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1.
Data Brief ; 53: 110037, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38317724

ABSTRACT

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.

2.
Biosens Bioelectron ; 246: 115857, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38029708

ABSTRACT

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.


Subject(s)
Biosensing Techniques , Hydrogen Peroxide , Biosensing Techniques/methods , Anti-Bacterial Agents , Tetracycline , Tetracyclines , Colorimetry/methods , Peroxidase
3.
Res Sq ; 2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37503252

ABSTRACT

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.

4.
Popul Health Metr ; 19(1): 32, 2021 06 28.
Article in English | MEDLINE | ID: mdl-34183013

ABSTRACT

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.


Subject(s)
Cell Phone , Noncommunicable Diseases , Adult , Health Surveys , Humans , Risk Factors , Surveys and Questionnaires
5.
RSC Adv ; 10(29): 17336-17344, 2020 Apr 29.
Article in English | MEDLINE | ID: mdl-35521477

ABSTRACT

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.

6.
Anal Biochem ; 551: 29-36, 2018 06 15.
Article in English | MEDLINE | ID: mdl-29753720

ABSTRACT

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.


Subject(s)
Acetaminophen/analysis , Electrochemical Techniques/methods , Acetaminophen/blood , Acetaminophen/toxicity , Analgesics, Non-Narcotic/analysis , Analgesics, Non-Narcotic/blood , Antipyretics/analysis , Antipyretics/blood , Biosensing Techniques/methods , Chitosan/chemistry , Cobalt/chemistry , Dielectric Spectroscopy , Humans , Hydrogen-Ion Concentration , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Microscopy, Electron, Scanning , Nanocomposites/chemistry , Nanocomposites/ultrastructure , Nanotubes, Carbon/chemistry , Nanotubes, Carbon/ultrastructure , Spectroscopy, Fourier Transform Infrared , Tablets/chemistry
7.
Euroasian J Hepatogastroenterol ; 7(1): 107-110, 2017.
Article in English | MEDLINE | ID: mdl-29201788

ABSTRACT

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.

8.
Glob Pediatr Health ; 4: 2333794X17696685, 2017.
Article in English | MEDLINE | ID: mdl-28491923

ABSTRACT

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.

9.
Am J Trop Med Hyg ; 96(4): 953-960, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28167594

ABSTRACT

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.


Subject(s)
Diarrhea/economics , Diarrhea/epidemiology , Respiratory Tract Infections/economics , Respiratory Tract Infections/epidemiology , Rural Population , Bangladesh/epidemiology , Child, Preschool , Female , Health Care Costs , Humans , Infant , Male
10.
Am J Trop Med Hyg ; 95(6): 1299-1304, 2016 Dec 07.
Article in English | MEDLINE | ID: mdl-27698273

ABSTRACT

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.


Subject(s)
Cholera/prevention & control , Drinking Water/chemistry , Halogenation , Vibrio cholerae , Bangladesh , Chlorine/chemistry , Cholera/transmission , Family Characteristics , Humans , Water Purification/methods , Water Supply/standards
11.
Int J Pediatr ; 2016: 4760610, 2016.
Article in English | MEDLINE | ID: mdl-27651802

ABSTRACT

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.

12.
Cell Cycle ; 15(8): 1134-43, 2016.
Article in English | MEDLINE | ID: mdl-27097374

ABSTRACT

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.


Subject(s)
Fanconi Anemia/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Apoptosis , Cell Line, Tumor , Enzyme Activation , Fanconi Anemia Complementation Group D2 Protein/metabolism , Gene Deletion , Humans , Multiprotein Complexes/metabolism , Nuclear Proteins/metabolism , Phosphoprotein Phosphatases/metabolism , Phosphorylation , Protein Binding , RNA, Small Interfering/metabolism
13.
Cell Rep ; 10(12): 1957-66, 2015 Mar 31.
Article in English | MEDLINE | ID: mdl-25818288

ABSTRACT

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.


Subject(s)
CCAAT-Enhancer-Binding Proteins/metabolism , DNA Damage/physiology , DNA Repair/physiology , DNA/metabolism , Endonucleases/metabolism , Fanconi Anemia/genetics , Humans , Ubiquitin/metabolism , Ubiquitin-Protein Ligases
14.
Int J Gynaecol Obstet ; 118 Suppl 2: S141-7, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22920618

ABSTRACT

Treating complications of unsafe abortion can be financially draining for health systems. This analysis assessed incremental health system costs of service delivery for abortion-related complications in the Bangladesh public health system and confirmed that providing postabortion care with vacuum aspiration is less expensive than using dilation and curettage (D&C). Implementing several evidence-based best practices, such as replacing D&C with vacuum aspiration, reducing use of high-level sedation, authorizing midlevel providers to offer postabortion care, and providing postabortion contraceptive counseling and services to women while still at the health facility, could increase the quality and cost efficiency of postabortion care in Bangladesh.


Subject(s)
Abortion, Induced/economics , Health Care Costs/statistics & numerical data , Postoperative Care/economics , Postoperative Complications/economics , Quality of Health Care , Bangladesh , Family Planning Services , Female , Humans , Length of Stay/statistics & numerical data , Pregnancy , Vacuum Curettage/statistics & numerical data
15.
Cancer Epidemiol ; 35(1): 30-6, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20708995

ABSTRACT

BACKGROUND: The association between a history of cancer and mortality has not been studied in a propensity-matched population of community-dwelling older adults. METHODS: Of the 5795 participants in the Cardiovascular Health Study, 827 (14%) had self-reported physician-diagnosed cancer at baseline. Propensity scores for cancer were used to assemble a cohort of 789 and 3118 participants with and without cancer respectively who were balanced on 45 baseline characteristics. Cox regression models were used to determine the association between cancer and all-cause mortality among matched patients, and to identify independent predictors of mortality among unmatched cancer patients. RESULTS: Matched participants had a mean (SD) age of 74 (6) years, 57% were women, 10% were African Americans, and 38% died from all causes during 12 years of follow-up. All-cause mortality occurred in 41% and 37% of matched participants with and without a history of cancer respectively (hazard ratio when cancer was compared with no cancer, 1.16; 95% confidence interval, 1.02-1.31; P=0.019). Among those with cancer, older age, male gender, smoking, lower than college education, fair-to-poor self-reported health, coronary artery disease, diabetes mellitus, chronic kidney disease, left ventricular hypertrophy, increased heart rate, low hemoglobin and low baseline albumin were associated with increased risk of mortality. CONCLUSIONS: Among community-dwelling older adults, a history of cancer was associated with increased mortality and among those with cancer, several socio-demographic variables and morbidities predicted mortality. These findings suggest that addressing traditional risk factors for cardiovascular mortality may help improve outcomes in older adults with a history of cancer.


Subject(s)
Neoplasms/mortality , Adult , Age Factors , Aged , Cohort Studies , Female , Humans , Male , Prospective Studies , Residence Characteristics , Risk Factors , Survival Rate
16.
J Am Geriatr Soc ; 58(12): 2323-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21143440

ABSTRACT

OBJECTIVES: To understand the potential roles of various patient and provider factors in the underuse of pneumococcal vaccination in Medicare-eligible older African Americans. DESIGN: The Cardiovascular Health Study. SETTING: Four U.S. states. PARTICIPANTS: Seven hundred ninety-five pairs of community-dwelling Medicare-eligible African-American and white adults aged 65 and older, balanced according to age and sex. MEASUREMENTS: Data on self-reported race, receipt of pneumococcal vaccination, and other important sociodemographic and clinical variables were collected at baseline. RESULTS: Participants had a mean age ± standard deviation of 73 ± 6; 63% were female. Pneumococcal vaccination rates were 22% for African Americans and 28% for whites (unadjusted odds ratios (OR) for African Americans=0.75; 95% confidence interval (CI)=0.60-0.94; P=.01). This association remained significant despite adjustment for sociodemographic and clinical confounders, including education, income, chronic obstructive pulmonary disease, and prior pneumonia (OR=0.74, 95% CI=0.56-0.97; P=.03), but the association was no longer significant after additional adjustment for the receipt of influenza vaccination (OR=0.79, 95% CI=0.59-1.06; P=.12). Receipt of influenza vaccination was associated with higher odds of receiving pneumococcal vaccination (unadjusted OR=6.43, 95% CI=5.00-8.28; P<.001), and the association between race and pneumococcal vaccination lost significance when adjusted for influenza vaccination alone (OR=0.81, 95% CI=0.63-1.03; P=.09). CONCLUSION: The strong association between receipt of influenza and pneumococcal vaccinations suggests that patient and provider attitudes toward vaccination, rather than traditional confounders such as education and income, may help explain the underuse of pneumococcal vaccination in older African Americans.


Subject(s)
Black or African American/statistics & numerical data , Patient Acceptance of Health Care/ethnology , Pneumococcal Vaccines/administration & dosage , Pneumonia, Bacterial/prevention & control , White People/statistics & numerical data , Aged , Cohort Studies , Confidence Intervals , Female , Health Knowledge, Attitudes, Practice , Humans , Immunization Programs , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Male , Medicare/statistics & numerical data , Odds Ratio , Pneumonia, Bacterial/ethnology , Residence Characteristics , Risk Factors , Surveys and Questionnaires , United States/epidemiology , Vaccination/statistics & numerical data
17.
Aging Cell ; 9(6): 1047-56, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20854421

ABSTRACT

Conserved metallo ß-Lactamase and ß-CASP (CPSF-Artemis-Snm1-Pso2) domain nuclease family member SNM1B/Apollo is a shelterin-associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in a mouse model. Snm1B/Apollo homozygous null mice die at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Snm1B/Apollo mutant mouse embryonic fibroblasts (MEFs) owing to high levels of telomeric end-to-end fusions. Deficiency of the nonhomologous end-joining (NHEJ) factor Ku70, but not p53, rescued the developmental defects and lethality observed in Snm1B/Apollo mutant mice as well as the impaired proliferation of Snm1B/Apollo-deficient MEFs. These findings demonstrate that SNM1B/Apollo is required to protect telomeres against NHEJ-mediated repair, which results in genomic instability and the consequent multi-organ developmental failure. Although Snm1B/Apollo-deficient MEFs exhibited high levels of apoptosis, abrogation of p53-dependent programmed cell death did not rescue the multi-organ developmental failure in the mice.


Subject(s)
Cell Proliferation , Embryonic Development , Telomere-Binding Proteins/physiology , Telomere/metabolism , Animals , Apoptosis , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Embryo, Mammalian/metabolism , Exodeoxyribonucleases , Female , Genomic Instability , Mice , Mice, Knockout , Pregnancy , Telomere-Binding Proteins/genetics , Telomere-Binding Proteins/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
18.
BMC Public Health ; 10: 545, 2010 Sep 09.
Article in English | MEDLINE | ID: mdl-20828412

ABSTRACT

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.


Subject(s)
Hand Disinfection , Health Behavior , Observation , Rural Population , Adult , Bangladesh , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Social Class
19.
Vaccine ; 28(31): 4903-12, 2010 Jul 12.
Article in English | MEDLINE | ID: mdl-20653079

ABSTRACT

We piloted a low-cost approach to measure the disease burden of Streptococcus pneumoniae, Hib and Salmonella Typhi by leveraging the existing infrastructure of high performing microbiology laboratories at two large paediatric hospitals in Dhaka Bangladesh, and assessing the hospital utilization of the catchment population of these hospitals for different syndromes. S. Typhi was the most common bacterium identified in culture and accounted for an estimated 211 hospitalizations per 100,000 children <5 years of age per year. Meningitis due to S. pneumoniae was the most common cause of mortality accounting for 8.0 deaths per 100,000 children <5 years of age per year. This low-cost approach can provide data to support vaccine introduction and the health impact of newly introduced vaccines.


Subject(s)
Cost of Illness , Population Surveillance , Vaccination/economics , Bangladesh/epidemiology , Child, Preschool , Communicable Disease Control , Haemophilus Infections/economics , Haemophilus Infections/epidemiology , Haemophilus Infections/prevention & control , Haemophilus influenzae type b , Hospitals, Pediatric , Humans , Incidence , Infant , Meningitis, Pneumococcal/economics , Meningitis, Pneumococcal/epidemiology , Meningitis, Pneumococcal/prevention & control , Pilot Projects , Salmonella typhi , Typhoid Fever/economics , Typhoid Fever/epidemiology , Typhoid Fever/prevention & control , Urban Population
20.
EMBO J ; 29(13): 2230-41, 2010 Jul 07.
Article in English | MEDLINE | ID: mdl-20551906

ABSTRACT

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.


Subject(s)
DNA Repair , Fibroblasts/metabolism , Telomere-Binding Proteins/metabolism , Telomere/metabolism , Aminopeptidases/metabolism , Animals , Ataxia Telangiectasia Mutated Proteins , Cell Cycle Proteins/metabolism , Chromosomes/metabolism , DNA Damage , DNA-Binding Proteins/metabolism , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism , Embryo, Mammalian/cytology , Exodeoxyribonucleases , Mice , Mice, Knockout , Protein Serine-Threonine Kinases/metabolism , Serine Proteases/metabolism , Shelterin Complex , Telomere-Binding Proteins/genetics , Tripeptidyl-Peptidase 1 , Tumor Suppressor Proteins/metabolism
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