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Objective: To determine the quality of life (QOL) of fistula patients in Bangladesh who have undergone ileal conduit (IC) urinary diversion operations, and to assess whether the risks and ethical challenges involved, outweigh the reality of leaving a woman with urinary incontinence for the rest of her life., Design: Observational study., Setting: LAMB Hospital, Bangladesh., Population: Seventeen women who had undergone IC between February 2012 and March 2016: 14 women previously had irreparable obstetric fistulas and three had bladder exstrophy., Methods: Demographic, obstetric, IC-related, stigma and discrimination information were collected by questionnaire. Univariate analysis was done using the two-sided t-test for comparison of differences before and after IC surgery., Main Outcome Methods: Change in stigma and discrimination scores. Health-related QOL assessed using the 36-item Short Form Health Survey., Results: Of the 17 women, 14 (82.3%) felt they were cured of their fistula disease. Three complained of occasional leakage due to insufficient seal of the bag, mainly at night, and all but one experienced no limits to their daily activities. Stigma and discrimination scores were significantly lower after having the IC surgery. The mean difference from when the woman had a fistula to when she had an IC for stigma score was 3.17 (1.12-4.16, P < 0.001), and for discrimination score was 3 (1.9-4.1, P < 0.001)., Conclusion: Overall, there has been improved QOL following IC among the women in this study and all would recommend IC to women in the same situation. They remain chronic patients with some physical symptoms, but are well re-integrated back into their communities., Tweetable Abstract: Improved QOL following ileal conduit in women with persistent fistula related disorder in Bangladesh., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Background: Prior studies have shown that using uterotonics to augment or induce labor before arrival at comprehensive Emergency Obstetric and Neonatal Care (CEmONC) settings (henceforth, "outside uterotonics") may contribute to perinatal mortality in low- and middle-income countries. We estimate its effect on perinatal mortality in rural Bangladesh., Methods: Using hospital records (23986 singleton term births, Jan 1, 2009-Dec 31, 2015) from rural Bangladesh, we use a logistic regression model to estimate the increased risk of perinatal death from uterotonics administered outside a CEmONC facility., Results: Among term births (≥37 weeks gestation), the risk of perinatal death adjusted for key confounders is significantly increased among women reporting uterotonic use outside of CEmONC (OR = 3 · 0, 95 % CI = 2 · 4,3 · 7). This increased risk is particularly high for fresh stillbirths (OR = 4 · 0, 95 % CI = 3 · 0,5 · 3) and intrapartum-related causes of early neonatal deaths (birth asphyxia) (OR = 3 · 1, 95 % CI = 2 · 2,4 · 5)., Conclusions: In this sample, outside uterotonic use was associated with substantially increased risk of fresh stillbirths, deaths due to birth asphyxia, and all perinatal deaths. In settings of high uterotonic use outside of controlled settings, substantial improvement in both stillbirth and early neonatal mortality may be made by reducing such use.

Background: Maternal undernutrition and newborn stunting [birth length-for-age z score (LAZ) <-2] are common in Bangladesh., Objective: The objective was to evaluate the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PLs) on birth outcomes., Design: We conducted a cluster-randomized effectiveness trial (the Rang-Din Nutrition Study) within a community health program in rural Bangladesh. We enrolled 4011 pregnant women at ≤20 gestational weeks; 48 clusters received iron and folic acid (IFA; 60 mg Fe + 400 μg folic acid) and 16 clusters received LNS-PLs (20 g/d, 118 kcal) containing essential fatty acids and 22 vitamins and minerals. Both of the supplements were intended for daily consumption until delivery. Primary outcomes were birth weight and length., Results: Infants in the LNS-PL group had higher birth weights (2629 ± 408 compared with 2588 ± 413 g; P = 0.007), weight-for-age z scores (-1.48 ± 1.01 compared with -1.59 ± 1.02; P = 0.006), head-circumference-for-age z scores (HCZs; -1.26 ± 1.08 compared with -1.34 ± 1.12; P = 0.028), and body mass index z scores (-1.57 ± 1.05 compared with -1.66 ± 1.03; P = 0.005) than those in the IFA group; in adjusted models, the differences in length (47.6 ± 0.07 compared with 47.4 ± 0.04 cm; P = 0.043) and LAZ (-1.15 ± 0.04 compared with -1.24 ± 0.02; P = 0.035) were also significant. LNS-PLs reduced the risk of newborn stunting (18.7% compared with 22.6%; RR: 0.83; 95% CI: 0.71, 0.97) and small head size (HCZ <-2) (20.7% compared with 24.9%; RR: 0.85; 95% CI: 0.73, 0.98). The effects of LNS-PL on newborn stunting were greatest in infants born before a 10-wk interruption in LNS-PL distribution (n = 1301; 15.7% compared with 23.6%; adjusted RR: 0.69; 95% CI: 0.53, 0.89) and in infants born to women ≤24 y of age or with household food insecurity., Conclusion: Prenatal lipid-based nutrient supplements can improve birth outcomes in Bangladeshi women, especially those at higher risk of fetal growth restriction. This trial was registered at clinicaltrials.gov as NCT01715038., (© 2016 American Society for Nutrition.)

Eighteen novel bicyclic 1-substituted benzyl octahydro- and tetrahydroisoquinolines were synthesized and evaluated for human thromboxane A(2)/prostaglandin H(2) (TP) receptor affinity and antagonism of TP receptor-mediated platelet aggregation. In both cases, potency depended more on the presence of methoxy groups on the 1-benzyl moiety than on nitrogen substitution or extent of oxidation of the isoquinoline ring system. The most potent of the bicyclic compounds retained the 5,8-ethanooctahydroisoquinoline ring structure of the parent molecule (1) and required the 3,4,5-trimethoxybenzyl substitution pattern found in the well-characterized tetrahydroisoquinoline antiplatelet agent trimetoquinol. Differences in nitrogen substituent SAR were noted between the mono-methoxylated compounds and the 3,4,5-trimethoxybenzyl derivatives.

Bacterial peptidoglycan is composed of a network of beta-[1,4]-linked glyan strands that are cross-linked through pendant peptide chains. The final product, the murein sacculus, is a single, covalently closed macromolecule that precisely defines the size and shape of the bacterial cell. The recent increase in bacterial resistance to cell wall active agents has led to a resurgence of activity directed toward improving our understanding of the resistance mechanisms at the molecular level. The biosynthetic enzymes and their natural substrates can be invaluable tools in this endeavor. While modern experimental techniques have led to isolation and purification of the biosynthetic enzymes utilized in peptidoglycan biosynthesis, securing useful quantities of their requisite substrates from natural substrates has remained problematic. In an effort to address this issue, we report the first total synthesis of lipid II (4), the final monomeric intermediate utilized by Gram positive bacteria for peptidoglycan biosynthesis.

[reaction: see text]. A synthesis of stereochemically pure and orthogonally protected N-acetyl-(2-deoxy-2-aminoglucopyranosyl)-beta-[1,4]-N-acetylmuramyl (NAG-NAM) monopeptide (2), the glycopeptide core of lipid II and of the bacterial cell wall repeating unit, is reported.

In our study of IOP-lowering agents, we have synthesized several bicyclic analogs of 1-benzyloctahydroisoquinoline. The target molecules were synthesized in an eleven-step process. Structures were proved through spectrometry, elemental analysis and, in selected cases, high resolution mass spectrometry. The final products were secondary or tertiary amines containing a 1-benzyl moiety substituted at the p-position with a methoxy, methyl or chloro group. All target molecules were analyzed in 1% solution in distilled water in normotensive rabbits. After topical administration, IOP was monitored in both eyes for up to seven hours. The 1-p-methoxybenzyl molecule 2 was the most active, and caused a maximal IOP drop of 8.8 +/- 1.9 (n = 7) mm Hg in the ipsilateral eye at 4 hours post-administration, with only partial recovery at seven hours. All other compounds tested either showed very weak activity (3-6) or were inactive (1). All compounds produced a contralateral effect, and 5 induced rebound ocular hypertension. We conclude that selected tertiary bicyclic 1-p-methoxybenzyl-octahydroisoquinolines, particularly N-methylated structures, exhibit a significant IOP-lowering effect in normotensive rabbits.

We have synthesized a number of novel bicyclic hexahydroaporphines containing a phenethylamine moiety for preliminary study as intraocular pressure lowering agents. The target molecules were synthesized in a twelve step process. The final products were secondary or tertiary amines containing either an aromatic methoxy or phenolic substituent. These molecules, in hydrochloride salt form, were assayed in doses ranging from 0.1-1.5%. All products and vehicle were administered topically to one eye of normotensive rabbits and intraocular pressure was measured in both eyes for up to six hours. Four of the five compounds examined produced a significant and, in some cases, prolonged, ocular hypotensive response. Secondary and N-methylated tertiary amines were equally effective, as were compounds containing either the 10-methoxy group of free phenol. Studies are currently in progress to optimize potency and identify functional and molecular mechanisms of action.