Therapeutic Phage Candidates for Targeting Prevalent Sequence Types of Carbapenem-Resistant Escherichia coli.

Carbapenem-resistant Escherichia coli (CREC) is a global threat to public health; therefore, alternative treatment options are urgently needed. Bacteriophages have emerged as promising candidates for combating CREC infections. This study aimed to investigate the genetic basis of phage sensitivity in CREC by evaluating carbapenem resistance among multidrug-resistant (MDR) E. coli isolated in Daegu, South Korea and analyzing their sequence types (STs) with phage susceptibility spectra. Among the 60 MDR E. coli isolates, 80.4% were identified as CREC, with 77.0% demonstrating resistance to imipenem and 66.6% to meropenem. Moreover, 70 lytic E. coli bacteriophages were isolated from hospital sewage water and evaluated against those 60 E. coli isolates. The phages exhibited lytic activity of 33%-60%, with average titers ranging from 5.6 × 1012 to 2.4 × 1013 PFU/mL (Plaque-Forming Unit). Furthermore, multilocus sequence typing (MLST) analysis of the bacterial isolates revealed 14 distinct STs, mostly belonging to ST131, ST410, and ST648. Notably, the phage susceptibility spectra of ST73, ST13003, ST648, ST2311, ST167, ST405, ST607, ST7962, and ST131 were significantly different. Thus, the isolated phages can effectively lyse CREC isolates, particularly those with clinically dominant STs. Conversely, ST410 exhibited a 14.2%-87.14% susceptibility spectrum, whereas ST1139, ST1487, ST10, and ST206 did not lyse, suggesting the presence of more resistant STs. Future studies are warranted to identify the reasons behind this resistance and address it. Ultimately, this study will aid in developing focused treatments to address these pressing global health issues.

Genome insight and probiotic potential of three novel species of the genus Corynebacterium.

Three bacterial strains, B5-R-101T, TA-R-1T, and BL-R-1T, were isolated from the feces of a healthy Korean individual. Cells of these strains were Gram-stain-positive, facultatively anaerobic, oxidase-negative, catalase-positive, rod-shaped, and non-motile. They were able to grow within a temperature range of 10-42°C (optimum, 32-37°C), at a pH range of 2.0-10.0 (optimum, pH 5.5-8.0), and at NaCl concentration of 0.5-10.5% (w/v). All the three strains exhibited 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities ranging from 58 ± 1.62 to 79 ± 1.46% (% inhibition). These strains survived in lower pH (2.0) and in 0.3% bile salt concentration for 4 h. They did not show hemolytic activity and exhibited antimicrobial activity against pathogenic bacteria, such as Escherichia coli, Acinetobacter baumannii, Staphylococcus aureus, and Salmonella enterica. The genomic analysis presented no significant concerns regarding antibiotic resistance or virulence gene content, indicating these strains could be potential probiotic candidates. Phylogenetic analysis showed that they belonged to the genus Corynebacterium, with 98.5-99.0% 16S rRNA gene sequence similarities to other members of the genus. Their major polar lipids were diphosphatidylglycerol and phosphatidylglycerol. The abundant cellular fatty acids were C16:0, C18:1ω9c, and anteiso-C19:0. Genomic analysis of these isolates revealed the presence of genes necessary for their survival and growth in the gut environment, such as multi-subunit ATPases, stress response genes, extracellular polymeric substance biosynthesis genes, and antibacterial genes. Furthermore, the genome of each strain possessed biosynthetic gene clusters with antioxidant and antimicrobial potentials, including terpenes, saccharides, polyketides, post-translationally modified peptides (RIPPs), and non-ribosomal peptides (NRPs). In silico DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values were lower than the thresholds to distinguish novel species. Based on phenotypic, genomic, phylogenomic, and phylogenetic analysis, these potential probiotic strains represent novel species within the genus Corynebacterium, for which the names Corynebacterium intestinale sp. nov. (type strain B5-R-101T = CGMCC 1.19408T = KCTC 49761T), Corynebacterium stercoris sp. nov. (type strain TA-R-1T = CGMCC 1.60014T = KCTC 49742T), and Corynebacterium faecium sp. nov. (type strain BL-R-1T = KCTC 49735T = TBRC 17331T) are proposed.

Recent drug development and treatments for fungal infections.

Fungal infections are now becoming a hazard to individuals which has paved the way for research to expand the therapeutic options available. Recent advances in drug design and compound screening have also increased the pace of the development of antifungal drugs. Although several novel potential molecules are reported, those discoveries have yet to be translated from bench to bedside. Polyenes, azoles, echinocandins, and flucytosine are among the few antifungal agents that are available for the treatment of fungal infections, but such conventional therapies show certain limitations like toxicity, drug interactions, and the development of resistance which limits the utility of existing antifungals, contributing to significant mortality and morbidity. This review article focuses on the existing therapies, the challenges associated with them, and the development of new therapies, including the ongoing and recent clinical trials, for the treatment of fungal infections. Advancements in antifungal treatment: a graphical overview of drug development, adverse effects, and future prospects.

Inhibition of Ribosome Assembly and Ribosome Translation Has Distinctly Different Effects on Abundance and Paralogue Composition of Ribosomal Protein mRNAs in Saccharomyces cerevisiae.

Many mutations in genes for ribosomal proteins (r-proteins) and assembly factors cause cell stress and altered cell fate, resulting in congenital diseases collectively called ribosomopathies. Even though all such mutations depress the cell's protein synthesis capacity, they generate many different phenotypes, suggesting that the diseases are not due simply to insufficient protein synthesis capacity. To learn more, we investigated how the global transcriptome in Saccharomyces cerevisiae responds to reduced protein synthesis generated in two different ways: abolishing the assembly of new ribosomes and inhibiting ribosomal function. Our results showed that the mechanism by which protein synthesis is obstructed affects the ribosomal protein transcriptome differentially: ribosomal protein mRNA abundance increases during the abolition of ribosome formation but decreases during the inhibition of ribosome function. Interestingly, the ratio between mRNAs from some, but not all, pairs of paralogous ribosomal protein genes encoding slightly different versions of a given r-protein changed differently during the two types of stress, suggesting that expression of specific ribosomal protein paralogous mRNAs may contribute to the stress response. Unexpectedly, the abundance of transcripts for ribosome assembly factors and translation factors remained relatively unaffected by the stresses. On the other hand, the state of the translation apparatus did affect cell physiology: mRNA levels for some other proteins not directly related to the translation apparatus also changed differentially, though not coordinately with the r-protein genes, in response to the stresses. IMPORTANCE Mutations in genes for ribosomal proteins or assembly factors cause a variety of diseases called ribosomopathies. These diseases are typically ascribed to a reduction in the cell's capacity for protein synthesis. Paradoxically, ribosomal mutations result in a wide variety of disease phenotypes, even though they all reduce protein synthesis. Here, we show that the transcriptome changes differently depending on how the protein synthesis capacity is reduced. Most strikingly, inhibiting ribosome formation and ribosome function had opposite effects on the abundance of mRNA for ribosomal proteins, while genes for ribosome translation and assembly factors showed no systematic responses. Thus, the process by which the protein synthesis capacity is reduced contributes decisively to global mRNA composition. This emphasis on process is a new concept in understanding ribosomopathies and other stress responses.

Exploring the role of astrocytic dysfunction and AQP4 in depression.

Aquaporin-4 (AQP4) is the water regulating channel found in the terminal processes of astrocytes in the brain and is implicated in regulating the astrocyte functions, whereas in neuropathologies, AQP4 performs an important role in astrocytosis and release of proinflammatory cytokines. However, several findings have revealed the modulation of the AQP4 water channel in the etiopathogenesis of various neuropsychiatric diseases. In the current article, we have summarized the recent studies and highlighted the implication of astrocytic dysfunction and AQP4 in the etiopathogenesis of depressive disorder. Most of the studies have measured the AQP4 gene or protein expression in the brain regions, particularly the locus coeruleus, choroid plexus, prefrontal cortex, and hippocampus, and found that in these brain regions, AQP4 gene expression decreased on exposure to chronic mild stress. Few studies also measured the peripheral AQP4 mRNA expression in the blood and AQP4 autoantibodies in the blood serum and revealed no change in the depressed patients in comparison with normal individuals.

Does Fish Farming Improve Household Nutritional Status? Evidence from Bangladesh.

In the present study, nutritional status was assessed using dietary diversity of fish and non-fish farming households in Mymensingh district of Bangladesh. It has determined the incidence of poverty in fish and non-fish farm households through a comparative analysis of family profile, food consumption, calories, and protein intake. A total of 420 farms were selected for data collection using structured questionnaires with 210 fish and 210 non-fish farm families. The study using both descriptive and functional analysis revealed that the respondent age of both farms was 45.10 years, family size was 5.70, average education was 4.64 schooling years, and average farm size was 0.514 hectares. As a result, due to the increase in household income, fish farm families improved their food consumption, calories, and protein intake in comparison with non-fish farms. On a direct calorie intake (DCI) basis, the overall absolute and hardcore poverty levels of fish farm households were 32 percent and 18 percent, respectively, while those of non-fish farm households were 22 percent and 10 percent, respectively. Therefore, the incidence of poverty was higher in non-fish farming families than in fish farming families. In principle, provision of various forms of government assistance through the Department of Fisheries (DOF) will further intensify and strengthen fish farming, which will easily bring fallow and uncultivated lands of the area under fish farming. Moreover, it is possible to inspire the younger generation through this research that will help them to become a fish farm-based entrepreneur. The main conclusion of the present study is that fish farming is more positively related to household income, family food intake, and nutritional status than any other type of farming.

Polyphenols inhibiting MAPK signalling pathway mediated oxidative stress and inflammation in depression.

Depression is one of the most debilitating psychiatric disorders affecting people of all ages worldwide. Despite significant heterogeneity between studies, increased inflammation and oxidative stress have been found in depression. Oxidative stress and inflammation are involved in the pathogenesis of depression. In the current review, we discussed the markers of oxidative stress and inflammation in depressive disorder and the association between these markers and the antidepressant treatment. The role of natural polyphenols in regulating various cell signaling pathways related to oxidative stress and inflammation has also been reviewed. The inhibitory effect of polyphenols on several cell signaling pathways reveals the vital role of polyphenols in the prevention and treatment of depressive disorder. Understanding the mechanism of polyphenols implicated in the regulation of cell signaling pathways is essential for the identification of lead compounds and the development of novel effective compounds for the prevention and treatment of depressive disorder.

Socio-Economic Context and Community Resilience among the People Involved in Fish Drying Practices in the South-East Coast of Bangladesh.

The south-east coast, specifically the Cox's Bazar region, of Bangladesh has achieved a tremendous impetus for producing a large volume of dried fish by involving thousands of marginalized coastal people. This study aimed to assess the socio-economic profile, livelihood strategies, and resilience of the communities engaged in fish drying on the south-east coast using a mixed-methods approach and an Analytic Hierarchy Process (AHP). The study's findings revealed that communities involved in drying were socio-economically undeveloped due to their lower literacy, unstable incomes, and labor-intensive occupations. Apart from notable child labor employed in fish drying in Nazirertek, female workers had relatively higher participation than males. Nevertheless, the female workers had less control over their daily wages and reported working at USD 3.54-5.89 per day, which was relatively lower than male workers who received USD 4.15-8.31 per day. Through fish drying activities, very few workers, producers, and traders were found to be self-reliant. In contrast, the livelihoods of the workers were not as secure as the processors and traders. In addition to suffering from various shocks and constraints, dried fish processors and workers, dried fish traders, off-season income, an abundance of fish species, fish drying facilities, trader's association, and social interrelationship played a significant role in maintaining community resilience. The study recommends appropriate interventions to alternative income diversification options, strong collaboration between communities, local authorities, and government for sustainable livelihoods and better community resilience.

Interaction between the assembly of the ribosomal subunits: Disruption of 40S ribosomal assembly causes accumulation of extra-ribosomal 60S ribosomal protein uL18/L5.

Inhibition of the synthesis of an essential ribosomal protein (r-protein) abrogates the assembly of its cognate subunit, while assembly of the other subunit continues. Ribosomal components that are not stably incorporated into ribosomal particles due to the disrupted assembly are rapidly degraded. The 60S protein uL18/L5 is an exception and this protein accumulates extra-ribosomally during inhibition of 60S assembly. Since the r-proteins in each ribosomal subunit are essential only for the formation of their cognate subunit, it would be predicted that accumulation of extra-ribosomal uL18/L5 is specific to restriction of 60S assembly and does not occur abolition of 40S assembly. Contrary to this prediction, we report here that repression of 40S r-protein genes does lead to accumulation of uL18/L5 outside of the ribosome. Furthermore, the effect varies depending on which 40S ribosomal protein is repressed. Our results also show extra-ribosomal uL18/L5 is formed during 60S assembly, not during degradation of mature cytoplasmic 60S subunits. Finally, we propose a model for the accumulation of extra-ribosomal uL18 in response to the abolition of 40S r-proteins.

Implementation of the World's largest measles-rubella mass vaccination campaign in Bangladesh: a process evaluation.

BACKGROUND: Gavi, the Vaccine Alliance, supported a mass vaccination Measles-Rubella Campaign (MRC) in Bangladesh during January-February 2014. METHODS: We conducted a mixed-method process evaluation to understand the successes and challenges in implementation of the MRC. We reviewed documents for the MRC and the immunization programme in Bangladesh; observed meetings, vaccination sessions, and health facilities; and conducted 58 key informant interviews, 574 exit interviews with caregivers and 156 brief surveys with stakeholders involved in immunization. Our theory of Change for vaccination delivery guided our assessment of ideal implementation milestones and indicators to compare with the actual implementation processes. RESULTS: We identified challenges relating to country-wide political unrest, administrative and budgetary delays, shortage of transportation, problems in registration of target populations, and fears about safety of the vaccine. Despite these issues, a number of elements contributed to the successful launch of the MRC. These included: the comprehensive design of the campaign; strong partnerships between immunization authorities in the government system, Alliance partners, and civil society actors; and motivated and skilled health workers at different levels of the health system. CONCLUSIONS: The successful implementation of the MRC in spite of numerous contextual and operational challenges demonstrated the adaptive capacity of the national immunization programme and its partners that has positive implications for future introductions of Gavi-supported vaccines.

The small and large ribosomal subunits depend on each other for stability and accumulation.

The 1:1 balance between the numbers of large and small ribosomal subunits can be disturbed by mutations that inhibit the assembly of only one of the subunits. Here, we have investigated if the cell can counteract an imbalance of the number of the two subunits. We show that abrogating 60S assembly blocks 40S subunit accumulation. In contrast, cessation of the 40S pathways does not prevent 60S accumulation, but does, however, lead to fragmentation of the 25S rRNA in 60S subunits and formation of a 55S ribosomal particle derived from the 60S. We also present evidence suggesting that these events occur post assembly and discuss the possibility that the turnover of subunits is due to vulnerability of free subunits not paired with the other subunit to form 80S ribosomes.

Re-evaluating the cost and cost-effectiveness of rotavirus vaccination in Bangladesh, Ghana, and Malawi: A comparison of three rotavirus vaccines.

INTRODUCTION: Diarrhea is a leading cause of mortality worldwide and rotavirus accounts for many of these deaths. As of August 2018, 96 countries have introduced rotavirus vaccines into their immunization programs. Two rotavirus vaccines, Rotarix® and RotaTeq®, have been WHO-prequalified since 2009, with Rotarix® being the preferred product of most Gavi-supported countries. ROTAVAC® and ROTASIIL® have both been prequalified recently. MATERIALS AND METHODS: We reevaluated the costs and cost-effectiveness of rotavirus vaccination in Bangladesh, Ghana, and Malawi and compared Rotarix®, ROTAVAC®, and ROTASIIL® in each country. For consistency with previously published analyses in these countries, we used the same Excel-based cohort model and much of the same data as the original analyses. We varied the expected price (with and without Gavi subsidy), wastage, and incremental health system costs associated with each vaccine. We assumed the same efficacy and waning assumptions following administration of two or three doses for the respective product. RESULTS: The discounted cost per DALY averted compared to no vaccination ranged from 0.3 to 1.3 times GNI per capita for each vaccine. With the Gavi subsidy, the average cost-effectiveness ratios were below 0.3 times GNI per capita in all three countries. Though critical empirical cost data are not yet available, Rotarix® is the least costly and most cost-effective product in the countries examined in this modelling study. However, small decreases in the incremental health system cost for other products could result in cost and cost-effectiveness outcomes that match or surpass those of Rotarix®. CONCLUSION: Countries may wish to consider new rotavirus vaccines entering the market. Countries should carefully examine multiple product attributes including price and the incremental health system costs associated with each vaccine. These costs will vary by country and may be a defining factor in determining the least costly and most cost-effective product for the population.

Factors influencing patients' satisfaction at different levels of health facilities in Bangladesh: Results from patient exit interviews.

There is a paucity in current literature about the level of patients' satisfaction and factors influencing it in Bangladesh health system. We aimed to measure the level of patients' satisfaction across different types and levels of healthcare facilities and to determine which factors influence this satisfaction level. A patient exit interview was carried out among 2207 patients attending selected health facilities in two administrative divisions of Bangladesh, namely Rajshahi and Sylhet. Information on healthcare experience and satisfaction with received care was collected through an electronic structured questionnaire. Information about 'overall satisfaction with healthcare' was collected on a 10-point scale and then dichotomized based on the median-split. Binomial logistic regressions, both simple and multivariable, were conducted to identify which factors contribute significantly to patients' satisfaction. We found that 63.2% of the participants were satisfied with the healthcare service they received. Patients attending the private facilities had the highest level of satisfaction (i.e. 73%) and patients attending the primary care facilities had the lowest level of satisfaction (i.e. 52%). Factors like convenient opening hours, asking related questions to the providers, facility cleanliness and privacy settings were significantly associated with patients' satisfaction. Being satisfied with facility cleanliness (multivariable OR 4.30; 95% CI: 3.29-5.62) and privacy settings (multivariable OR 1.68; 95% CI: 1.28-2.21) were the strongest predictors of patients' satisfaction. In conclusion, a significant portion of the patients in Bangladesh are not satisfied with their received care. Patients' satisfaction can be increased by focusing on improving facility cleanliness, privacy settings and providers' interpersonal skills.

General service and child immunization-specific readiness assessment of healthcare facilities in two selected divisions in Bangladesh.

BACKGROUND: Service readiness of health facilities is an integral part of providing comprehensive quality healthcare to the community. Comprehensive assessment of general and service-specific (i.e. child immunization) readiness will help to identify the bottlenecks in healthcare service delivery and gaps in equitable service provision. Assessing healthcare facilities readiness also helps in optimal policymaking and resource allocation. METHODS: A health facility survey was conducted between March 2015 and December 2015 in two purposively selected divisions in Bangladesh; i.e. Rajshahi division (high performing) and Sylhet division (low performing). A total of 123 health facilities were randomly selected from different levels of service, both public and private, with variation in sizes and patient loads from the list of facilities. Data on various aspects of healthcare facility were collected by interviewing key personnel. General service and child immunization specific service readiness were assessed using the Service Availability and Readiness Assessment (SARA) manual developed by World Health Organization (WHO). The analyses were stratified by division and level of healthcare facilities. RESULTS: The general service readiness index for pharmacies, community clinics, primary care facilities and higher care facilities were 40.6%, 60.5%, 59.8% and 69.5%, respectively in Rajshahi division and 44.3%, 57.8%, 57.5% and 73.4%, respectively in Sylhet division. Facilities at all levels had the highest scores for basic equipment (ranged between 51.7% and 93.7%) and the lowest scores for diagnostic capacity (ranged between 0.0% and 53.7%). Though facilities with vaccine storage capacity had very high levels of service readiness for child immunization, facilities without vaccine storage capacity lacked availability of many tracer items. Regarding readiness for newly introduced pneumococcal conjugate vaccine (PCV) and inactivated polio vaccine (IPV), most of the surveyed facilities reported lack of sufficient funding and resources (antigen) for training programs. CONCLUSIONS: Our study suggested that health facilities suffered from lack of readiness in various aspects, most notably in diagnostic capacity. Conversely, with very few challenges, nearly all the health facilities designated to provide immunization services were ready to deliver routine childhood immunization services as well as newly introduced PCV and IPV.

Analysis of cell cycle parameters during the transition from unhindered growth to ribosomal and translational stress conditions.

Abrogation of ribosome synthesis (ribosomal stress) leads to cell cycle arrest. However, the immediate cell response to cessation of ribosome formation and the transition from normal cell proliferation to cell cycle arrest have not been characterized. Furthermore, there are conflicting conclusions about whether cells are arrested in G2/M or G1, and whether the cause is dismantling ribosomal assembly per se, or the ensuing decreased number of translating ribosomes. To address these questions, we have compared the time kinetics of key cell cycle parameters after inhibiting ribosome formation or function in Saccharomyces cerevisiae. Within one-to-two hours of repressing genes for individual ribosomal proteins or Translation Elongation factor 3, configurations of spindles, spindle pole bodies began changing. Actin began depolarizing within 4 hours. Thus the loss of ribosome formation and function is sensed immediately. After several hours no spindles or mitotic actin rings were visible, but membrane ingression was completed in most cells and Ace2 was localized to daughter cell nuclei demonstrating that the G1 stage was reached. Thus cell division was completed without the help of a contractile actin ring. Moreover, cell wall material held mother and daughter cells together resulting in delayed cell separation, suggesting that expression or function of daughter gluconases and chitinases is inhibited. Moreover, cell development changes in very similar ways in response to inhibition of ribosome formation and function, compatible with the notion that decreased translation capacity contributes to arresting the cell cycle after abrogation of ribosome biogenesis. Potential implications for the mechanisms of diseases caused by mutations in ribosomal genes (ribosomopathies) are discussed.

Impact and cost-effectiveness of rotavirus vaccination in Bangladesh.

INTRODUCTION: Diarrheal disease is a leading cause of child mortality globally, and rotavirus is responsible for more than a third of those deaths. Despite substantial decreases, the number of rotavirus deaths in children under five was 215,000 per year in 2013. Of these deaths, approximately 41% occurred in Asia and 3% of those in Bangladesh. While Bangladesh has yet to introduce rotavirus vaccination, the country applied for Gavi support and plans to introduce it in 2018. This analysis evaluates the impact and cost-effectiveness of rotavirus vaccination in Bangladesh and provides estimates of the costs of the vaccination program to help inform decision-makers and international partners. METHODS: This analysis used Pan American Health Organization's TRIVAC model (version 2.0) to examine nationwide introduction of two-dose rotavirus vaccination in 2017, compared to no vaccination. Three mortality scenarios (low, high, and midpoint) were assessed. Benefits and costs were examined from the societal perspective over ten successive birth cohorts with a 3% discount rate. Model inputs were locally acquired and complemented by internationally validated estimates. RESULTS: Over ten years, rotavirus vaccination would prevent 4000 deaths, nearly 500,000 hospitalizations and 3 million outpatient visits in the base scenario. With a Gavi subsidy, cost/disability adjusted life year (DALY) ratios ranged from $58/DALY to $142/DALY averted. Without a Gavi subsidy and a vaccine price of $2.19 per dose, cost/DALY ratios ranged from $615/DALY to $1514/DALY averted. CONCLUSION: The discounted cost per DALY averted was less than the GDP per capita for nearly all scenarios considered, indicating that a routine rotavirus vaccination program is highly likely to be cost-effective. Even in a low mortality setting with no Gavi subsidy, rotavirus vaccination would be cost-effective. These estimates exclude the herd immunity benefits of vaccination, so represent a conservative estimate of the cost-effectiveness of rotavirus vaccination in Bangladesh.

Evaluation of impact of measles rubella campaign on vaccination coverage and routine immunization services in Bangladesh.

BACKGROUND: Like other countries in Asia, measles-rubella (MR) vaccine coverage in Bangladesh is suboptimal whereas 90-95 % coverage is needed for elimination of these diseases. The Ministry of Health and Family Welfare (MOHFW) of the Government of Bangladesh implemented MR campaign in January-February 2014 to increase MR vaccination coverage. Strategically, the MOHFW used both routine immunization centres and educational institutions for providing vaccine to the children aged 9 months to <15 years. The evaluation was carried out to assess the impact of the campaign on MR vaccination and routine immunization services. METHODS: Both quantitative and qualitative evaluations were done before and after implementation of the campaign. Quantitative data were presented with mean (standard deviation, SD) for continuous variables and with proportion for categorical variables. The overall and age- and sex-specific coverage rates were calculated for each region and then combined. Categorical variables were compared by chi-square statistics. Multiple logistic regression analysis were performed to estimate odds ratios (OR) and 95 % confidence intervals (CI) of coverage associated with covariates, with adjustment for other covariates. Qualitative data were analyzed using content analysis. RESULTS: The evaluations found MR coverage was very low (<13 %) before the campaign and it rose to 90 % after the campaign. The pre-post campaign difference in MR coverage in each stratum was highly significant (p < 0.001). The campaign achieved high coverage despite relatively low level (23 %) of interpersonal communication with caregivers through registration process. Child registration was associated with higher MR coverage (OR 2.91, 95 % CI 1.91-4.44). Children who attended school were more likely to be vaccinated (OR 8.97, 95 % CI 6.17-13.04) compared to those who did not attend school. Children of caregivers with primary or secondary or higher education had higher coverage compared to children of caregivers with no formal education. Most caregivers mentioned contribution of the campaign in vaccination for the children not previously vaccinated. CONCLUSIONS: The results of the evaluation indicated that the campaign was successful in terms of improving MR coverage and routine immunization services. The evaluation provided an important guideline for future evaluation of similar efforts in Bangladesh and elsewhere.

The extended loops of ribosomal proteins uL4 and uL22 of Escherichia coli contribute to ribosome assembly and protein translation.

Nearly half of ribosomal proteins are composed of a domain on the ribosome surface and a loop or extension that penetrates into the organelle's RNA core. Our previous work showed that ribosomes lacking the loops of ribosomal proteins uL4 or uL22 are still capable of entering polysomes. However, in those experiments we could not address the formation of mutant ribosomes, because we used strains that also expressed wild-type uL4 and uL22. Here, we have focused on ribosome assembly and function in strains in which loop deletion mutant genes are the ONLY: sources of uL4 or uL22 protein. The uL4 and uL22 loop deletions have different effects, but both mutations result in accumulation of immature particles that do not accumulate in detectable amounts in wild-type strains. Thus, our results suggest that deleting the loops creates kinetic barriers in the normal assembly pathway, possibly resulting in assembly via alternate pathway(s). Furthermore, deletion of the uL4 loop results in cold-sensitive ribosome assembly and function. Finally, ribosomes carrying either of the loop-deleted proteins responded normally to the secM translation pausing peptide, but the uL4 mutant responded very inefficiently to the cmlA(crb) pause peptide.

Use of mobile phones for improving vaccination coverage among children living in rural hard-to-reach areas and urban streets of Bangladesh.

In Bangladesh, full vaccination rates among children living in rural hard-to-reach areas and urban streets are low. We conducted a quasi-experimental pre-post study of a 12-month mobile phone intervention to improve vaccination among 0-11 months old children in rural hard-to-reach and urban street dweller areas. Software named "mTika" was employed within the existing public health system to electronically register each child's birth and remind mothers about upcoming vaccination dates with text messages. Android smart phones with mTika were provided to all health assistants/vaccinators and supervisors in intervention areas, while mothers used plain cell phones already owned by themselves or their families. Pre and post-intervention vaccination coverage was surveyed in intervention and control areas. Among children over 298 days old, full vaccination coverage actually decreased in control areas--rural baseline 65.9% to endline 55.2% and urban baseline 44.5% to endline 33.9%--while increasing in intervention areas from rural baseline 58.9% to endline 76*8%, difference +18.8% (95% CI 5.7-31.9) and urban baseline 40.7% to endline 57.1%, difference +16.5% (95% CI 3.9-29.0). Difference-in-difference (DID) estimates were +29.5% for rural intervention versus control areas and +27.1% for urban areas for full vaccination in children over 298 days old, and logistic regression adjusting for maternal education, mobile phone ownership, and sex of child showed intervention effect odds ratio (OR) of 3.8 (95% CI 1.5-9.2) in rural areas and 3.0 (95% CI 1.4-6.4) in urban areas. Among all age groups, intervention effects on age-appropriate vaccination coverage were positive: DIDs +13.1-30.5% and ORs 2.5-4.6 (p<0.001 in all comparisons). Qualitative data showed the intervention was well-accepted. Our study demonstrated that a mobile phone intervention can improve vaccination coverage in rural hard-to-reach and urban street dweller communities in Bangladesh. This small-scale successful demonstration should serve as an example to other low-income countries with high mobile phone usage.