Obesity and peri-implantation endometrium

Obesity is a global health problem and the current available evidence from the literature suggests that obese women may suffer from a wide spectrum of reproductive complications. The current understanding of obesogenic effects on the peri-implantation endometrium is limited and has become an important research topic as the emerging clinical evidence from the published studies indicate the possible role of the endometrium. The first part of this thesis addresses the clinical question of whether an early pregnancy outcome is affected by the body mass index and whether there is any difference in time taken to achieve pregnancy in obese women with recurrent miscarriage when compared to normal weight women. The results are in chapters 3 and 4, where we demonstrated that obese women were more likely to have miscarriage of empty gestational sac or anembryonic pregnancies. In recurrent miscarriage context, the obese women were more ‘super-fertile’ suggesting the possible loss of an endometrial ability to select normal from abnormal pregnancies. The second part of this thesis provides an analysis of the peri-implantation endometrial stromal compartment in normal weight and obese women. In chapter 5, using immunohistochemical methods it was shown that there was no difference in the uterine natural killer cell and macrophage density in the peri-implantation endometrium of different weight groups. This suggests that the endometrial dysfunction in obese women with reproductive failure does not appear to be immune cell mediated. In chapter 6 it was shown that the clonogenecity of endometrial mesenchymal stem cells (W5C5+) was significantly negatively correlated with the BMI. The obese women had significantly reduced cloning efficiency of W5C5+ cells when compared to normal weight women, suggesting of a possible sub-optimal regenerative capacity of the endometrium in obese women. Finally, chapter 7 showed a potential association between obesogenic environment and impaired stromal cell decidualisation. Using an in-vitro model, it was shown that there was no significant difference in the expression of decidualisation markers (PRL and IGFBP1) in the decidualising endometrial stromal cells from normal weight women when compared to high BMI women. However, when the stromal cells were decidualised in an artificial obesogenic environment, the PRL expression was significantly inhibited in the presence of supernatant from adipose tissue explants of obese women when compared to normal weight women. In summary, the findings from my work have provided an understanding of the peri-implantation endometrium in obese women and evidence to suggest that the endometrial stromal function is possibly facilitated by metabolic influences

Ultrathin CVD Cu Seed Layer Formation Using Copper Oxynitride Deposition and Room Temperature Remote Hydrogen Plasma Reduction

Cu seed layers for future interconnects must have conformal step coverage, smooth surface morphology, and strong adhesion. Conformal deposition had been achieved by chemical vapor deposition (CVD), but CVD Cu films have rough surfaces and poor adhesion. In this paper, conformal, smooth, adherent, continuous, and thin (95% step coverage in 40:1 aspect ratio holes). The CuON films were then reduced with remote hydrogen plasma near room temperature to minimize agglomeration of the thin Cu films during reduction. After reduction, CuON films having a Cu2O crystal structure showed a higher density Cu film (95%) than those having a Cu3N crystal structure (84%). Both reduced Cu films had a smooth morphology (~1 nm rms roughness). Thus, deposition of a CuON film having a Cu2O crystal structure and then reduction with remote hydrogen plasma can make Cu layers that can serve as seed layers of future Cu interconnects.Chemistry and Chemical Biolog

Deficiency in clonogenic endometrial mesenchymal stem cells in obese women with reproductive failure – a pilot study

The mechanisms of obesity associated reproductive complications remain poorly understood. Endometrial mesenchymal stem-cells are critical for cyclic renewal and uterine function. Recently, W5C5+ cells, with high clonogenicity, capable of producing endometrial stroma in vivo, have been described. We sought to investigate the abundance and cloning efficiency of W5C5+ and W5C5− endometrial cells in relation to Body Mass Index, age and reproductive outcome. Design W5C5+ and W5C5− cells were purified from mid-luteal endometrial biopsies (n = 54) by magnetic bead separation and subjected to in vitro colony-forming assays. Results First trimester pregnancy losses were significantly higher in obese subjects (n = 12) compared to overweight (n = 20) and subjects with normal Body Mass Index (n = 22) (P0.05). Conclusions Our observations suggest that the regenerative capacity and plasticity of the endometrium of obese women is suboptimal, which in turn may account for the increased risk of reproductive complications associated with obesity

Chemical Vapor Deposition (CVD) of Manganese Self-Aligned Diffusion Barriers for Cu Interconnections in Microelectronics

Barriers to prevent diffusion of copper, oxygen and water vapor were formed by CVD using a manganese precursor vapor that reacts with silica surfaces. The manganese metal penetrates only a few nanometers into the silica to make conformal amorphous manganese silicate layers. This MnSixOy was found to be an excellent barrier to the diffusion of Cu, O2 and H2O vapor. The adhesion strength of Cu to the MnSixOy was found to be sufficiently strong to satisfy the semiconductor industry requirements for interconnections in future microelectronic devices. CVD Mn dissolves into copper surfaces and then diffuses to increase adhesion to SiCNO capping layers.Chemistry and Chemical Biolog

Chemical Vapor Deposition of Cobalt Nitride and its Application as an Adhesion-Enhancing Layer for Advanced Copper Interconnects

An interlayer of face centered cubic (fcc) Co4N has demonstrated significant improvements in adhesion between copper and diffusion barrier layers. This fcc phase of Co4N was prepared by chemical vapor deposition (CVD) using bis(N-tert-butyl-N′-ethyl-propionamidinato)cobalt(II) and a reactant mixture of NH3 and H2 at substrate temperatures from 100 to 180°C. The Co/N atomic ratio and the phase of cobalt nitride film can be modified by adjusting the ratio of NH3 and H2 in the gas feedstock. The cobalt nitride films prepared by CVD are smooth, highly conformal, and stable against intermixing with copper up to at least 400°C. This fcc cobalt nitride material has very strong adhesion to copper due to the small lattice mismatch (−1 to 2%) between $fcc-Co_4N$ and fcc Cu. Copper wires should be stabilized against failure by electromigration when fcc cobalt nitride interlayers are placed between the copper and surrounding diffusion barriers.Chemistry and Chemical BiologyEngineering and Applied Science

Quantitative Evaluation of Cobalt Disilicide/Si Interfacial Roughness

The formation of smooth, conformal cobalt disilicide (CoSi2) without facets or voids is critical for microelectronic device reliability owing to the ultra-shallow contact areas. Here we demonstrate the formation of smooth and conformal CoSi2 films by chemical vapor deposition (CVD) of cobalt nitride (CoxN) films on silicon (Si) or on silicon on insulator (SOI) substrates, followed by in-situ rapid thermal annealing (RTA) at 700°C. To reveal the CoSi2/Si interfacial morphology, we report a back-to-front sample preparation method, in which mechanical polishing, anisotropic tetramethylammonium hydroxide (TMAH) wet etching, hydrofluoric acid (HF) wet etching, and isotropic xenon difluoride (XeF2) dry etching are employed to remove the SOI substrate from the back side to expose the CoSi2/Si interface. This method offers a robust and reliable procedure for quantitative assessment of the CoSi2/Si interfacial roughness, as well as analytical support for advanced fabrication process development.Chemistry and Chemical BiologyEngineering and Applied Science

Preparation and Evaluation of Nano-vesicles of Brimonidine Tartrate as an Ocular Drug Delivery System

The objective of the present investigation was to design a vesicular formulation of brimonidine tartrate and evaluate its ability to reduce the dosing frequency and improve the therapeutic efficacy of the drug. Nano-vesicles of brimonidine tartrate were prepared by film hydration method. The prepared vesicles were evaluated for photomicroscopic characteristics, entrapment efficiency, in vitro, and ex-in vitro drug release and in vivo intraocular pressure (IOP) lowering activity. The methods employed for preparation of vesicles produced nano vesicles of acceptable shape and size. The in vitro, and ex-in vitro drug release studies showed that there was slow and prolonged release of the drug, which followed zero-order kinetics. The IOP-lowering activity of nano vesicles was determined and compared with that of pure drug solution and showed that the IOP-lowering action of nano-vesicles sustained for a longer period of time. Stability studies revealed that the vesicle formulations were stable at the temperature range of 2-8°C, with no change in shape and drug content. The results of the study indicate that it is possible to develop a safe and physiologically effective topical formulation that is also convenient for patients

Impact of an Integrated Health, Nutrition, and Early Child Stimulation and Responsive Care Intervention Package Delivered to Preterm or Term Small for Gestational Age Babies During Infancy on Growth and Neurodevelopment: Study Protocol of an Individually Randomized Controlled Trial in India (Small Babies Trial)

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. DISCUSSION: The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. TRIAL REGISTRATION: The trial has been registered prospectively in Clinical Trial Registry - India # CTRI/2021/11/037881, Registered on 08 November 2021

Impact of an integrated health, nutrition, and early child stimulation and responsive care intervention package delivered to preterm or term small for gestational age babies during infancy on growth and neurodevelopment: study protocol of an individually randomized controlled trial in India (Small Babies Trial)

Background: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. Methods: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. Discussion: The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. Trial registration: The trial has been registered prospectively in Clinical Trial Registry - India # CTRI/2021/11/037881, Registered on 08 November 2021. Keywords: Child health; Early child stimulation; Growth failure; Intrauterine growth restriction; Responsive stimulation; Small for gestational age; Small vulnerable newborns; preterm. © 2024. The Author(s).The study was funded by Centre for Intervention Science in Maternal and Child Health at the University of Bergen (Bergen, Norway). The funding agency did not play any role in the design of the study and is neither involved in nor has any influence over the collection of analysis or interpretation of data.publishedVersio

Breastfeeding practices based on the gestational age and weight at birth in the first six months of life in a population-based cohort of infants from North India

BackgroundShort and long term benefits of early Initiation of breastfeeding (EIBF) and exclusive breastfeeding (EBF) in the first six months of life are well established and recommended globally. However, reliable estimates of breastfeeding practices and impact of breastfeeding counselling interventions according to gestational age and weight at birth are not available in low and middle income countries.ObjectiveTo assess the impact of breastfeeding counselling on EIBF and EBF during the first 6 months of life according to gestational age and weight at birth.MethodsWe analysed the data collected from the Women and Infants Integrated Interventions for Growth Study (WINGS), an individually randomized factorial design trial. Mothers were counselled on EIBF during third trimester of pregnancy. They were supported throughout the first 6 months to continue EBF by early problem identification, frequent home visits and assistance in expressing breastmilk when direct breastfeeding was not possible. Breastfeeding practices were ascertained through 24 h recalls at infant ages 1, 3 and 5 months for both the intervention and control groups by an independent outcome ascertainment team. The World Health Organization (WHO) definitions were used for classification of infant breastfeeding practices. Generalized linear models of the Poisson family with a log-link function were used to estimate the effect of interventions on breastfeeding practices. The relative measures of effect on breastfeeding practices were estimated in term appropriate for gestational age (T-AGA), term small for gestational age (T-SGA), preterm AGA (PT-AGA), preterm SGA (PT-SGA) infants.ResultsAmongst all infants irrespective of gestational age and weight at birth, EIBF was (51.7%) higher amongst the intervention group (IRR 1.38, 95% CI 1.28–1.48) compared with the control group. The proportion of exclusively breastfed infants at ages 1 month (IRR 1.37, 95% CI 1.28–1.48), 3 months (IRR 2.13, 95% CI 1.30–1.44) and 5 months (IRR 2.78, 95% CI 2.58–3.00) were higher in intervention group than control group. We identified significant interaction (p value for interaction <0.05) between intervention and infant size and gestation at birth on exclusive breastfeeding at 3 and 5 months of age. Subgroup analysis showed that the impact of the intervention was greater on exclusive breastfeeding in PT- SGA infants at 3 months (IRR 3.30, 95% CI 2.20–4.96) and 5 months of age (IRR 5.26, 95% CI 2.98–9.28).ConclusionThis is one of the first studies wherein impact of breastfeeding counselling interventions in the first 6 months of life was assessed according to infant size and gestation at birth wherein gestational age was reliably estimated. The impact of this intervention was higher in preterm and SGA babies compared to other infants. This finding is important as preterm and SGA infants have a higher burden of mortality and morbidity during early infancy. Intensive breastfeeding counselling to these vulnerable infants is likely to improve overall breastfeeding rates and reduce the adverse outcomes.Clinical Trial Registration: [http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339%26EncHid=%26userName=societyforappliedstudies], identifier [#CTRI/2017/06/008908]