Insights into the structure-activity relationship of a type III secretion system inhibitor, aurodox.

Aurodox was originally isolated in 1972 as a linear polyketide compound exhibiting antibacterial activity against Gram-positive bacteria. We have since identified aurodox as a specific inhibitor of the bacterial type III secretion system (T3SS) using our original screening system for inhibition of T3SS-mediated hemolysis in enteropathogenic Escherichia coli (EPEC). In this research, we synthesized 15 derivatives of aurodox and evaluated EPEC T3SS inhibitory activity as well as antibacterial activity against EPEC. One of the derivatives was highly selective for T3SS inhibition, equivalent to that of aurodox, but without exhibiting antibacterial activity (69-fold selectivity). This work revealed the structure-activity relationship for the inhibition of T3SS by aurodox and suggests that the target of T3SS is distinct from the target for antibacterial activity.

Confluenine G, a new compound from a basidiomycetous yeast Moesziomyces sp. FKI-9540 derived from the gut of a moth Acherontia lachesis (Lepidoptera, Sphingidae).

Most natural products derived from microorganisms have been sought from actinomycetes and filamentous fungi. As an attempt to develop new microbial resources in the exploratory research for natural products, we searched for new compounds from unexploited microbial taxa presumed to have biosynthetic gene clusters. A new compound confluenine G (1) and a known compound (2Z)-2-octyl-2-pentenedioic acid (2) were isolated from a cultured broth of basidiomycetous yeast, Moesziomyces sp. FKI-9540, derived from the gut of a moth Acherontia lachesis (Lepidoptera, Sphingidae). Based on the results of HR-ESI-MS and NMR analyses, the planar structure of 1 was elucidated. Confluenine G (1) was a new analog of nitrogen-oxidized isoleucine and had rare substructures with oxime and hydroxamic acid in molecule.

Promoting and maintaining urinary continence: Follow-up from a cluster-randomized trial of elderly village women in Bangladesh.

AIMS: Pelvic floor and mobility exercises were shown to be effective in managing incontinence in a cluster-randomized trial (CRT) of village women aged 60 to 75 years in Bangladesh. The present analysis examines continence 12 months after the CRT and exercise program implementation with village paramedics as preceptors. METHODS: Women from nine villages in the exercise arm of the CRT were followed-up 12 months after the 6-month intervention. They provided information about exercise since the CRT and a 3-day continence record (3DCR). Posttrial, a further 6-month exercise intervention led by village paramedics was initiated in 20 villages. Women completed the two-item Sandvik severity questionnaire before and after the intervention. Paramedics kept a record of each woman's attendance at the 48 exercise sessions RESULTS: A total of 130 of 150 women from the CRT completed the 12-month follow-up; 61.5% were dry on the 3DCR at follow-up. Total continence was related to the continuation of exercises carried out in the home and absence of urinary tract infection at follow-up. Those exercising at follow-up had an odds ratio (OR) of 3.49 (95% confidence interval [CI], 1.86-6.58) of being continent at follow-up. Higher end-of-CRT body mass index was associated with greater follow-up leakage. In the 20-village roll-out, with 316 incontinent women, improvement in both severity and total continence on the Sandvik questionnaire were related to a total number of sessions attended (OR = 1.09; 95% CI, 1.05-1.13). At roll-out, 38.6% achieved continence, comparable to 43.0% in the CRT using physiotherapy preceptors CONCLUSIONS: Group exercise classes led by paramedics resulted in a marked improvement in continence but maintenance requires exercise postintervention.

The effect on income of providing near vision correction to workers in Bangladesh: The THRIVE (Tradespeople and Hand-workers Rural Initiative for a Vision-enhanced Economy) randomized controlled trial.

INTRODUCTION: Presbyopia, the leading cause of vision impairment globally, is common during working years. However, no trials have assessed presbyopia's impact on income. METHODS: In April 2017, we conducted a census among 59 Bangladesh villages to identify persons aged 35 to 65 years with presbyopia (presenting distance vision > = 6/12 bilaterally and correctable inability to see 6/13 at 40 cm with both eyes), who never had owned glasses. Participants were randomized (1:1) to receive immediate free reading glasses (intervention) or glasses delivered 8 months later (control). Visual demand of different jobs was stratified into three levels. Outcomes were between-group differences in the 8 month change in: self-reported monthly income (primary) and Near Vision Related Quality of Life (NVRQOL, secondary). RESULTS: Among 10,884 census participants, 3,655 (33.6%) met vision criteria and 863 (23.6%) comprised a sample enriched for near vision-intensive jobs, but 39 (4.52%) could not be reached. All participants allocated to intervention (n = 423, 51.3%) and control (n = 401, 48.7%) received the appropriate intervention, and follow-up was available for 93.4% and 96.8% respectively. Groups were similar at baseline in all characteristics: mean age was 47 years, 50% were male, 35% literate, and about half engaged in "most near vision-intensive" occupations. Glasses wear at 8-month follow-up was 88.3% and 7.81% in intervention and control respectively. At baseline, both the intervention and control groups had a self-reported median monthly income of US$35.3. At endline, the median income for the intervention group was US$47.1 compared with US$35.3 for control, a difference of 33.4%. Predictors of greater income increase in multivariate models included intervention group allocation (OR 1.45, 95% CI 1.12, 1.88, P = 0.005), male sex (OR 2.41, 95% CI 1.84, 3.16, P <0.001), and not engaging in income-producing work at baseline (OR 2.35, 95% CI 1.69, 3.26, P<0.001). CONCLUSION: Provision of reading glasses increases income in near vision-intensive occupations, and may facilitate return to work for those currently unemployed.

Source specific sedimentary response towards the differential anthropogenic impacts in terms of potentially toxic elements in an urban river.

To investigate the interplay between varying anthropogenic activities and sediment dynamics in an urban river (Turag, Bangladesh), this study involved 37-sediment samples from 11 different sections of the river. Neutron activation analysis and atomic absorption spectrometry were utilized to quantify the concentrations of 14 metal(oid)s (Al, Ti, Co, Fe, As, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Zn). This study revealed significant toxic metal trends, with Principal coordinate analysis explaining 62.91 % of the variance from upstream to downstream. The largest RSDs for Zn(287 %), Mn(120 %), and Cd(323 %) implies an irregular regional distribution throughout the river. The UNMIX-model and PMF-model were utilized to identify potential sources of metal(oid)s in sediments. ∼63.65-66.7 % of metal(oid)s in sediments originated from anthropogenic sources, while remaining attributed to natural sources in both models. Strikingly, all measured metal(oid)s' concentrations surpassed the threshold effect level, with Zn and Ni exceeding probable effect levels when compared to SQGs.

A Combination Strategy of Multidrug-Sensitive Budding Yeast and Chemical Modifications Enabling to Find a New Overlooked Antifungal Compound, Sakurafusariene, from In-House Fractionated Library.

In this report, we disclose our discovery of a new antifungal natural product, sakurafusariene (1), from an in-house fractionated library of the culture broth of Fusarium sp. FKI-7550 strain by using a combination strategy of multidrug-sensitive yeast and chemical modification. Throughout our investigation, we encountered challenges in the isolation of natural product 1. A chemical modification strategy via alkylation of 1 allowed for removal of the impurities enabling us to elucidate the structure of 1. Furthermore, we synthesized ester derivatives using a method inspired by the isolation study of 1, which gave us valuable information to understand a preliminary structure-activity relationship against Pyricularia oryzae growth inhibitory activity.

Re-evaluation and a Structure-Activity Relationship Study for the Selective Anti-anaerobic Bacterial Activity of Luminamicin toward Target Identification.

Luminamicin (1) isolated in 1985, is a macrodiolide compound exhibiting selective antibacterial activity against anaerobes. However, the antibacterial activity of 1 was not fully examined. In this research, re-evaluation of the antibacterial activity of 1 revealed that 1 is a narrow spectrum and potent antibiotic againstClostridioides difficile(C. difficile) and effective against fidaxomicin resistantC. difficilestrain. This prompted us to obtain luminamicin resistantC. difficilestrains for the determination of the molecular target of 1 inC. difficile. Sequence analysis of 1-resistantC. difficileindicated that the mode of action of 1 differs from that of fidaxomicin. This is because no mutation was observed in RNA polymerase and mutations were observed in a hypothetical protein and cell wall protein. Furthermore, we synthesized derivatives from 1 to study the structure-activity relationship. This research indicated that the maleic anhydride and the enol ether moieties seem to be pivotal functional groups to maintain the antibacterial activity againstC. difficileand the 14-membered lactone may contribute to taking an appropriate molecular conformation.

Rediscovery of Tetronomycin as a Broad-Spectrum and Potent Antibiotic against Drug-Resistant Gram-Positive Bacteria.

Tetronomycin (1), first isolated from a cultured broth of Streptomyces sp. by Juslen et al. in 1974, is a polycyclic polyether compound. However, the biological activity of 1 has not been thoroughly examined. In this study, we found that 1 exhibits more potent antibacterial activity than two well-known antibacterial drugs (vancomycin and linezolid) and is effective against several drug-resistant clinical isolates including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. Furthermore, we reassigned the 13C NMR spectra of 1 and performed a preliminary structure-activity relationship study of 1 to synthesize a chemical probe for target identification, which implied different targets based on its ionophore activity.

Heavy metals in popularly sold branded cigarettes in Bangladesh and associated health hazards from inhalation exposure.

Tobacco products are widely recognized as a major contributor to death. Cigarette smoke contains several toxic chemicals including heavy metals particulate causing high health risks. However, limited information has been available on the health risks associated with the heavy metals in cigarettes commonly sold in the Bangladeshi market. This study evaluated the concentrations and potential health risks posed by ten concerned heavy metals in ten widely consumed cigarette brands in Bangladesh using an atomic absorption spectrometer. The concentration (mg/kg) ranges of heavy metals Pb, Cd, Cr, As, Co, Ni, Mn, Fe, Cu, and Zn vary between 0.46-1.05, 0.55-1.03, 0.80-1.2, 0.22-0.40, 0.46-0.78, 2.59-3.03, 436.8-762.7, 115.8-184.4, 146.6-217.7, and 34.0-42.7, respectively. We assume that the heavy metals content among cigarette brands is varied due to the differences in the source of tobacco they use for cigarette preparation. The carcinogenic risks posed by heavy metals follow the order of Cr > Co > Cd > As > Ni > Pb, while the non-carcinogenic risks for Cu, Zn, Fe, and Mn were greater than unity (HQ > 1), except for Fe. The existence of toxic heavy metals in cigarette tobacco may thus introduce noticeable non-carcinogenic and carcinogenic health impacts accompanying inhalation exposure. This study provides the first comprehensive report so far on heavy metal concentration and associated health risks in branded cigarettes commonly sold in Bangladesh. Hence, this data and the information provided can serve as a baseline as well as a reference for future research and have potential implications for policy and legislation in Bangladesh.

Ketosis-Prone Type 2 Diabetes (Flatbush Diabetes) in Remission: A Report of Two Cases.

Diabetic ketoacidosis (DKA) is a triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration. It is a well-known manifestation of type 1 diabetes mellitus (T1DM). However, it can also be the first presentation of type 2 diabetes mellitus (T2DM). This subtype of diabetes shares the characteristics of both T1DM and T2DM and is called 'Flatbush diabetes,' also known as 'ketosis-prone T2DM.' This article highlights the importance of early identification of ketosis-prone T2DM (KPD). We describe two cases of African American men with no past medical histories who presented with unproved DKA as the first presentation of T2DM requiring initial intensive insulin therapy, which was gradually withdrawn with the addition of metformin. Both patients are currently insulin independent for more than 15 months. It is an essential clinical entity to recognize as insulin independence positively impacts the quality of life and decreases the economic burden on the health care system.

Fermentation optimization of cellulase production from sugarcane bagasse by Bacillus pseudomycoides and molecular modeling study of cellulase.

Degradation of cellulosic carbon, the most important natural carbon reservoirs on this planet by cellulase is very essential for valuable soluble sugars. This cellulase has potential biotechnological applications in many industrial sectors. Thus the demand of cellulase is increasing more frequently than ever. Agro industrial byproducts and suitable microbes are of an important source for the production of cellulase. Bacillus pseudomycoides and sugarcane bagasse were used for the production of cellulase and different process parameters influencing the production of cellulase were optimized here. The bacterium showed maximum cellulase production in the presence of sugarcane bagasse, peptone and magnesium sulfate at pH 7, 40 °C in 72 h of incubation. Primary structures of the cellulase is consists of 400 amino acid residues having molecular weight 44,790 Dalton and the theoretical PI is 9.11. Physiochemical properties of cellulase indicated that the protein has instability index 25.77. Seven hydrogen bonds were observed at multiple sites of the cellulase enzyme; His269, Asp237, Asn235, Tyr271, Ser272, Gln309, Asn233. This protein structure may play first hand in further development of exploring cellulase and cellulose interaction dynamics in Bacillus sp. Thus this bacterium may be useful in various industrial applications owing to its cellulase producing capability.

Patients with Clostridium difficile infection and prior appendectomy may be prone to worse outcomes.

BACKGROUND: Clostridium difficile infection (CDI) occurs due to a dysbiosis in the colon. The appendix is considered a 'safe house' for gut microbiota and may help repopulate gut flora of patients with CDI. AIM: To study the impact of prior appendectomy on the severity and outcomes of CDI. METHODS: We retrospectively reviewed data of 1580 patients with CDI, admitted to our hospital between 2008 to 2018. Patients were grouped based on the presence or absence of the appendix. The primary aim was to (1) assess all-cause mortality and (2) the severity of CDI. Severity was defined as per the Infectious Diseases Society of America criteria. Logistic regression, and propensity score analysis using inverse probability of treatment weights (IPTW) was performed. RESULTS: Of the 1580 patients, 12.5% had a history of appendectomy. There was no statistical difference in mortality between patients with a prior appendectomy or without (13.7% vs 14%, P = 0.877). However, a history of appendectomy affected the severity of CDI [odds ratio (OR) = 1.32, 95% confidence interval: 1.01-1.75]. On IPTW, this association remained significant (OR = 1.59, P < 0.05). On multivariable analysis of secondary outcomes, prior appendectomy was also associated with toxic megacolon (OR = 5.37, P < 0.05) and colectomy (OR = 2.77, P < 0.05). CONCLUSION: Prior appendectomy may affect the severity of CDI, development of toxic megacolon and the eventual need for colectomy. Since treatment of CDI is governed by its severity, stronger antibiotic regimens or earlier use of fecal microbiota transplant may be a viable option for patients with prior appendectomy.

Heavy metal contamination and ecological risk assessment in water and sediments of the Halda river, Bangladesh: A natural fish breeding ground.

This study reports the mass fractions of Al, Cr, Mn, Fe, Co, Zn, As, Ni, Cu, Cd, Hg, and Pb in water and sediments of the Halda river, Bangladesh, and studies the distribution, contamination, and potential ecological risks of the metals and metalloid. The average mass fractions of As, Cd, and Pb are relatively higher in sediments compared to those in background values, whereas Al, Fe, Mn, and Pb concentration fractions in water are higher than the international guideline values. The results of the different contamination indices indicate that Halda river sediments are minorly contaminated by As and Pb and moderately to considerably contaminated by Cd. The ecological risk assessments indicate considerable to high ecological risk due to Cd. Multivariate statistical analysis reveals the origin of the contaminants in the river, and indicate that Cr, Zn, Pb, and Cd are from anthropogenic activities while the other metals originate from natural lithogenic actions.

Exercise intervention in the management of urinary incontinence in older women in villages in Bangladesh: a cluster randomised trial.

BACKGROUND: Group exercise-based programmes for urinary incontinence appear to be promising low-cost interventions for women in developing countries, but no evidence exists to support whether they could be implemented or effective in such populations. We aimed to evaluate whether a group intervention that comprised pelvic floor muscle training, mobility exercises, and bladder education would be more effective than education alone, and report changes between villages (ie, clusters) rather than between individual participants. METHODS: In this cluster randomised trial, we recruited women from 16 pairs of villages in Bangladesh, with each pair comprising similar villages from the same sub-district. Women aged 60-75 years were interviewed to establish eligibility. Women were eligible if they had current urinary incontinence, and were excluded if they had a third degree or higher uterine prolapse, if they were unable to walk or stand without help, or if they had insufficient intellectual capacity to understand questions and follow instructions. The villages were randomly assigned within each pair to either exercise plus education or education-only intervention by use of a random number generator from a fixed seed. Women were excluded after consenting if they lived too far from the centre of the village. The exercise intervention was a physiotherapist-led group exercise class that was held twice weekly for 12 weeks, with home exercises between classes and to 24 weeks. Both groups received bladder-health education. Participants were followed up for 24 weeks. A 3-day continence record was collected at recruitment and every 4 weeks up until 24 weeks. This record involved the participant tying a knot in ribbons worn under the clothing each time they had an episode of urinary leakage. The primary outcome was change in number of knots (recorded leakage episodes) from recruitment to 24 weeks. Safety was assessed in all participants in the exercise intervention group. The trial is registered at ClinicalTrials.gov, number NCT02453100. FINDINGS: Between Aug 22, 2015, and July 2, 2018, of 3577 women aged 60-75 years identified, 1003 were eligible, of whom 625 consented to participate (n=335 exercise plus education villages, and n=290 in education-only villages). Of these consenting women, 46 were excluded (n=37 exercise plus education, n=9 education only) because they lived too far from the centre of the village. At week 24, 283 (95%) of 298 in the exercise plus education group and 274 (98%) of 281 in the education-only group completed a 3-day continence record. The estimate of change in number of leakage episodes between baseline and 24 weeks was -7·7 (95% CI -10·6 to -4·8) at the village level in an unadjusted model, and -6·64 (-7·95 to -5·33) in a random-effects model accounting for cluster randomisation. No adverse events were reported. INTERPRETATION: A structured group-exercise intervention has the potential to manage urinary incontinence in older women in communities largely outside the reach of pharmaceutical or surgical interventions. FUNDING: Canadian Institutes for Health Research.

Effects of Different Sources of Nitrogen on Endophytic Colonization of Rice Plants by Azospirillum sp. B510.

Azospirillum sp. B510, a free-living nitrogen-fixing bacterium isolated from the stems of rice (Oryza sativa cv. Nipponbare), was investigated to establish effective conditions for the colonization of rice plants. We analyzed the effects of the nitrogen sources KNO3, NH4Cl, urea (CO[NH2]2), and NH4NO3 at different concentrations (0.01-10 mM) on this colonization. Nitrogen promoted plant growth in a concentration-dependent manner, with minor differences being observed among the different nitrogen sources. Bacterial colonization was markedly suppressed on media containing NH4+ concentrations higher than 1 mM. Since concentrations of up to and including 10 mM NH4+ did not exhibit any antibacterial activity, we analyzed several factors affecting the NH4+-dependent inhibition of endophytic colonization, including the accumulation of the reactive oxygen species H2O2 and the secretion of the chemotactic substrate malic acid. The accumulation of H2O2 was increased in rice roots grown on 1 mM NH4Cl. The amounts of malic acid secreted from NH4-grown rice plants were lower than those secreted from plants grown without nitrogen or with KNO3. Although the bacterium exhibited chemotactic activity, moving towards root exudates from plants grown without nitrogen and KNO3-grown plants, this activity was not observed with root exudates from NH4+-grown plants. NH4+, but not NO3-, caused the acidification of growth media, which inhibited plant bacterial colonization. These NH4+-dependent phenomena were markedly suppressed by the stabilization of medium pH using a buffer. These results demonstrate that the type and concentration of nitrogen fertilizer affects the colonization of rice plants by Azospirillum sp. B510.

Evaluation of Chromogenic Medium for Selective Isolation of Yersinia.

Cefsulodin-irgasan-novobiocin agar (CIN) has been used as a selective agar to detect Yersinia in food or human patients; however, its components can inhibit the growth of some strains of Yersinia enterocolitica serovar O3 and Y. pseudotuberculosis. Recently, a new Yersinia selective agar, CHROMagar Yersinia enterocolitica (CAYe), was developed and evaluated as a novel selective agar for pathogenic Y. enterocolitica. In this research, a total of 251Yersinia strains (176 pathogenic Y. enterocolitica, 59 Y. pseudotuberculosis, and 16 non-pathogenic Yersinia) were cultured on both CIN and CAYe for comparison. Except for 10 of 104 pathogenic Y. enterocolitica O3 strains and 59 Y. pseudotuberculosis strains, 198 Yersinia isolates grew on both media after 48 hr of incubation at 32℃. Of the 10 pathogenic Y. enterocolitica O3 which could not grow on CIN or CAYe, 9 strains could not grow on CIN with supplements and 1 strain could not grow CAYe with supplements. Of 9 strains which did not grow on CIN with supplements, 3 strains could not grow on CIN without supplements. However, 1 strain which did not grow on CAYe with supplements could grow on CAYe without supplements. All of the Y. pseudotuberculosis strains could grow on CIN with/without supplements and on CAYe without supplements. The results indicate that the inhibition of the growth of Y. enterocolitica O3 on CIN is related to the components of CIN; however, the inhibition on CAYe appears to be related to the supplements in CAYe. Therefore, CAYe may be a more useful selective medium than CIN for pathogenic Y. enterocolitica .

Elemental distribution of metals in urban river sediments near an industrial effluent source.

To study the compositional trends associated with the spatial and layer wise distribution of heavy metals as well as the sediment response towards the untreated chemical wastes, we have analyzed river (Buriganga, Bangladesh) sediments by instrumental neutron activation analysis (INAA) and energy dispersive X-ray fluorescence (EDXRF). In nine sediment samples 27 elements were determined where Na, Al, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Zn, As, Rb, Cs, La, Ce, Sm, Dy, Hf, Th and U were determined by INAA and Cu, Sr, Ba, Hg and Pb were determined by EDXRF. Pollution level and the origin of pollutants were evaluated by the aid of geo-accumulation index (Igeo), enrichment factor (EF), pollution load index (PLI) and the inter-element correlation analysis. Major elements are somehow buffered even though the pollution level is severe while the trace metals seem to be highly responsive. Among the heavy metals, Cr is the dominant pollutant, though the pollution level varies systematically with the sampling depth and the distance from the contamination source. Positive linear correlation between Cr and Zn (0.94) ensures the similar anthropogenic source(s) for these two metals, but the sediments of this study respond differently depending upon their geochemical behavior. Rare earth elements (here La, Ce, Sm and Dy), Th and U seem to have crustal origin and the Th/U ratio varies from 2.58 to 4.96.