A cost study for mobile phone health surveys using interactive voice response for assessing risk factors of noncommunicable diseases.

BACKGROUND: This is the first study to examine the costs of conducting a mobile phone survey (MPS) through interactive voice response (IVR) to collect information on risk factors for noncommunicable diseases (NCD) in three low- and middle-income countries (LMIC); Bangladesh, Colombia, and Uganda. METHODS: This is a micro-costing study conducted from the perspective of the payer/funder with a 1-year horizon. The study evaluates the fixed costs and variable costs of implementing one nationally representative MPS for NCD risk factors of the adult population. In this costing study, we estimated the sample size of calls required to achieve a population-representative survey and associated incentives. Cost inputs were obtained from direct economic costs incurred by a central study team, from country-specific collaborators, and from platform developers who participated in the deployment of these MPS during 2017. Costs were reported in US dollars (USD). A sensitivity analysis was conducted assessing different scenarios of pricing and incentive strategies. Also, costs were calculated for a survey deployed targeting only adults younger than 45 years. RESULTS: We estimated the fixed costs ranging between $47,000 USD and $74,000 USD. Variable costs were found to be between $32,000 USD and $129,000 USD per nationally representative survey. The main cost driver was the number of calls required to meet the sample size, and its variability largely depends on the extent of mobile phone coverage and access in the country. Therefore, a larger number of calls were estimated to survey specific harder-to-reach sub-populations. CONCLUSION: Mobile phone surveys have the potential to be a relatively less expensive and timely method of collecting survey information than face-to-face surveys, allowing decision-makers to deploy survey-based monitoring or evaluation programs more frequently than it would be possible having only face-to-face contact. The main driver of variable costs is survey time, and most of the variability across countries is attributable to the sampling differences associated to reaching out to population subgroups with low mobile phone ownership or access.

Enhanced amperometric detection of paracetamol by immobilized cobalt ion on functionalized MWCNTs - Chitosan thin film.

In the present study, a nanocomposite of f-MWCNTs-chitosan-Co was prepared by the immobilization of Co(II) on f-MWCNTs-chitosan by a self-assembly method and used for the quantitative determination of paracetamol (PR). The composite was characterized by field emission scanning electron microscopy (FESEM) and energy dispersive x-ray analysis (EDX). The electroactivity of cobalt immobilized on f-MWCNTs-chitosan was assessed during the electro-oxidation of paracetamol. The prepared GCE modified f-MWCNTs/CTS-Co showed strong electrocatalytic activity towards the oxidation of PR. The electrochemical performances were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). Under favorable experimental conditions, differential pulse voltammetry showed a linear dynamic range between 0.1 and 400 µmol L-1 with a detection limit of 0.01 µmol L-1 for the PR solution. The fabricated sensor exhibited significant selectivity towards PR detection. The fabricated sensor was successfully applied for the determination of PR in commercial tablets and human serum sample.

SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair.

Progressive telomere attrition or deficiency of the protective shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks. SNMIB/Apollo is a shelterin-associated protein and a member of the SMN1/PSO2 nuclease family that localizes to telomeres through its interaction with TRF2. Here, we generated SNMIB/Apollo knockout mouse embryo fibroblasts (MEFs) to probe the function of SNMIB/Apollo at mammalian telomeres. SNMIB/Apollo null MEFs exhibit an increased incidence of G2 chromatid-type fusions involving telomeres created by leading-strand DNA synthesis, reflective of a failure to protect these telomeres after DNA replication. Mutations within SNMIB/Apollo's conserved nuclease domain failed to suppress this phenotype, suggesting that its nuclease activity is required to protect leading-strand telomeres. SNMIB/Apollo(-/-)ATM(-/-) MEFs display robust telomere fusions when Trf2 is depleted, indicating that ATM is dispensable for repair of uncapped telomeres in this setting. Our data implicate the 5'-3' exonuclease function of SNM1B/Apollo in the generation of 3' single-stranded overhangs at newly replicated leading-strand telomeres to protect them from engaging the non-homologous end-joining pathway.

Data on the factors driving the decision of rural people to move into the city.

The data set explores the driving factors of migration of rural people to the cities. Primary data were collected purposively from 172 farm households from three upazilas of kishoreganj district in Bangladesh. Among 172 households, 89 households had at least one migrant member and 83 households were without any migrant member. Probit model was used to analyze factors of migration decision at the household level. Data set reveals that various factors motivate the decision of the farm households for their member to move into the city. Among which household head age, number of active male member in the family and value of the household asset holding significantly influence migration decision. Beside econometric analysis, household's perception on different motivating factors of migration was also assessed. Most of the households perceived that too many family members, poor living condition, migrant's family influence and job availability in the city mostly motivate the people for migration into the city along with other driving factors.

Electrochemical assisted enhanced nanozymatic activity of functionalized borophene for H2O2 and tetracycline detection.

This study unveils the electrochemically-enhanced nanozymatic activity exhibited by borophene during the reaction of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. Herein, the surface of the pristine borophene was first modified with the addition of thiocyanate groups to improve hydroxyl radical (•OH) scavenging activity. Then, the oxidation reaction of TMB was accelerated under applied electrochemical potential. Both factors significantly improved the detection limit and drastically decreased the detection time. DPPH testing revealed that the radical scavenging nature of borophene was more than 70%, boosting its catalytic activity. In the presence of H2O2, borophene catalyzed the oxidation of TMB and produced a blue-colored solution that was linearly correlated with the concentration of H2O2 and allowed for the detection of H2O2 up to 38 nM. The present finding was further extended to nanozymatic detection of tetracyclines (TCs) using a target-specific aptamer, and the results were colorimetrically quantifiable up to 1 µM with a LOD value of 150 nM. Moreover, transferring the principles of the discussed detection method to form a portable and disposable paper-based system enabled the quantification of TCs up to 0.2 µM. All the sensing experiments in this study indicate that the nanozymatic activity of borophene has significantly improved under electrochemical potential compared to conventional nanozyme-based colorimetric detection. Hence, the present discovery of electrochemically-enhanced nanozymatic activity would be promising for various sensitive and time-dependent colorimetric sensor development initiatives in the future.

Inflammation induced by tumor-associated nerves promotes resistance to anti-PD-1 therapy in cancer patients and is targetable by interleukin-6 blockade.

While the nervous system has reciprocal interactions with both cancer and the immune system, little is known about the potential role of tumor associated nerves (TANs) in modulating anti-tumoral immunity. Moreover, while peri-neural invasion is a well establish poor prognostic factor across cancer types, the mechanisms driving this clinical effect remain unknown. Here, we provide clinical and mechniastic association between TANs damage and resistance to anti-PD-1 therapy. Using electron microscopy, electrical conduction studies, and tumor samples of cutaneous squamous cell carcinoma (cSCC) patients, we showed that cancer cells can destroy myelin sheath and induce TANs degeneration. Multi-omics and spatial analyses of tumor samples from cSCC patients who underwent neoadjuvant anti-PD-1 therapy demonstrated that anti-PD-1 non-responders had higher rates of peri-neural invasion, TANs damage and degeneration compared to responders, both at baseline and following neoadjuvant treatment. Tumors from non-responders were also characterized by a sustained signaling of interferon type I (IFN-I) - known to both propagate nerve degeneration and to dampen anti-tumoral immunity. Peri-neural niches of non-responders were characterized by higher immune activity compared to responders, including immune-suppressive activity of M2 macrophages, and T regulatory cells. This tumor promoting inflammation expanded to the rest of the tumor microenvironment in non-responders. Anti-PD-1 efficacy was dampened by inducing nerve damage prior to treatment administration in a murine model. In contrast, anti-PD-1 efficacy was enhanced by denervation and by interleukin-6 blockade. These findings suggested a potential novel anti-PD-1 resistance drived by TANs damage and inflammation. This resistance mechanism is targetable and may have therapeutic implications in other neurotropic cancers with poor response to anti-PD-1 therapy such as pancreatic, prostate, and breast cancers.

Cdc5L interacts with ATR and is required for the S-phase cell-cycle checkpoint.

Cell division cycle 5-like protein (Cdc5L) is a core component of the putative E3 ubiquitin ligase complex containing Prp19/Pso4, Plrg1 and Spf27. This complex has been shown to have a role in pre-messenger RNA splicing from yeast to humans; however, more recent studies have described a function for this complex in the cellular response to DNA damage. Here, we show that Cdc5L interacts physically with the cell-cycle checkpoint kinase ataxia-telangiectasia and Rad3-related (ATR). Depletion of Cdc5L by RNA-mediated interference methods results in a defective S-phase cell-cycle checkpoint and cellular sensitivity in response to replication-fork blocking agents. Furthermore, we show that Cdc5L is required for the activation of downstream effectors or mediators of ATR checkpoint function such as checkpoint kinase 1 (Chk1), cell cycle checkpoint protein Rad 17 (Rad17) and Fanconi anaemia complementation group D2 protein (FancD2). In addition, we have mapped the ATR-binding region in Cdc5L and show that a deletion mutant that is unable to interact with ATR is defective in the rescue of the checkpoint deficiency in Cdc5L-depleted cells. These findings show a new function for Cdc5L in the regulation of the ATR-mediated cell-cycle checkpoint in response to genotoxic agents.

The multifunctional SNM1 gene family: not just nucleases.

The archetypical member of the SNM1 gene family was discovered 30 years ago in the budding yeast Saccharomyces cerevisiae. This small but ubiquitous gene family is characterized by metallo-beta-lactamase and beta-CASP domains, which together have been demonstrated to comprise a nuclease activity. Three mammalian members of this family, SNM1A, SNM1B/Apollo and Artemis, have been demonstrated to play surprisingly divergent roles in cellular metabolism. These pathways include variable (diversity) joining recombination, nonhomologous end-joining of double-strand breaks, DNA damage and mitotic cell cycle checkpoints, telomere maintenance and protein ubiquitination. Not all of these functions are consistent with a model in which these proteins act only as nucleases, and indicate that the SNM1 gene family encodes multifunctional products that can act in diverse biochemical pathways. In this article we discuss the various functions of SNM1A, SNM1B/Apollo and Artemis.

Observed hand cleanliness and other measures of handwashing behavior in rural Bangladesh.

BACKGROUND: We analyzed data from the baseline assessment of a large intervention project to describe typical handwashing practices in rural Bangladesh, and compare measures of hand cleanliness with household characteristics. METHODS: We randomly selected 100 villages from 36 districts in rural Bangladesh. Field workers identified 17 eligible households per village using systematic sampling. Field workers conducted 5-hour structured observations in 1000 households, and a cross-sectional assessment in 1692 households that included spot checks, an evaluation of hand cleanliness and a request that residents demonstrate their usual handwashing practices after defecation. RESULTS: Although 47% of caregivers reported and 51% demonstrated washing both hands with soap after defecation, in structured observation, only 33% of caregivers and 14% of all persons observed washed both hands with soap after defecation. Less than 1% used soap and water for handwashing before eating and/or feeding a child. More commonly people washed their hands only with water, 23% after defecation and 5% before eating. Spot checks during the cross sectional survey classified 930 caregivers (55%) and 453 children (28%) as having clean appearing hands. In multivariate analysis economic status and water available at handwashing locations were significantly associated with hand cleanliness among both caregivers and children. CONCLUSIONS: A minority of rural Bangladeshi residents washed both hands with soap at key handwashing times, though rinsing hands with only water was more common. To realize the health benefits of handwashing, efforts to improve handwashing in these communities should target adding soap to current hand rinsing practices.

A dopamine electrochemical sensor based on a platinum-silver graphene nanocomposite modified electrode.

A platinum-silver graphene (Pt-Ag/Gr) nanocomposite modified electrode was fabricated for the electrochemical detection of dopamine (DA). Electrochemical studies of the Pt-Ag/Gr nanocomposite towards DA detection were performed by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The CV analysis showed that Pt-Ag/Gr/GCE had enhanced electrocatalytic activity towards DA oxidation due to the synergistic effects between the platinum-silver nanoparticles and graphene. The DPV results showed that the modified sensor demonstrated a linear concentration range between 0.1 and 60 µM with a limit of detection of 0.012 µM. The Pt-Ag/Gr/GCE presented satisfactory results for reproducibility, stability and selectivity. The prepared sensor also showed acceptable recoveries for a real sample study.

SNM1A acts downstream of ATM to promote the G1 cell cycle checkpoint.

We have shown previously that SNM1A colocalizes with 53BP1 at sites of double-strand breaks (DSBs) induced by IR, and that these proteins interact with or without DNA damage. However, the role of SNM1A in the DNA damage response has not been elucidated. Here, we show that SNM1A is required for an efficient G1 checkpoint arrest after IR exposure. Interestingly, the localization of SNM1A to sites of DSBs does not require either 53BP1 or H2AX, nor does the localization of 53BP1 require SNM1A. However, the localization of SNM1A does require ATM. Furthermore, SNM1A is shown to be a phosphorylation substrate of ATM in vitro, and to interact with ATM in vivo particularly after exposure of cells to IR. In addition, in the absence of SNM1A the activation of the downstream ATM target p53 is reduced. These findings suggest that SNM1A acts with ATM to promote the G1 cell cycle checkpoint.

Allergic lung inflammation affects central noradrenergic control of cholinergic outflow to the airways in ferrets.

Brain stem noradrenergic cell groups mediating autonomic responses to stress project to airway-related vagal preganglionic neurons (AVPNs). In ferrets, their activation produces withdrawal of cholinergic outflow to the airways via release of norepinephrine and activation of alpha(2A)-adrenergic receptors (alpha(2A)-AR) expressed by AVPNs. In these studies, we examined the effects of allergen exposure of the airway (AE) with ovalbumin on noradrenergic transmission regulating the activity of AVPNs and, consequently, airway smooth muscle tone. Experiments were performed in vehicle control (Con) and AE ferrets. Microperfusion of an alpha(2A)-AR agonist (guanabenz) in close proximity to AVPNs elicited more pronounced effects in Con than AE ferrets, including a decrease in unit activity and reflexly evoked responses of putative AVPN neurons with a corresponding decrease in cholinergic outflow to the airways. Although no differences were found in the extent of noradrenergic innervation of the AVPNs, RT-PCR and Western blot studies demonstrated that AE and repeated exposure to antigen significantly reduced expression of alpha(2A)-ARs at message and protein levels. These findings indicate that, in an animal model of allergic asthma, sensitization and repeated challenges with a specific allergen diminish central inhibitory noradrenergic modulation of AVPNs, possibly via downregulation of alpha(2A)-AR expression by these neurons.

Deficiency in SNM1 abolishes an early mitotic checkpoint induced by spindle stress.

Spindle poisons represent an important class of anticancer drugs that act by interfering with microtubule polymerization and dynamics and thereby induce mitotic checkpoints and apoptosis. Here we show that mammalian SNM1 functions in an early mitotic stress checkpoint that is distinct from the well-characterized spindle checkpoint that regulates the metaphase-to-anaphase transition. Specifically, we found that compared to wild-type cells, Snm1-deficient mouse embryonic fibroblasts exposed to spindle poisons exhibited elevated levels of micronucleus formation, decreased mitotic delay, a failure to arrest in mitosis prior to chromosome condensation, supernumerary centrosomes, and decreased viability. In addition, we show that both Snm1 and 53BP1, previously shown to interact, coimmunoprecipitate with components of the anaphase-promoting complex (APC)/cyclosome. These findings suggest that Snm1 is a component of a mitotic stress checkpoint that negatively targets the APC prior to chromosome condensation.

Incidences and Costs of Illness for Diarrhea and Acute Respiratory Infections for Children < 5 Years of Age in Rural Bangladesh.

AbstractUnderstanding illness costs associated with diarrhea and acute respiratory infections (ARI) could guide prevention and treatment strategies. This study aimed to determine incidence of childhood diarrhea and ARI and costs of homecare, hospitalization, and outpatient treatment by practitioner type in rural Bangladesh. From each of 100 randomly selected population clusters we sampled 17 households with at least one child < 5 years of age. Childhood diarrhea incidence was 3,451 and ARI incidence was 5,849/1,000 child-years. For diarrhea and ARI outpatient care per 1,000 child-years, parents spent more on unqualified ($2,361 and $4,822) than qualified health-care practitioners ($113 and $947). For outpatient care, visits to unqualified health-care practitioners were at least five times more common than visits to qualified practitioners. Costs for outpatient care treatment by unqualified health-care practitioners per episode of illness were similar to those for qualified health-care practitioners. Homecare costs were similar for diarrhea and ARI ($0.16 and $0.24) as were similar hospitalization costs per episode of diarrhea and ARI ($35.40 and $37.76). On average, rural Bangladeshi households with children < 5 years of age spent 1.3% ($12 of $915) of their annual income managing diarrhea and ARI for those children. The majority of childhood illness management cost comprised visits to unqualified health-care practitioners. Policy makers should consider strategies to increase the skills of unqualified health-care practitioners, use community health workers to provide referral, and promote homecare for diarrhea and ARI. Incentives to motivate existing qualified physicians who are interested to work in rural Bangladesh could also be considered.

Prevalence of Hepatitis B Virus and Hepatitis C Virus in a Tea Garden of Bangladesh.

INTRODUCTION: The overall health status of workers of tea garden of Bangladesh is below the national standard. Also, almost nothing has been reported about status of hepatitis virus infection among these population and there is also a lack of consensus. MATERIALS AND METHODS: Several health-related facts, especially those of liver diseases, were collected from 130 workers of tea garden via questionnaire. Sera were also collected from these subjects to assess positivity of hepatitis B surface antigen (HBsAg) and antibody to hepatitis C virus (anti-HCV). Hepatitis B virus (HBV) genotype was also done using genotype-specific primers in HBsAg-positive sera. RESULTS: Out of 130 tea garden workers, 5 were positive for HBsAg; however, none was reactive to anti-HCV. Genotyping of HBV deoxyribonucleic acid of 4 sera samples revealed that 2 belonged to genotype A, 1 to genotype C, and 1 to genotype D. Various risk factors were documented in HBV-infected subjects by analyzing the questionnaire. CONCLUSION: Hepatitis B virus in considerable high percentage is prevalent among workers of tea garden in Bangladesh, and immediate vaccination against HBV should be employed. Also, health education system should be accentuated in specific population like tea garden workers.How to cite this article: Al Mahtab M, Akhter S, Mollick KU, Uddin MH, Khan SI, Akbar SMF. Prevalence of Hepatitis B Virus and Hepatitis C Virus in a Tea Garden of Bangladesh. Euroasian J Hepato-Gastroenterol 2017;7(1):107-110.

Risk Factors for Death in Bangladeshi Children Under 5 Years of Age Hospitalized for Diarrhea and Severe Respiratory Distress in an Urban Critical Care Ward.

Children with diarrhea hospitalized for respiratory distress often have fatal outcome in resource-limited settings, although data are lacking on risk factors for death in such children. We sought to evaluate clinical predictors for death in such children. In this prospective cohort study, we enrolled under-5 children with diarrhea admitted with severe respiratory distress to the intensive care unit of Dhaka Hospital of International Centre for Diarhoeal Disease Research, Bangladesh, from September 2014 through September 2015. We compared clinical and laboratory characteristics between study children those who died (n = 29) and those who survived (n = 62). In logistic regression analysis, after adjusting for potential confounders, the independent predictors for death in children hospitalized for diarrhea and severe respiratory distress were severe sepsis and hypoglycemia (P < .05 for all). Thus, recognition of these simple parameters may help clinicians identify children with diarrhea at risk of deaths in order to initiate prompt management for the better outcome, especially in resource-poor settings.

FANCI is a negative regulator of Akt activation.

Akt is a critical mediator of the oncogenic PI3K pathway, and its activation is regulated by kinases and phosphatases acting in opposition. We report here the existence of a novel protein complex that is composed minimally of Akt, PHLPP1, PHLPP2, FANCI, FANCD2, USP1 and UAF1. Our studies show that depletion of FANCI, but not FANCD2 or USP1, results in increased phosphorylation and activation of Akt. This activation is due to a reduction in the interaction between PHLPP1 and Akt in the absence of FANCI. In response to DNA damage or growth factor treatment, the interactions between Akt, PHLPP1 and FANCI are reduced consistent with the known phosphorylation of Akt in response to these stimuli. Furthermore, depletion of FANCI results in reduced apoptosis after DNA damage in accord with its role as a negative regular of Akt. Our findings describe an unexpected function for FANCI in the regulation of Akt and define a previously unrecognized intersection between the PI3K-Akt and FA pathways.

Factors Associated with Klebsiella Bacteremia and Its Outcome in Under-Five Children Admitted with Diarrhea.

Although Klebsiella bacteremia in children is perceived to be associated with fatal consequences, data are scarce on those children presenting with diarrhea. We evaluated the factors associated with Klebsiella bacteremia in such children. In this retrospective chart analysis, data of all diarrheal children was retrieved from electronic medical record system (named as SHEBA) of Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), from January 1, 2010, to December 31, 2012, who had their blood culture done. This was a study having a case-control design where comparison of clinical and laboratory characteristics was done among children with Klebsiella bacteremia (cases = 30) and those without any bacteraemia (controls = 90). Controls were selected randomly. The cases more often had fatal outcome (p < 0.001). In logistic regression analysis, after adjusting for potential confounders such as young age, severe dehydration, severe wasting, abnormal mentation, hypotension, and fast breathing, the cases were independently associated with hospital-acquired infection and positive stool growth (for all, p < 0.05). The study highlights the importance of obtaining blood cultures in hospitalized children under five years old with diarrheal illness in the presence of either hospital-acquired infection or positive stool culture to have better outcome.

Chlorination of Household Drinking Water Among Cholera Patients' Households to Prevent Transmission of Toxigenic Vibrio cholerae in Dhaka, Bangladesh: CHoBI7 Trial.

Household members of cholera patients are at a 100 times higher risk of cholera infections than the general population because of shared contaminated drinking water sources and secondary transmission through poor household hygiene practices. In this study, we investigated the bactericidal concentration of free chlorine required to inactivate Vibrio cholerae in household drinking water in Dhaka, Bangladesh. In laboratory experiments, we found that the concentrations of free chlorine required to inactivate 105 colony-forming units (CFU)/mL of V. cholerae serogroups O1 and O139 were 0.1 mg/L and 0.2 mg/L, respectively. The concentration of free chlorine generated by a single chlorine tablet (sodium dichloroisocyanurate [33 mg]) after a 30-minute reaction time in a 10-L sealed vessel containing Dhaka city municipal supply water was 1.8 mg/L; and the concentration declined to 0.26 mg/L after 24 hours. In field measurements, water collected from 165 households enrolled in a randomized controlled trial (RCT) of a chlorine and handwashing with soap intervention (Cholera-Hospital-Based-Intervention-for-7-Days [CHoBI7]), we observed significantly higher free chlorine concentrations in the 82 intervention arm households (mean = 1.12 mg/L, standard deviation [SD] = 0.52, range = 0.07-2.6 mg/L) compared with the 83 control households (0.017 mg/L, SD = 0.01, range = 0-0.06 mg/L) (P < 0.001) during spot check visits. These findings suggest that point-of-use chlorine tablets present an effective approach to inactivate V. cholerae from drinking water in households of cholera patients in Dhaka city. This result is consistent with the findings from the RCT of CHoBI7 which found that this intervention led to a significant reduction in symptomatic cholera infections among household members of cholera patients and no stored drinking water samples with detectable V. cholerae.

UHRF1 contributes to DNA damage repair as a lesion recognition factor and nuclease scaffold.

We identified ubiquitin-like with PHD and RING finger domain 1 (UHRF1) as a binding factor for DNA interstrand crosslink (ICL) lesions through affinity purification of ICL-recognition activities. UHRF1 is recruited to DNA lesions in vivo and binds directly to ICL-containing DNA. UHRF1-deficient cells display increased sensitivity to a variety of DNA damages. We found that loss of UHRF1 led to retarded lesion processing and reduced recruitment of ICL repair nucleases to the site of DNA damage. UHRF1 interacts physically with both ERCC1 and MUS81, two nucleases involved in the repair of ICL lesions. Depletion of both UHRF1 and components of the Fanconi anemia (FA) pathway resulted in increased DNA damage sensitivity compared to defect of each mechanism alone. These results suggest that UHRF1 promotes recruitment of lesion-processing activities via its affinity to recognize DNA damage and functions as a nuclease recruitment scaffold in parallel to the FA pathway.