Lung Surfactant Protein B Peptide Mimics Interact with the Human ACE2 Receptor.

Lung surfactant is a complex mixture of phospholipids and surfactant proteins that is produced in alveolar type 2 cells. It prevents lung collapse by reducing surface tension and is involved in innate immunity. Exogenous animal-derived and, more recently, synthetic lung surfactant has shown clinical efficacy in surfactant-deficient premature infants and in critically ill patients with acute respiratory distress syndrome (ARDS), such as those with severe COVID-19 disease. COVID-19 pneumonia is initiated by the binding of the viral receptor-binding domain (RBD) of SARS-CoV-2 to the cellular receptor angiotensin-converting enzyme 2 (ACE2). Inflammation and tissue damage then lead to loss and dysfunction of surface activity that can be relieved by treatment with an exogenous lung surfactant. Surfactant protein B (SP-B) is pivotal for surfactant activity and has anti-inflammatory effects. Here, we study the binding of two synthetic SP-B peptide mimics, Super Mini-B (SMB) and B-YL, to a recombinant human ACE2 receptor protein construct using molecular docking and surface plasmon resonance (SPR) to evaluate their potential as antiviral drugs. The SPR measurements confirmed that both the SMB and B-YL peptides bind to the rhACE2 receptor with affinities like that of the viral RBD-ACE2 complex. These findings suggest that synthetic lung surfactant peptide mimics can act as competitive inhibitors of the binding of viral RBD to the ACE2 receptor.

Can birth weight predict offspring's lung function in adult age? Evidence from two Swedish birth cohorts.

BACKGROUND: Associations between birth weight (BW) and adult lung function have been inconsistent and limited to early adulthood. We aimed to study this association in two population-based cohorts and explore if BW, adjusted for gestational age, predicts adult lung function. We also tested adult lung function impairment according to the mis-match hypothesis-small babies growing big as adults. METHODS: We included 3495 individuals (aged 46.4 ± 5.4 years) from the Malmo Preventive Project (MPP), Sweden, born between 1921 and 1949, and 1401 young to middle-aged individuals (aged 28.6 ± 6.7 years) from the Malmo Offspring Study (MOS) with complete data on BW and gestational age. Adult lung function (forced vital capacity [FVC], forced expiratory volume in one second [FEV1] and the FEV1/FVC-ratio) were analysed as level of impairment (z-score), using multiple linear and logistic regressions. RESULTS: BW (z-score) did not predict adult lung function in MPP, whereas BW was a significant (p = 0.003) predictor of FEV1 following full adjustment in MOS. For every additional unit increase in BW, children were 0.77 (95% CI 0.65-0.92) times less likely to have impaired adult lung function (FEV1). Moreover, adults born with lower BW (< 3510 g) showed improved lung function (FEV1 and FEV1/FVC in MOS and MPP, respectively) if they achieved higher adult body weight. CONCLUSIONS: Adults born with lower birth weight, adjusted for gestational age, are more likely to have impaired lung function, seen in a younger birth cohort. Postnatal growth pattern may, however, compensate for low birth weight and contribute to better adult lung function.

A Randomized, Placebo-Controlled Study to Evaluate the Effect of Bio-Enhanced Turmeric Formulation on Radiation-Induced Oral Mucositis.

INTRODUCTION: Oral mucositis is the most common toxicity of chemoradiotherapy treatment of head and neck cancers. The present study was performed to evaluate the effect of a researched turmeric formulation on oral mucositis in patients receiving chemoradiotherapy for oral cancer. METHODS: This randomized double-blinded placebo-controlled trial included 60 patients with oral cancer who had undergone radical surgery. Patients were equally randomized into 3 arms. Bio-enhanced turmeric formulation (BTF) capsules (low dose [1 g/day] or high dose [1.5 g/day]) or placebo was administered daily for 6 weeks with concurrent chemoradiotherapy. Study endpoints included the impact of the treatment on chemoradiotherapy-induced oral mucositis along with dysphagia, oral pain, dermatitis, and weight loss. RESULTS: The incidence of grade 3 toxicity of oral mucositis, oral pain, dysphagia, and dermatitis was significantly lower in patients who received BTF than placebo. Twenty-five and 20% patients in BTF 1 g/day (p = 0.011) and 1.5 g/day (p = 0.004) arms, respectively, developed grade 3 oral mucositis compared to 65% patients in the placebo arm. Thirty-five and 30% patients in BTF 1 g/day (p = 0.027) and 1.5 g/day (p = 0.011) arms, respectively, developed grade 3 oral pain compared to 70% patients in the placebo arm. Twenty-five and 20% patients in BTF 1 g/day (p = 0.025) and 1.5 g/day (p = 0.010) arms, respectively, developed grade 3 dysphagia compared to 60% patients in the placebo arm. Ten and 5% patients in BTF 1 g/day (p = 0.114) and 1.5 g/day (p = 0.037) arms. respectively, developed grade 3 dermatitis compared to 30% patients in the placebo arm. Patients under BTF supplementation experienced significantly less weight loss and greater compliance with treatment than placebo. CONCLUSION: BTF (BCM-95®) can significantly reduce chemoradiotherapy-induced severe oral mucositis, dysphagia, oral pain, and dermatitis in oral cancer patients. TRIAL REGISTRATION: Clinical Trials Registry, India (Registration No. CTRI) (CTRI/2015/12/006413 dated December 4, 2015).

Structural and functional stability of the sulfur-free surfactant protein B peptide mimic B-YL in synthetic surfactant lipids.

BACKGROUND: Optimal functionality of synthetic lung surfactant for treatment of respiratory distress syndrome in preterm infants largely depends on the quality and quantity of the surfactant protein B (SP-B) peptide mimic and the lipid mixture. B-YL peptide is a 41-residue sulfur-free SP-B mimic with its cysteine and methionine residues replaced by tyrosine and leucine, respectively, to enhance its oxidation resistance. AIM: Testing the structural and functional stability of the B-YL peptide in synthetic surfactant lipids after long-term storage. METHODS: The structural and functional properties of B-YL peptide in surfactant lipids were studied using three production runs of B-YL peptides in synthetic surfactant lipids. Each run was held at 5 °C ambient temperature for three years and analyzed with structural and computational techniques, i.e., MALDI-TOF mass spectrometry, ATR-Fourier Transform Infrared Spectroscopy (ATR-FTIR), secondary homology modeling of a preliminary B-YL structure, and tertiary Molecular Dynamic simulations of B-YL in surfactant lipids, and with functional methods, i.e., captive bubble surfactometry (CBS) and retesting in vivo surface activity in surfactant-deficient young adult rabbits. RESULTS: MALDI-TOF mass spectrometry showed no degradation of the B-YL peptide as a function of stored time. ATR-FTIR studies demonstrated that the B-YL peptide still assumed stable alpha-helical conformations in synthetic surfactant lipids. These structural findings correlated with excellent in vitro surface activity during both quasi-static and dynamic cycling on CBS after three years of cold storage and in vivo surface activity of the aged formulations with improvements in oxygenation and dynamic lung compliance approaching those of the positive control surfactant Curosurf®. CONCLUSIONS: The structure of the B-YL peptide and the in vitro and in vivo functions of the B-YL surfactant were each maintained after three years of refrigeration storage.

Evaluation of a training program for life skills education and financial literacy to community health workers in India: a quasi-experimental study.

BACKGROUND: Accredited Social Health Activists (ASHA) are community health workers responsible for improving the health status of people by facilitating their access to healthcare services. The life skills of ASHA are known to be effective in negotiating behaviour change in the community; however, there has been a meagre focus towards improving them. Considering this gap, we adopted a comprehensive training program, known as Personal Advancement and Career Enhancement (P.A.C.E.), to empower ASHAs on life skills and financial literacy. The present study intends to assess the training program in two districts of Uttar Pradesh, India, by examining changes in knowledge, perceptions, and practices of ASHAs about life skills and financial literacy. METHODS: We conducted a quasi-experimental, non-randomized, controlled study with pre-and post-test assessments. Data were collected on socio-demographic characteristics, knowledge, and practices related to life skills (communication skills, self-confidence, problem-solving and decision-making skills, time and stress management skills) and financial literacy. Additionally, change perceptions on gender-, life skills-, and savings-related practices at the personal, community, and workplace levels were assessed in the intervention group. Factor analysis was performed to obtain the change patterns by assessing the degree to which the four life skills, financial literacy, and change perceptions on practices were correlated. A general linear regression model was performed to assess associations among change pattern scores and socio-demographic variables. RESULTS: We analyzed the data of 171 ASHAs (intervention group:86 and control group:85). There was a significant improvement in the average post-test scores of all the life skills and financial literacy in the intervention group (p < 0.001). Three distinct change patterns were found post-training in the intervention group. Factor 1 (high loadings for change perceptions on practices) was positively associated with ASHAs aged 38 and above and with experience of ≤12 years. On the contrary, the change in financial literacy and self-confidence scores was common among ASHAs with more than 12 years of experience. CONCLUSIONS: The P.A.C.E training program was found effective in improving the life skills and financial literacy of ASHAs in India.

A possible association between early life factors and burden of functional bowel symptoms in adulthood.

OBJECTIVE: The studies of early life factors and development of functional bowel diseases show inconsistent results. We therefore examined associations between certain early life factors and functional bowel symptoms in adulthood. DESIGN: Population-based cross-sectional study. SETTING: Weight and height were measured and questionnaires were completed at the time point of enrollment in MOS. SUBJECTS: 1013 participants in the Malmö Offspring Study (MOS) without organic bowel disease with data available from the Swedish Medical Birth Registry. MAIN OUTCOME MEASURES: Associations were calculated between gestational age, birth weight, small-for-gestational-age and Apgar score from the Birth Registry, and symptoms according to the visual analog scale for irritable bowel syndrome (VAS-IBS) (abdominal pain, diarrhea, constipation, bloating and flatulence, vomiting and nausea, and symptoms' influence on daily life) or self-reported IBS using logistic regression. RESULTS: In all, 253 (25.0%) participants reported bowel symptoms during the past 2 weeks and 179 (17.7%) self-reported IBS; conditions which were strongly associated (p < 0.001). Female sex and chronic stress were two independent factors more common among participants with bowel symptoms compared with asymptomatic participants (p < 0.001). Early life factors were not associated with presence of overall bowel symptoms (p = 0.080), any specific bowel symptoms or self-reported IBS. Lower birth weight (p = 0.038) and being born small for gestational age (p = 0.043) were associated with severe influence of intestinal symptoms on daily life in adulthood. CONCLUSIONS: Lower birth weight and small for gestational age are not associated with the presence of overall bowel symptoms but with more pronounced influence of such symptoms on daily adult life.Key pointsLower gestational age tended to be associated with functional bowel symptoms in adulthood.Lower birth weight and being small for gestational age are associated with increased negative influences of symptoms on daily life in adulthood.Patients born preterm or with low birth weights may be at increased risk to develop functional bowel symptoms later in life.

Evaluation of a community-based intervention for health and economic empowerment of marginalized women in India.

BACKGROUND: Empowered women have improved decision-making capacity and can demand equal access to health services. Community-based interventions based on building women's groups for awareness generation on maternal and child health (MCH) are the best and cost-effective approaches in improving their access to health services. The present study evaluated a community-based intervention aimed at improving marginalized women's awareness and utilization of MCH services, and access to livelihood and savings using the peer-led approach from two districts of India. METHODS: We used peer educators as mediators of knowledge transfer among women and for creating a supportive environment at the household and community levels. The intervention was implemented in two marginalized districts of Uttar Pradesh, namely Banda and Kaushambi. Two development blocks in each of the two districts were selected randomly, and 24 villages in each of the four blocks were selected based on the high percentage of a marginalized population. The evaluation of the intervention involved a non-experimental, 'post-test analysis of the project group' research design, in a mixed-method approach. Data were collected at two points in time, including qualitative interviews at the end line and tracking data of the intervention population (n = 37,324) through an online management information system. RESULTS: Most of the women in Banda (90%) and Kaushambi (85%) attended at least 60% of the education sessions. Around 39% of women in Banda and 35% of women in Kaushambi registered for the livelihood scheme, and 94 and 80% of them had worked under the scheme in these two places, respectively. Women's awareness about MCH seemed to have increased post-intervention. The money earned after getting work under the livelihood scheme or from daily savings was deposited in the bank account by the women. These savings helped the women investing money at times of need, such as starting their work, in emergencies for the medical treatment of their family members, education of their children, etc. CONCLUSION: Peer-led model of intervention can be explored to improve the combined health and economic outcomes of marginalized women.

Associations between birth weight and adult apolipoproteins: The LifeGene cohort.

BACKGROUND: Early life factors may predict cardiovascular disease (CVD), but the pathways are still unclear. There is emerging evidence of an association of early life factors with apolipoproteins, which are linked to CVD. The study objective was to assess the associations between birth variables and adult apolipoproteins (apoA1 and apoB, and their ratio) in a population-based cohort. METHODS: The LifeGene Study is a prospective cohort comprising index participants randomly sampled from the general population. Blood samples were collected between 2009 and 2016. In this sub-study, we used birth variables, obtained from a national registry for all participants born 1973 or later, including birth weight and gestational age, while adult CVD risk factors included age, sex, body mass index (BMI), lipids, and smoking history. We employed univariate and multivariate general linear regression to explore associations between birth variables, lipid levels and other adult CVD risk factors. The outcomes included non-fasting apoA1 and apoB and their ratio, as well as total cholesterol and triglycerides. A total of 10,093 participants with both birth information and lipoprotein levels at screening were included. Of these, nearly 42.5% were men (n = 4292) and 57.5% were women (n = 5801). RESULTS: The mean (standard deviation) age of men was 30.2 (5.7) years, and for women 28.9 (5.8) years. There was an increase of 0.022 g/L in apoA1 levels per 1 kg increase in birth weight (p = 0.005) after adjusting for age, sex, BMI, gestational age, and smoking history. Similarly, there was a decrease of 0.023 g/L in apoB levels per 1 kg increase in birth weight (p<0.001) after adjusting for the same variables. There were inverse associations of birth weight with the apoB/apoA1 ratio. No independent association was found with total cholesterol, but with triglyceride levels (ẞ-coefficient (95% Confidence Interval); -0.067 (-0.114, -0.021); p-value 0.005). CONCLUSIONS: Lower birth weight was associated with an adverse adult apolipoprotein pattern, i.e., a higher apoB/apoA1 ratio, indicating increased risk of future CVD manifestations. The study highlights the need of preconception care and pregnancy interventions that aim at improving maternal and child outcomes with long-term impacts for prevention of cardiovascular disease by influencing lipid levels.

Assessing universal maternal health service coverage and their determinants in India: A multicentric cross-sectional study.

Introduction: Universal maternal health coverage (UHC) envisages access to quality healthcare services by pregnant and lactating women without any financial hardship. Our present study attempts to assess the UHC for maternal health services and their determinants, including access to quality antenatal care (ANC), quality postnatal care (PNC), and child immunization among the marginalized populations of India. Methods: It was a community-based cross-sectional study across five states of India among pregnant or lactating women. Quality ANC score was calculated using four indicators, including ANC registration month, attendance of four or more ANC visits, receiving at least one tetanus toxoid injection, and consumption of 100 iron-folic acid (IFA) tablets. Similarly, quality PNC care score was calculated using four indicators, including PNC within 48 h, breastfeeding initiation time, institutional delivery, and accessing conditional maternity benefit scheme. Logistic or generalized linear regression was used to depict associations depending on the outcome variables. Results: A total of 12,976 pregnant women's and 18,061 lactating mothers' data were analyzed. Illiterate women, women from below the poverty line, and rural areas had low-quality ANC and PNC scores compared with their counterparts. Marginalized women had lower odds of immunization of children and lower quality PNC scores than nonmarginalized. Conclusions: Sociodemographic factors, such as caste, education of women, area of residence, and economic status, are major determinants of quality ANC and PNC scores and immunization of children. Hence, interventionists ought to design community-based interventions that address the challenges in the uptake of health services.

Associations between birth parameters and skin autofluorescence advanced glycation end products and ankle-brachial index in young adulthood: the Malmö Offspring Study.

BACKGROUND: Low birth weight (LBW), advanced glycation end-products (AGE), and ankle-brachial index (ABI) have all been independently associated with risk of cardiovascular disease. Evidence is lacking on the effect of LBW on adult AGE, a marker of glucose metabolism, and ABI, a marker of peripheral atherosclerosis. The objective was to study these associations in a population-based cohort. METHODS: Data from the Malmö Offspring Study, Sweden, were used for 2012 participants (958 men, 1054 women) born between 1973 and 2000, linked to the Medical Birth Register. General linear regression analysis (with ß coefficients and 95% confidence intervals) was applied for associations between birth weight and skin auto-fluorescence (sf)AGE as well as mean ABI (right/left), before and after adjusting for gestational age, sex, glucose, lipids, smoking, BMI and SBP. RESULTS: The mean (SD) age of men was 29.3 (7.3) and of women 28.6 (7.3) years. There was an average 0.054 decrease in sfAGE value per 1 kg increase in birth weight (adjusted for gestational age and sex). Similarly, 1 kg increase in birth weight (adjusted for gestational age and confounders) was associated with an average 0.016 decrease in mean ABI. CONCLUSION: Birth weight, adjusted for gestational age and other confounding variables, is inversely associated with ABI in young adulthood, an age range when ABI may represent hemodynamic changes more than atherosclerosis, but for sfAGE, the association was attenuated upon further adjustment. These risk markers may, therefore, represent mediating pathways for early life factors affecting cardiovascular risk later in life.

Optical Coherence Tomography Angiography Parameters of the Retina in SARS-CoV-2 Recovered Subjects.

INTRODUCTION: This study aims to evaluate retinochoroidal optical coherence tomography angiography (OCTA) parameters in patients recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This study was an observational study that included 80 subjects being discharged after having negative reports on the reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 to evaluate OCTA parameters of the retina. The subjects underwent an ophthalmic evaluation that included best-corrected visual acuity (BCVA), intraocular pressure (IOP), color vision (CV), contrast sensitivity (CS), and optical coherence tomography (OCT) parameters. OCTA was done for all patients and was evaluated for foveal avascular zone (FAZ) area, perimeter, and circularity index, and vessel density (VD) in superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR), outer retina chorio-capillaries (ORCC), chorio-capillaries (CC), and choroid (C) using 3 x 3 mm scans. The OCTA parameters were compared with normative data of the Indian population for various parameters in question. RESULTS: The subjects included 54/80 (67.5%) males and 26/80 (32.5%) females having a mean age of 52.40 ± 15.71 (18-60) years. The systemic evaluation revealed 38.75% of subjects had hypertension, 30% had diabetes, 20% had kidney disease, 5% had tuberculosis, and 3.75% had coronary artery disease. The mean distance BCVA was logarithm of the minimum angle of resolution (LogMAR) (1.17 ± 0.22), mean IOP was 17.0 ± 4.0 mmHg, mean CS was 2.13 ± 0.36, 50.62% of subjects had normal CV on Farnsworth test while 47% had tritanopia, and none of the subjects had red-green CV defect on Ishihara plates. The OCT scan was normal in 90% of eyes while the posterior vitreous detachment was seen in 4% of eyes, broad vitreomacular adhesion in 2.5% of eyes, and the globally adherent epiretinal membrane was seen in 2.5% of eyes. The mean central macular thickness (CMT) measured 245.14 ± 28.41 micrometers. The mean FAZ area measured 0.37 ± 0.15 mm2, the perimeter was 3.28 ± 1.08 mm, and the circularity index measured 0.41 ± 0.10. The average VD in SCP measured 16.06 ± 12.29, in DCP measured 9.11 ± 8.75, in OR measured 6.38 ± 7.37, in ORCC measured 42.53 ± 12.46, in CC measured 25.83 ± 16.31, and in C measured 25.52 ± 17.49. The VD in coronavirus disease 2019 (COVID-19) subjects was significantly lesser than that in the healthy Indian population in all layers except ORCC. CONCLUSIONS: The SARS-CoV-2 recovered subjects have a reduced VD in retinochoroidal layers from COVID-19, an underlying systemic disease, or both. The CS values fall within normal limits. Several subjects show tritanopia on the Farnsworth test but no red-green CV defect on Ishihara plates.

Selective reciprocity in antimicrobial activity versus cytotoxicity of hBD-2 and crotamine.

Recent discoveries suggest cysteine-stabilized toxins and antimicrobial peptides have structure-activity parallels derived by common ancestry. Here, human antimicrobial peptide hBD-2 and rattlesnake venom-toxin crotamine were compared in phylogeny, 3D structure, target cell specificity, and mechanisms of action. Results indicate a striking degree of structural and phylogenetic congruence. Importantly, these polypeptides also exhibited functional reciprocity: (i) they exerted highly similar antimicrobial pH optima and spectra; (ii) both altered membrane potential consistent with ion channel-perturbing activities; and (iii) both peptides induced phosphatidylserine accessibility in eukaryotic cells. However, the Na(v) channel-inhibitor tetrodotoxin antagonized hBD-2 mechanisms, but not those of crotamine. As crotamine targets eukaryotic ion channels, computational docking was used to compare hBD-2 versus crotamine interactions with prototypic bacterial, fungal, or mammalian Kv channels. Models support direct interactions of each peptide with Kv channels. However, while crotamine localized to occlude Kv channels in eukaryotic but not prokaryotic cells, hBD-2 interacted with prokaryotic and eukaryotic Kv channels but did not occlude either. Together, these results support the hypothesis that antimicrobial and cytotoxic polypeptides have ancestral structure-function homology, but evolved to preferentially target respective microbial versus mammalian ion channels via residue-specific interactions. These insights may accelerate development of anti-infective or therapeutic peptides that selectively target microbial or abnormal host cells.

Early life factors in relation to albuminuria and estimated glomerular filtration rate based on cystatin C and creatinine in adults from a Swedish population-based cohort study.

BACKGROUND: Early life factors influence the number of nephrons a person starts life with and a consequence of that is believed to be premature kidney ageing. Thus, we aimed to identify early life factors associated with cystatin C and creatinine-based estimated glomerular filtration (eGFR) rate equations and urine -albumin-to-creatinine ratio after a follow-up of 46-67 years. METHODS: The study included 593 Swedish subjects without diabetes mellitus from the Malmo Diet Cancer Cohort. Perinatal data records including birth weight, gestational age, placenta weight and maternal related risk factors were analysed. eGFR was determined by Chronic Kidney Disease Epidemiology (CKD-EPI), the Lund-Malmö revised and Caucasian, Asian, Paediatric, and Adult (CAPA) equations. Postnatal growth phenotypes were defined as low (≤ 0) or high (> 0) birth weight z-score, or low (≤ median) or high (> median) body mass index at 20 years of age. RESULTS: In women, lower birth weight was associated with lower eGFR (CAPA; CKD-EPI cystatin C). Birth weight z-score predicted adult albuminuria specifically in men (OR 0.75, 95% CI [0.58; 0.96]). Women with high birth weight z-score and low BMI at 20 years had lower eGFR (CAPA; CKD-EPI cystatin C; p = 0.04). Men with high birth weight z-score and high BMI at 20 years had lower risk for albuminuria (OR 0.35, 95% CI [0.12; 0.93]). CONCLUSIONS: Lower birth weight, prematurity and postnatal growth curve have a potential sex- specific effect of early exposure to an adverse environment on lower cystatin C-based eGFR and albuminuria later in life. Cystatin C compared to creatinine -eGFR equations shows a higher ability to detect these findings.

Mental Health Interventions among Adolescents in India: A Scoping Review.

Early adolescence is the period of the emergence of most mental disorders contributing significantly to the mental health burden globally, including India. The major challenges in India are early identification of mental health problems, treatment gap, lack of professionals, and interventions that address the same. Our review aimed to assess the effectiveness of mental health interventions among adolescents in India. We systematically searched PubMed, PsycINFO, and Cochrane databases and used cross-referencing to review the interventions published from 2010 to 2020. Eleven interventions were included in this review; nine were school-based, one community, and one digital. Most of the school-based programs used a life skills curriculum. Additionally, coping skills and resilience curricula showed improvement in depressive symptoms, cognitive abilities, academic stress, problem-solving, and overall mental well-being. The multi-component whole-school intervention was quite promising and helped in improving the overall school climate and various other mental health outcomes. Hence, school-based programs should be implemented as an entry point for screening mental health problems. However, there is a need for a more comprehensive mental health program in the country for adolescents. Additionally, there is a need to address the gap by conducting more interventions for early and out-of-school adolescents.

Predictors of Retinal Nerve Fiber Layer Parameters Following Scleral Buckling Surgery in Primary Rhegmatogenous Retinal Detachment.

OBJECTIVE: This study aimed to examine predictors of retinal nerve fiber layer (RNFL) parameters following scleral buckling (SB) surgery for primary rhegmatogenous retinal detachment (RRD) and to determine the influence of the magnitude of change in qualitative and quantitative parameters on RNFL. METHODS:  In an observational prospective study, 40 subjects who underwent successful retinal reattachment with SB surgery done within one month of RRD were evaluated for the parameters of best-corrected visual acuity (BCVA), refractive error, intraocular pressure (IOP), axial length (AL), anterior chamber depth (ACD), angle opening distance (AOD 500 and AOD 750), trabecular iris surface area (TISA 500 and TISA 750), visual fields, and ganglion cell count (GCC) and RNFL before and three months after SB. We additionally noted qualitative factors like extent, location, and type of buckle; phakic status; and grade of proliferative vitreoretinopathy in the affected eye. The change in value of quantitative parameters was found. The influence of baseline values and magnitude of change of quantitative and qualitative parameters on average RNFL thickness and magnitude of change of RNFL thickness after SB was found. RESULTS:  Post-SB, average RNFL thickness reduced from 108.58±20.38 microns to 103.73±17.98 microns (p =0.042). The baseline temporal upper (TU), temporal lower (TL), and nasal lower (NL) RNFL thickness (p=0.01, p=0.02, p=0.01, respectively) and total deviation (TD) values of visual fields (p=0.01) correlated positively while baseline GCC gross loss of volume (p=0.01) correlated negatively with post-operative RNFL thickness. The TU, TL, and NL RNFL thickness (p=0.04, p=0.01, p=0.01, respectively) and average GCC (p=0.04) correlated negatively with the magnitude of change in RNFL. The magnitude of change in baseline parameters after surgery was correlated with the magnitude of change in average RNFL thickness. It was noticed that change in AL (p<0.01), TISA 500 (p=0.02), TISA 750 (p<0.01), GCC focal loss of volume (p=0.02), and temporal RNFL thickness (p<0.01) correlated positively while the change in refractive error correlated negatively (p=0.04). Except for the grade of proliferative vitreoretinopathy (PVR) (p=0.04), none of the qualitative parameters, including extent, type, and location of the buckle; and phakic status, had a significant association with post-operative average RNFL thickness or magnitude of its change. CONCLUSIONS:  The predictors of average RNFL thickness following SB include AL; myopic shift; TISA; visual fields TD; average, TU, TL, and NL RNFL thickness; average GCC, gross and focal loss of volume; and grade of PVR. So an early surgery to prevent preoperative ganglion cell and RNFL loss and progression of PVR is recommended.

Emulation of the structure of the Saposin protein fold by a lung surfactant peptide construct of surfactant Protein B.

The three-dimensional structure of the synthetic lung Surfactant Protein B Peptide Super Mini-B was determined using an integrative experimental approach, including mass spectrometry and isotope enhanced Fourier-transform infrared (FTIR) spectroscopy. Mass spectral analysis of the peptide, oxidized by solvent assisted region-specific disulfide formation, confirmed that the correct folding and disulfide pairing could be facilitated using two different oxidative structure-promoting solvent systems. Residue specific analysis by isotope enhanced FTIR indicated that the N-terminal and C-terminal domains have well defined α-helical amino acid sequences. Using these experimentally derived measures of distance constraints and disulfide connectivity, the ensemble was further refined with molecular dynamics to provide a medium resolution, residue-specific structure for the peptide construct in a simulated synthetic lung surfactant lipid multilayer environment. The disulfide connectivity combined with the α-helical elements stabilize the peptide conformationally to form a helical hairpin structure that resembles critical elements of the Saposin protein fold of the predicted full-length Surfactant Protein B structure.

Evaluating the Quantitative Foveal Avascular Zone and Retino-Choroidal Vessel Density Using Optical Coherence Tomography Angiography in a Healthy Indian Population.

OBJECTIVE: The foveal avascular zone (FAZ) is the round capillary-free zone within the macula and is supplied only by a single-layered parafoveal capillary arcade. This study aimed to evaluate the quantitative FAZ and retino-choroidal vessel density (VD) using optical coherence tomography angiography (OCTA) in a healthy Indian population. METHODS: This was a cross-sectional observational study that was conducted for evaluating the quantitative FAZ and retino-choroidal VD of 200 eyes of 100 healthy Indian subjects, including 62 males and 38 females (age range 17-50 years) having the best-corrected visual acuity (BCVA) of logMAR 0 (20/20; 6/6) and spherical equivalent refractive error of not more than 1 D. The subjects were examined using OCTA automated software on spectral-domain OCT (SD-OCT; Nidek RS 3000 Advance 2; Nidek, Inc., Fremont, CA) on a 3 x 3 mm OCTA macular scan centred on the fovea. The FAZ size, perimeter and circularity index, VD in superficial, deep, and outer retina (OR), outer retinal chorio-capillaries (ORCC), chorio-capillaries (CC) and choroid (C) were analysed in the circular and quadrant-segmented zones. A correlation was found between the FAZ size, perimeter and circularity, and VD in retino-choroidal layers, and between BCVA, age, central foveal thickness (CFT) and sub-foveal choroidal thickness (SFCT), and OCTA parameters. RESULTS: The FAZ and surrounding vascular arcades were intact in all eyes, showing either a vertical or horizontal oval-shaped symmetrical formation without gaps, holes or interruption of the capillary network. The mean value of CFT was 237.5±26.0 microns and SFCT was 269.6±53.0 microns. The mean FAZ area was 0.42±0.23 mm2, FAZ perimeter was 3.3±1.0 mm and FAZ circularity index was 0.46±0.1. The mean VD in superficial capillary plexus (SCP) was 23.87±10.66, in deep capillary plexus (DCP) was 16.03±9.90, in OR was 13.22± 12.27, in ORCC was 39.74±14.32, in CC was 37.02±16.43 and in choroid was 37.43±16.76. The increasing order of VD in different retino-choroidal layers was OR

Direct detection of products from the pyrolysis of 2-phenethyl phenyl ether.

The pyrolysis of 2-phenethyl phenyl ether (PPE, C(6)H(5)C(2)H(4)OC(6)H(5)) in a hyperthermal nozzle (300-1350 °C) was studied to determine the importance of concerted and homolytic unimolecular decomposition pathways. Short residence times (<100 µs) and low concentrations in this reactor allowed the direct detection of the initial reaction products from thermolysis. Reactants, radicals, and most products were detected with photoionization (10.5 eV) time-of-flight mass spectrometry (PIMS). Detection of phenoxy radical, cyclopentadienyl radical, benzyl radical, and benzene suggest the formation of product by the homolytic scission of the C(6)H(5)C(2)H(4)-OC(6)H(5) and C(6)H(5)CH(2)-CH(2)OC(6)H(5) bonds. The detection of phenol and styrene suggests decomposition by a concerted reaction mechanism. Phenyl ethyl ether (PEE, C(6)H(5)OC(2)H(5)) pyrolysis was also studied using PIMS and using cryogenic matrix-isolated infrared spectroscopy (matrix-IR). The results for PEE also indicate the presence of both homolytic bond breaking and concerted decomposition reactions. Quantum mechanical calculations using CBS-QB3 were conducted, and the results were used with transition state theory (TST) to estimate the rate constants for the different reaction pathways. The results are consistent with the experimental measurements and suggest that the concerted retro-ene and Maccoll reactions are dominant at low temperatures (below 1000 °C), whereas the contribution of the C(6)H(5)C(2)H(4)-OC(6)H(5) homolytic bond scission reaction increases at higher temperatures (above 1000 °C).

A conceptual model and framework of nutrition-sensitive and specific interventions across Life stages in India.

A large segment of the maternal and child population in low- and middle-income countries (LMIC) is malnourished. There has been a considerable amount of literature on different evidence-based actions that work well with pregnant women or lactating mothers. However, we lack a comprehensive framework of evidence-based nutrition interventions for LMIC that endorse actions along the life course, that is, from adolescence to lactation and childhood, for improved child health and nutrition. Considering the need, this study aimed to explore and design a model and framework for improving maternal and child nutrition. A systematic review of the literature was conducted to identify evidence-based interventions that reduce malnutrition and improve maternal and child health and nutrition. The literature search was made using Google, Google Scholar, and PubMed. The search of the literature in the last 5 years was made. Our conceptual model illustrates key nutrition approaches at different levels (from individual to system levels). The promotion, prevention, monitoring, and management framework (based on nutrition-specific interventions) sorts out actions across each set of the population (pregnant, lactating, and newly married women and adolescent girls) for improved nutrition and health. Our nutrition-sensitive intervention framework, in the way to target basic causes of undernutrition, highlight actions that may result in improved maternal and child health and nutrition in the long run. Encapsulating the wide array of interventions across the life course, our model and framework hold importance as they contain evidence-based actions as suggested by the international agencies and are contextualized for India.

Preeclampsia and high blood pressure in early pregnancy as risk factors of severe maternal cardiovascular disease during 50-years of follow-up.

OBJECTIVES: Studies suggest preeclampsia as a risk factor for long term cardiovascular diseases (CVD), while evidence is limited regarding the risk of high blood pressures (BP) in early pregnancy. STUDY DESIGN: A register-based follow-up of 2434 mothers in the Helsingborg Birth Cohort. Associations of high BP in early pregnancy (>95th percentile systolic [SBP], diastolic [BDP], or mean arterial BP [MAP]) during the first antenatal visit and/or preeclampsia with an incident CVD event (ischemic heart disease or stroke) were assessed. To model risks and adjust for co-variables, Cox proportional hazard regression was used. RESULTS: Of the included women, 120 (4.9%) had high SBP, 49 (2%) high DBP, 104 (4.3%) high MAP in early pregnancy; and 115 (4.7%) developed preeclampsia. During 52 years of follow-up, totalling 121,457 person-years, 534 (21.9%) women experienced a CVD event. Women with preeclampsia had a higher risk of developing CVD compared to women without preeclampsia (HR 1.5, 95%CI: 1.1-2.2), while risks among women with high BPs were slightly higher. In adjusted analysis, risk estimates were approximately 50% higher than that of the reference groups for all four studied exposures. Of women with later CVD, 35 (6.6%) had preeclampsia, and another 31 (5,8%) women high SBP or high MAP. Without later preeclampsia, high SBP constituted a significant risk factor (HR 1.6, 95%CI: 1.1-2.4) for CVD. CONCLUSIONS: Women with SBP > 95th percentile in early pregnancy, but without later preeclampsia, have a higher risk of developing CVD that is comparable to women with history of preeclampsia.