ABSTRACT
Nutrition in early life plays a key role in shaping an infant's future health. There is limited understanding of the perspectives of Vietnamese mothers with children under 24 months of age regarding breastmilk expression, donation and use. In this cross-sectional study, an online survey was administered through two parenting social media communities to assess opinions on breastmilk expression, breastmilk donation including contributions from bereaved mothers and the use of donor human milk. A 4-point Likert scale was used to evaluate respondents' opinions, and demographic and breastfeeding information was collected. Among 375 respondents, almost 30% had received breastmilk from another woman, either through direct breastfeeding (14.7%), expressed breastmilk (12.5%) or from a human milk bank (2.7%). In this survey of 375 mothers, 84.0% indicated they would store excess breastmilk, while 75.7% and 69.6% would donate to a human milk bank or another mother, respectively. When faced with insufficient breastmilk, 88.5% of mothers would seek ways to increase supply, whereas 23.8% considered using commercial milk formula. Regarding milk expression among the 375 mothers, 78.4% preferred electric pumps, compared to 48.6% for manual pumps and 45.9% for hand expression. Additionally, 80.5% of the 375 mothers would suggest donating stored milk to bereaved peers and 85.6% would suggest mothers with mild COVID-19 to continue breastfeeding with precautions. These findings indicate that this sample has positive views on breastfeeding, breastmilk donation and the use of donor human milk.
ABSTRACT
BACKGROUND: Breastfeeding is the biological norm for feeding infants and young children. When mothers' breastmilk is unavailable, donor human milk (DHM) from a human milk bank (HMB) becomes the next option for small vulnerable newborns. A comprehensive cost analysis is essential for understanding the investments needed to establish, operate, and scale up HMBs. This study aims to estimate and analyze such costs at the first facility established in Vietnam. METHODS: An activity-based costing ingredients (ABC-I) approach was employed, with the cost perspective from service provision agencies (specifically, the project conducted at Da Nang Hospital for Women and Children and Development Partners). Estimated financial costs, based on actual expenditures, were measured in 2023 local currency and then converted to 2023 US dollars (USD). We examined three scenarios: 1) direct start-up costs + indirect start-up costs + implementation costs, 2) direct start-up costs + implementation costs, and 3) capital costs + implementation costs over the 6.5 years of operation. RESULTS: The total start-up cost was USD 616,263, with total expenditure on direct activities at USD 228,131 and indirect activities at USD 388,132. Investment in equipment accounted for the largest proportion (USD 84,213). The monthly costs of Da Nang HMB were USD 25,217, 14,565, and 9,326, corresponding to scenarios 1, 2, and 3, respectively. Over HMB's 6.5 years of operation, on average, the unit costs were USD 166, USD 96, and USD 62 for DHM received and USD 201, USD 116, and USD 74 for pasteurized DHM meeting specified criteria in the corresponding scenarios. Unit costs were highest in the initial six months, decreased, and reached their lowest levels after a year. Then, the unit costs experienced an increase in late 2020 and early 2021. CONCLUSION: Although the unit cost of DHM in Da Nang HMB is comparable to that in certain neighboring countries, intentional measures to reduce disposal rates, improve HMB efficiency, motivate more community-based donors, and establish an HMB service network should be implemented to lower costs.
Subject(s)
Costs and Cost Analysis , Milk Banks , Milk, Human , Humans , Vietnam , Milk Banks/economics , Female , Infant, Newborn , Infant , Breast Feeding/economicsABSTRACT
Economic and environmental concerns over the accumulation of end-of-life carbon fibre composite waste have led to increased attention to sustainable materials with low environmental impact. Over decades of research, vitrimers, a modern class of covalent adaptable networks, have bridged the gap between thermoplastics and thermosets. With the distinguishing feature of dynamic covalent bonds, vitrimers can be rearranged and reprocessed within their existing network structures in response to external stimuli such as heat or light. This poses a unique solution to repairing damaged composites, extending their service life, and reducing post-consumer waste. However, the synthesis of vitrimers often requires petrochemical consumption, which increases their carbon footprint. Using bio-based materials could be a promising solution to reduce the reliance on petrochemicals and their related pollution. This review compiles the contemporary requirements for bio-based vitrimers regarding their properties, scalability, and recycling features. This article also presents a comprehensive overview of the pathways to produce sustainable bio-based vitrimers and an overview of promising studies showing the potential uses of bio-derived vitrimers on carbon fibre composite productions.
ABSTRACT
BACKGROUND: Five distinct respiratory phenotypes based on latent classes of longitudinal patterns of wheezing, allergic sensitization. and pulmonary function measured in urban children from ages from 0 to 7 years have previously been described. OBJECTIVE: Our aim was to determine whether distinct respiratory phenotypes are associated with early-life upper respiratory microbiota development and environmental microbial exposures. METHODS: Microbiota profiling was performed using 16S ribosomal RNA-based sequencing of nasal samples collected at age 12 months (n = 120) or age 36 months (n = 142) and paired house dust samples collected at 3 months (12-month, n = 73; 36-month, n = 90) from all 4 centers in the Urban Environment and Childhood Asthma (URECA) cohort. RESULTS: In these high-risk urban children, nasal microbiota increased in diversity between ages 12 and 36 months (ß = 2.04; P = .006). Age-related changes in microbiota evenness differed significantly by respiratory phenotypes (interaction P = .0007), increasing most in the transient wheeze group. At age 12 months, respiratory illness (R2 = 0.055; P = .0001) and dominant bacterial genus (R2 = 0.59; P = .0001) explained variance in nasal microbiota composition, and enrichment of Moraxella and Haemophilus members was associated with both transient and high-wheeze respiratory phenotypes. By age 36 months, nasal microbiota was significantly associated with respiratory phenotypes (R2 = 0.019; P = .0376), and Moraxella-dominated microbiota was associated specifically with atopy-associated phenotypes. Analysis of paired house dust and nasal samples indicated that 12 month olds with low wheeze and atopy incidence exhibited the largest number of shared bacterial taxa with their environment. CONCLUSION: Nasal microbiota development over the course of early childhood and composition at age 3 years are associated with longitudinal respiratory phenotypes. These data provide evidence supporting an early-life window of airway microbiota development that is influenced by environmental microbial exposures in infancy and associates with wheeze- and atopy-associated respiratory phenotypes through age 7 years.
Subject(s)
Microbiota , Phenotype , Respiratory Sounds , Urban Population , Humans , Infant , Child, Preschool , Male , Female , Longitudinal Studies , Asthma/microbiology , Asthma/epidemiology , Dust/analysis , Dust/immunology , Environmental Exposure , Nose/microbiology , RNA, Ribosomal, 16S/genetics , ChildABSTRACT
The prevalence of early and exclusive breastfeeding in Vietnam remains sub-optimal. The objective of this study was to determine factors associated with early initiation of breastfeeding (EIBF) and exclusive breastfeeding for the first 3 days after birth (EBF3D). We conducted a population-based, cross-sectional survey of 726 mothers with children aged 0-11 months in two provinces and one municipality from May to July 2020. Multinomial logistic regression was used to examine factors associated with EIBF and EBF3D. The prevalence of EIBF was 39.7% and EBF3D 18.0%. The EIBF prevalence is positively associated with immediate and uninterrupted skin-to-skin contact (SSC) for 10-29 min (aOR: 2.55; 95% CI: 1.49, 4.37), 30-59 min (aOR: 4.15; 95% CI: 2.08, 8.27), 60-80 min (aOR: 4.35; 95% CI: 1.50, 12.6), or ≥90 min (aOR: 5.87; 95% CI: 3.14, 10.98). EIBF was negatively associated with cesarean birth (aOR: 0.24; 95% CI: 0.11, 0.51), bringing infant formula to the birth facility (aOR: 0.49; 95% CI: 0.30, 0.78), purchased it after arrival (aOR: 0.37; 95% CI: 0.24, 0.60), or did both (aOR: 0.43; 95% CI: 0.21, 0.89). EBF3D was negatively associated with cesarean section birth (aOR: 0.15; 95% CI: 0.06, 0.39), vaginal birth with episiotomy (aOR: 0.40; 95% CI: 0.18, 0.88), bringing formula to the maternity facility (aOR: 0.03; 95% CI: 0.01, 0.07), purchased it after arrival (aOR: 0.02; 95% CI: 0.01, 0.06) or did both (aOR: 0.04; 95% CI: 0.02, 0.10). Receiving counseling from any source was not significantly associated with early breastfeeding practices. Policy and health service delivery interventions should be directed at eliminating infant formula from birthing environments, reducing unnecessary cesarean sections and episiotomies, providing immediate and uninterrupted SSC for all births, and improving breastfeeding counseling and support.
ABSTRACT
Commercial milk formula for pregnant women (CMF-PW) is an expensive, ultra-processed food with a high concentration of sugar, the consumption of which may be linked to negative health outcomes. However, CMF-PWs are promoted as beneficial for pregnant women and lactating mothers as well as their children. To date, little is known about the factors associated with the use of CMF-PW among pregnant women. We performed this analysis to examine the association between the use of CMF-PW and related beliefs and norms among pregnant women in Vietnam. We interviewed 268 pregnant women in their second and third trimesters from two provinces and one municipality representing diverse communities in Vietnam. Multinomial (polytomous) logistic regression, structural equation modeling (SEM), and propensity score matching (PSM) analysis were used to examine associations between beliefs and social norms related to CMF-PW and reported consumption, characterized as occasional, recent, and never during the current pregnancy. Overall, 64.6% of pregnant women reported using CMF-PW during the current pregnancy and 34.7% consumed CMF-PW on the day prior to the interview. Strong beliefs that CMF-PW will make a child smart and healthy (53.7%) and the perception that use of CMF-PW is common (70.9%) were associated with increased use on the previous day (beliefs: aOR: 3.56; 95% Confidence Interval (95% CI): 1.65, 7.71; p < 0.01 and social norms aOR: 2.29; 95% CI: 1.13, 4.66; p < 0.05). SEM and PSM analyses confirmed these findings for both occasional and regular CMF-PW use. Results are consistent with observations of CMF-PW product labels and marketing tactics in Vietnam. The prevalent use of CMF-PW in Vietnam is associated with the belief that these products make children smart and healthy and the perceived social norm that most mothers use these products, which mirrors marketing messages and approaches employed by the CMF industry.
Subject(s)
Diet, Healthy/psychology , Drinking Behavior , Feeding Behavior/psychology , Milk Substitutes/statistics & numerical data , Pregnant Women/psychology , Culture , Female , Humans , Latent Class Analysis , Logistic Models , Pregnancy , Propensity Score , Social Norms , VietnamSubject(s)
Milk Banks , Milk, Human , Breast Feeding , Female , Humans , Infant, Newborn , Infant, Premature , VietnamABSTRACT
BACKGROUND AND OBJECTIVES: Excessive use of antibiotics has been noted in children with respiratory tract infections in Vietnam, but antibiotic use in hospitalised children is poorly documented. Antibiotic use and direct healthcare costs in children hospitalised with pneumonia in central Vietnam were assessed. METHODS: A prospective descriptive study of children under 5 years old admitted with a primary admission diagnosis of 'pneumonia' to the Da Nang Hospital for Women and Children over 1 year. RESULTS: Of 2911 children hospitalised with pneumonia, 2735 (94.0%) were classified as 'non-severe' pneumonia by the admitting physician. In total, 2853 (98.0%) children received antibiotics. Intravenous antibiotics were given to 336 (12.3%) children with 'non-severe' and 157/176 (89.2%) children with 'severe' pneumonia; those with 'non-severe' pneumonia accounted for 68.2% (336/493) of intravenous antibiotics given. Only 19.3% (95/493) of children on intravenous antibiotics were stepped down to an oral antibiotic. Cefuroxime was the preferred oral agent, and ceftriaxone was the preferred injectable agent. Hospital admission for oral antibiotics in 'non-severe' pneumonia was a major cost driver, with an average direct cost of US$78.9 per patient, accounting for 54.0% of the total hospitalisation cost in the study cohort. In addition, 336 (12.3%) children with non-severe pneumonia received intravenous antibiotics without indication, accounting for a further 23.2% of hospitalisation costs. CONCLUSION: Limiting unnecessary hospitalisation and considering early intravenous to oral step down antibiotic will reduce direct health system costs and morbidity in children with respiratory tract infections in Vietnam.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Health Care Costs/statistics & numerical data , Hospitalization/statistics & numerical data , Inappropriate Prescribing/statistics & numerical data , Medical Overuse/statistics & numerical data , Pneumonia/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Administration, Intravenous , Administration, Oral , Anti-Bacterial Agents/economics , Child, Preschool , Female , Hospitalization/economics , Humans , Inappropriate Prescribing/economics , Infant , Male , Medical Overuse/economics , Pneumonia/diagnosis , Pneumonia/economics , Practice Patterns, Physicians'/economics , Prospective Studies , Severity of Illness Index , VietnamABSTRACT
BACKGROUND: Pneumonia is the leading cause of antibiotic use and hospitalization in Vietnam. There is a need for better prediction of unlikely bacterial pneumonia and adverse pneumonia outcome in order to guide hospital admission and improve rational antibiotic use. METHODS: All children under 5 admitted with pneumonia (per clinician assessment) to the Da Nang Hospital for Women and Children were prospectively enrolled. Children were classified as having likely or unlikely bacterial pneumonia and followed for outcome assessment. A Bayesian model averaging approach was used to identify predictors of unlikely bacterial pneumonia and adverse pneumonia outcome, which guided the development of a pragmatic management algorithm. RESULTS: Of 3817 patients assessed, 2199 (57.6%) met World Health Organization (WHO) pneumonia criteria. In total, 1594 (41.7%) children were classified as having unlikely and 129 (3.4%) as having likely bacterial pneumonia. The remainder (2399; 62.9%) were considered to have disease of uncertain etiology. Factors predictive of unlikely bacterial pneumonia were no fever, no consolidation on chest radiograph, and absolute neutrophil count <5 × 109/L at presentation, which had a negative predictive value (NPV) for likely bacterial pneumonia of 99.0%. Among those who met WHO pneumonia criteria, 8.6% (189/2199) experienced an adverse outcome. Not having any WHO danger sign or consolidation on chest radiograph had an NPV of 96.8% for adverse pneumonia outcome. CONCLUSIONS: An algorithm that screens for predictors of likely bacterial pneumonia and adverse pneumonia outcome could reduce unnecessary antibiotic use and hospital admission, but its clinical utility requires validation in a prospective study.
Subject(s)
Pneumonia, Bacterial , Pneumonia , Bayes Theorem , Child , Female , Hospitalization , Hospitals , Humans , Infant , Pneumonia/epidemiology , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/epidemiology , Prospective Studies , Vietnam/epidemiologyABSTRACT
BACKGROUND: In infants, distinct nasopharyngeal bacterial microbiotas differentially associate with the incidence and severity of acute respiratory tract infection and childhood asthma development. OBJECTIVE: We hypothesized that distinct nasal airway microbiota structures also exist in children with asthma and relate to clinical outcomes. METHODS: Nasal secretion samples (n = 3122) collected after randomization during the fall season from children with asthma (6-17 years, n = 413) enrolled in a trial of omalizumab (anti-IgE) underwent 16S rRNA profiling. Statistical analyses with exacerbation as the primary outcome and rhinovirus infection and respiratory illnesses as secondary outcomes were performed. Using A549 epithelial cells, we assessed nasal isolates of Moraxella, Staphylococcus, and Corynebacterium species for their capacity to induce epithelial damage and inflammatory responses. RESULTS: Six nasal airway microbiota assemblages, each dominated by Moraxella, Staphylococcus, Corynebacterium, Streptococcus, Alloiococcus, or Haemophilus species, were observed. Moraxella and Staphylococcus species-dominated microbiotas were most frequently detected and exhibited temporal stability. Nasal microbiotas dominated by Moraxella species were associated with increased exacerbation risk and eosinophil activation. Staphylococcus or Corynebacterium species-dominated microbiotas were associated with reduced respiratory illness and exacerbation events, whereas Streptococcus species-dominated assemblages increased the risk of rhinovirus infection. Nasal microbiota composition remained relatively stable despite viral infection or exacerbation; only a few taxa belonging to the dominant genera exhibited relative abundance fluctuations during these events. In vitro, Moraxella catarrhalis induced significantly greater epithelial damage and inflammatory cytokine expression (IL-33 and IL-8) compared with other dominant nasal bacterial isolates tested. CONCLUSION: Distinct nasal airway microbiotas of children with asthma relate to the likelihood of exacerbation, rhinovirus infection, and respiratory illnesses during the fall season.
Subject(s)
Asthma/microbiology , Eosinophils/immunology , Microbiota/genetics , Nasal Mucosa/microbiology , RNA, Ribosomal, 16S/analysis , Respiratory System/pathology , Respiratory Tract Infections/microbiology , A549 Cells , Adolescent , Asthma/immunology , Cell Death , Child , Disease Progression , Female , Humans , Infant , Inflammation , Male , Nasal Mucosa/immunology , Respiratory Tract Infections/immunologyABSTRACT
Pneumonia is the most common reason for paediatric hospital admission in Vietnam. The potential value of using the World Health Organization (WHO) case management approach in Vietnam has not been documented.We performed a prospective descriptive study of all children (2-59â months) admitted with "pneumonia" (as assessed by the admitting clinician) to the Da Nang Hospital for Women and Children to characterise their disease profiles and assess risk factors for an adverse outcome. The disease profile was classified using WHO pneumonia criteria, with tachypnoea or chest indrawing as defining clinical signs. Adverse outcome was defined as death, intensive care unit admission, tertiary care transfer or hospital stay >10â days.Of 4206 admissions, 1758 (41.8%) were classified as "no pneumonia" using WHO criteria and only 252 (6.0%) met revised criteria for "severe pneumonia". The inpatient death rate was low (0.4% of admissions) with most deaths (11 out of 16; 68.8%) occurring in the "severe pneumonia" group. An adverse outcome was recorded in 18.7% of all admissions and 60.7% of the "severe pneumonia" group. Children were hospitalised for a median of 7â days at an average cost of 253 USD per admission. Risk factors for adverse outcome included WHO-classified "severe pneumonia", age <1â year, low birth weight, previous recent admission with an acute respiratory infection and recent tuberculosis exposure. Breastfeeding, day-care attendance and pre-admission antibiotic use were associated with reduced risk.Few hospital admissions met WHO criteria for "severe pneumonia", suggesting potential unnecessary hospitalisation and use of intravenous antibiotics. Better characterisation of the underlying diagnosis requires careful consideration.
Subject(s)
Hospitalization/statistics & numerical data , Pneumonia/classification , Pneumonia/mortality , Anti-Bacterial Agents/therapeutic use , Case Management , Child, Preschool , Female , Humans , Infant , Logistic Models , Male , Multivariate Analysis , Pneumonia/therapy , Prospective Studies , Risk Factors , Severity of Illness Index , Vietnam/epidemiology , World Health OrganizationABSTRACT
AIM: To characterise paediatricians' antibiotic-prescribing behaviour when managing community acquired pneumonia. METHODS: We conducted a knowledge and attitudes survey of paediatric doctors practicing at a regional provincial hospital in central Vietnam over a 2-week period (from 12 December 2017 to 29 December 2017). RESULTS: Of 79 eligible paediatric doctors, 69 (87.3%) completed the questionnaire, of whom 65 (94.2%) thought that antibiotics were overused in Vietnam. Thirty-eight doctors (55.1%) indicated that they routinely hospitalised children with pneumonia to provide intravenous antibiotics. Most doctors reported discharging children with non-severe pneumonia after 5 days (76.9%) and those with severe pneumonia after 7-10 days (88.4%); older doctors generally continued intravenous antibiotics for longer. The two most important factors driving discharge decisions were clinical assessment (95.6%) and completion of the full course of intravenous antibiotics (80.0%). Antibiotic prescription was influenced by local guidelines (62.3%), drugs used before admission (50.0%) and the opinion of senior clinicians (37.7%). Most doctors believed antibiotic stewardship was necessary (98.6%) and that over-the-counter use of antibiotics should be restricted (97.1%). CONCLUSIONS: Paediatricians recognised an urgent need for more effective regulation and antibiotic stewardship in Vietnam. Routinely completing a full course of intravenous antibiotics leads to unnecessary and prolonged hospitalisation.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship/standards , Pneumonia/drug therapy , Adult , Child , Community-Acquired Infections/drug therapy , Female , Humans , Male , Middle Aged , Pediatricians , VietnamABSTRACT
BACKGROUND: Neonatal mortality accounts for nearly three quarters of all infant deaths in Vietnam. The nursing team are the largest professional group working with newborns, however do not routinely receive neonatal training and there is a lack of research into the impact of educational provision. This study explored changes in nursing perceptions towards their role following a neonatal educational intervention. Parents perceptions of nursing care were explored to determine any changes as nurses gained more experience. METHOD: Semi-Structured qualitative interviews were conducted every 6 months over an 18 month period with 16 nurses. At each time point, parents whose infant was resident on the neonatal unit were invited to participate in an interview to explore their experiences of nursing care. A total of 67 parents participated over 18 months. Interviews were conducted and transcribed in Vietnamese before translation into English for manifest content analysis facilitated by NVivo V14. RESULTS: Analysis of nursing transcripts identified 14 basic categories which could be grouped (23) into 3 themes: (1) perceptions of the role of the neonatal nurse, (2) perception of the parental role and (3) professional recollections. Analysis of parent transcripts identified 14 basic categories which could be grouped into 3 themes: (1) information sharing, (2) participation in care, and (3) personal experience. CONCLUSIONS: Qualitative interviews highlighted the short term effect that the introduction of an educational intervention can have on both nursing attitudes towards and parental experience of care in one neonatal unit in central Vietnam. Nurses shared a growing awareness of their role along with its ethical issues and challenges, whilst parents discussed their overall desire for more participation in their infants care. Further research is required to determine the long term impact of the intervention, the ability of nurses to translate knowledge into clinical practice through assessment of nursing knowledge and competence, and the impact and needs of parents. A greater understanding will allow us to continue to improve the experiences of nurses and parents, and highlight how these areas may contribute towards the reduction of infant mortality and morbidity in Vietnam.
Subject(s)
Attitude of Health Personnel , Attitude to Health , Education, Nursing, Continuing , Neonatal Nursing/education , Nurses, Neonatal/psychology , Parents/psychology , Developing Countries , Female , Humans , Infant, Newborn , Intensive Care, Neonatal/psychology , Interviews as Topic , Longitudinal Studies , Male , Nurse's Role , Nurses, Neonatal/education , Professional-Family Relations , Qualitative Research , VietnamABSTRACT
AIM: This study explored neonatal morbidity and mortality in hospitalised patients in central Vietnam and risk factors associated with mortality. METHODS: We conducted a prospective cohort study of all newborn infants (<28 days) hospitalised in a neonatal unit over a 1-year period and followed until discharge. The main outcome measures were case fatality rate and the rate of different clinical diagnoses. RESULTS: There were 2555 admissions during the study period. The leading primary causes of admissions were infections (41%), haematological problems such as jaundice (23%) and prematurity and its complications (18%). The overall case fatality rate was 8.6%, and it was 59% among very low-birthweight (<1500 g) neonates. Mortality was inversely associated with birthweight and gestational age. Of the 220 deaths, 57% occurred within the first 7 days of life. Although the causes of death were often multifactorial, the leading primary causes were infections (32%), prematurity and its complications (25%), birth defects (24%) and birth asphyxia (6%). Risk factors associated with death were being outborn, early gestational age, small for gestational age, confirmed sepsis and birth defects. CONCLUSION: Mortality rates were high among hospitalised neonates in central Vietnam, and this paper suggests interventions that might improve outcomes.
Subject(s)
Cause of Death , Infant Mortality , Female , Humans , Infant , Infant, Newborn , Male , Patient Admission/statistics & numerical data , Prospective Studies , Vietnam/epidemiologyABSTRACT
As an important aspect of computer-aided drug design, structure-based drug design brought a new horizon to pharmaceutical development. This in silico method permeates all aspects of drug discovery today, including lead identification, lead optimization, ADMET prediction and drug repurposing. Structure-based drug design has resulted in fruitful successes drug discovery targeting proteinligand and protein-protein interactions. Meanwhile, challenges, noted by low accuracy and combinatoric issues, may also cause failures. In this review, state-of-the-art techniques for protein modeling (e.g. structure prediction, modeling protein flexibility, etc.), hit identification/ optimization (e.g. molecular docking, focused library design, fragment-based design, molecular dynamic, etc.), and polypharmacology design will be discussed. We will explore how structure-based techniques can facilitate the drug discovery process and interplay with other experimental approaches.
Subject(s)
Computer-Aided Design , Drug Design , Proteins/metabolism , Drug Delivery Systems , Drug Discovery/methods , High-Throughput Screening Assays/methods , Humans , Models, Molecular , Protein Conformation , Proteins/chemistry , Structure-Activity RelationshipABSTRACT
Neonatal morbidity and mortality are major global public health challenges representing an increasing proportion of overall under-5 child mortality, with the vast majority of neonatal deaths occurring in resource-limited settings. In the Association of Southeast Asian Nations (ASEAN) region, it is estimated that approximately 200 000 neonatal deaths occur annually with reported estimates of the neonatal mortality rate ranging from 1 to over 30 per 1000 live-births, depending on the setting. The aim of this study is to conduct a systematic review of published data on neonatal morbidity and mortality from the ASEAN region over the last 10 years. Very few published studies reporting neonatal morbidity and mortality in this region were found. Importantly, data are available from just a few countries, with an underrepresentation of the most resource-limited settings. The majority of the studies describing mortality and morbidity were retrospective surveys or focussed on a specific cause of neonatal morbidity. Studies included findings from a range of settings, from neonatal intensive care to community settings utilizing verbal autopsy. Therefore, comprehensive and prospective data are needed to inform priorities and potential interventions to improve neonatal care and reduce neonatal mortality in this region.
ABSTRACT
Molecular docking is often performed with rigid receptors. This can be a serious limitation, since the receptor often differs between bound and unbound forms or between bound forms with different ligands. We recently developed a normal-mode based docking method and showed that it is possible to obtain reasonable estimates of the complexed form of the pleckstrin homology (PH) domain of Akt, starting with the free form of the receptor. With inositol (1,3,4,5)-tetrakisphosphate (IP4) as the ligand the docked results agree with the known high-resolution X-ray crystal structure of the IP4-Akt PH domain complex. We also tested our methods with PH4, SC66, and PIT-1, several recently designed PH domain inhibitors. The results are shown to be consistent with available experimental data and previous modeling studies. The method we described can be used for molecular docking analysis even when only an approximation of the experimental structure or model is known.
Subject(s)
Blood Proteins/chemistry , Phosphoproteins/chemistry , Proto-Oncogene Proteins c-akt/chemistry , Crystallography, X-Ray , Models, Molecular , Protein ConformationABSTRACT
Intrinsically disordered proteins (IDPs) are functional proteins that do not fold into well-defined three-dimensional structures under physiological conditions. IDP sequences have low hydrophobicity, and hence, recent experiments have focused on quantitative studies of conformational ensembles of archetypal IDP sequences such as polyglutamine and glycine-serine block copolypeptides. Results from these experiments show that, despite the absence of hydrophobic residues, polar IDPs prefer ensembles of collapsed structures in aqueous milieus. Do these preferences originate in interactions that are unique to polar sidechains? The current study addresses this issue by analyzing conformational equilibria for polyglycine and a glycine-serine block copolypeptide in two environments, namely, water and 8 M urea. Polyglycine, a poly secondary-amide, has no sidechains and is a useful model system for generic polypeptide backbones. Results based on large-scale molecular dynamics simulations show that polyglycine forms compact, albeit disordered, globules in water and swollen, disordered coils in 8 M urea. There is minimal overlap between conformational ensembles in the two environments. Analysis of order parameters derived from theories for flexible polymers show that water at ambient temperatures is a poor solvent for generic polypeptide backbones. Therefore, the experimentally observed preferences for polyglutamine and glycine-serine block copolypeptides must originate, at least partially, in polypeptide backbones. A preliminary analysis of the driving forces that lead to distinct conformational preferences for polyglycine in two different environments is presented. Implications for describing conformational ensembles of generic IDP sequences are also discussed.
Subject(s)
Peptides/chemistry , Computer Simulation , Fluorescence Resonance Energy Transfer , Glycine/analogs & derivatives , Glycine/chemistry , Kinetics , Monte Carlo Method , Protein Conformation , Solutions , Thermodynamics , Urea/chemistry , Water/chemistryABSTRACT
Our focus is on an appropriate theoretical framework for describing highly denatured proteins. In high concentrations of denaturants, proteins behave like polymers in a good solvent and ensembles for denatured proteins can be modeled by ignoring all interactions except excluded volume (EV) effects. To assay conformational preferences of highly denatured proteins, we quantify a variety of properties for EV-limit ensembles of 23 two-state proteins. We find that modeled denatured proteins can be best described as follows. Average shapes are consistent with prolate ellipsoids. Ensembles are characterized by large correlated fluctuations. Sequence-specific conformational preferences are restricted to local length scales that span five to nine residues. Beyond local length scales, chain properties follow well-defined power laws that are expected for generic polymers in the EV limit. The average available volume is filled inefficiently, and cavities of all sizes are found within the interiors of denatured proteins. All properties characterized from simulated ensembles match predictions from rigorous field theories. We use our results to resolve between conflicting proposals for structure in ensembles for highly denatured states.