Vulnerability to Mental Health Problems in Indian Population during Lockdown amidst COVID-19 Pandemic: An Alarm not to Snooze

Background: Lockdown measures are being implemented in several parts of the world to control the spread of novel coronavirus. This unprecedented crisis has significantly affected the lives of people in different ways. Aim: To understand the experiences and vulnerability to mental health problems during lockdown among the Indian population during COVID-19 pandemic. Materials and Methods: A cross-sectional study was conducted using an online survey form circulated through various social media platforms from April 12 to May 3, 2020 containing self-reported questionnaires to collect lockdown related experiences and scales to assess anxiety (GAD-7) and depression (PHQ-9). A convenience sampling method was used. Results: 442 valid responses were received from different states of India. Statistical analysis revealed that one-third of the respondents suffered from some form of anxiety and depression during a lockdown. Less than 10% of them had severe levels of symptoms. The majority were males aged 18-45 years and private sector employees. Delivering essential services was involved with significant anxiety and depression. Availability of food and daily essentials was the most common problem. Difficulty in availing medicines and financial crisis were significant predictors of anxiety and depression. Worsening of interpersonal relationships was associated with higher levels of anxiety and depression. Conclusions: The study concluded that experiences during the lockdown and associated psychological outcomes are important factors to consider and appropriate preventive measures to be taken in case of any future lockdowns

Role of melatonin in the management of substance addiction: a systematic review.

Recent evidence links melatonin hormone and its receptor to the etiology and behavioral manifestation of addiction. The role of exogenous melatonin in addiction treatment is still inconsistent and unclear. The present study aimed to review the literature on randomized clinical trials that evaluated the role of melatonin supplementation, compared to placebo, in the treatment of various substance addictions. The literature searches of relevant articles published in the English language in MEDLINE and Google Scholar databases were performed from inception up to May 2021. We included only randomized clinical trials investigating the effect of melatonin treatment, compared to placebo, on substance addiction-related parameters. Non-randomized clinical trials, observation studies, and animal studies were excluded. The risk of bias-2 was used to assess the quality of the studies. Of 537 articles, 12 randomized control trials (RCT) met our inclusion criteria. Studies have been conducted on substances of addiction including benzodiazepine (BZD), alcohol, nicotine, and opioids. Our results indicated that melatonin treatment had mixed results in improving sleep quality and was not found beneficial in BDZ cessation/discontinuation rate among patients with BDZ dependence. Sleep quality and mental health had improved by melatonin supplements in opioid addiction. In nicotine addiction, melatonin treatment showed effectiveness only on mood changes but not in performance tests. In patients with alcohol use disorder (AUD), melatonin treatment did not show any improvement in sleep quality. We found that the use of exogenous melatonin in substance addiction has mixed results which do not provide sufficient evidence, relative to randomized clinical trials, to establish its role

Perceptions regarding child care and perinatal depression during COVID-19 pandemic – A cross-sectional community-based survey from Uttar Pradesh

Background: High levels of stress among pregnant women have been reported during the coronavirus disease 2019 (COVID-19) pandemic because of various infection-related and lockdown measures. Concerns about safe delivery, breastfeeding, and child care may increase the risk of depression in vulnerable women during the perinatal period. Aim: To study the perceptions regarding child care and prevalence of perinatal depression during the COVID-19 pandemic. Materials and Methods: A cross-sectional community-based survey was conducted among 750 lactating mothers post delivery between September 2020 and February 2021 in 51 districts of Uttar Pradesh. A convenient purposive sampling technique was used. A semi-structured questionnaire was used to collect the socio-demographic details and perceptions regarding child care during the COVID-19 pandemic. Assessment of depression symptoms was performed with the help of patient health questionnaire 9 (PHQ-9). Results: A total of 440 participants were suffering from some form of depression symptoms; the majority had mild depression. Depression was found to be higher among homemakers and young mothers (age <25 years). Depression was found in more than 40% of the respondents who felt fear of COVID infection during breast feeding and hospital stay. Similarly, more than 50% of the respondents who feared unavailability of timely health services and social ignorance had depression. More than 60% of the mothers who did not have any knowledge about safe breast-feeding and child care practices had some form of depression, and the results were statistically significant. Conclusions: Perinatal depression is highly prevalent during the ongoing pandemic. Hence, regular screening, psychoeducation, awareness regarding safe breast feeding, and child care practices are recommended

Sustained delivery of a heterodimer bone morphogenetic protein-2/7 via a collagen hydroxyapatite scaffold accelerates and improves critical femoral defect healing

Despite the glimmer of hope provided by the discovery and commercialization of bone morphogenetic protein-2 (BMP-2) as a bone graft substitute, side effects related to the use of supraphysiological doses have hindered its clinical usage. In this study, we compared the osteoinductive potential of BMP-2 homodimer with a heterodimer of BMP-2/7, both delivered via a collagen-hydroxyapatite (CHA) scaffold delivery system, with the aim to reduce the overall therapeutic BMP doses and the associated side-effects. We first show that the incorporation of hydroxyapatite in collagen-based BMP delivery systems is pivotal for achieving efficient BMP sequestration and controlled release. Using an ectopic implantation model, we then showed that the CHA+BMP-2/7 was more osteoinductive than CHA+BMP-2. Further evaluation of the molecular mechanisms responsible for this increased osteoinductivity at an early stage in the regeneration process indicated that the CHA+BMP-2/7 enhanced progenitor cell homing at the implantation site, upregulated the key transcriptomic determinants of bone formation, and increased the production of bone extracellular matrix components. Using fluorescently labelled BMP-2/7 and BMP-2, we demonstrated that the CHA scaffold provided a long-term delivery of both molecules for at least 20 days. Finally, using a rat femoral defect model, we showed that an ultra-low dose (0.5 µg) of BMP-2/7 accelerated fracture healing and performed at a level comparable to 20-times higher BMP-2 dose. Our results indicate that the sustained delivery of BMP-2/7 via a CHA scaffold could bring us a step closer in the quest for the use of physiological growth factor doses in fracture healing. STATEMENT OF SIGNIFICANCE: • Incorporation of hydroxyapatite (HA) in a collagen scaffold dramatically improves bone morphogenic protein (BMP) sequestration via biophysical interactions with BMP, thereby providing more controlled BMP release compared with pristine collagen. • We then investigate the molecular mechanisms responsible for increased osteoinductive potential of a heterodimer BMP-2/7 with is clinically used counterpart, the BMP-2 homodimer. • The superior osteoinductive properties of BMP-2/7 are a consequence of its direct positive effect on progenitor cell homing at the implantation site, which consequently leads to upregulation of cartilage and bone related genes and biochemical markers. • An ultra-low dose of BMP-2/7 delivered via a collagen-HA (CHA) scaffold leads to accelerated healing of a critical femoral defect in rats while a 20-times higher BMP-2 dose was required to achieve comparable results

Sustained delivery of a heterodimer bone morphogenetic protein-2/7 via a collagen hydroxyapatite scaffold accelerates and improves critical femoral defect healing

Despite the glimmer of hope provided by the discovery and commercialization of bone morphogenetic protein-2 (BMP-2) as a bone graft substitute, side effects related to the use of supraphysiological doses have hindered its clinical usage. In this study, we compared the osteoinductive potential of BMP-2 homodimer with a heterodimer of BMP-2/7, both delivered via a collagen-hydroxyapatite (CHA) scaffold delivery system, with the aim to reduce the overall therapeutic BMP doses and the associated side-effects. We first show that the incorporation of hydroxyapatite in collagen-based BMP delivery systems is pivotal for achieving efficient BMP sequestration and controlled release. Using an ectopic implantation model, we then showed that the CHA+BMP-2/7 was more osteoinductive than CHA+BMP-2. Further evaluation of the molecular mechanisms responsible for this increased osteoinductivity at an early stage in the regeneration process indicated that the CHA+BMP-2/7 enhanced progenitor cell homing at the implantation site, upregulated the key transcriptomic determinants of bone formation, and increased the production of bone extracellular matrix components. Using fluorescently labelled BMP-2/7 and BMP-2, we demonstrated that the CHA scaffold provided a long-term delivery of both molecules for at least 20 days. Finally, using a rat femoral defect model, we showed that an ultra-low dose (0.5 μg) of BMP-2/7 accelerated fracture healing and performed at a level comparable to 20-times higher BMP-2 dose. Our results indicate that the sustained delivery of BMP-2/7 via a CHA scaffold could bring us a step closer in the quest for the use of physiological growth factor doses in fracture healing. STATEMENT OF SIGNIFICANCE: : • Incorporation of hydroxyapatite (HA) in a collagen scaffold dramatically improves bone morphogenic protein (BMP) sequestration via biophysical interactions with BMP, thereby providing more controlled BMP release compared with pristine collagen. • We then investigate the molecular mechanisms responsible for increased osteoinductive potential of a heterodimer BMP-2/7 with is clinically used counterpart, the BMP-2 homodimer. • The superior osteoinductive properties of BMP-2/7 are a consequence of its direct positive effect on progenitor cell homing at the implantation site, which consequently leads to upregulation of cartilage and bone related genes and biochemical markers. • An ultra-low dose of BMP-2/7 delivered via a collagen-HA (CHA) scaffold leads to accelerated healing of a critical femoral defect in rats while a 20-times higher BMP-2 dose was required to achieve comparable results