Prevalence and risk factors of postpartum depression in sub-Himalayan region.

Background: Postpartum depression (PPD) is a common problem faced by women after childbirth. The adverse effects of PPD upon the maternal-infant relationship and child development reinforce the need for early identification and effective treatment models. This study intends to add to the existing knowledge about the prevalence of PPD and its associated risk factors in the hilly region in Himachal Pradesh. Methods: A hospital-based cross-sectional study was conducted on 426 women presenting for a postpartum visit at 6 weeks postpartum. Sociodemographic characteristics were recorded on a pretested questionnaire. Women were screened for postpartum depression using a validated EPDS (Edinburgh postnatal depression scale) prestructured questionnaire with 10 questions. Women were divided into two groups based on screening results. Results: The overall prevalence of PPD in the study was 17.4%. Out of sociodemographic factors, age (0.010) and family structure (0.008) were found to be significant. Nuclear family women were more prone to PPD. Domestic abuse (<0.001) is also a leading factor for PPD. By comparing obstetric and gender issues, it was found that the total number of previous living children (p-value <0.001), gender of previous living children (<0.001), and gender of newborns (<0.001) are the major determining factors of PPD. Another factor that was significantly related to PPD was an unwanted pregnancy. Conclusions: We have found a high prevalence of PPD in our region that does not have screening protocols for the screening of such patients. We, therefore, propose routine screening for postpartum depression at 6 weeks postpartum.

In vitro Evaluation of Shear Bond Strength of Orthodontic Brackets Bonded with Different Adhesives.

Background: To endure the orthodontic forces used throughout treatment, the bond strength of bonded orthodontic brackets must be enough with assessment of shear bond strength when bonding orthodontic brackets with various adhesives. Materials and Methods: Overall, forty extracted premolars due to orthodontic treatment were included. They were split into four equal cohorts with various primers. With both adhesives, shear bond strength had been assessed with and without salivary contamination. SPSS software was used to assess the outcomes. Consideration was given to statistical significance of P value of less than 0.05. Results: Several groups' average bond strengths in MPa were assessed in both dry and contaminated saliva conditions. When it was dry, Transbond Plus demonstrated greater shear bond strength. Conclusion: Hydrophilic Transbond Plus resin outperformed hydrophobic Transbond XT resin in terms of shear bond strength under both situations.

De novo design of highly selective miniprotein inhibitors of integrins αvß6 and αvß8.

The RGD (Arg-Gly-Asp)-binding integrins αvß6 and αvß8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous αvß6 and αvß8 and other RGD integrins, stabilize specific conformational states, and have high thermal stability could have considerable therapeutic utility. Existing small molecule and antibody inhibitors do not have all these properties, and hence new approaches are needed. Here we describe a generalized method for computationally designing RGD-containing miniproteins selective for a single RGD integrin heterodimer and conformational state. We design hyperstable, selective αvß6 and αvß8 inhibitors that bind with picomolar affinity. CryoEM structures of the designed inhibitor-integrin complexes are very close to the computational design models, and show that the inhibitors stabilize specific conformational states of the αvß6 and the αvß8 integrins. In a lung fibrosis mouse model, the αvß6 inhibitor potently reduced fibrotic burden and improved overall lung mechanics, demonstrating the therapeutic potential of de novo designed integrin binding proteins with high selectivity.

De novo design of highly selective miniprotein inhibitors of integrins αvß6 and αvß8.

The RGD (Arg-Gly-Asp)-binding integrins αvß6 and αvß8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between the two closely related integrin proteins and other RGD integrins, stabilize specific conformational states, and have sufficient stability enabling tissue restricted administration could have considerable therapeutic utility. Existing small molecules and antibody inhibitors do not have all of these properties, and hence there is a need for new approaches. Here we describe a method for computationally designing hyperstable RGD-containing miniproteins that are highly selective for a single RGD integrin heterodimer and conformational state, and use this strategy to design inhibitors of αvß6 and αvß8 with high selectivity. The αvß6 and αvß8 inhibitors have picomolar affinities for their targets, and >1000-fold selectivity over other RGD integrins. CryoEM structures are within 0.6-0.7Å root-mean-square deviation (RMSD) to the computational design models; the designed αvß6 inhibitor and native ligand stabilize the open conformation in contrast to the therapeutic anti-αvß6 antibody BG00011 that stabilizes the bent-closed conformation and caused on-target toxicity in patients with lung fibrosis, and the αvß8 inhibitor maintains the constitutively fixed extended-closed αvß8 conformation. In a mouse model of bleomycin-induced lung fibrosis, the αvß6 inhibitor potently reduced fibrotic burden and improved overall lung mechanics when delivered via oropharyngeal administration mimicking inhalation, demonstrating the therapeutic potential of de novo designed integrin binding proteins with high selectivity.

Knowledge, attitude, and practices of healthcare providers about perinatal depression in Himachal Pradesh-A cross-sectional study.

Introduction: Perinatal depression is defined as depression occurring in a woman during pregnancy or within 12 months of delivery. It has been associated with many poor outcomes, including maternal, child, and family unit challenges. This study aimed to assess the knowledge, attitude, and practices of obstetricians and primary healthcare professionals so that the knowledge gap could be assessed and they could be educated regarding the screening and treatment/referral of patients with peripartum depression. Methods: The study used a cross-sectional study design with convenience sampling. The data were collected through an online survey among healthcare providers using the Google Forms application. Submission of filled questionnaire implied consent for participation. Ethical approval for the study was obtained from the institutional ethics committee. The results were reported as mean and percentages. All data were analysed using Excel software 2019. Results: A total of 53 doctors responded to participate in the study. More than 98% of them were aware of an entity called perinatal depression. Around 89% of the participants do not screen patients for the perinatal period routinely using a screening questionnaire. About 90% of participants agreed with the need for screening for perinatal depression. Less than 50% of participants had heard about the screening questionnaire for the same. Around 89% agreed that all health professionals should have skills in recognising and managing depression. Conclusion: There is a need to educate healthcare workers including obstetricians about screening for perinatal depression, thus improving the quality of life of perinatal women and preventing complications due to untreated depression.

Anti-adipogenic ß-sitosterol and lupeol from Moringa oleifera suppress adipocyte differentiation through regulation of cell cycle progression.

Triterpenes and phytosterols enriched herbal formulations are known for glucose regulation and lipid metabolism. In this study, triterpenes and phytosterols from Moringa oleifera stem bark have been tested for their role in adipocyte differentiation. Chromatographic analysis revealed a wide range of phenolics, highlighting the presence of flavonoids (kaempferol, quercetin, and rutin), terpenoids (lupeol), and phytosterol (stigmasterol, ß-sitosterol). Lupeol and ß-sitosterol reduced cell viability in a dose-dependent manner showcasing increased G1 phase cell accumulation while reducing other cell cycle phases (S and G2 /M) and significant lowering of intracellular lipid accumulation. Additionally, lupeol (35.37% at 32 µM) and ß-sitosterol (42.97% at 16 µM) inhibited reactive oxygen species generation and increased glucose uptake in adipocytes. Collectively, our results indicate that lupeol and ß-sitosterol efficaciously attenuated adipogenesis via a controlled cell cycle progression and enhanced glucose uptake in adipocytes. PRACTICAL APPLICATIONS: Active components of Moringa oleifera effectively regulate adipocyte differentation suggest that it can be good medicial supllement for control of obesity.

The Etiology of Anemia Among Pregnant Women in the Hill State of Himachal Pradesh in North India: A Cross-Sectional Study.

Background and objective Anemia during pregnancy is a major cause of maternal and fetal complications including mortality. A study of the etiology of anemia is required to formulate guidelines for the prevention and treatment of the condition. To this end, we conducted a study among anemic women in northern India. Materials and methods A cross-sectional study was conducted among anemic antenatal women attending the outpatient department at a tertiary care hospital in Himachal Pradesh, India, involving 172 participants. Complete blood count, serum ferritin level, serum B12, serum folate levels, high-performance liquid chromatography (HPLC), liver function tests, and renal function tests were performed. Results The mean hemoglobin level among the subjects was 8.87 g/dl with a standard deviation of 0.79; 50% of women had serum ferritin levels of less than 15 ng/ml, 48.8% had serum B12 levels of less than 150 pg/ml. and 33.72% of women had serum folate levels of less than 3 ng/ml. Of note, 13.37% of women had either low or deficient levels for all three parameters; 14 women had abnormal results on HPLC. All nutrient deficiencies (ferritin, folate, and vitamin B12) were found in all morphological types of anemia. Significantly, 73.26% of iron-deficient anemic women had additional folate or vitamin B12 deficiencies, suggesting that additional methods would be required to decrease the prevalence of anemia. Two-thirds of the women in our study were vegetarians, a contributing factor towards a high percentage of vitamin B12 deficiency among women. ß-thalassemia trait was the most common abnormality found, consistent with the high prevalence of ß-thalassemia in north India. Conclusion Multiple deficiencies should be treated simultaneously in anemic women. Vitamin B12 deficiency is an important contributor to anemia, in addition to iron and folate deficiency.

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2.

We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo-electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.

De novo design of ACE2 protein decoys to neutralize SARS-CoV-2.

There is an urgent need for the ability to rapidly develop effective countermeasures for emerging biological threats, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a generalized computational design strategy to rapidly engineer de novo proteins that precisely recapitulate the protein surface targeted by biological agents, like viruses, to gain entry into cells. The designed proteins act as decoys that block cellular entry and aim to be resilient to viral mutational escape. Using our novel platform, in less than ten weeks, we engineered, validated, and optimized de novo protein decoys of human angiotensin-converting enzyme 2 (hACE2), the membrane-associated protein that SARS-CoV-2 exploits to infect cells. Our optimized designs are hyperstable de novo proteins (∼18-37 kDa), have high affinity for the SARS-CoV-2 receptor binding domain (RBD) and can potently inhibit the virus infection and replication in vitro. Future refinements to our strategy can enable the rapid development of other therapeutic de novo protein decoys, not limited to neutralizing viruses, but to combat any agent that explicitly interacts with cell surface proteins to cause disease.

Assessment of serum leptin and resistin levels in association with the metabolic risk factors of pre- and post-menopausal rural women in South India.

OBJECTIVES: Menopausal status is related with weight gain, abnormal lipid and glucose metabolism leading to metabolic syndrome susceptibility. The aim of this study is to determine circulating serum leptin and resistin levels and to correlate these levels in relationship with the metabolic factors in pre- and post-menopausal women. METHODS: A cross-sectional study has been carried out for 34 subjects who were in post-menopause and 31 subjects who had regular menstruation in south Indian rural women. Anthropometric indices, blood pressure, fasting blood sugar (FBS), fasting lipid profile, fasting leptin and resistin levels were measured. RESULTS: In a total of 65 subjects, the mean age of pre-menopausal group was 38.65±6.21 and that of post-menopausal group was 55.32±6.32. Fasting serum leptin level was increased considerably in post-menopausal women when compared to pre-menopausal women (P=0.018). Resistin has no significant relationship with metabolic factors except Body Mass Index (BMI) in both the groups. Triglycerides and FBS were lower in pre-menopausal group when compared to post-menopausal group (P<0.001). Leptin was well correlated with BMI in pre-menopausal women (r(2)=0.7120, P<0.0001) as well as post-menopausal women (r(2)=0.2470, P=0.0028). Leptin also had significant correlation with FBS in both pre (r(2)=0.1373, P=0.0402) and post-menopausal women (r(2)=0.2141, P=0.0401). Systolic blood pressure was positively associated with the leptin levels in post-menopausal women (P<0.001). CONCLUSION: Leptin was found to have significant association with metabolic factors when compared to resistin in pre- and post-menopausal women and there is no doubt that association of BMI and FBS elevates the level of leptin in both the category.