Carbon-Sulfur Bond Cleavage in Methanesulfonate on Diorganotin Quinaldate Platform - Synthesis and Characterization of [(n-Bu2SnL)2SO4].

The synthesis of mixed ligand di-n-butyltin complexes, [(n-Bu2SnL1-3)2SO4], 2-4 (HL1-3=2-quinoline/ 1-isoquinoline/ 4-methoxy-2-quinoline carboxylic acid) has been realized by reacting n-Bu2Sn(OMe)OSO2Me, 1 a with the corresponding quinaldic acid under solvothermal conditions. The observed transformation of methane sulfonate to sulfate anion represents a rare example of C-S bond cleavage on the organotin scaffolds, n-Bu2Sn(L1-3)OSO2Me, which have been identified as en route intermediates by NMR and X-ray crystallography. Analogous reaction when extended with Me2Sn(OMe)OSO2Me, 1 b and HL2 yields [(Me2Sn)2(L2)3(OSO2Me)], 5 as partially disproportionated product of Me2Sn(L2)OSO2Me. The solid-state structures of 2-5 reveal variable modes of coordination of the ligands to afford molecular and polymeric motifs.

Factors associated with concerns about falling and activity restriction in older adults after hip fracture: a mixed-methods systematic review.

PURPOSE: To investigate factors contributing to concerns about falling and activity restriction in the community among older adults who had a hip fracture. METHODS: A mixed method systematic review with a convergent segregated approach. We searched Medline, Embase, PsycInfo, PEDRo, CINAHL and the Cochrane library. Results were synthesised narratively considering physical, psychological, environmental, care, and social factors and presented in tables. Critical appraisal was completed in duplicate. RESULTS: We included 19 studies (9 qualitative, 9 observational, 1 mixed methods) representing 1480 individuals and 23 factors related to concerns about falling and activity restriction. Physical factors included falls history, comorbidities, balance, strength, mobility and functionality. Psychological factors included anxiety and neuroticism scores, perceived confidence in/control over rehabilitation and abilities, and negative/positive affect about the orthopaedic trauma, pre-fracture abilities and future needs. Environmental factors included accessibility in the home, outdoors and with transport. Social and care factors related to the presence or absence of formal and informal networks, which reduced concerns and promoted activity by providing feedback, advice, encouragement, and practical support. CONCLUSION: These findings highlight that to improve concerns about falling and activity restriction after hip fracture, it is important to: improve physical and functional abilities; boost self-confidence; promote positive affect; involve relatives and carers; increase access to clinicians, and; enhance accessibility of the home, outdoors and transport. Most factors were reported on by a small number of studies of varying quality and require replication in future research.

Azithromycin for Bacterial Watery Diarrhea: A Reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) Trial Incorporating Molecular Diagnostics.

BACKGROUND: Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera. METHODS: AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2-23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies. RESULTS: Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, -11.6 [95% confidence interval {CI}, -15.6 to -7.6]) and possible bacterial etiology (RDpossible, -8.7 [95% CI, -13.0 to -4.4]) but not in other children (RDunlikely, -0.3% [95% CI, -2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, -3.1 [95% CI, -5.3 to -1.0]; RDpossible, -2.3 [95% CI, -4.5 to -.01]; RDunlikely, -0.6 [95% CI, -1.9 to .6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella. CONCLUSIONS: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment. CLINICAL TRIALS REGISTRATION: NCT03130114.

Prediction of gestational age using urinary metabolites in term and preterm pregnancies.

Assessment of gestational age (GA) is key to provide optimal care during pregnancy. However, its accurate determination remains challenging in low- and middle-income countries, where access to obstetric ultrasound is limited. Hence, there is an urgent need to develop clinical approaches that allow accurate and inexpensive estimations of GA. We investigated the ability of urinary metabolites to predict GA at time of collection in a diverse multi-site cohort of healthy and pathological pregnancies (n = 99) using a broad-spectrum liquid chromatography coupled with mass spectrometry (LC-MS) platform. Our approach detected a myriad of steroid hormones and their derivatives including estrogens, progesterones, corticosteroids, and androgens which were associated with pregnancy progression. We developed a restricted model that predicted GA with high accuracy using three metabolites (rho = 0.87, RMSE = 1.58 weeks) that was validated in an independent cohort (n = 20). The predictions were more robust in pregnancies that went to term in comparison to pregnancies that ended prematurely. Overall, we demonstrated the feasibility of implementing urine metabolomics analysis in large-scale multi-site studies and report a predictive model of GA with a potential clinical value.

Multiomics Characterization of Preterm Birth in Low- and Middle-Income Countries.

Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies. Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB. Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019. Exposures: Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites. Main Outcomes and Measures: The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation. Results: Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways. Conclusions and Relevance: This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB.

Lower-Dose Zinc for Childhood Diarrhea - A Randomized, Multicenter Trial.

BACKGROUND: The World Health Organization recommends 20 mg of zinc per day for 10 to 14 days for children with acute diarrhea; in previous trials, this dosage decreased diarrhea but increased vomiting. METHODS: We randomly assigned 4500 children in India and Tanzania who were 6 to 59 months of age and had acute diarrhea to receive 5 mg, 10 mg, or 20 mg of zinc sulfate for 14 days. The three primary outcomes were a diarrhea duration of more than 5 days and the number of stools (assessed in a noninferiority analysis) and the occurrence of vomiting (assessed in a superiority analysis) within 30 minutes after zinc administration. RESULTS: The percentage of children with diarrhea for more than 5 days was 6.5% in the 20-mg group, 7.7% in the 10-mg group, and 7.2% in the 5-mg group. The difference between the 20-mg and 10-mg groups was 1.2 percentage points (upper boundary of the 98.75% confidence interval [CI], 3.3), and that between the 20-mg and 5-mg groups was 0.7 percentage points (upper boundary of the 98.75% CI, 2.8), both of which were below the noninferiority margin of 4 percentage points. The mean number of diarrheal stools was 10.7 in the 20-mg group, 10.9 in the 10-mg group, and 10.8 in 5-mg group. The difference between the 20-mg and 10-mg groups was 0.3 stools (upper boundary of the 98.75% CI, 1.0), and that between the 20-mg and 5-mg groups was 0.1 stools (upper boundary of the 98.75% CI, 0.8), both of which were below the noninferiority margin (2 stools). Vomiting within 30 minutes after administration occurred in 19.3%, 15.6%, and 13.7% of the patients in the 20-mg, 10-mg, and 5-mg groups, respectively; the risk was significantly lower in the 10-mg group than in the 20-mg group (relative risk, 0.81; 97.5% CI, 0.67 to 0.96) and in the 5-mg group than in the 20-mg group (relative risk, 0.71; 97.5% CI, 0.59 to 0.86). Lower doses were also associated with less vomiting beyond 30 minutes after administration. CONCLUSIONS: Lower doses of zinc had noninferior efficacy for the treatment of diarrhea in children and were associated with less vomiting than the standard 20-mg dose. (Funded by the Bill and Melinda Gates Foundation; ZTDT ClinicalTrials.gov number, NCT03078842.).

The Prevalence of Chlamydia trachomatis and Three Other Non-Viral Sexually Transmitted Infections among Pregnant Women in Pemba Island Tanzania.

Efforts to map the burden of infections globally have shown a high prevalence of genital infections, including Chlamydia trachomatis, in sub-Saharan Africa. This retrospective study aimed to investigate the prevalence of selected non-viral genital infections among pregnant women in Pemba Island, Tanzania. Vaginal swabs were collected during pregnancy and stored in eNAT buffer. Detection of C. trachomatis, Neisseria gonorrheae, Trichomonas vaginalis, and Mycoplasma genitalium pathogens was performed by PCR using validated detection kits. Vaginal samples of 439 pregnant women between 16 and 48 years were tested. In fifty-five (12.5%) of them, at least one genital pathogen was detected. The most prevalent pathogen was T. vaginalis (7.1%), followed by C. trachomatis (4.6%) and M. genitalium (2.1%). None of the vaginal samples tested positive for N. gonorrheae. Consequently, among positive samples, 7.3% were for C. trachomatis and at least one other genital pathogen. This study provides insights on the burden of the four studied genital infections, and on the coinfections among pregnant women in Pemba Island, Tanzania. These results offer a starting point that can be useful to design further research in the field of maternal and child health in Pemba Island.

Detection of high-risk human papillomavirus (HPV) by the novel AmpFire isothermal HPV assay among pregnant women in Pemba Island, Tanzania.

INTRODUCTION: human papillomavirus (HPV) is the most common sexually transmitted virus in the world. Prevalence of infection differs, with highest rates reported in sub-Saharan African, including the country of Tanzania. In pregnancy, the hormonal changes and immune changes seem to facilitate HPV persistence, increasing the cancer risk and the risk of vertical transmission towards the placenta and the fetus. The burden of HPV infection is still high despite multiple screening and detection test available. The AmpFire® HPV assay is a novel nucleic acid isothermal amplification with real-time fluorescence detection assay that can test simultaneously 15 high-risk HPV. This nested cohort study aims to contribute evidence on the prevalence of HPV infection and persistence across two time points among pregnant women in Pemba island, Tanzania. METHODS: vaginal swabs that were previously collected during pregnancy were stored in eNAT buffer (n1=385 and n2=187) and were tested with AmpFire® screening assay, for simultaneous detection of the HPV 16, 18 and other high-risk HPV genotypes 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. RESULTS: the AmpFire® HPV assay detected an 11% and 6% high-risk HPV prevalence at the two time points among pregnant women in Pemba island, consecutively. For the 133 women whose samples were tested at both time points, the persistence rate of high-risk HPV was 64%. CONCLUSION: novel isothermal HPV assay, such as the AmpFire®, might be feasible to use in low-income regions.

Extracellular α-Galactosidase from Trichoderma sp. (WF-3): Optimization of Enzyme Production and Biochemical Characterization.

Trichoderma spp. have been reported earlier for their excellent capacity of secreting extracellular α-galactosidase. This communication focuses on the optimization of culture conditions for optimal production of enzyme and its characterization. The evaluation of the effects of different enzyme assay parameters such as stability, pH, temperature, substrate concentrations, and incubation time on enzyme activity has been made. The most suitable buffer for enzyme assay was found to be citrate phosphate buffer (50 mM, pH 6.0) for optimal enzyme activity. This enzyme was fairly stable at higher temperature as it exhibited 72% activity at 60°C. The enzyme when incubated at room temperature up to two hours did not show any significant loss in activity. It followed Michaelis-Menten curve and showed direct relationship with varying substrate concentrations. Higher substrate concentration was not inhibitory to enzyme activity. The apparent Michaelis-Menten constant (K m ), maximum rate of reaction (V max), K cat, and catalytic efficiency values for this enzyme were calculated from the Lineweaver-Burk double reciprocal plot and were found to be 0.5 mM, 10 mM/s, 1.30 U mg(-1), and 2.33 U mg(-1) mM(-1), respectively. This information would be helpful in understanding the biophysical and biochemical characteristics of extracellular α-galactosidase from other microbial sources.

A novel promising strain of Trichoderma evansii (WF-3) for extracellular α-galactosidase production by utilizing different carbon sources under optimized culture conditions.

A potential fungal strain of Trichoderma sp. (WF-3) was isolated and selected for the production of α-galactosidase. Optimum conditions for mycelial growth and enzyme induction were determined. Basal media selected for the growth of fungal isolate containing different carbon sources like guar gum (GG), soya bean meal (SM), and wheat straw (WS) and combinations of these carbon substrates with basic sugars like galactose and sucrose were used to monitor their effects on α-galactosidase production. The results of this study indicated that galactose and sucrose enhanced the enzyme activity in guar gum (GG) and wheat straw (WS). Maximum α-galactosidase production (213.63 U mL(-1)) was obtained when the basic medium containing GG is supplemented with galactose (5 mg/mL). However, the presence of galactose and sucrose alone in the growth media shows no effect. Soya meal alone was able to support T. evansii to produce maximum enzyme activity (170.36 U mL(-1)). The incubation time, temperature, and pH for the maximum enzyme synthesis were found to be 120 h (5 days), 28°C, and 4.5-5.5, respectively. All the carbon sources tested exhibited maximum enzyme production at 10 mg/mL concentration. Among the metal ions tested, Hg was found to be the strongest inhibitor of the enzyme. Among the chelators, EDTA acted as stronger inhibitor than succinic acid.

Isolation and characterization of some phytochemicals from Indian traditional plants.

The present study was designed to evaluate relative contribution of different polyphenols (total phenolics, flavonoids, flavonols) and their antioxidants activities in aqueous extracts of different parts of some plants; Argemone mexicana, Datura metel, Calotropis procera, Thevetia peruviana, and Cannabis sativa. The antioxidants (total phenolics, flavonoids, flavones) were determined by chemical methods. The antioxidant capacities of these extracts were evaluated by FRAP assay. The results demonstrated that phenolic content was maximally present in leaves of T. peruviana. This plant exhibited minimum phenolic content in its flower as compared to other plants. The flower of D. metel contained maximum phenolic content. The flavonoids were present in highest quantity in leaves of C. procera while T. peruviana flowers showed maximum flavonoid content. The fruits of C. sativa contained maximum quantity of flavonoid as compared to other plants tested. The flower extract of C. sativa possessed highest FRAP value followed by A. mexicana and fruit of C. procera. The values of ratios of different polyphenolic compounds present in plant extracts indicated that flower of D. metel contained maximum total flavonoids and minimum phenolics. These results suggested that levels of total phenolics, flavonoids and their FRAP indices exhibited specificity to different plants and their parts.