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Sickle cell disease (SCD) affects approximately 5% of the world’s population, and India has been the second highest country in the numbers of predicted SCD births. Despite the high burden in India, there is no state-led public health programme, and very few interventions dealing with the treatment and management of SCD are available. This review highlights the dearth of SCD-related interventions, and demonstrates that these interventions effectively improve patients' conditions and are feasible to implement in India. We systematically searched three databases—PubMed/Medline, Google Scholar and Web of Science—for articles from India on SCD-related interventions. The PRISMA guidelines were followed during this review. We included 22 studies, of which 19 dealt with specific therapeutic interventions, and 3 with comprehensive SCD care. Hydroxyurea therapy was the main therapy in 15 studies and is efficacious. Three studies demonstrated the feasibility of comprehensive care in resource-limited settings. The low number of SCD-related intervention studies does not match the huge burden of SCD in India. Governments of endemic countries should consider the findings of available interventions and include them in their countries’ programmes. Comprehensive care is feasible in India and other low-resource settings, from screening to treatment and psychosocial support.

An experiment was conducted during Kharif season (July – October) 2021 on crop research farm Department of Soil Science & Agricultural chemistry at SHUATS. The experiment was laid out in Randomized Block Design having three levels of Neem Cake @ 0%, 50%, 100% and three levels of Biofertilizer (Rhizobium) @ 0%, 50% and 100% respectively. The results show that the application of different levels combination of Neem Cake and Biofertilizer increased growth, the yield of cluster bean and improved soil chemical properties. However, some parameters of soil’s physical properties decreased. It was recorded from the application of Neem Cake and Biofertilizer (Rhizobium) treatment T9[ NC @ 100% + R @ 100%] maximum Bulk density 1.177 Mg m-3 at 0-15 cm and 1.382 Mg m-3 at 15-30 cm, Particle density 2.145 Mg m-3 at 0-15 cm and 2.410 Mg m-3 at 15-30 cm, % pore space 45.11% at 0-15 cm and 42.66% at 15-30 cm, Water holding Capacity 59.09 % in 0-15 cm and 48.44 % at 15-30 cm, pH 7.25 at 0-15 cm and 7.46 at 15-30 cm, EC 0.260 dSm-1 at 0-15 cm and 0.230 dSm-1 at 15-30 cm, % Organic Carbon 0.615 % at 0-15 cm and 0.464 % at 15-30 cm, Available Nitrogen 215.12 kg ha-1 at 0-15 cm and 286.90 at 15-30 cm kg ha-1, Available Phosphorus 30.72 kg ha-1 at 0-15 cm and 28.35 kg ha-1 at 15-30 cm, Available Potassium 232.55 kg ha-1 at 0-15 cm and 196.10 kg ha-1 at 15-30 cm.

Objective To describe the development and implementation of a population-based screening programme for sickle cell disease (SCD) implemented in 12 SCD-endemic and tribal-dominated primary/community health centres (PHCs/CHCs) across six districts of India. Setting India reports a huge burden of SCD, especially among indigenous (tribal) communities. However, there is no state-led SCD programme in many places, and systematic screening is absent. This situation necessitates developing a model of population screening. Methods This programme was meant to screen all people and was carried out in three tiers. The first tier was a symptomatic survey carried out by community health workers. Regular health workers then screened those referred by sickle cell solubility test at sub-health centres as the second tier. The third tier was confirmation by haemoglobin electrophoresis at PHCs/CHCs. Communities were mobilised and prepared to accept the screening. Capacity building of health facilities was ensured through training and supply of equipment and material. Results Initial observation based on six months’ data revealed that out of the 110,754 tribal population of 12 PHCs/CHCs, 8418 (7.6%) were identified in the symptomatic survey. Subsequently, 9416 people, including the above 8418, underwent the solubility test, and 2607 (27.7%) were found to be positive. Of these, 1978 (78.9%) underwent electrophoresis. About 64.2% were found to be positive for sickle haemoglobin (233 (18.4%) SCD and 1036 (81.6%) SCD trait). Conclusions The study demonstrates the feasibility of establishing a population-based screening programme in the primary health care system. It is easy to implement in tribal habitations as part of the proposed national SCD/haemoglobinopathies programme.

This study reports the extent of sickle cell disease (SCD)-related knowledge and management practices of peripheral health workers located in tribal areas of India. This formative qualitative study used a grounded theory approach and collected data through in-depth interviews. It was implemented in six districts endemic to SCD. From each district, four primary health centre (PHC) areas, predominantly inhabited by tribal communities, were included. The participants were 120 peripheral health workers, in two categories-regular health workers (RHWs) and community health workers (CHWs), working in 24 PHCs. Most of the RHWs and a little lesser number of CHWs were aware of SCD, and most of them knew it as a blood disorder. About half of the health workers reported that SCD is hereditary; however, some attributed it to malnutrition and considered it anaemia. Many health workers could tell some typical symptoms of SCD, including anaemia and severe pain. None of the PHCs offered management/treatment of SCD. And none of the health workers has any expertise in managing SCD patients. However, some health workers dealt with SCD cases and provided symptomatic treatment. Though several health workers said that SCD is preventable, comprehensive knowledge on prevention was lacking. Some health workers mentioned mass screening, counselling, and creating awareness. Thus, this paper reports the inadequacy of SCD-related knowledge and management practices among health workers. Health workers should know their roles and capabilities in managing SCD. They should be provided in-service, regular, and structured training programmes as part of the comprehensive SCD programme.

Parkinson’s Disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. Though significant insights into the molecular-biochemical-cellular-behavioral basis of PD have been understood, there is no appreciable treatment available till date. Current therapies provide symptomatic relief without any influence on the progression of the disease. Stem cell therapy has been vigorously explored to treat PD. In this comprehensive review, we analyze various stem cell candidates for treating PD and discuss the possible mechanisms. We advocate the advantage of using neural crest originated Dental Pulp Stem Cells (DPSC) due to their predisposition towards neural differentiation and their potential to regenerate neurons far better than commonly used bone marrow derived mesenchymal stem cells (BM-MSCs). Eventually, we highlight the current challenges in the field and the strategies, which may be used for overcoming the impediments.

Friction stir welding of AA2014 aluminium alloy was performed at seven diffrent speed combinations. Optical microscopy and FESEM were used to investigate the metallurgical behavior of the weld joints. Microhardness and corrosion resistance were found higher at low rotation speed and high traverse speed. Higher microhardness is the result of high traverse i.e. 90 mm/min (from traverse speed variations) and low rotational speed i.e. 508 rpm (from rotation speed variations). These parameters results in reasonably smaller matrix grain size that impacted the joint’s microhardness. There exists a small difference in both weld joint’s percentage elongation, whereas their tensile strength is similar.

The genetic mechanisms underlying the expansion in size and complexity of the human brain remains poorly understood. L1 retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution is largely unknown. Using multi-omic profiling we here demonstrate that L1-promoters are dynamically active in the developing and adult human brain. L1s generate hundreds of developmentally regulated and cell-type specific transcripts, many which are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived lncRNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPRi-silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.

Punjab Agriculture is trapped in the complex nexus of groundwater depletion and food insecurity. The policymakers are concerned about reducing groundwater extraction at any cost for irrigation without jeopardizing food security. In this regard, the Government of Punjab introduced the “Punjab Preservation of Subsoil Water Act, 2009”. The present paper examines the impact of the “Preservation of Sub Soil Water Act, 2009” on pre- and post-water levels in Punjab using the difference-in-difference (DiD) approach. The state has witnessed a severe fall of 0.50 m per year and 0.43 m per year for the post-monsoon and pre-monsoon season, respectively. Only 2.62 per cent of wells were in the range of 20–40 m depth in the state in 1996, which increased to 42 per cent and 67 per cent in 2018 for the pre-monsoon period, and post monsoon period respectively, depicting an increase of 25 times. The groundwater depth in high rice-growing(treated) districts declined by 1.53 and 1.39 m than the low rice-growing (control) districts in the pre-monsoon and post-monsoon periods respectively post the enactment of PPSW Act, 2009. A groundwater governance framework is urgently needed to manage the existing and future challenges connected with the groundwater resource.

Antimicrobial peptides harboring S- and or O-linked glycans are known as glycocins. Glycocins were first discovered and best characterized in Firmicutes. S-glycosylation is an enzymatic process catalyzed by S-glycosyltransferases of the GT2 family. Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. Although UDP-GlcNAc served as the donor in the cellular milieu, SvGT could also utilize UDP-Glc and UDP-GalNAc as donors in vitro. Using mass spectrometry and western blotting, we provide evidence that an anti-O-GlcNAc antibody (CTD110.6) cross-reacts with S-GlcNAc and may be used to detect S-GlcNAcylated glycoconjugates directly. With an understanding of enzyme specificities, we finally employed SvGT to generate two proof-of-concept neoglycocins against Listeria monocytogenes. In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering.

Huntington's disease is a neurodegenerative disorder caused by CAG expansions in the huntingtin (HTT) gene. Modelling Huntington's disease is challenging, as rodent and cellular models poorly recapitulate the disease as seen in ageing humans. To address this, we generated induced neurons through direct reprogramming of human skin fibroblasts, which retain age-dependent epigenetic characteristics. Huntington's disease induced neurons (HD-iNs) displayed profound deficits in autophagy, characterized by reduced transport of late autophagic structures from the neurites to the soma. These neurite-specific alterations in autophagy resulted in shorter, thinner and fewer neurites specifically in HD-iNs. CRISPRi-mediated silencing of HTT did not rescue this phenotype but rather resulted in additional autophagy alterations in control induced neurons, highlighting the importance of wild-type HTT in normal neuronal autophagy. In summary, our work identifies a distinct subcellular autophagy impairment in adult patient derived Huntington's disease neurons and provides a new rationale for future development of autophagy activation therapies.

Traumatic brain injury (TBI) is a leading cause of chronic brain impairment and results in a robust, but poorly understood, neuroinflammatory response that contributes to the long-term pathology. We used snRNA-seq to study transcriptomic changes in different cell populations in human brain tissue obtained acutely after severe, life-threatening TBI. This revealed a unique transcriptional response in oligodendrocyte precursors and mature oligodendrocytes, including the activation of a robust innate immune response, indicating an important role for oligodendroglia in the initiation of neuroinflammation. The activation of an innate immune response correlated with transcriptional upregulation of endogenous retroviruses in oligodendroglia. This observation was causally linkedin vitrousing human glial progenitors, implicating these ancient viral sequences in human neuroinflammation. In summary, this work provides a unique insight into the initiating events of the neuroinflammatory response in TBI, which has new therapeutic implications.

Sickle cell disease (SCD) is a progressively debilitating genetic disease, and India is the second most affected nation in the prevalence of births with SCD. This SCD prevalence is high among Indian indigenous tribal communities, whose healthcare is pluralistic. Traditional healers are an essential part of tribal pluralistic care. This study aimed to understand the extent of SCD-related knowledge and practices of traditional healers and their willingness to participate in the SCD programme, which is primarily meant to screen and treat SCD. Following the grounded theory approach, data were collected by in-depth interviews with 40 traditional healers selected from five SCD endemic districts. Text data were coded through a deductive approach, and thematic content analysis was carried out. A few healers knew about SCD. However, almost all are aware of anaemia and its symptoms. Most healers were unaware of the cause of SCD and mentioned that malnutrition and anaemia are reasons for the recurrence of SCD-related symptoms. Most of the traditional healers did not give any treatment. Some gave symptomatic treatment and provided herbal medicines along with some rituals. Though some healers treated some of the typical symptoms of SCD like spleen enlargement, jaundice, swelling and pains in joints, they did not link them with SCD. All traditional healers expressed concern and said they support the government-run SCD programme. The programme should recognise the role and importance of traditional healers. Necessary education on SCD may be given to the healers. Such involvement and education empower the healers in appropriately guiding the people concerning SCD care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12687-022-00614-y.

Background Sickle cell disease (SCD) is a serious public health problem, with >300 000 affected births worldwide each year. About 73% of the SCD-affected people in India belong to the tribal population. The Government of India is planning to implement a programme for SCD and hence people's knowledge of SCD is crucial. This paper reports the SCD-related knowledge among the Indian tribal population. Methods As part of a formative assessment before an intervention, data were collected from 9837 adults from 24 primary health centre areas of six states. Each community's knowledge of SCD was elicited through an interviewer-administered pretested questionnaire. Univariate and multivariate analyses were conducted. Results Overall, 32.1% (CI 31.2 to 33.1%) of participants had heard of SCD, 7.9% (CI: 7.3 to 8.4%) knew that SCD is hereditary, 19.4% (CI: 18.7 to 20.3%) knew that a blood test can diagnose SCD and 23.9% (CI: 23.1 to 24.8%) knew that SCD is treatable. Only 13.1% (CI: 12.4 to 13.8%) knew that SCD can be prevented. No more than 16% knew about any SCD symptoms. Multiple logistic regression revealed some predictors of basic knowledge (i.e. had heard of SCD). Conclusions There is a gross inadequacy of knowledge about SCD in the Indian tribal population. This study warrants implementing a health education programme as a part of the SCD programme.

Cell migration is an essential process in health and in disease, including cancer metastasis. A comprehensive inventory of migration factors is nonetheless lacking—in part due to the difficulty in assessing migration using high‐throughput technologies. Hence, there are currently very few screens that systematically reveal factors controlling cell migration. Here, we introduce MigExpress as a platform for the ‘identification of Migration control genes by differential Expression’. MigExpress exploits the combination of in‐depth molecular profiling and the robust quantitative analysis of migration capacity in a broad panel of samples and identifies migration‐associated genes by their differential expression in slow‐ versus fast‐migrating cells. We applied MigExpress to investigate non‐small cell lung cancer (NSCLC), which is the most frequent cause of cancer mortality mainly due to metastasis. In 54 NSCLC cell lines, we comprehensively determined mRNA and protein expression. Correlating the transcriptome and proteome profiles with the quantified migration properties led to the discovery and validation of FLNC, DSE, CPA4, TUBB6, and BICC1 as migration control factors in NSCLC cells, which were also negatively correlated with patient survival. Notably, FLNC was the least expressed filamin in NSCLC, but the only one controlling cell migration and correlating with patient survival and metastatic disease stage. In our study, we present MigExpress as a new method for the systematic analysis of migration factors and provide a comprehensive resource of transcriptomic and proteomic data of NSCLC cell lines related to cell migration., Cell migration is an essential process in development and disease—prominently in cancer metastasis. We present MigExpress, a high‐throughput approach to systematically identify factors governing cell migration by combining migration quantification with molecular profiling. MigExpress on a panel of 54 NSCLC cell lines discovered differentially expressed mRNAs, circRNAs, and proteins between fast‐ and slow‐migrating cells, which controlled migration. ​

The study investigates the effect and compares three techniques-video-eyeglasses earphone system, Digital screens and verbal methods as distracting technique to assess dental pain reaction in children during administration of local anesthesia (LA).Pain or its anticipation can cause fear and anxiety in a child which could complicate further dental treatment. This cross-sectional study consists of 97 children of age-group 4-8 years who required local anesthesia for their dental treatment were selected. Children were randomly allocated into three groups namely- Verbal method (group A), video eyeglass/earphone system (group B) and digital screens (group C). In group A, instructions were given to the patient by the dentist while administering local anesthesia. In group B, VR box was used to show age appropriate videos according to subjects' choice. In group C, digital screens were placed on dental chair for patient to watch while nerve block was administered. Pain was measured using face, legs, activity, cry, consolability (FLACC) scale behavioral anxiety/pain assessment scale.FLACC score was found to be significantly different among three groups. The mean FLACC scale score for pain was less in video eyeglass/earphone (1.94) than digital screens (3.67) and highest in Verbal group (6.88).Video eyeglasses/earphone method proved to be most effective as a distraction method in children and helped in reducing children's disruptive behavior in the dental setting.This study was conducted to find a better distraction technique among video eyeglasses/earphone system, digital screens and Verbal command that will make child less apprehensive during administration of local anesthesia.Sharma Y, Bhatia HP, Soods S

Background India is in the process of strengthening the trauma care system, and assessment of the current situation using standard guidelines has immense use. This study reports the status of trauma care facilities in India, with a broad framework of guidelines for essential trauma care by the World Health Organization. Materials and methods This study is part of a multicentric intervention study to standardize structured trauma care services in five Indian cities. Thirty trauma care facilities (five level I, 10 level II, and 15 level III facilities) were included. Data on the availability of equipment and manpower were collected. Availability of knowledge + skills and equipment + supplies was assessed based on the guidelines for essential trauma care by World Health Organization. Results There is almost 100% availability of services and equipment in level I hospitals, but availability varied between 50% and 100% at level II facilities. Very fewer number of services are available at level III facilities. Inadequacy of equipment is reported in level II and III facilities. Only level I facilities have required human resources. Availability of resources in terms of knowledge and equipment of different skills indicated that overall optimal level is observed in level I hospitals. Level II facilities are more deficient in nursing and paramedic staff, and level III facilities reported deficiencies in all categories. Conclusions A significant imbalance between recommended resources and the resources that are available in the trauma care facilities was noted. Hence, the study warrants urgent strengthening of trauma care facilities, particularly of level II and III facilities.

Nonstop or stop-loss mutations convert a stop into a sense codon, resulting in translation into the 3′ untranslated region as a nonstop extension mutation to the next in-frame stop codon or as a readthrough mutation into the poly-A tail. Nonstop mutations have been characterized in hereditary diseases, but not in cancer genetics. In a pan-cancer analysis, we curated and analysed 3,412 nonstop mutations from 62 tumour entities, generating a comprehensive database at http://NonStopDB.dkfz.de. Six different nonstop extension mutations affected the tumour suppressor SMAD4, extending its carboxy terminus by 40 amino acids. These caused rapid degradation of the SMAD4 mutants via the ubiquitin–proteasome system. A hydrophobic degron signal sequence of ten amino acids within the carboxy-terminal extension was required to induce complete loss of the SMAD4 protein. Thus, we discovered that nonstop mutations can be functionally important in cancer and characterize their loss-of-function impact on the tumour suppressor SMAD4. Dhamija et al. profile 3,412 nonstop mutations from 62 tumour entities and as proof of concept demonstrate that six such mutations cause degradation and loss of the tumour suppressor SMAD4.

Cell replacement is a long-standing and realistic goal for the treatment of Parkinsonʼs disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single-cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of recently identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model. What happens to cells on engrafting into the brain in animal models to treat Parkinson’s disease is unclear. Here, the authors use scRNA-seq to examine ventral midbrain (VM)-patterned human embryonic stem cells after functional maturation in a pre-clinical rat model for Parkinson’s disease and identify perivascular-like cells.

Gilbert’s syndrome is a genetic disorder characterised by non-hemolytic unconjugated hyperbilirubinemia. It is caused by mutations in the UGT1A1 gene which codes for the enzyme uridine diphosphate glucoronosyl transferase-1, which conjugates bilirubin for excretion. Affected individuals are usually asymptomatic apart from a mild jaundice and investigations reveal a mild isolated indirect hyperbilirubinemia. This may be exacerbated in the face of environmental and physical stressors. It is very similar in presentation to Criggler-Najjar syndrome (CNS) type 2. There is a small risk of kernicterus in patients with CNS type 2 needing daily phenobarbitone therapy. This risk is miniscule in Gilbert’s syndrome. Genetic testing for polymorphisms of the UGT1A1 gene is the diagnostic clincher for Gilbert’s syndrome, but it can also be picked up by evaluating the response to phenobarbitone and fasting, particularly in resource poor settings. Due to limited availability, case reports documenting the genetic mutational analysis are sparse. We reported one such rare case with an unusually high indirect hyperbilirubinemia in Gilbert’s syndrome confirmed by both phenobarbitone response and genetic analysis.

Viral infections are progressively becoming a global health burden, as witnessed in the ongoing COVID-19 pandemic. Respiratory Syncytial Virus (RSV) is another highly contagious negative-sense RNA virus that causes lower respiratory tract infections and high mortality in infants. Palivizumab (SynagisThe online version contains supplementary material available at 10.1007/s42485-022-00086-1.

Peer reviewed: True, Funder: New York Stem Cell Foundation; Id: http://dx.doi.org/10.13039/100003194, Funder: Parkinsonfonden; Id: http://dx.doi.org/10.13039/100008444, Funder: Lund University; Id: http://dx.doi.org/10.13039/501100003252, Funder: HORIZON EUROPE Marie Sklodowska-Curie Actions, Significant efforts are ongoing to develop refined differentiation protocols to generate midbrain dopamine (DA) neurons from pluripotent stem cells for application in disease modeling, diagnostics, drug screening and cell-based therapies for Parkinson's disease. An increased understanding of the timing and molecular mechanisms that promote the generation of distinct subtypes of human midbrain DA during development will be essential for guiding future efforts to generate molecularly defined and subtype-specific DA neurons from pluripotent stem cells. Here, we use droplet-based single-cell RNA sequencing to transcriptionally profile the developing human ventral midbrain (VM) when the DA neurons are generated (6-11 weeks post-conception) and their subsequent differentiation into functional mature DA neurons in primary fetal 3D organoid-like cultures. This approach reveals that 3D cultures are superior to monolayer conditions for their ability to generate and maintain mature DA neurons; hence, they have the potential to be used for studying human VM development. These results provide a unique transcriptional profile of the developing human fetal VM and functionally mature human DA neurons that can be used to guide stem cell-based therapies and disease modeling approaches in Parkinson's disease.