Disparity in physician-patient communication by ethnicity: evidence from Bangladesh.

BACKGROUND: Physician-patient communication behavior (PPCB) is the primary process by which medical decision-making occurs and health outcome depends. Physician-patient communication differences may partly from the ethnic disparities. To examine this problem, this study aims to explore whether physician-patient communication differs by ethnicity during primary care medical consultations. METHODS: The study was conducted among the Bengali and ethnic minority patients (N = 850) who visited a physician for medical consultations. Data were collected using a structured post-consultation questionnaire. T-test was conducted to compare the communication between the Bengali and ethnic minority patients. Multiple linear regression analyses were performed to identify the factors associated with favorable communication behavior from the physicians. RESULTS: Bengali patients received more supportive communication behaviors from the Bengali doctors than that of ethnic minority patients including physicians' cheerful greetings, encouraging patients to express health problems and asking questions, listening carefully, responding to questions and concerns, explaining to patients about medical examination procedures, medication, probable side effects, discussing treatment options, involved the patients in decisions, and spending adequate time. Results of linear regression showed that respondents' level of education, internet use, knowledge about the health issue, having a pre-organized plan about the content of medical consultation, information seeking about the health problem, visiting female doctors, and a quiet ambience of the doctor's room are significantly associated with a better PPCB score for the Bengali patients. In contrast, age, being the resident of an urban area, perception of affecting a minor health problem, having a pre-organized plan about the content of medical consultation, patients' involvement in physicians' decision-making about the treatment, and talking time resulted in better physician-patient communication for the ethnic minority patients. CONCLUSION: This study suggests that reducing disparity in the socio-economic status of the ethnic minority groups through development programs and educating healthcare providers on how to use patient-centered communication skills to engage with their patients is one solution to improve equity in the delivery of healthcare and ensure than patients are receiving high-quality treatment, no matter their race or ethnicity.

Expression and DNA methylation of SERK, BBM, LEC2 and WUS genes in in vitro cultures of Boesenbergia rotunda (L.) Mansf.

The process of somatic embryogenesis and plant regeneration involve changes in gene expression and have been associated with changes in DNA methylation. Here, we report the expression and DNA methylation patterns of SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK), BABY BOOM (BBM), LEAFY COTYLEDON 2 (LEC2) and WUSCHEL (WUS) in meristematic block of newly emerged shoots from rhizome, embryogenic and non-embryogenic calli, prolonged cell suspension culture, ex vitro leaf, and in vitro leaf of regenerated plants of Boesenbergia rotunda. Among all seven samples, based on qRT-PCR, the highest level of expression of SERK, BBM and LEC2 was in embryogenic callus, while WUS was most highly expressed in meristematic block tissue followed by embryogenic callus. Relatively lower expression was observed in cell suspension culture and watery callus for SERK, LEC2 and WUS and in in vitro leaf for BBM. For gene specific methylation determined by bisulfite sequencing data, embryogenic callus samples had the lowest levels of DNA methylation at CG, CHG and CHH contexts of SERK, LEC2 and WUS. We observed negative correlation between DNA methylation at the CG and CHG contexts and the expression levels of SERK, BBM, LEC2 and WUS. Based on our results, we suggest that relatively higher expression and lower level of DNA methylation of SERK, BBM, LEC2 and WUS are associated with somatic embryogenesis and plant regeneration in B. rotunda.

Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response.

Persistent infection of basal keratinocytes with high-risk human papillomavirus (hrHPV) may cause cancer. Keratinocytes are equipped with different pattern recognition receptors (PRRs) but hrHPV has developed ways to dampen their signals resulting in minimal inflammation and evasion of host immunity for sustained periods of time. To understand the mechanisms underlying hrHPV's capacity to evade immunity, we studied PRR signaling in non, newly, and persistently hrHPV-infected keratinocytes. We found that active infection with hrHPV hampered the relay of signals downstream of the PRRs to the nucleus, thereby affecting the production of type-I interferon and pro-inflammatory cytokines and chemokines. This suppression was shown to depend on hrHPV-induced expression of the cellular protein ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in keratinocytes. UCHL1 accomplished this by inhibiting tumor necrosis factor receptor-associated factor 3 (TRAF3) K63 poly-ubiquitination which lead to lower levels of TRAF3 bound to TANK-binding kinase 1 and a reduced phosphorylation of interferon regulatory factor 3. Furthermore, UCHL1 mediated the degradation of the NF-kappa-B essential modulator with as result the suppression of p65 phosphorylation and canonical NF-κB signaling. We conclude that hrHPV exploits the cellular protein UCHL1 to evade host innate immunity by suppressing PRR-induced keratinocyte-mediated production of interferons, cytokines and chemokines, which normally results in the attraction and activation of an adaptive immune response. This identifies UCHL1 as a negative regulator of PRR-induced immune responses and consequently its virus-increased expression as a strategy for hrHPV to persist.

Comparative dataset on productivity, proximate, biochemical and pigment content of marine Gonyostomum sp. and freshwater Tetraedron sp. microalgae.

The dataset includes a comparative analysis of Gonyostomum sp. and Tetraedron sp. to characterize their productivity, proximate composition, biochemical composition and pigments. Growth data were collected through cell density and optical density and subsequently mass-cultured to utilize biomass for other analyses. The onset of the stationary phase (12 to 18 days) varied between the species. Volumetric productivity, areal productivity, and SGR were also significantly higher (p ˂ 0.05) in Gonyostomum sp. whereas, Tetraedron sp. showed significantly higher (p ˂ 0.05) cell duplication time and cell doublings per day (K). Gonyostomum sp. showed significantly higher (p ˂ 0.05) protein (42.86±1.13%), carbohydrate (13.56±0.48%) and lipid (27.4 ± 0.69%) content than Tetraedron sp. Significantly higher (p ˂ 0.05) polyunsaturated fatty acids (PUFA) were obtained from both Gonyostomum sp. and Tetraedron sp. Non-essential amino acids were prevalent in both microalgae than essential amino acids. Significantly higher (p ˂ 0.05) chlorophyll-a (5.51±0.00), chlorophyll-b (2.27±0.04) and phycobiliprotein (2.32±0.05) were found in Tetraedron sp. Conversely, Gonyostomum sp. exhibited higher (p ˂ 0.05) carotenoid content (2.48±0.05). These findings may contribute to the screening and utilization of these microalgae in the aquaculture, pharmaceuticals, and nutraceuticals sectors.

Dataset representing growth performance, nutritional assay and biochemical profile of Oscillatoria spp.

Cyanobacteria are regarded as vital constituents of aquatic ecosystems which recently become viable option for bioremediation since it can remove contaminants from polluted water. They possess intriguing metabolic properties and exhibit differential growth patterns. This study elucidates the isolation and identification of two marine and two freshwater indigenous Oscillatoria spp., their growth performance, nutritional composition along with intricate biochemical profiles. Agar streak plate method was used for the isolation, growth curve was determined through chlorophyll content and optical density. Freshwater and marine Oscillatoria spp. were mass cultured in commercial Bold Basal Media and Conway media respectively. Wet biomass was harvested through centrifugation at the early stationary phase of their respective growth curve and oven-dried at 40 °C to determine the nutritional and biochemical profiles. Oscillatoria sp. 2 displayed significantly higher (p ˂ 0.05) chlorophyll-a (22.72 ± 0.04 µg/mL) and OD value (1.87 ± 0.03) in the stationary phase (9th to 11th day) than the other species. Crude protein contents (%) varied from 21.56 ± 0.09 to 56.97 ± 0.03. Crude lipid (%) ranged from 9.07 ± 0.07 to 17.13 ± 0.13 and Crude fiber content (%) showed the range from 7.49 ± 0.15 to 17.04 ± 0.08. Fatty acid and amino acid were also found variable among the species. Present study will contribute to the meticulous selection and characterization of Oscillatoria sp. to utilize it in the rigorous scientific investigations and diverse commercial applications.

Potable water scarcity: options and issues in the coastal areas of Bangladesh.

In the coastal areas of Bangladesh, scarcity of drinking water is acute as freshwater aquifers are not available at suitable depths and surface water is highly saline. Households are mainly dependent on rainwater harvesting, pond sand filters and pond water for drinking purposes. Thus, individuals in these areas often suffer from waterborne diseases. In this paper, water consumption behaviour in two southwestern coastal districts of Bangladesh has been investigated. The data for this study were collected through a survey conducted on 750 rural households in 39 villages of the study area. The sample was selected using a random sampling technique. Households' choice of water source is complex and seasonally dependent. Water sourcing patterns, households' preference of water sourcing options and economic feasibility of options suggest that a combination of household and community-based options could be suitable for year-round water supply. Distance and time required for water collection were found to be difficult for water collection from community-based options. Both household and community-based options need regular maintenance. In addition to installation of water supply facilities, it is necessary to make the residents aware of proper operation and maintenance of the facilities.

Does climate change affect the transmission of COVID-19? A Bayesian regression analysis.

Aim: Coronavirus is an airborne and infectious disease and it is crucial to check the impact of climatic risk factors on the transmission of COVID-19. The main objective of this study is to determine the effect of climate risk factors using Bayesian regression analysis. Methods: Coronavirus disease 2019, due to the effect of the SARS-CoV-2 virus, has become a serious global public health issue. This disease was identified in Bangladesh on March 8, 2020, though it was initially identified in Wuhan, China. This disease is rapidly transmitted in Bangladesh due to the high population density and complex health policy setting. To meet our goal, The MCMC with Gibbs sampling is used to draw Bayesian inference, which is implemented in WinBUGS software. Results: The study revealed that high temperatures reduce confirmed cases and deaths from COVID-19, but low temperatures increase confirmed cases and deaths. High temperatures have decreased the proliferation of COVID-19, reducing the virus's survival and transmission. Conclusions: Considering only the existing scientific evidence, warm and wet climates seem to reduce the spread of COVID-19. However, more climate variables could account for explaining most of the variability in infectious disease transmission.

Effect of long-term intermittent supplementation with multiple micronutrients compared with iron-and-folic acid supplementation on Hb and micronutrient status of non-anaemic adolescent schoolgirls in rural Bangladesh.

The present study examined whether long-term supplementation with once- and twice-weekly multiple micronutrients (MMN-1 and MMN-2) can improve Hb and micronutrient status more than twice-weekly Fe-folic acid (IFA-2) supplementation in non-anaemic adolescent girls in Bangladesh. An equal number of 324 rural schoolgirls aged 11-17 years were given MMN-1 or MMN-2 or IFA-2 supplements for 52 weeks in a randomised, double-blind trial. Blood samples were collected at baseline, and at 26 and 52 weeks of supplementation. The girls receiving IFA-2 supplements were more likely to be anaemic than the girls receiving MMN-2 supplements for 26 weeks (OR 5·1, 95% CI 1·3, 19·5; P = 0·018). All three supplements reduced Fe deficiency effectively. Both the MMN-1 and MMN-2 groups showed significantly greater improvements in vitamins A, B(2) and C status than the girls in the IFA-2 group, as might be expected. Receiving a MMN-1 supplement was found to be less effective than MMN-2 supplement in improving Fe, vitamins A, B(2) and folic acid status. Receiving micronutrient supplements beyond 26 weeks showed little additional benefit in improving micronutrient status. In conclusion, given twice-weekly for 26 weeks, MMN supplements can improve micronutrient status effectively with no significant increase in Hb concentration compared with IFA supplements in non-anaemic Bangladeshi adolescent girls. However, it significantly reduces the risk of anaemia. Before any recommendations can be made, further research, including into cost-effectiveness, is needed to see whether MMN supplementation has any additional longer-term health benefits over that of IFA supplementation in this population.

Effects of climate variables on the COVID-19 mortality in Bangladesh.

Infectious diseases such as severe acute respiratory syndrome (SARS) and influenza are influenced by weather conditions. Climate variables, for example, temperature and humidity, are two important factors in the severity of COVID-19's impact on the human respiratory system. This study aims to examine the effects of these climate variables on COVID-19 mortality. The data are collected from March 08, 2020, to April 30, 2022. The parametric regression under GAM and semiparametric regression under GAMLSS frameworks are used to analyze the daily number of death due to COVID-19. Our findings revealed that temperature and relative humidity are commencing to daily deaths due to COVID-19. A positive association with COVID-19 daily death counts was observed for temperature range and a positive association for humidity. In addition, one-unit increase in daily temperature range was only associated with a 1.08% (95% CI: 1.06%, 1.10%), and humidity range was only associated with a 1.03% (95% CI: 1.02%, 1.03%) decrease in COVID-19 deaths. A flexible regression model within the framework of Generalized Additive Models for Location Scale and Shape is used to analyze the data by adjusting the time effect. We used two adaptable predictor models, such as (i) the Fractional polynomial model and (ii) the B-spline smoothing model, to estimate the systematic component of the GAMLSS model. According to both models, high humidity and temperature significantly (and drastically) lessened the severity of COVID-19 death. The findings on the epidemiological trends of the COVID-19 pandemic and weather changes may interest policymakers and health officials.

Bivalent BET Bromodomain Inhibitors Confer Increased Potency and Selectivity for BRDT via Protein Conformational Plasticity.

Bromodomain and extraterminal domain (BET) proteins are important regulators of gene transcription and chromatin remodeling. BET family members BRD4 and BRDT are validated targets for cancer and male contraceptive drug development, respectively. Due to the high structural similarity of the acetyl-lysine binding sites, most reported inhibitors lack intra-BET selectivity. We surmised that protein-protein interactions induced by bivalent inhibitors may differ between BRD4 and BRDT, conferring an altered selectivity profile. Starting from nonselective monovalent inhibitors, we developed cell-active bivalent BET inhibitors with increased activity and selectivity for BRDT. X-ray crystallographic and solution studies revealed unique structural states of BRDT and BRD4 upon interaction with bivalent inhibitors. Varying spacer lengths and symmetric vs unsymmetric connections resulted in the same dimeric states, whereas different chemotypes induced different dimers. The findings indicate that the increased intra-BET selectivity of bivalent inhibitors is due to the differential plasticity of BET bromodomains upon inhibitor-induced dimerization.

Discovery of Dual TAF1-ATR Inhibitors and Ligand-Induced Structural Changes of the TAF1 Tandem Bromodomain.

Bromodomains regulate chromatin remodeling and gene transcription through recognition of acetylated lysines on histones and other proteins. Bromodomain-containing protein TAF1, a subunit of general transcription factor TFIID, initiates preinitiation complex formation and cellular transcription. TAF1 serves as a cofactor for certain oncogenic transcription factors and is implicated in regulating the p53 tumor suppressor. Therefore, TAF1 is a potential target to develop small molecule therapeutics for diseases arising from dysregulated transcription, such as cancer. Here, we report the ATR kinase inhibitor AZD6738 (Ceralasertib) and analogues thereof as bona fide inhibitors of TAF1. Crystallographic and small-angle X-ray scattering studies established that newly identified and previously reported inhibitors stabilize distinct structural states of the TAF1 tandem bromodomain through "open-closed" transitions and dimerization. Combined with functional studies on p53 signaling in cancer cell lines, the data provide new insights into the feasibility and challenges of TAF1 inhibitors as chemical probes and therapeutics.

Effects of shipwrecks on spatiotemporal dynamics of metal/loids in sediments and seafood safety in the Bay of Bengal.

Metal/loid pollution from shipwrecking activities has drawn significant concern due to their persistent threat to the marine ecosystem and human health. We investigated the spatiotemporal distribution, pollution characteristics, risks, sources, and potential impact of metal/loids in the sediments and seafood in the Bay of Bengal at nearby open beaching shipwrecking yards in Bangladesh. We collected 78 sediments and 208 seafood samples from the exposed and control sites from 2018 to 2020 during the dry and wet seasons. The concentrations of 16 elements, including cadmium, arsenic, lead, chromium, manganese, copper, zinc, iron, tin, antimony, nickel, cobalt, molybdenum, vanadium, selenium, and thallium were measured using validated inductively coupled plasma-mass spectrometry (ICP-MS) methods. Based on the pollution indices (enrichment factor, geoaccumulation index, pollution index, and pollution load index), lead, arsenic, cadmium, selenium, copper, zinc, and tin from the dry season showed higher contaminations compared to the wet and their concentrations were increased from 2018 to 2020 with seasonal fluctuations. Sediment cadmium and arsenic posed relatively higher and moderate ecological risks. Health risk analysis indicated that lead, cadmium, and inorganic arsenic (estimated) in seafood species pose a possible health threat to the general population. Further, there were possible ecological and health risks for the metal/loids in combination based on the ecological risk index in sediment and the hazard index in seafood, respectively. Source apportionment suggested that anthropogenic activities through uncontrolled shipwrecking operations over the last four decades were the largest polluting dominator, contributing 55-77% of the metal/loid concentrations. Therefore, the data may inform mitigation strategies for emission control at the shipwrecking yards to protect marine ecosystems and their local population.

Alcohol-based Hand Sanitizers amid COVID-19: Chemical Formulation, Analysis, Safety.

Alcohol-based hand sanitizers (ABHSs) containing ethanol (EtOH) or isopropyl alcohol (IPA) to inactivate microorganisms help prevent the spread of respiratory diseases. These products have become very popular during the COVID-19 pandemic. Apart from vaccines or other preventative antiseptic measures, the majority of consumers have relied on different types of ABHSs to disinfect their hands. As a result, there has been a global rush in the demand for these ABHSs and other antiseptic hygiene products. This has resulted in the formation of many new commercial sanitizer producers. There are around fifty companies of varying sizes that have been marketing their ABHSs in Bangladesh, most of which have only been manufacturing their products for the first time since the COVID-19 pandemic. To monitor the quality and components of these products, the Bangladesh Council of Scientific and Industrial Research (BCSIR) analyzed approximately 200 different hand sanitizer samples using GC-FID method. All samples were alcohol-based except for 3 which were alcohol-free aqueous hand sanitizers. Of the supplied formulated ABHSs, 80 samples were found to contain only IPA and 54 contained only EtOH. However, 28 samples were found to be contaminated with methanol (MeOH), 7 samples contained only MeOH and 18 samples contained both EtOH and IPA. This is the first study to explore the analysis of alcohol content in formulated ABHSs and their marketing status in Bangladesh, but the findings could be of use in other jurisdictions as similar issues have been raised in many parts of the world.

TSPAN6 is a suppressor of Ras-driven cancer.

Oncogenic mutations in the small GTPase RAS contribute to ~30% of human cancers. In a Drosophila genetic screen, we identified novel and evolutionary conserved cancer genes that affect Ras-driven tumorigenesis and metastasis in Drosophila including confirmation of the tetraspanin Tsp29Fb. However, it was not known whether the mammalian Tsp29Fb orthologue, TSPAN6, has any role in RAS-driven human epithelial tumors. Here we show that TSPAN6 suppressed tumor growth and metastatic dissemination of human RAS activating mutant pancreatic cancer xenografts. Whole-body knockout as well as tumor cell autonomous inactivation using floxed alleles of Tspan6 in mice enhanced KrasG12D-driven lung tumor initiation and malignant progression. Mechanistically, TSPAN6 binds to the EGFR and blocks EGFR-induced RAS activation. Moreover, we show that inactivation of TSPAN6 induces an epithelial-to-mesenchymal transition and inhibits cell migration in vitro and in vivo. Finally, low TSPAN6 expression correlates with poor prognosis of patients with lung and pancreatic cancers with mesenchymal morphology. Our results uncover TSPAN6 as a novel tumor suppressor receptor that controls epithelial cell identify and restrains RAS-driven epithelial cancer.

Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh.

BACKGROUND: Chronic arsenic exposure has been shown to cause liver damage. However, serum hepatic enzyme activity as recognized on liver function tests (LFTs) showing a dose-response relationship with arsenic exposure has not yet been clearly documented. The aim of our study was to investigate the dose-response relationship between arsenic exposure and major serum enzyme marker activity associated with LFTs in the population living in arsenic-endemic areas in Bangladesh. METHODS: A total of 200 residents living in arsenic-endemic areas in Bangladesh were selected as study subjects. Arsenic concentrations in the drinking water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The study subjects were stratified into quartile groups as follows, based on concentrations of arsenic in the drinking water, as well as in subjects' hair and nails: lowest, low, medium and high. The serum hepatic enzyme activities of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) were then assayed. RESULTS: Arsenic concentrations in the subjects' hair and nails were positively correlated with arsenic levels in the drinking water. As regards the exposure-response relationship with arsenic in the drinking water, the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates. With internal exposure markers (arsenic in hair and nails), the ALP, AST and ALT activity profiles assumed a similar shape of dose-response relationship, with very few differences seen in the higher groups compared to the lowest group, most likely due to the temporalities of exposure metrics. CONCLUSIONS: The present study demonstrated that arsenic concentrations in the drinking water were strongly correlated with arsenic concentrations in the subjects' hair and nails. Further, this study revealed a novel exposure- and dose- response relationship between arsenic exposure metrics and serum hepatic enzyme activity. Elevated serum hepatic enzyme activities in the higher exposure gradients provided new insights into arsenic-induced liver toxicity that might be helpful for the early prognosis of arsenic-induced liver diseases.

Risk factors of suicidality among married adults: A cross-sectional survey in Rajshahi City, Bangladesh.

BACKGROUND: Suicide is a serious public health concern all over the world including Bangladesh. About 9% of the patients admitted with suicidal ideation (SI) or suicide attempt (SA) later complete suicide. To understand and prevent suicide, the study of SI and SA is necessary but research in this area is scanty in Bangladesh. Therefore, we studied suicidality (SI and SA) among married adults in Rajshahi City, Bangladesh. METHODS: This was a household cross-sectional study. A total of 708 married adults were selected for this study using a multi-stage random sampling. Suicidality was measured based on two factors: (i) suicidal ideation, and (ii) suicide attempt. Frequency distribution, Chi-square test and multiple binary logistic regression model were used in this study according to our objectives. RESULTS: The prevalence of suicidal ideation, suicide attempt, and suicidality was 5.8%, 3.4%, and 8.3% respectively among married adults. A multiple binary logistic regression model provided the following risk factors of suicidality: (i) joint family (AOR = 0.310, p<0.01), (ii) ≥26 years of age at the first marriage (AOR = 0.379, p<0.05), (iii) twice or more marriage (AOR = 0.214, p<0.01), (iv) conjugal life of ≥16 years (AOR = 0.410, p<0.05), (v) having no child (AOR = 6.343, p<0.01) and (vi) having 1-2 children (AOR = 6.190, p<0.01), (vii) medical comorbidity (AOR = 0.421, p<0.01), (viii) mental comorbidity (AOR = 0.253, p<0.01), (ix) stress-anxiety (AOR = 0.311, p<0.01), (x) family history of mental disorders (AOR = 0.059, p<0.01), (xi) family history of suicide/suicide attempt (AOR = 0.009, p<0.01), (xii) substance abuse (AOR = 0.065, p<0.01), (xiii) poor relationship with spouse (AOR = 0.209, p<0.01), and (xiv) poor relationship with other family members (AOR = 0.347, p<0.05). CONCLUSION: The prevalence of suicidality is remarkable in Rajshahi city, Bangladesh. The government and non-government agencies can use the findings of this study to identify the vulnerable groups and undertake measures for preventing and reducing suicidality.

Moringa oleifera is a Prominent Source of Nutrients with Potential Health Benefits.

Nowadays, the socioeconomic status has been changed a lot, so people are now more concerned about their life style and health. They have knowledge about the detrimental effects of synthetic products. That is why they are interested in natural products. Utilization of natural products of plant origin having fewer side effects has gained popularity over the years. There is immense scope for natural products that can intimate health benefits beyond traditional nutrients. Moringa oleifera is one such tree having tremendous nutritional and medicinal benefits. It is rich in macro- and micronutrients and other bioactive compounds which are important for normal functioning of the body and prevention of certain diseases. Leaves, flowers, seeds, and almost all parts of this tree are edible and have immense therapeutic properties including antidiabetic, anticancer, antiulcer, antimicrobial, and antioxidant. Most of the recent studies suggested that Moringa should be used as a functional ingredient in food. The aim of this review is to focus the use of Moringa oleifera as a potential ingredient in food products.

Differential BET Bromodomain Inhibition by Dihydropteridinone and Pyrimidodiazepinone Kinase Inhibitors.

BRD4 and other members of the bromodomain and extraterminal (BET) family of proteins are promising epigenetic targets for the development of novel therapeutics. Among the reported BRD4 inhibitors are dihydropteridinones and benzopyrimidodiazepinones originally designed to target the kinases PLK1, ERK5, and LRRK2. While these kinase inhibitors were identified as BRD4 inhibitors, little is known about their binding potential and structural details of interaction with the other BET bromodomains. We comprehensively characterized a series of known and newly identified dual BRD4-kinase inhibitors against all eight individual BET bromodomains. A detailed analysis of 23 novel cocrystal structures of BET-kinase inhibitor complexes in combination with direct binding assays and cell signaling studies revealed significant differences in molecular shape complementarity and inhibitory potential. Collectively, the data offer new insights into the action of kinase inhibitors across BET bromodomains, which may aid the development of drugs to inhibit certain BET proteins and kinases differentially.

Long-term intermittent multiple micronutrient supplementation enhances hemoglobin and micronutrient status more than iron + folic acid supplementation in Bangladeshi rural adolescent girls with nutritional anemia.

Previous short-term supplementation studies showed no additional hematologic benefit of multiple micronutrients (MMN) compared with iron + folic acid (IFA) in adolescent girls. This study examines whether long-term once- or twice-weekly supplementation of MMN can improve hemoglobin (Hb) and micronutrient status more than twice-weekly IFA supplementation in anemic adolescent girls in Bangladesh. Anemic girls (n = 324) aged 11-17 y attending rural schools were given once- or twice-weekly MMN or twice-weekly IFA, containing 60 mg iron/dose in both supplements, for 52 wk in a randomized double-blind trial. Blood samples were collected at baseline and 26 and 52 wk. Intent to treat analysis showed no significant difference in the Hb concentration between treatments at either 26 or 52 wk. However, after excluding girls with hemoglobinopathy and adjustment for baseline Hb, a greater increase in Hb was observed with twice-weekly MMN at 26 wk (P = 0.045). Although all 3 treatments effectively reduced iron deficiency, once-weekly MMN produced significantly lower serum ferritin concentrations than the other treatments at both 26 and 52 wk. Both once- and twice-weekly MMN significantly improved riboflavin, vitamin A, and vitamin C status compared with IFA. Overall, once-weekly MMN was less efficacious than twice-weekly MMN in improving iron, riboflavin, RBC folic acid, and vitamin A levels. Micronutrient supplementation beyond 26 wk was likely important in sustaining improved micronutrient status. These findings highlight the potential usefulness of MMN intervention in this population and have implications for programming.