Maternal time investment in caregiving activities to promote early childhood development: evidence from rural India.

Introduction: Intervention strategies that seek to improve early childhood development outcomes are often targeted at the primary caregivers of children, usually mothers. The interventions require mothers to assimilate new information and then act upon it by allocating sufficient physical resources and time to adopt and perform development promoting behaviours. However, women face many competing demands on their resources and time, returning to familiar habits and behaviours. In this study, we explore mothers' allocation of time for caregiving activities for children under the age of 2, nested within a cluster randomised controlled trial of a nutrition and care for development intervention in rural Haryana, India. Methods: We collected quantitative maternal time use data at two time points in rural Haryana, India, using a bespoke survey instrument. Data were collected from 704 mothers when their child was 12 months old, and 603 mothers when their child was 18 months old. We tested for significant differences in time spent by mothers on different activities when children are 12 months of age vs. 18 months of age between arms as well as over time, using linear regression. As these data were collected within a randomised controlled trial, we adjusted for clusters using random effects when testing for significant differences between the two time points. Results: At both time points, no statistically significant difference in maternal time use was found between arms. On average, mothers spent most of their waking time on household chores (over 6 h and 30 min) at both time points. When children were aged 12 months, approximately three and a half hours were spent on childcare activities for children under the age of 2 years. When children were 18 months old, mothers spent more time on income generating activities (30 min) than when the children were 12 years old, and on leisure (approximately 4 h and 30 min). When children were 18 months old, less time was spent on feeding/breastfeeding children (30 min less) and playing with children (15 min). However, mothers spent more time talking or reading to children at 18 months than at 12 months. Conclusion: We find that within a relatively short period of time in early childhood, maternal (or caregiver) time use can change, with time allocation being diverted away from childcare activities to others. This suggests that changing maternal time allocation in resource poor households may be quite challenging, and not allow the uptake of new and/or optimal behaviours.

Can home visits for early child development be implemented with sufficient coverage and quality at scale? Evidence from the SPRING program in India and Pakistan.

Introduction: There is limited evidence from low and middle-income settings on the effectiveness of early child development interventions at scale. To bridge this knowledge-gap we implemented the SPRING home visiting program where we tested integrating home visits into an existing government program (Pakistan) and employing a new cadre of intervention workers (India). We report the findings of the process evaluation which aimed to understand implementation. Methods and materials: We collected qualitative data on acceptability and barriers and facilitators for change through 24 in-depth interviews with mothers; eight focus group discussions with mothers, 12 with grandmothers, and 12 with fathers; and 12 focus group discussions and five in-depth interviews with the community-based agents and their supervisors. Results: Implementation was sub-optimal in both settings. In Pakistan issues were low field-supervision coverage and poor visit quality related to issues scheduling supervision, a lack of skill development, high workloads and competing priorities. In India, issues were low visit coverage - in part due to employing new workers and an empowerment approach to visit scheduling. Coaching caregivers to improve their skills was sub-optimal in both sites, and is likely to have contributed to caregiver perceptions that the intervention content was not new and was focused on play activities rather than interaction and responsivity - which was a focus of the coaching. In both sites caregiver time pressures was a key reason for low uptake among families who received visits. Discussion: Programs need feasible strategies to maximize quality, coverage and supervision including identifying and managing problems through monitoring and feedback loops. Where existing community-based agents are overstretched and system strengthening is unlikely, alternative implementation strategies should be considered such as group delivery. Core intervention ingredients such as coaching should be prioritized and supported during training and implementation. Given that time and resource constraints were a key barrier for families a greater focus on communication, responsivity and interaction during daily activities could have improved feasibility.

Effect of the SPRING home visits intervention on early child development and growth in rural India and Pakistan: parallel cluster randomised controlled trials.

Introduction: Almost 250 million children fail to achieve their full growth or developmental potential, trapping them in a cycle of continuing disadvantage. Strong evidence exists that parent-focussed face to face interventions can improve developmental outcomes; the challenge is delivering these on a wide scale. SPRING (Sustainable Programme Incorporating Nutrition and Games) aimed to address this by developing a feasible affordable programme of monthly home visits by community-based workers (CWs) and testing two different delivery models at scale in a programmatic setting. In Pakistan, SPRING was embedded into existing monthly home visits of Lady Health Workers (LHWs). In India, it was delivered by a civil society/non-governmental organisation (CSO/NGO) that trained a new cadre of CWs. Methods: The SPRING interventions were evaluated through parallel cluster randomised trials. In Pakistan, clusters were 20 Union Councils (UCs), and in India, the catchment areas of 24 health sub-centres. Trial participants were mother-baby dyads of live born babies recruited through surveillance systems of 2 monthly home visits. Primary outcomes were BSID-III composite scores for psychomotor, cognitive and language development plus height for age z-score (HAZ), assessed at 18 months of age. Analyses were by intention to treat. Results: 1,443 children in India were assessed at age 18 months and 1,016 in Pakistan. There was no impact in either setting on ECD outcomes or growth. The percentage of children in the SPRING intervention group who were receiving diets at 12 months of age that met the WHO minimum acceptable criteria was 35% higher in India (95% CI: 4-75%, p = 0.023) and 45% higher in Pakistan (95% CI: 15-83%, p = 0.002) compared to children in the control groups. Discussion: The lack of impact is explained by shortcomings in implementation factors. Important lessons were learnt. Integrating additional tasks into the already overloaded workload of CWs is unlikely to be successful without additional resources and re-organisation of their goals to include the new tasks. The NGO model is the most likely for scale-up as few countries have established infrastructures like the LHW programme. It will require careful attention to the establishment of strong administrative and management systems to support its implementation.

New insights into the structure and function of an emerging drug target CysE.

The antimicrobial resistant strains of several pathogens are major culprits of hospital-acquired nosocomial infections. An active and urgent action is necessary against these pathogens for the development of unique therapeutics. The cysteine biosynthetic pathway or genes (that are absent in humans) involved in the production of L-cysteine appear to be an attractive target for developing novel antibiotics. CysE, a Serine Acetyltransferase (SAT), catalyzes the first step of cysteine synthesis and is reported to be essential for the survival of persistence in several microbes including Mycobacterium tuberculosis. Structure determination provides fundamental insight into structure and function of protein and aid in drug design/discovery efforts. This review focuses on the overview of current knowledge of structure function, regulatory mechanism, and potential inhibitors (active site as well as allosteric site) of CysE. Despite having conserved structure, slight modification in CysE structure lead to altered the regulatory mechanism and hence affects the cysteine production. Due to its possible role in virulence and vital metabolism of pathogens makes it a potential target in the quest to develop novel therapeutics to treat multi-drug-resistant bacteria.

Using the Mothers Object Relations Scale for early childhood development research in rural India: Findings from the Early Life Stress Sub-study of the SPRING Cluster Randomised Controlled Trial (SPRING-ELS).

Background: The World Health Organization and others promote responsive caregiving to support all children to thrive, particularly in low- and middle-income countries. The 14-item Mother's Object Relations Scales - Short Form (MORS-SF) may be of use in research and public health programmes because of its basis in attachment theory and ability to capture parental feelings towards their child. Methods: We culturally adapted the MORS-SF for use with mothers in the SPRING home visits trial when their infants were 12 months old. The same dyads were assessed using the HOME inventory concurrently and Bayley Scales of Infant Development III (BSID-III) at 18 months of age. Mixed effects linear regression was used to examine associations between MORS-SF (explanatory variable) and HOME-IT, and the cognitive, language and motor domains of BSID-III (outcome variables). Results: 1273 dyads completed all assessments. For the motor and language BSID-III scales and for HOME-IT there were strong and positive associations with the MORS-SF warmth sub-scale, and strong and negative associations with the invasion sub-scale. Important but less strong associations were seen with the BSID-III cognitive scale. Evidence of interaction suggested that both are individually important for child development. Conclusions: This is the first time MORS-SF has been used in India where optimising responsive caregiving is of importance in supporting all children to reach their potential. It is also the first time that the tool has been used in relation to child development. MORS-SF could be a valuable addition to evaluation in early childhood development.

Observed feeding behaviours and effects on child weight and length at 12 months of age: Findings from the SPRING cluster-randomized controlled trial in rural India.

BACKGROUND: Child undernutrition results in poor growth in early childhood, undermines optimal development and increases the risk of mortality. Responsive feeding has been promoted as a key intervention for improving nutritional status, however measurement of this remains difficult and has rarely considered child behaviour. We therefore developed a new observed feeding tool to assess both child and caregiver behaviours, as well as their interaction during feeding, and investigate the effect of these on children anthropometric measures at 12-months of age in rural India. METHODS: Our study was nested within the SPRING cluster-randomized controlled trial in Rewari, North India. Outcomes were children length-for-age (LAZ), weight-for-length (WLZ) and weight-for-age (WAZ) Z scores at 12 months of age, based on the WHO Child Growth standards. Trained non-specialists live-coded feeding episodes using the newly designed tool. Scores were then created using principal components analysis representing child behaviour, caregiver behaviour and caregiver-child interaction. Mixed effects linear regression was used to assess associations between feeding behaviours and anthropometric outcomes. RESULTS: 857 children had a meal observation and were included. Anthropometric status was poor (mean length-for-age -1.59 (SD = 1.11); mean weight-for-length -0.58 (0.95); mean weight-for-age -1.22 (1.04)). There were positive linear differences in weight-for-length per unit increase in caregiver responsive behaviours score (adjusted ß-coeff = 0.006, 95%CI = (0.001, 0.011), p = 0.01), in length-for-age and weight-for-age per unit increase in child responsive behaviours score (respectively adjusted ß-coeff = 0.004, 95%CI = (0.001, 0.007), p = 0.02, and adjusted ß-coeff = 0.003, 95%CI = (0.00001, 0.006), p = 0.049), and in both weight-for-length and weight-for-age per unit increase in caregiver-child interaction score (respectively adjusted ß-coeff = 0.007, 95%CI = (0.003, 0.012), p = 0.001, and adjusted ß-coeff = 0.005, 95%CI = (0.001, 0.011), p = 0.01). No association was seen between child behaviours and weight-for-length, caregiver behaviours and length and caregiver-child interaction and length. CONCLUSIONS: We found that trained non-specialists could assess feeding episodes using a newly designed checklist. Further, child and caregiver behaviours were associated with weight and length at only 12 months of age, a reminder of the importance of interventions to improve responsive feeding quality as we strive towards achievement of the sustainable development goals.

Proof of Concept of a Gamified DEvelopmental Assessment on an E-Platform (DEEP) Tool to Measure Cognitive Development in Rural Indian Preschool Children.

Over 250 million children in developing countries are at risk of not achieving their developmental potential, and unlikely to receive timely interventions because existing developmental assessments that help identify children who are faltering are prohibitive for use in low resource contexts. To bridge this "detection gap," we developed a tablet-based, gamified cognitive assessment tool named DEvelopmental assessment on an E-Platform (DEEP), which is feasible for delivery by non-specialists in rural Indian households and acceptable to all end-users. Here we provide proof-of-concept of using a supervised machine learning (ML) approach benchmarked to the Bayley's Scale of Infant and Toddler Development, 3rd Edition (BSID-III) cognitive scale, to predict a child's cognitive development using metrics derived from gameplay on DEEP. Two-hundred children aged 34-40 months recruited from rural Haryana, India were concurrently assessed using DEEP and BSID-III. Seventy percent of the sample was used for training the ML algorithms using a 10-fold cross validation approach and ensemble modeling, while 30% was assigned to the "test" dataset to evaluate the algorithm's accuracy on novel data. Of the 522 features that computationally described children's performance on DEEP, 31 features which together represented all nine games of DEEP were selected in the final model. The predicted DEEP scores were in good agreement (ICC [2,1] > 0.6) and positively correlated (Pearson's r = 0.67) with BSID-cognitive scores, and model performance metrics were highly comparable between the training and test datasets. Importantly, the mean absolute prediction error was less than three points (<10% error) on a possible range of 31 points on the BSID-cognitive scale in both the training and test datasets. Leveraging the power of ML which allows iterative improvements as more diverse data become available for training, DEEP, pending further validation, holds promise to serve as an acceptable and feasible cognitive assessment tool to bridge the detection gap and support optimum child development.

Allosteric inhibition and kinetic characterization of Klebsiella pneumoniae CysE: An emerging drug target.

The emergence and spread of multidrug-resistant strains of Klebsiella pneumoniae is a major concern that necessitates the development of unique therapeutics. The essential requirement of serine acetyltransferase (SAT/CysE) for survival of several human pathogens makes it a very promising target for inhibitor designing and drug discovery. In this study, as an initial step to structure-based drug discovery, CysE from K. pneumonia was structurally and biochemically characterized. Subsequently, blind docking of selected natural products into the X-ray crystallography determined 3D structure of the target was carried out. Experimental validation of the inhibitory potential of the top-scorers established quercetin as an uncompetitive inhibitor of Kpn CysE. Molecular dynamics simulations carried out to elucidate the binding mode of quercetin reveal that this small molecule binds at the trimer-trimer interface of hexameric CysE, a site physically distinct from the active site of the enzyme. Detailed analysis of conformational differences incurred in Kpn CysE structure on binding to quercetin provides mechanistic understanding of allosteric modulation. Binding of quercetin to CysE leads to conformation changes in the active site loops and proximal loops that affect its internal dynamics and consequently its affinity for substrate/co-factor binding, justifying the reduced enzyme activity.

Development, feasibility and acceptability of a gamified cognitive DEvelopmental assessment on an E-Platform (DEEP) in rural Indian pre-schoolers - a pilot study.

Background: Assessment of cognitive development is essential to identify children with faltering developmental attainment and monitor the impact of interventions. A key barrier to achieving these goals is the lack of standardized, scalable tools to assess cognitive abilities. Objective: This study aimed to develop a tablet-based gamified assessment of cognitive abilities of 3-year-old children which can be administered by non-specialist field workers. Methods: Workshops among domain experts, literature search for established and gamified paradigms of cognitive assessments and rapid review of mobile games for 3-year-old children was done to conceptualize games for this study. Formative household visits (N = 20) informed the design and content of the games. A cross-sectional pilot study (N = 100) was done to assess feasibility of the tool and check if increasing levels of difficulty and the expected variability between children were evident in game metrics. In-depth interviews (N = 9) were conducted with mothers of participating children to assess its acceptability. Results: Six cognitive domains were identified as being integral to learning - divided attention, response inhibition, reasoning, visual form perception and integration and memory. A narrative, musical soundtrack and positive reinforcement were incorporated into the tool to enhance participant engagement. Child performance determined level timers and difficulty levels in each game. Pilot data indicate that children differ in their performance profile on the tool as measured by the number of game levels played and their accuracy and completion time indicating that it might be possible to differentiate children based on these metrics. Qualitative data suggest high levels of acceptability of the tool amongst participants. Conclusions: A DEvelopmental assessment on an E-Platform (DEEP) has been created comprising distinct games woven into a narrative, which assess six cognitive domains, and shows high levels of acceptability and generates metrics which may be used for validation against gold standard cognitive assessments.

The contribution of childhood adversity to cortisol measures of early life stress amongst infants in rural India: Findings from the early life stress sub-study of the SPRING cluster randomised controlled trial (SPRING-ELS).

BACKGROUND: The majority of the world's children live in low- and middle-income countries and face multiple obstacles to optimal wellbeing. The mechanisms by which adversities - social, cultural, psychological, environmental, economic - get 'under the skin' in the early days of life and become biologically embedded remain an important line of enquiry. We therefore examined the contribution of childhood adversity through pregnancy and the first year of life to hair and salivary cortisol measures of early life stress in the India SPRING home visits cluster RCT which aims to improve early childhood development. METHODS: We assessed 22 adversities across four domains: socioeconomic, maternal stress, family-child relationship, and child and summed them to make a cumulative adversity score & quintiles, and four subscale scores. We cut 3 cm of hair from the posterior vertex and took three saliva samples from morning till late afternoon on each of two days (total six samples). We analysed both for cortisol concentration using ELISA techniques. We used multiple linear regression techniques to assess the relationship between cumulative adversity and log hair cortisol concentration and saliva diurnal slope and area under the curve. RESULTS: We assessed 712 children for hair, and 752 children for saliva cortisol at 12 months of age. We found a strong positive relationship between adversity and hair cortisol; each additional adversity factor was associated with hair cortisol increases of 6.1% (95% CI 2.8, 9.4, p < 0.001) and the increase from adversity quintile one to five was 59.4%. Socioeconomic, relationship and child scales were independent predictors of hair cortisol (socioeconomic 6.4% (95% CI -0.4, 13.6); relationship 11.8% (95% CI 1.4, 23.2); child 7.9% (95% CI -0.5, 16.9). We did not find any association between any measures of adversity and either of the saliva cortisol outcomes. DISCUSSION: This is the largest study of hair cortisol in young children, and the first in a low- and middle-income country setting. Whilst the short-term diurnal measures of cortisol did not appear to be linked with adversity, chronic exposure over several months appears to be strongly associated with cumulative adversity. These findings should spur further work to understand the specific ways in which adversity becomes biologically embedded, and how this can be tackled. They also lend support to ongoing action to tackle childhood adversity in communities around the world.

Facile synthesis of chitosan-silver nanoparticles onto linen for antibacterial activity and free-radical scavenging textiles.

Green chemistry mediated synthesis of nanoparticles is becoming an emerging area of research due to the environmental issues associated with toxic reagents involved in conventional synthesis. In this work, we present a straightforward and rapid green chemistry-based method to fabricate chitosan-based silver nanoparticles onto linen fabric in the presence of pineapple crown extract biomolecules such as sucrose, fructose and glucose. The resultant nanoparticles were studied by UV-vis, TEM, EDX, and their coating onto linen was supported by results from Scanning electron microscopy, EDX with mapping images, FTIR spectroscopy and TGA technique. This one step process yields spherical particles that are well dispersed and non-aggregated. Using chitosan polysaccharide, the colouring, antibacterial and radical scavenging activity of Ag nanoparticles (NPs) could be transferred to the linen fabric surface. Chitosan not only favours coating and stabilization of the silver ions, but synergistically with silver nanoparticles also exhibited strong antibacterial and antioxidant effects onto linen surface. The colouring properties of coated linen fabrics were measured in terms of CIELa*b* values using reflectance spectroscopy. The coated linen was also screened for their antibacterial activity against E. coli and S. aureus, while as antioxidant activity was investigated photometrically by DPPH assay. The results demonstrate that chitosan­silver nanoparticles can be used as safer and greener alternative to chemical functional agents currently being practiced.

Recombinant production of active Streptococcus pneumoniae CysE in E. coli facilitated by codon optimized BL21(DE3)-RIL and detergent.

The emergence of drug resistance in Streptococcus pneumoniae (Spn) is a global health threat and necessitates discovery of novel therapeutics. The serine acetyltransferase (also known as CysE) is an enzyme of cysteine biosynthesis pathway and is reported to be essential for the survival of several pathogenic bacteria. Therefore, it appears to be a very attractive target for structure-function understanding and inhibitor design. This study describes the molecular cloning of cysE from Spn in the pET21c vector and efforts carried out for expression and purification of active recombinant CysE. Significant expression of recombinant Spn cysE could be achieved in codon optimized BL21(DE3)-RIL strain as opposed to conventional BL21(DE3) strain. Analysis of codon adaptation index (CAI) with levels of eukaryotic genes and prokaryotic cysEs expressed in heterologous E. coli host suggests that codon optimized E. coli BL21(DE3)-RIL may be a better host for expressing genes with low CAI. Here, an efficient protocol has been developed for recovery of recombinant Spn CysE in soluble and biologically active form by the usage of nonionic detergent Triton X-100 at a concentration as low as 1%. Altogether, this study reports a simple strategy for producing functionally active Spn CysE in E. coli.

Impact of adversity on early childhood growth & development in rural India: Findings from the early life stress sub-study of the SPRING cluster randomised controlled trial (SPRING-ELS).

INTRODUCTION: Early childhood development is key to achieving the Sustainable Development Goals and can be negatively influenced by many different adversities including violence in the home, neglect, abuse and parental ill-health. We set out to quantify the extent to which multiple adversities are associated with impaired early childhood growth & development. METHODS: This was a substudy of the SPRING cluster randomised controlled trial covering the whole population of 120 villages of rural India. We assessed all children born from 18 June 2015 for adversities in the first year of life and summed these to make a total cumulative adversity score, and four subscale scores. We assessed the association of each of these with weight-for-age z-score, length-for-age z-score, and the motor, cognitive and language developmental scales of the Bayley Scales of Infant Development III assessed at 18 months. RESULTS: We enrolled 1726 children soon after birth and assessed 1273 of these at both 12 and 18 months of age. There were consistent and strongly negative relationships between all measures of childhood adversity and all five child growth & development outcome measures at 18 months of age. For the Bayley motor scale, each additional adversity was associated with a 1.1 point decrease (95%CI -1.3, -0.9); for the cognitive scales this was 0.8 points (95%CI -1.0, -0.6); and for language this was 1.4 points (95%CI -1.9, -1.1). Similarly for growth, each additional adversity was associated with a -0.09 change in weight-for-age z-score (-0.11, -0.06) and -0.12 change in height-for-age z-score (-0.14, -0.09). DISCUSSION: Our results are the first from a large population-based study in a low/middle-income country to show that each increase in adversity in multiple domains increases risk to child growth and development at a very early age. There is an urgent need to act to improve these outcomes for young children in LMICs and these findings suggest that Early Childhood programmes should prioritise early childhood adversity because of its impact on developmental inequities from the very start.

Protein Based Nanostructures for Drug Delivery.

The key role of protein based nanostructures has recently revolutionized the nanomedicine era. Protein nanoparticles have turned out to be the major grounds for the transformation of different properties of many conventional materials by virtue of their size and greater surface area which instigates them to be more reactive to some other molecules. Protein nanoparticles have better biocompatibilities and biodegradability and also have the possibilities for surface modifications. These nanostructures can be synthesized by using protein like albumin, gelatin, whey protein, gliadin, legumin, elastin, zein, soy protein, and milk protein. The techniques for their fabrication include emulsification, desolvation, complex coacervation, and electrospray. The characterization parameters of protein nanoparticles comprise particle size, particle morphology, surface charge, drug loading, determination of drug entrapment, and particle structure and in vitro drug release. A plethora of protein nanoparticles applications via different routes of administration are explored and reported by eminent researchers which are highlighted in the present review along with the patents granted for protein nanoparticles as drug delivery carriers.

Role of Nanotechnology in Cosmeceuticals: A Review of Recent Advances.

Nanotechnology manifests the progression in the arena of research and development, by increasing the efficacy of the product through delivery of innovative solutions. To overcome certain drawbacks associated with the traditional products, application of nanotechnology is escalating in the area of cosmeceuticals. Cosmeceuticals are regarded as the fastest growing segment of the personal care industry and the use has risen drastically over the years. Nanocosmeceuticals used for skin, hair, nail, and lip care, for conditions like wrinkles, photoaging, hyperpigmentation, dandruff, and hair damage, have come into widespread use. Novel nanocarriers like liposomes, niosomes, nanoemulsions, microemulsion, solid lipid nanoparticles, nanostructured lipid carrier, and nanospheres have replaced the usage of conventional delivery system. These novel nanocarriers have advantages of enhanced skin penetration, controlled and sustained drug release, higher stability, site specific targeting, and high entrapment efficiency. However, nanotoxicological researches have indicated concern regarding the impact of increased use of nanoparticles in cosmeceuticals as there are possibilities of nanoparticles to penetrate through skin and cause health hazards. This review on nanotechnology used in cosmeceuticals highlights the various novel carriers used for the delivery of cosmeceuticals, their positive and negative aspects, marketed formulations, toxicity, and regulations of nanocosmeceuticals.

Is perturbation in the quaternary structure of bacterial CysE, another regulatory mechanism for cysteine synthesis?

Drug resistance to almost all antibiotics of Shigella flexneri, a major cause of shigellosis in developing countries, necessitates continuous discovery of novel therapeutics. This study reports a structure-function analysis of a potential drug target serine acetyltransferase (CysE), an enzyme of de novo cysteine biosynthesis pathway that is absent in humans. Analysis of CysE sequences of S. flexneri species and serotypes displayed only two variants that differed by a single amino acid substitution at position 241. Structural inspection of the available crystal structure disclosed this site to be distinct from the substrate/cofactor binding pockets or dimer/trimer interfaces. This study discovers that V241 variant of S. flexneri CysE has nearly null enzymatic activity. The observation is explained by molecular dynamic studies which reveal that the disorder generated by A241V substitution is the basis of dissociation of the quaternary assembly of S. flexneri CysE leading to loss of enzymatic activity and stability. The study provides the first evidence that position 241 of CysE, affects the catalytic efficiency of enzyme and suggests this locus as a 'hot spot' for the propagation of conformational changes. It may be postulated that transient quaternary structure of CysE maybe another mechanism for regulating the intracellular level of cysteine.

Mothers explanatory models of infant stress & adversity in rural Haryana, India: qualitative findings from the Early Life Stress sub-study of the SPRING cluster-randomised controlled trial (SPRING-ELS).

Background   Exposure to a range of biological and psychosocial adversities in early childhood is of negative consequence through the lifecourse. This is particularly important for children in low- and middle-income countries where at least 250 million children are at high-risk of not meeting their developmental potential. Minimal evidence describes mothers' views of this. We therefore elicited an explanatory model exploring mothers' perceptions of infant stress and adversity in rural Haryana, India. Methods We did eight focus-group discussions to explore the perspectives of mothers in the general population of this rural area of India using a discussion guide based on Kleinman's explanatory model. Data were coded by two analysts and arranged in themes for presentation. Illustrative quotations were used for presentation of findings. Results All mothers identified several causes of adversity and stress for children, including poverty, neglect and violence. They described the consequences of this for emotions, behaviour and school readiness of children, and that some of the consequences were reversible with appropriate management. Mothers described younger children as being unable to be affected by adversity, because they were "too young to understand". Conclusions Mothers agreed with much of the current biomedical model for early childhood development, however the predominant view was that young infants were "too young to understand" is an important deviation. These findings are of importance in designing behaviour change strategies for this crucial period of early childhood which is rising up the global policy agenda with the aim of giving every child the opportunity to thrive.

Recombinant human keratinocyte growth factor attenuates apoptosis in elastase induced emphysematous mice lungs.

Alveolar cell apoptosis is one of the potential factors involved in the pathogenesis of emphysema. Recently, exogenous recombinant human keratinocyte growth factor (rHuKGF) has been reported to induce the regeneration of gas exchange structures. Therefore, the rationale of the present study was to investigate the potential effect of rHuKGF in ameliorating tissue destruction in the emphysematous mice lungs. Four experimental groups (i.e. control-, emphysema-, therapy- and therapy control-group) were prepared. Subsequently, lungs from each mouse were collected for comet assay, elastase activity assay, antioxidant activity assay and real-time PCR based analyses. Comet assay analysis demonstrated the reduced tail DNA % and olive tail moment in therapy group. rHuKGF supplementation in emphysematous mice caused a significant reduction in the elastase activity levels along with reduction in activity of CAT, SOD and GPx. Furthermore, based on mRNA expression studies, the supplementation of rHuKGF ameliorated the induced apoptosis pathway in emphysematous mice lungs. Moreover, due to rHuKGF supplementation, TNF-α and p53 expression and production were markedly decreased in emphysematous mice lungs. Thus, therapeutic supplementation of rHuKGF might have reversed the alveolar cell loss in elastase induced emphysematous mice lungs by reducing DNA damage and maintaining antioxidant activities.