malt barley (Hordeum vulgare L.). Factorial randomized block design (F-RBD) was used comprising 15 treatment combinations involved 3 fertility levels, viz. 50 N + 25 P2O5 + 15 K2O kg/ha; 60 N + 30 P2O5 + 20 K2O kg/ha; and 70 N + 40 P2O5 + 25 K2O kg/ha; alongside 5 liquid biofertilizers, viz. control; Azotobacter; Phosphorous solubilizing bacteria; Potassium mobilizing bacteria; and Azotobacter + Phosphorous solubilizing bacteria + Potassium mobilizing bacteria. The findings indicate that applying a fertilizer combination of 70 N + 40 P2O5 + 25 K2O kg/ha to malt barley crop significantly enhanced plant height at harvest (118.74 cm), dry- matter accumulation/m row at harvest (356.88 g), leaf area index (LAI) at 50 DAS (days after sowing) (1.69) and 75 DAS (2.87), number of total tillers (89.97) and growth efficiency values, substantially greater than other fertility levels. The findings demonstrated that inoculating seeds with a combination of liquid biofertilizers containing Azotobacter + Phosphorous solubilizing bacteria + Potassium mobilizing bacteria significantly improved growth parameters, viz. plant height at harvest (117.55 cm), dry-matter accumulation/m row at harvest (371.25 g), LAI at 50 DAS (1.68) and 75 DAS (2.96), number of total tillers (90.08) and growth efficiency values

Genome-wide evolutionary dynamics of influenza B viruses on a global scale

The global-scale epidemiology and genome-wide evolutionary dynamics of influenza B remain poorly understood compared with influenza A viruses. We compiled a spatio-temporally comprehensive dataset of influenza B viruses, comprising over 2,500 genomes sampled worldwide between 1987 and 2015, including 382 newly-sequenced genomes that fill substantial gaps in previous molecular surveillance studies. Our contributed data increase the number of available influenza B virus genomes in Europe, Africa and Central Asia, improving the global context to study influenza B viruses. We reveal Yamagata-lineage diversity results from co-circulation of two antigenically-distinct groups that also segregate genetically across the entire genome, without evidence of intra-lineage reassortment. In contrast, Victoria-lineage diversity stems from geographic segregation of different genetic clades, with variability in the degree of geographic spread among clades. Differences between the lineages are reflected in their antigenic dynamics, as Yamagata-lineage viruses show alternating dominance between antigenic groups, while Victoria-lineage viruses show antigenic drift of a single lineage. Structural mapping of amino acid substitutions on trunk branches of influenza B gene phylogenies further supports these antigenic differences and highlights two potential mechanisms of adaptation for polymerase activity. Our study provides new insights into the epidemiological and molecular processes shaping influenza B virus evolution globally

Human protein reference database—2006 update

Human Protein Reference Database (HPRD) () was developed to serve as a comprehensive collection of protein features, post-translational modifications (PTMs) and protein–protein interactions. Since the original report, this database has increased to >20 000 proteins entries and has become the largest database for literature-derived protein–protein interactions (>30 000) and PTMs (>8000) for human proteins. We have also introduced several new features in HPRD including: (i) protein isoforms, (ii) enhanced search options, (iii) linking of pathway annotations and (iv) integration of a novel browser, GenProt Viewer (), developed by us that allows integration of genomic and proteomic information. With the continued support and active participation by the biomedical community, we expect HPRD to become a unique source of curated information for the human proteome and spur biomedical discoveries based on integration of genomic, transcriptomic and proteomic data

Gabapentin for chronic pelvic pain in women (GaPP2):a multicentre, randomised, double-blind, placebo-controlled trial

BackgroundChronic pelvic pain affects 2–24% of women worldwide and evidence for medical treatments is scarce. Gabapentin is effective in treating some chronic pain conditions. We aimed to measure the efficacy and safety of gabapentin in women with chronic pelvic pain and no obvious pelvic pathology.MethodsWe performed a multicentre, randomised, double-blind, placebo-controlled randomised trial in 39 UK hospital centres. Eligible participants were women with chronic pelvic pain (with or without dysmenorrhoea or dyspareunia) of at least 3 months duration. Inclusion criteria were 18–50 years of age, use or willingness to use contraception to avoid pregnancy, and no obvious pelvic pathology at laparoscopy, which must have taken place at least 2 weeks before consent but less than 36 months previously. Participants were randomly assigned in a 1:1 ratio to receive gabapentin (titrated to a maximum dose of 2700 mg daily) or matching placebo for 16 weeks. The online randomisation system minimised allocations by presence or absence of dysmenorrhoea, psychological distress, current use of hormonal contraceptives, and hospital centre. The appearance, route, and administration of the assigned intervention were identical in both groups. Patients, clinicians, and research staff were unaware of the trial group assignments throughout the trial. Participants were unmasked once they had provided all outcome data at week 16–17, or sooner if a serious adverse event requiring knowledge of the study drug occurred. The dual primary outcome measures were worst and average pain scores assessed separately on a numerical rating scale in weeks 13–16 after randomisation, in the intention-to-treat population. Self-reported adverse events were assessed according to intention-to-treat principles. This trial is registered with the ISRCTN registry, ISCRTN77451762.FindingsParticipants were screened between Nov 30, 2015, and March 6, 2019, and 306 were randomly assigned (153 to gabapentin and 153 to placebo). There were no significant between-group differences in both worst and average numerical rating scale (NRS) pain scores at 13–16 weeks after randomisation. The mean worst NRS pain score was 7·1 (standard deviation [SD] 2·6) in the gabapentin group and 7·4 (SD 2·2) in the placebo group. Mean change from baseline was −1·4 (SD 2·3) in the gabapentin group and −1·2 (SD 2·1) in the placebo group (adjusted mean difference −0·20 [97·5% CI −0·81 to 0·42]; p=0·47). The mean average NRS pain score was 4·3 (SD 2·3) in the gabapentin group and 4·5 (SD 2·2) in the placebo group. Mean change from baseline was −1·1 (SD 2·0) in the gabapentin group and −0·9 (SD 1·8) in the placebo group (adjusted mean difference −0·18 [97·5% CI −0·71 to 0·35]; p=0·45). More women had a serious adverse event in the gabapentin group than in the placebo group (10 [7%] of 153 in the gabapentin group compared with 3 [2%] of 153 in the placebo group; p=0·04). Dizziness, drowsiness, and visual disturbances were more common in the gabapentin group.InterpretationThis study was adequately powered, but treatment with gabapentin did not result in significantly lower pain scores in women with chronic pelvic pain, and was associated with higher rates of side-effects than placebo. Given the increasing reports of abuse and evidence of potential harms associated with gabapentin use, it is important that clinicians consider alternative treatment options to off-label gabapentin for the management of chronic pelvic pain and no obvious pelvic pathology.FundingNational Institute for Health Research

International train the trainer neonatal antibiotic stewardship program for South African pharmacists

Hospital-acquired antimicrobial-resistant infections are a leading cause of neonatal mortality in South African (SA) neonatal intensive care units (NICU). There is an urgent need for NICU Antibiotic Stewardship Programs (ASP). We describe the development of an international Train-the-Trainer (TTT) NICU-ASP mentoring program for SA pharmacists. A partnership between the South Africa Antimicrobial Stewardship in 2019. A baseline assessment of four SA NICUs was done to guide the development of a TTT NICU-ASP mentoring of SA pharmacists utilizing the existing workforce. The program included bilateral site visits. Pre-post surveys were used to assess SA mentee's NICU experiences, barriers to clinical pharmacy services and confidence to train additional pharmacists in NICU ASP. Four mentees from private (n = 1) and public hospitals (n = 3) completed a 2-week TTT NICU-ASP in the US that included; education, patient care rounds, role-playing, peer-to-peer sessions and behavioral interventions followed by ongoing support and mentoring by SAASP mentors. None of the hospitals had pharmacists participating in daily patient care rounds or had multidisciplinary NICU-ASPs due to lack of NICU trained pharmacists and dedicated time for ASP. Post surveys showed improved confidence to train additional pharmacists in NICU-ASP. Subsequently, these SA mentees provided NICU-ASP education to over 700 health care professionals and trained six additional pharmacists in NICU-ASP. Mentors and mentees developed a comprehensive NICU ASP toolkit for ongoing training of additional pharmacists. A new research collaboration between TTT NICUASP mentors, mentees and physician members of the South Africa National Neonatal Sepsis Task Force has formed and the first national NICU-ASP study is underway in 12 hospitals. Shared leadership between U.S. and SA mentors led to developing a TTT NICU-ASP for pharmacists tailored to existing resources and local needs.Merck; Pfizer; Bill and Melinda Gates Foundation grant.http://wileyonlinelibrary.com/journal/jac5am2022Pharmacolog

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety