Assessment of Vitamin D Levels and Other Bone Related Biochemical Markers in Healthy Adults in Rural Population of Uttarakhand, India.

Despite being close to equator and receiving sufficient sun rays, evidences revealed that Indians have severe deficiency of vitamin D (vit D) ranging from 41 to 100% in different geographical locations. Therefore, in this study levels of 25(OH)D (physiologically measurable form) along with other bone metabolism associated biochemical markers were determined in serum sample of 300 apparently healthy study subjects (rural) from Doiwala block of Dehradun district in the state of Uttarakhand. Demographic data was also obtained based on a structured questionnaire to establish an association between 25(OH)D levels and various dietary and socio-cultural factors. Results demonstrated that of all study subjects, 197 (65%) had 25(OH)D levels below < 12 ng/mL (deficient) and 65 (21%) had 25(OH)D levels between 12 and 20 ng/mL (insufficient) with all other markers falling within respectively established reference ranges. Further, in univariate analysis, gender, occupation (indoor and outdoor), education were independently associated with vitamin D status. Additionally, parathyroid hormone associated significantly with gender and occupation, while calcium associated significantly with gender, occupation and education. Lastly, regression analysis revealed that gender and occupation independently associated with vitamin D status of subjects. In conclusion, apparently healthy subjects showed considerable vitamin D deficiency thereby generating an urgent need for formulating and implementing better government policies for enrichment of vitamin D levels among rural adults of Uttarakhand in future. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01048-6.

Arthrospira platensis (Spirulina) fortified functional foods ameliorate iron and protein malnutrition by improving growth and modulating oxidative stress and gut microbiota in rats.

The present study was aimed at developing Arthrospira platensis (Spirulina) fortified traditional foods of the Indian subcontinent, namely sattu (multigrain beverage mix) and chikki (peanut bar) and evaluating their ability to promote recovery from protein and iron deficiency anaemia (IDA) using albino Wistar rats. Addition of Spirulina (at 4% w/w Spirulina inclusion levels) enriched the protein content by 20.33% in sattu and 15.65% in chikki while the iron content was enhanced by 45% in sattu and 29.6% in chikki. In addition, the total carotenoid and polyphenol content and antioxidant capacity of the food products improved after Spirulina incorporation. Supplementation of 100 g of Spirulina fortified food products meets more than 50% of recommended dietary allowances (RDA) of protein, dietary fiber, iron and zinc for the age group 3 to 10 years of children. Spirulina contributed between 11% and 22% of RDA for protein and iron, respectively; however it contributed very negligibly to RDA of dietary fibre with respect to the nutrient requirements for the target age group. Supplementation of Spirulina fortified foods individually promoted bodyweight gain in malnourished rats and restored haemoglobin, serum protein, albumin, serum iron, and hepcidin levels and reduced the iron binding capacity indicating recovery from IDA. Spirulina supplementation ameliorated malnutrition induced oxidative stress in the liver, spleen and kidneys by reducing the lipid peroxidation and enhancing superoxide dismutase and glutathione activities. Histopathological analysis revealed that supplementation of Spirulina fortified foods reversed pathological changes such as fatty changes in the liver cells, thinning of cardiac muscle fibers and degeneration of intestinal villi. Fe-protein deficiency significantly altered the gut microflora by reducing the abundance of beneficial microbes. However, supplementation of Spirulina fortified foods improved the levels of beneficial gut microbes such as Lactobacillus reuteri and Akkermansia muciniphila while reducing the abundance of Helicobacteraceae, Enterobacteria and Clostridia. In summary, supplementation of Spirulina fortified foods promoted recovery from protein and iron deficiency indicating the bioavailability of nutrients (iron and protein) from Spirulina at par with casein and ferrous ascorbate.

In-vitro cytotoxicity of nickel oxide nanoparticles against L-6 cell-lines: MMP, MTT and ROS studies.

In the present work we synthesize nickel oxide nanoparticles (NiO NPs) using Rhododendron arboretum (flower) (RNi), Tinospora cordifolia (stems) (GNi), Corylus jacquemontii (seeds) (CNi), and Nardostachys jatamansi (roots) (NNi) extracts by co-precipitation method. The synthesized NiO NPs were characterized in detail in terms of their morphological, crystalline nature, structural and antiproliferative activity against rat skeletal myoblast (L-6) cell lines. Morphological studies confirmed the formation of nanoparticles, while the structural and compositional characterization revealed the well-crystallinity and high purity of the synthesized nanoparticles. For biological applications and cytotoxicity examinations of the synthesized NPs, the rat skeletal myoblast (L-6) cell lines were subjected to study. By detailed cytotoxic investigations, it was observed that among the four kinds of NiO NPs prepared through different plant extracts, the Tinospora cordifolia (stems) showed strong antiproliferative activity against rat skeletal myoblast (L-6) cell lines and the calculated IC50 was 1.671 mg/mL. The observed antiproliferative activity towards different NiO NPs were in the order of GNi > NNi > RNi > CNi. The present studies demonstrate that simply synthesized NiO can efficiently be used as antiproliferative agents.

Yoga as a Preventive Intervention for Cardiovascular Diseases and Associated Comorbidities: Open-Label Single Arm Study.

Aim: Common Yoga Protocol (CYP) is a standardized yoga protocol authored by experts from all over the world under the aegis of the Ministry of AYUSH, Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa Rigpa and Homeopathy (AYUSH). The potential of CYP can be determined as a cost-effective lifestyle modification to prevent the risk of developing cardiovascular diseases (CVD). Methods: In this prospective trial, we compared the effect of CYP at baseline and after 1 month. A total of 374 yoga-naïve participants performed CYP under the supervision of experienced trainers. Physiological [body mass index (BMI), blood pressure, percent oxygen saturation], biochemical (fasting blood glucose and lipid profile), and neurocognitive parameters were measured before and after the intervention. Results: At day 30 of yoga practice, serum levels of low-density lipoprotein (LDL), total cholesterol (TC), and high-density lipoprotein (HDL) were found significantly improved as compared to the baseline levels observed at the time of enrollment. Similarly, the lipid profile was also obtained from experienced trainers and found to be significantly different from those of yoga-naïve volunteers. When the intervention was compared between the healthy yoga-naïve participants with yoga-naïve participants suffering from medical issues, it was found that cholesterol profile improved significantly in the healthy-naive group as compared to the diseased group (hypertension, diabetes, underwent surgery, and CVD). Conclusion: These results highlight the need for further research to better understand the effects of yoga on the primary prevention of CVD.

Role of family physicians in providing primary healthcare during COVID-19 pandemic.

According to the World Health Organization, over 41 million cases of COVID-19 and 1 million deaths have been reported globally. More than 7 million cases of coronavirus have been reported in India alone. The growing number of cases of coronavirus worldwide poses numerous challenges to the country's current healthcare delivery system, especially in developing nations such as India. In such a situation, the task of maintaining continuity in the provision of comprehensive primary healthcare services in the community becomes a big challenge. This article discusses how family physicians can help to augment the healthcare system at the time of pandemic by providing easily accessible, holistic healthcare and by use of telemedicine. It also talks about the need to mainstream family medicine into the undergraduate and postgraduate medical curriculum and establish a robust network of family physicians trained in outbreak response and disease preparedness. For this study we looked for all papers with the terms 'Family physician', 'COVID-19', 'pandemic', and 'Primary health care'. Databases searched include PubMed, Google Scholar and DOAJ, using key words - family physician, family medicine, primary healthcare, COVID-19, and pandemic in different combinations.

Thiamine-responsive acute severe pulmonary hypertension in exclusively breastfeeding infants: a prospective observational study.

OBJECTIVES: Severe pulmonary hypertension (PH) causing right heart failure can occur due to thiamine deficiency in exclusively breastfeeding infants. This study describes the clinical profile and management of thiamine-responsive acute pulmonary hypertension. METHODS: A prospective observational study of infants presenting with severe PH without any other significant heart or lung disease. History of symptoms, clinical examination, echocardiography and basic investigations were performed. Dietary patterns of mothers were recorded. Thiamine was administered and serial echocardiography was performed. RESULTS: A total of 250 infants had severe PH and 231 infants responded to thiamine. The mean age was 3.2±1.2 months. Fast breathing, poor feeding, vomiting and aphonia were the main symptoms. Tachypnoea, tachycardia and hepatomegaly were found on examination. Echocardiogram revealed grossly dilated right heart with severe PH. Intravenous thiamine was administered to all the babies based on clinical suspicion. Clinical improvement with complete resolution of PH was noticed within 24-48 hours. Babies were followed up to a maximum of 60 months with no recurrence of PH. All the mothers consumed polished rice and followed postpartum food restriction. CONCLUSION: Thiamine deficiency is still prevalent in selected parts of India. It can cause life-threatening PH in exclusively breastfeeding infants of mothers who are on a restricted diet predominantly consisting of polished rice. It can contribute to infant mortality. Thiamine administration based on clinical suspicion leads to remarkable recovery. High degree of awareness and thiamine supplementation in relevant geographical areas is required to tackle this fatal disease.

A Checklist for Implementing Rural Pathways to Train, Develop and Support Health Workers in Low and Middle-Income Countries.

Background: There is an urgent need to scale up global action on rural workforce development. This World Health Organization-sponsored research aimed to develop a Rural Pathways Checklist. Its purpose was to guide the practical implementation of rural workforce training, development, and support strategies in low and middle-income countries (LMICs). It was intended for any LMICs, stakeholder, health worker, context, or health problem. Method: Multi-methods involved: (1) focus group concept testing; (2) a policy analysis; (3) a scoping review of LMIC literature; (4) consultation with a global Expert Reference Group and; (5) field-testing over an 18-month period. Results: The Checklist included eight actions for implementing rural pathways in LMICs: establishing community needs; policies and partners; exploring existing workers and scope; selecting health workers; education and training; working conditions for recruitment and retention; accreditation and recognition of workers; professional support/up-skilling and; monitoring and evaluation. For each action, a summary of LMICs-specific evidence and prompts was developed to stimulate reflection and learning. To support implementation, rural pathways exemplars from different WHO regions were also compiled. Field-testing showed the Checklist is fit for purpose to guide holistic planning and benchmarking of rural pathways, irrespective of LMICs, stakeholder, or health worker type. Conclusion: The Rural Pathways Checklist provides an agreed global conceptual framework for the practical implementation of "grow your own" strategies in LMICs. It can be applied to scale-up activity for rural workforce training and development in LMICs, where health workers are most limited and health needs are greatest.

Emergency and primary care collaboration during COVID-19 pandemic: A quick systematic review of reviews.

COVID-19 is one of the deadliest viral infections to have hit the planet. There is urgent need to bridge the gaps in handling this pandemic by methodically synthesising available literature through a unique holistic perspective. A systematic review of articles regarding emergency and primary care during COVID-19 pandemic was carried out. PubMed, Scopus, Science Direct, Web of Science, and Google Scholar were screened for articles and qualitative data across various studies were coded and thematically analyzed. Narrative synthesis was achieved by themes identified from findings of studies. Out of n = 953 articles retrieved, we identified and critically appraised n = 7 articles of which n = 5 were narrative reviews, one was systematic review and one was scoping review from researchers across ten countries. Nine overlapping themes were identified under three broad domains - clinical understanding of the disease, social aspects of the disease, and its contextual implications during pandemic. This narrative synthesis draws up a holistic picture of recent reviews on clinical and social understanding of COVID-19 as a disease and as a pandemic. The overlap among nine themes identified in this review could mean that primary care-level screening, triaging, referral, and emergency care of COVID-19 patients in the backdrop of current clinical understanding of the pandemic are all intertwined. Coping with COVID-19 co-habitation and managing undifferentiated illnesses require a syndromic approach and deft handling at grass root levels. Inclusive health policy empowering inherent holistic specialties like family medicine and emergency medicine could be the prudent way forward during this pandemic.

Unveiling molecular associations of polymorphic variants of VDR gene (FokI, BsmI and ApaI) in multiple myeloma patients of Indian population.

Multiple myeloma (MM) is a plasma cell malignancy frequently accompanied with skeletal co-morbidity. Vitamin D (1,25(OH)2D) is an important mediator of skeletal homeostasis that mediates its effect by binding to vitamin D receptor (VDR), a steroid family receptor and modulates various downstream pathways. Multiple polymorphisms have been determined in VDR gene that witnessed significant association with cancer development and progression. Therefore, in this maiden study, we recruited 75 newly diagnosed MM patients and 75 control subjects. 25-hydroxy vitamin D (25(OH)D) levels were measured in all recruited study subjects. Further, PCR-RFLP was performed in DNA samples of recruited study subjects. Results demonstrated significantly decreased 25(OH)D levels in MM patients compared to controls. Additionally, decreased 25(OH)D levels in MM patients inversely associated with disease severity. Further, single nucleotide polymorphism (SNP) analysis of VDR gene showed significantly higher risk of MM disease development in Ff + ff, Aa + aa, and Bb + bb genotypes. Additionally, FokI f, ApaI a and BsmI b alleles were significantly associated with MM occurrence. In conclusion, this study provided initial evidences of association between 25(OH)D insufficiency, VDR gene polymorphism and MM development. Thus, we suggest that a study involving assessment of 25(OH)D levels and VDR gene polymorphism in large patients' cohort might substantiate their role in MM development which would further provide impetus to give 25(OH)D supplementation along with conventional chemotherapeutic agents for myeloma treatment in future.

Aggregation, adhesion and efficacy studies of probiotic candidate Pediococcus acidilactici NCDC 252: a strain of dairy origin.

Aggregation and adhesion capability and survival efficacy of candidate probiotic strain Pediococcus acidilactici NCDC 252 under simulated gastric, intestinal and vaginal conditions was studied. The strain exhibited strong autoaggregation phenotype and coaggregation with other Lactic acid bacteria (LAB) and E. coli. The adhesion studies of NCDC 252 to pig's intestinal epithelial cells showed its adhesive ability. Aggregation and adhesiveness were related through cell surface proteins as removal/extraction of surface proteins resulted in altered aggregation and no adhesiveness. Cell surface proteins were analysed by SDS-PAGE and also in silico analysed from its genome. SDS-PAGE analysis of cell surface proteins of NCDC 252 revealed two potential proteins of approximately 74.3 and 53.6 kDa to be involved in host-probiotic interaction. Removal of cell surface proteins by LiCl-treatment (5 mol l-1) resulted in loss of aggregation and adhesiveness. Further survival of NCDC 252 under simulated gastrointestinal and vaginal conditions in terms of high viable counts confirmed its efficacy for its survival under gut and urogenital conditions. These observations suggest that it can be used further in functional foods, nutraceuticals and in combating urogenital infections. As NCDC 252 was able to survive in intestinal conditions, interaction of its cell surface proteins with intestinal mucins was studied in silico by docking. Highest affinity of adhesion was observed for MUC3B. In conclucion, NCDC 252, exhibited aggregation phenotype and adhesion capability. Survivability of NCDC 252 under simulated conditions and its interaction with human mucins confirms its efficacy to be used as probiotic.

A holistic approach to remove the bottlenecks and to improve the quality of medical research in India.

The current trend of conducting research and publishing the same to fulfill the academic or professional requirements can jeopardise what research actually means in health sciences. Rather than highlighting how many publications one can have, or showcase the expertise as a researcher, research can inform knowledge gaps and address the same in a replicable and scientific manner. More importantly, for low- and middle- income countries like India, research can be a powerful tool to assess healthcare problems at the primary care and develop innovative solutions to strengthen health systems at the grass root level. It can be argued that, enriching research portfolio for an individual is a misleading approach whereas research has much more to offer to the society at large. In the context of in primary care, academic and implementation research is important for several distinct reasons. The practice-based research can inform better practice through communicating the concerns or findings from research with key stakeholders of primary care. If the primary care practitioners are equipped with fundamental research skills, it may help them to become better critics and evidence-based practitioners. Publishing research findings in a good scientific journal is not an easy job. A lot of time and resources are often required from the submission process to publication. There are many obstacles for publishing a research, some are inherent some are man-made. In this article we describe our experiences about the bottlenecks that we have faced while conducting medical research and we have also prescribed some possible solutions which can help to the researchers in future while conducting medical research.

India achieves WHO recommended doctor population ratio: A call for paradigm shift in public health discourse!

The Indian medical education system has been able to pull through a major turnaround and has been successfully able to double the numbers of MBBS graduate (modern medicine training) positions during recent decades. With more than 479 medical schools, India has reached the capacity of an annual intake of 67,218 MBBS students at medical colleges regulated by the Medical Council of India. Additionally, India produces medical graduates in the "traditional Indian system of medicine," regulated through Central Council for Indian Medicine. Considering the number of registered medical practitioners of both modern medicine (MBBS) and traditional medicine (AYUSH), India has already achieved the World Health Organization recommended doctor to population ratio of 1:1,000 the "Golden Finishing Line" in the year 2018 by most conservative estimates. It is indeed a matter of jubilation and celebration! Now, the time has come to critically analyze the whole premise of doctor-population ratio and its value. Public health experts and policy makers now need to move forward from the fixation and excuse of scarcity of doctors. There is an urgent need to focus on augmenting the fiscal capacity as well as development of infrastructure both in public and private health sectors toward addressing pressing healthcare needs of the growing population. It is also an opportunity to call for change in the public health discourse in India in the background of aspirations of attaining sustainable development goals by 2030.

YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction.

Yin and yang 1 (YY1) is a well-known zinc-finger transcription factor with crucial roles in normal development and malignancy. YY1 acts both as a repressor and as an activator of gene expression. We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic features that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth restriction, feeding problems, and various congenital malformations. Our combined clinical and molecular data define "YY1 syndrome" as a haploinsufficiency syndrome. Through immunoprecipitation of YY1-bound chromatin from affected individuals' cells with antibodies recognizing both ends of the protein, we show that YY1 deletions and missense mutations lead to a global loss of YY1 binding with a preferential retention at high-occupancy sites. Finally, we uncover a widespread loss of H3K27 acetylation in particular on the YY1-bound enhancers, underscoring a crucial role for YY1 in enhancer regulation. Collectively, these results define a clinical syndrome caused by haploinsufficiency of YY1 through dysregulation of key transcriptional regulators.

Deregulation of allopathic prescription and medical practice in India: Benefits and pitfalls.

In the background of debates on Universal Health Coverage, skill transfer from the medical practice license holders to other health-care providers such as nurse practitioner has become a global norm. In India, where the world's largest numbers of medical graduates are produced, this discussion is expanding to extremes and serious suggestions are coming forward for the development of legal framework for allowing dentists, homeopaths, pharmacists, and half duration trained doctors; permission to issue allopathic prescription. Allopathic medical prescription. It is noteworthy that this discussion only pertains to the pharmaceutical products retailed through "allopathic medical prescriptions." A prescription is not only advice for patient's recovery but it also is a legitimate order for the sale of controlled drugs and pharmaceutical product; thereby functions as a regulatory tool for consumption of pharmaceutical products at retail level. Who is ultimately going to benefit from this prescription deregulation? This editorial explores benefits and pitfalls of prescription and medical practice deregulation.

Helicopter Dropping of 50 Free Allopathic Medicines; Prescribed by Homoeopathic Doctors at Ground: Sorry this is not Universal Health Coverage.

The provision of Universal Health Coverage (UHC) is being discussed in India. Crippled by the charges of corruption and unethical practice by media and public at large, medical professionals are largely unaware, disinterested, isolated and edged out from this debate. The traditional general practitioner is a dying breed and deficiency of doctors willing to work in community settings is rampant. Is UHC model proposed in present form good for an ordinary Indian citizen? This editorial looks into the underlying politics of health care in India in the past and how this ongoing debate could impact the future of primary care and health care of people in India.

A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability.

The discovery of mutations causing human disease has so far been biased toward protein-coding regions. Having excluded all annotated coding regions, we performed targeted massively parallel resequencing of the nonrepetitive genomic linkage interval at Xq28 of family MRX3. We identified in the binding site of transcription factor YY1 a regulatory mutation that leads to overexpression of the chromatin-associated transcriptional regulator HCFC1. When tested on embryonic murine neural stem cells and embryonic hippocampal neurons, HCFC1 overexpression led to a significant increase of the production of astrocytes and a considerable reduction in neurite growth. Two other nonsynonymous, potentially deleterious changes have been identified by X-exome sequencing in individuals with intellectual disability, implicating HCFC1 in normal brain function.

Water deficit induced oxidative damage in tea (Camellia sinensis) plants.

When the tea (Camellia sinensis) leaf water potential was -1.1 MPa (Moderate water deficit), there was 58% inhibition of photosynthesis accompanied by increased zeaxanthin, malondialdehyde, oxidized proteins and superoxide dismutase activity. When the leaf water potential was -2MPa (severe water deficit), there was nearly complete inhibition of photosynthesis apart from a decrease in chlorophylls, beta-carotene, neoxanthin and lutein. Water deficit at this level caused further conversion of violaxanthin to zeaxanthin, suggesting damage to the photosynthetic apparatus. There were consistent decreases in antioxidants and pyridine nucleotides, and accumulation of catalytic Fe, malondialdehyde and oxidized proteins. It is inferred that, in tea plants, the increase in catalytic Fe and the decrease in antioxidant protection may be involved in the oxidative damage caused by severe water deficit, but not necessarily in the incipient stress induced by moderate water deficit.