Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Altered distributions in circulating follicular helper and follicular regulatory T cells accountable for imbalanced cytokine production in multiple sclerosis.

Follicular T helper (Tfh) and regulatory (Tfr) cells are distinct subsets of CD4+ T lymphocytes, regulating humoral immune responses in the germinal center. It is widely accepted that dysregulated Tfh and Tfr cells are associated with autoimmunity. In this study, we evaluated the frequencies of circulating chemokine receptor (CXCR)5+ programmed cell death 1 (PD-1+ ) Tfh (cTfh) and CXCR5+ PD-1+ forkhead box protein 3 (FoxP3+ ) CD25+ Tfr (cTfr) cells, and their corresponding cytokines from the peripheral blood mononuclear cells of 28 patients with relapsing-remitting multiple sclerosis (MS) and 16 age- and sex-matched healthy controls (HC). Subsets of cTfh cells by Th1- and Th17-related surface markers (CXCR3 and CCR6) were also evaluated. We found that the frequency of cTfh cells was significantly higher in MS patients compared to that of HC. Conversely, the frequency of cTfr cells was lower in MS patients than that of HC. Interleukin (IL)-21-producing cTfh cells were significantly increased in MS patients, while IL-10-secreting cTfr cells were lower in MS patients compared to levels in HC. Among cTfh cells, cTfh17.1 cells were the major subtypes that were significantly increased in MS patients compared to HC, with the frequency of IL-21-secreting cells being the highest. These results suggest that an imbalanced distribution of cTfh and cTfr exist in MS patients, which contributes to the reciprocally altered IL-21 and IL-10 production.

Haloferax volcanii for biotechnology applications: challenges, current state and perspectives.

Haloferax volcanii is an obligate halophilic archaeon with its origin in the Dead Sea. Simple laboratory culture conditions and a wide range of genetic tools have made it a model organism for studying haloarchaeal cell biology. Halophilic enzymes of potential interest to biotechnology have opened up the application of this organism in biocatalysis, bioremediation, nanobiotechnology, bioplastics and the biofuel industry. Functionally active halophilic proteins can be easily expressed in a halophilic environment, and an extensive genetic toolkit with options for regulated protein overexpression has allowed the purification of biotechnologically important enzymes from different halophiles in H. volcanii. However, corrosion mediated damage caused to stainless-steel bioreactors by high salt concentrations and a tendency to form biofilms when cultured in high volume are some of the challenges of applying H. volcanii in biotechnology. The ability to employ expressed active proteins in immobilized cells within a porous biocompatible matrix offers new avenues for exploiting H. volcanii in biotechnology. This review critically evaluates the various application potentials, challenges and toolkits available for using this extreme halophilic organism in biotechnology.

Haloferax volcanii as immobilised whole cell biocatalyst: new applications for halophilic systems.

Enzyme-mediated synthesis of pharmaceutical compounds is a 'green' alternative to traditional synthetic chemistry, and microbial engineering opens up the possibility of using whole cells as mini-factories. Whole-cell biocatalysis reduces cost by eliminating expensive enzyme purification and cofactor addition steps, as well as resulting in increased enzyme stability. Haloferax volcanii is a model halophilic archaeon encoding highly salt and organic solvent tolerant enzymes such as alcohol dehydrogenase (HvADH2), which catalyses the reduction of aldehydes and ketone in the presence of NADPH/NADH cofactor. A H. volcanii strain for constitutive HvADH2 expression was generated using a strong synthetic promoter (p.syn). The strain was immobilised in calcium alginate beads and repeatedly used as a whole-cell biocatalyst. The reduction of acetophenone, used as test substrate, was very successful and high yields were detected from immobilised whole cells over repeated biotransformation cycles. The immobilised H. volcanii retained stability and high product yields after 1 month of storage at room temperature. This newly developed system offers halophilic enzyme expression in its native environment, high product yield, stability and reusability without the addition of any expensive NADPH/NADH cofactor. This is the first report of whole cell-mediated biocatalysis by the halophilic archaeon H. volcanii.

Seasonality and within-subject clustering of rotavirus infections in an eight-site birth cohort study.

Improving understanding of the pathogen-specific seasonality of enteric infections is critical to informing policy on the timing of preventive measures and to forecast trends in the burden of diarrhoeal disease. Data obtained from active surveillance of cohorts can capture the underlying infection status as transmission occurs in the community. The purpose of this study was to characterise rotavirus seasonality in eight different locations while adjusting for age, calendar time and within-subject clustering of episodes by applying an adapted Serfling model approach to data from a multi-site cohort study. In the Bangladesh and Peru sites, within-subject clustering was high, with more than half of infants who experienced one rotavirus infection going on to experience a second and more than 20% experiencing a third. In the five sites that are in countries that had not introduced the rotavirus vaccine, the model predicted a primary peak in prevalence during the dry season and, in three of these, a secondary peak during the rainy season. The patterns predicted by this approach are broadly congruent with several emerging hypotheses about rotavirus transmission and are consistent for both symptomatic and asymptomatic rotavirus episodes. These findings have practical implications for programme design, but caution should be exercised in deriving inferences about the underlying pathways driving these trends, particularly when extending the approach to other pathogens.

Association of vitamin D status with incidence of enterotoxigenic, enteropathogenic and enteroaggregative Escherichia coli diarrhoea in children of urban Bangladesh.

OBJECTIVE: To evaluate the association between vitamin D status and diarrhoeal episodes by enterotoxigenic (ETEC), enteropathogenic (EPEC) and enteroaggregative (EAEC) E. coli in underweight and normal-weight children aged 6-24 months in urban Bangladesh. METHODS: Cohorts of 446 normal-weight and 466 underweight children were tested separately for ETEC, EPEC and EAEC from diarrhoeal stool samples collected during 5 months of follow-up while considering vitamin D status at enrolment as the exposure. Cox proportional hazards models with unordered failure events of the same type were used to determine diarrhoeal risk factors after adjusting for sociodemographic and concurrent micronutrient status. RESULTS: Vitamin D status was not independently associated with the risk of incidence of ETEC, EPEC and EAEC diarrhoea in underweight children, but moderate-to-severe retinol deficiency was associated with reduced risk for EPEC diarrhoea upon adjustment. Among normal-weight children, insufficient vitamin D status and moderate-to-severe retinol deficiency were independently associated with 44% and 38% reduced risk of incidence of EAEC diarrhoea, respectively. These children were at higher risk of ETEC diarrhoea with vitamin D deficiency status when adjusted for micronutrient status only. CONCLUSION: This study demonstrates for the first time that normal-weight children with insufficient vitamin D status have a reduced risk of EAEC diarrhoea than children with sufficient status. Moderate-to-severe deficiency of serum retinol is associated with reduced risk of EPEC and EAEC diarrhoea in underweight and normal-weight children.

Association between serum vitamin D, retinol and zinc status, and acute respiratory infections in underweight and normal-weight children aged 6-24 months living in an urban slum in Bangladesh.

We conducted a longitudinal assessment in 466 underweight and 446 normal-weight children aged 6-24 months living in the urban slum of Dhaka, Bangladesh to determine the association between vitamin D and other micronutrient status with upper respiratory tract infection (URI) and acute lower respiratory infection (ALRI). Incidence rate ratios of URI and ALRI were estimated using multivariable generalized estimating equations. Our results indicate that underweight children with insufficient and deficient vitamin D status were associated with 20% and 23-25% reduced risk of URI, respectively, compared to children with sufficient status. Underweight children, those with serum retinol deficiency were at 1·8 [95% confidence interval (CI) 1·4-2·4] times higher risk of ALRI than those with retinol sufficiency. In normal-weight children there were no significant differences between different vitamin D status and the incidence of URI and ALRI. However, normal-weight children with zinc insufficiency and those that were serum retinol deficient had 1·2 (95% CI 1·0-1·5) times higher risk of URI and 1·9 (95% CI 1·4-2·6) times higher risk of ALRI, respectively. Thus, our results should encourage efforts to increase the intake of retinol-enriched food or supplementation in this population. However, the mechanisms through which vitamin D exerts beneficial effects on the incidence of childhood respiratory tract infection still needs further research.

Benefit/risk for adjuvant breast cancer therapy with tamoxifen or aromatase inhibitor use by age, and race/ethnicity.

In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.

Impact of neighborhood biomass cooking patterns on episodic high indoor particulate matter concentrations in clean fuel homes in Dhaka, Bangladesh.

Exposure to particulate matter (PM2.5 ) from the burning of biomass is associated with increased risk of respiratory disease. In Dhaka, Bangladesh, households that do not burn biomass often still experience high concentrations of PM2.5 , but the sources remain unexplained. We characterized the diurnal variation in the concentrations of PM2.5 in 257 households and compared the risk of experiencing high PM2.5 concentrations in biomass and non-biomass users. Indoor PM2.5 concentrations were estimated every minute over 24 h once a month from April 2009 through April 2010. We found that households that used gas or electricity experienced PM2.5 concentrations exceeding 1000 µg/m(3) for a mean of 35 min within a 24-h period compared with 66 min in biomass-burning households. In both households that used biomass and those that had no obvious source of particulate matter, the probability of PM2.5 exceeding 1000 µg/m(3) were highest during distinct morning, afternoon, and evening periods. In such densely populated settings, indoor pollution in clean fuel households may be determined by biomass used by neighbors, with the highest risk of exposure occurring during cooking periods. Community interventions to reduce biomass use may reduce exposure to high concentrations of PM2.5 in both biomass and non-biomass using households.

Indoor exposure to particulate matter and the incidence of acute lower respiratory infections among children: a birth cohort study in urban Bangladesh.

Approximately half of all children under two years of age in Bangladesh suffer from an acute lower respiratory infection (ALRI) each year. Exposure to indoor biomass smoke has been consistently associated with an increased risk of ALRI in young children. Our aim was to estimate the effect of indoor exposure to particulate matter (PM2.5 ) on the incidence of ALRI among children in a low-income, urban community in Bangladesh. We followed 257 children through two years of age to determine their frequency of ALRI and measured the PM2.5 concentrations in their sleeping space. Poisson regression was used to estimate the association between ALRI and the number of hours per day that PM2.5 concentrations exceeded 100 µg/m(3) , adjusting for known confounders. Each hour that PM2.5 concentrations exceeded 100 µg/m(3) was associated with a 7% increase in incidence of ALRI among children aged 0-11 months (adjusted incidence rate ratio (IRR) 1.07, 95% CI 1.01-1.14), but not in children 12-23 months old (adjusted IRR 1.00, 95% CI 0.92-1.09). Results from this study suggest that reducing indoor PM2.5 exposure could decrease the frequency of ALRI among infants, the children at highest risk of death from these infections.

Thermodynamic Analysis of a Flat Plate Solar Collector with Different Hybrid Nanofluids as Working Medium-A Thermal Modelling Approach.

In this study, the performance of hybrid nanofluids in a flat plate solar collector was analysed based on various parameters such as entropy generation, exergy efficiency, heat transfer enhancement, pumping power, and pressure drop. Five different base fluids were used, including water, ethylene glycol, methanol, radiator coolant, and engine oil, to make five types of hybrids nanofluids containing suspended CuO and MWCNT nanoparticles. The nanofluids were evaluated at nanoparticle volume fractions ranging from 1% to 3% and flow rates of 1 to 3.5 L/min. The analytical results revealed that the CuO-MWCNT/water nanofluid performed the best in reducing entropy generation at both volume fractions and volume flow rate when compared to the other nanofluids studied. Although CuO-MWCNT/methanol showed better heat transfer coefficients than CuO-MWCNT/water, it generated more entropy and had lower exergy efficiency. The CuO-MWCNT/water nanofluid not only had higher exergy efficiency and thermal performance but also showed promising results in reducing entropy generation.

Combinatorial topology and geometry of fracture networks.

A map is proposed from the space of planar surface fracture networks to a four-parameter mathematical space, summarizing the average topological connectivity and geometrical properties of a network idealized as a convex polygonal mesh. The four parameters are identified as the average number of nodes and edges, the angular defect with respect to regular polygons, and the isoperimetric ratio. The map serves as a low-dimensional signature of the fracture network and is visually presented as a pair of three-dimensional graphs. A systematic study is made of a wide collection of real crack networks for various materials, collected from different sources. To identify the characteristics of the real materials, several well-known mathematical models of convex polygonal networks are presented and worked out. These geometric models may correspond to different physical fracturing processes. The proposed map is shown to be discriminative, and the points corresponding to materials of similar properties are found to form closely spaced groups in the parameter space. Results for the real and simulated systems are compared in an attempt to identify crack networks of unknown materials.

Knowledge of Stroke and its Risk Factors among Stroke Survivors: A Hospital Based Study.

Significant variations observed in stroke incidence, risk factors and sufferings between high & resource poor countries. Considering lack of study in our country perspective, the study was designed to assess the knowledge of stroke and its risk factors among stroke survivors in Bangladeshi population. This hospital based cross-sectional study was conducted at the Department of Medicine and Department of Neurology in Uttara Adhunik Medical College & Hospital (UAMCH), Dhaka, Bangladesh. Patients aged >18 years who were admitted with stroke (Ischemic and hemorrhagic) were included in the study. Before enrollment informed consent was ensured. Total 50 patients were interviewed and assessed. Separate case record form was used during data collection. Final analysis was done by SPSS 22.00 version software. A 'good' knowledge of stroke was defined by correct answer to ≥4 out of 7 questions about location, cause, risk factor, warning sign, treatment, complication and prevention of stroke. Among 50 stroke survivors, mean age was 58.34±12.90 (SD) years. Male-female ratio was 1.08:1. Overall 78% patients had good knowledge of stroke. Brain was correctly identified as center of stroke by 52% stroke survivors and disturbance of blood supply to brain as a cause of stroke was recognized by 12%. Stress was the most common risk factor identified (50%). At least one warning sign was identified by 76% stroke survivors. Seventy-four percent stroke survivors knew that they have to be taken to nearest health facility and if possible, in hospital where neurological care is available. Only 4% knew about the golden hour of taking the stroke patient. On average knowledge about treatment, complication and prevention of stroke was good. Stroke knowledge was not significantly associated with demographic and socio-economic profile of stroke survivors. More than two thirds of the patients had knowledge regarding stroke and its risk factors but no uniform pattern of knowledge is noticed.

Rehabilitation Approach of a Patient with Myositis Ossificans: Non-surgical Management, Hazard of being Unguided Over Exercised.

Myositis ossificans (MO) is a condition where calcification occurs in the soft tissue as well as around the bone following fracture, vigorous exercise or trauma. Although it is a radiological diagnosis, it often leads physician to an incorrect or missed diagnosis as recurrent fracture. Frequently, it follows haemorrhage into the muscle in the tissue space. We report a 45 years old house-wife presented with the complaints of weakness of right side of body and pain with restricted range of motion (ROM) in right lower limb. She was a diagnosed case of recurrent stroke with rheumatic valvular heart disease. After discharge, vigorous physical exercise was done at home by local physiotherapist without appropriate guidance from physiatrist. Gradually pain was so severe that she didn't allow moving her right lower limb. Over the course of time, she became incapacite and bed bound. She denied any positive family history. With the hip and lower limb problems she consulted with orthopedic surgeon and was referred to Physical Medicine and Rehabilitation department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh for further management & rehabilitation. This case is presented to focus on hazard of being unguided, over-exercised and non-surgical management approach of this rare condition.

Anaphylaxis to patent blue V: a case series and proposed diagnostic protocol.

Patent blue V is widely used in the identification of sentinel lymph nodes in patients with breast cancer and other malignancies. Individual case reports of allergy to patent blue V have been described in the medical literature since the 1960s. However, there is little data on clinical features and little experience of which allergy tests are appropriate or useful. We gathered all cases of patent blue V allergy that had been seen and diagnosed in the Department of Allergy, Addenbrooke's Hospital over a 3-year period. We collected clinical details of each case including skin test results. For comparison we recruited 12 healthy control subjects who then underwent skin testing to patent blue V. Six cases of patent blue V allergy were identified, all occurring during sentinel lymph node identification for breast carcinoma. All 6 had positive skin prick tests to neat patent blue V (25 mg/ml). Skin prick testing with a 1 : 10 dilution (2.5 mg/ml) produced positive results in 3 of 4 patients tested, and intradermal testing at a 1 : 100 dilution was (0.25 mg/ml) was positive in all patients tested. Of 12 control subjects, 11 had negative skin prick tests to both neat and 1 : 10 patent blue V with one subject showing a positive reaction to the higher concentration only. On the basis of our experience of patent blue V allergy, we propose a diagnostic protocol that can be safely and reliably utilised in centres equipped for allergy testing.

Circadian clock genes of goldfish, Carassius auratus: cDNA cloning and rhythmic expression of period and cryptochrome transcripts in retina, liver, and gut.

Clock genes are known to be the molecular core of biological clocks of vertebrates. They are expressed not only in those tissues considered central pacemakers, but also in peripheral tissues. In the present study, partial cDNAs for 6 of the principal clock genes (Period 1-3 and Cryptochrome 1-3) were cloned from a teleost fish, the goldfish (Carassius auratus ). These genes showed high homology (approximately 90%) with the respective cDNAs of zebrafish (Danio rerio), the only other teleost from which clock genes have been cloned. The daily expression pattern of each gene in retina, gut, and liver of goldfish was investigated using quantitative RT-PCR and cosinor analysis. All clock genes analyzed in the retina showed circadian rhythmicity; however, only Per 2-3 and Cry 2-3 were rhythmic in goldfish liver and gut. The amplitude and phase of the expression in liver and gut were different from those found in goldfish retina. Such differences suggest that other cues, such as feeding time, may contribute to the entrainment of oscillators in goldfish liver and gut. Our results support the use of goldfish as a teleost model to investigate the location and functioning of the circadian oscillators.

Design and microfabrication strategies for thin-film, flexible optical neural implant.

Advanced polymer science and design technologies are constantly evolving to meet ever-growing expectations for flexible optical MEMS. In this work, we present design and microfabrication considerations for designed flexible Polymeric Opto-Electro-Mechanical Systems (POEMS). The presented methods integrate waveguide fabrication and laser diode (LD) chip assembly with Lawrence Livermore National Laboratory's (LLNL's) flexible thin-film technology to enable LLNL's first neural optoelectrode that can deliver guided light for neural activation. We support our findings with electrical and optical bench verification tests, present thermal simulation models to analyze heat dissipation of laser light sources on polymer substrates and discuss potential modifications for next generation prototypes. This fully integrated approach will allow spatial precision, scalability and more particularly, longer lifetime, needed to enable chronic studies of brain activities.

Antimalarial activity of tigecycline, a novel glycylcycline antibiotic.

Tigecycline is a novel glycylcycline antibiotic with a broad antibacterial spectrum. Tigecycline was tested with 66 clinical isolates of Plasmodium falciparum from Bangladesh using the histidine-rich protein 2 in vitro drug susceptibility assay. The 50% and 90% inhibitory concentrations of tigecycline were 699 (95% confidence interval, 496 to 986) and 5,905 nM (4,344 to 8,028). Tigecycline shows no activity correlation with traditional antimalarials and has substantial antimalarial activity on its own.

Binding of DDT to lecithin.

An interaction between DDT and lecithin is indicated by the reciprocal effects of each compound on the proton magnetic resonance spectrum of the other. The phosphoryl choline moiety of the lecithin and the benzylic proton of the DDT seem to be involved. The most pronounced response in the proton magnetic resonance spectrum of the lecithin produced by increasing concentration s of DDT was a change in the chemical shift of the resonance peak due to the protons of the choline methyl groups. Increasing concentrations of lecithin produced changes in the chemical shift of the resonance peaks of the benzylic proton and adjacent ring protons of the DDT. Equilibrium constant of 0.597 +/-0.015 molal(-1) was obtained for this interaction.

Cervical cancer in Bangladesh: community perceptions of cervical cancer and cervical cancer screening.

We investigated the awareness of, and the attitude towards screening for, cervical cancer in Bangladesh. We performed a qualitative study using focus group discussions (FGD). The framework approach to qualitative analysis was used. The study was performed in the catchment areas of Addin Hospital, Jessore, Southern Bangladesh (peri-urban) and LAMB hospital, Parbatipur, North West Bangladesh (rural). A total of 220 men, women and adolescents participated in 28 FGDs. Awareness of cervical cancer was widespread. Knowledge about causes was often inadequate. The perceived consequences of cervical cancer were numerous and awareness of the need for cervical cancer treatment was present. Barriers to accessing care include: low priority for seeking help for symptoms, limited availability of health services and cost. Most women were unaware of the possibility of screening via speculum examination, which was considered acceptable to women (and men), as long as the examination was done by a female healthcare provider in an environment with sufficient privacy. In conclusion, adequate gynaecological services are not available or accessible for most women in rural and peri-urban Bangladesh. However, awareness of cervical cancer is widespread. Screening for cervical cancer in these communities is acceptable if done by a female healthcare provider under conditions with sufficient privacy.