Search

Introduction Up to 2/3rd of the stroke subjects may experience impairment in any of the somatosensory modalities such as light touch, proprioception, and stereognosis. The sensory recovery is strongly associated with the level of motor recovery. Very negligible sensory-based interventions have been developed and found to be evident in enhancing the sensory deficit and associated motor recovery. The possible factor for the ineffectiveness of these sensory interventions could be lack of the neuroscientific basis in formulation of the program. Thus, the objective of the study is to determine the effectiveness of a neuralplasticity-principles-based sensory-rehabilitation protocol on motor and sensory recovery, and disability of the post-stroke hemiparetic subjects. Methods We propose to recruit 122 poststroke subjects in a randomized controlled, assessor blinded trial to be conducted in a rehabilitation-institute. The key eligibility criteria is age between 20 to 80 years, hemiparesis (right or left), ischemic or hemorrhagic stroke, 1 to 12 months poststroke, and impairment in any of the sensory modalities. The participants in the experimental group will receive NEuroplasticity-Principles-based SEnsory-Rehabilitation (NEPSER) protocol comprising active, repetitive, and meaningful training of the specific sensory modalities utilizing visuo-perceptual, cognitive, motor, and functional tasks will be imparted for 8 weeks, 5 sessions / week, each of 2 h. The control subjects will undergo only standard rehabilitation based on neurophysiological, biomechanical, and rehabilitative approaches. All the participants will be assessed for motor (Fugl-Meyer assessment, upper extremity section) and sensory recovery [Nottingham Sensory assessment (Erasmus MC modification of the revised version)] at baseline, 8-week, and 12-week follow-up. The Semmes weinstein monofilament, two-point discrimination test and modified rankin scale (disability) will be applied as secondary measures. A repeated-measures 2-way ANOVA will be used to estimate difference for the post intervention and follow-up scores between the groups. Perspective The proposed study will lead to development of a novel rehabilitation protocol that will not only enhance the sensory recovery but also the motor and functional recovery. This may reduce the impact of stroke disability and enhance the quality of life. Trial registration The trial has been registered under Clinical Trial Registry of India (CTRI) as CTRI/2019/09/021442 on 30th September 2019.

Background Micronutrient deficiency (MD) is associated with deficits in cognitive functioning of children. However, no comprehensive multicentric study has been conducted in India to explore the role of multiple MD in cognition of children and adolescents. The present study aimed to explore association of MD with level of general intelligence and specific cognitive functions, in urban school-going children and adolescents across ten cities of India. Method Cross-sectional multicentric study, enrolled participants aged 6–16 years. Blood samples were collected for biochemical analysis of calcium, iron, zinc, selenium, folate, vitamin A, D and B12. Colored Progressive Matrices / Standard Progressive Matrices (CPM/SPM), Coding, Digit Span and Arithmetic tests were used for the assessment of cognitive functions of participants. Height and weight measures were collected along with socio-economic status. Results From April-2019 to February-2020, 2428 participants were recruited from 60 schools. No MD was found in 7.0% (134/1918), any one MD in 23.8% (457/1918) and ≥ 2 MD in 69.2% (1327/1918) participants. In presence of ≥ 2 MD, adjusted odds ratio (OR) for borderline or dull normal in CPM/SPM was 1.63, (95% CI: 1.05–2.52), coding was 1.66 (95% CI: 1.02–2.71), digit span was 1.55 (95% CI: 1.06–2.25) and arithmetic was 1.72 (95% CI: 1.17–2.53), controlling for gender, socioeconomic status and anthropometric indicators. Conclusion Since ≥ 2 MD were found in more than 2/3rd of participants and was associated with impairment in cognitive function, attempts must be made to ameliorate them on priority in school going children in India. Trial registration number CTRI/2019/02/017783.

Introduction Childhood and adolescence require adequate amount of micronutrients for normal growth and development. The primary objective of study was to assess the prevalence of deficiencies of Vitamins (Vitamin A, 25 Hydroxy Vitamin D, Vitamin B12 and Folate) and minerals (Calcium, Zinc, Selenium and Iron), among urban school going children aged 6–11 and 12–16 years in ten cities of India. Secondary objective was to find the association between micronutrient deficiencies with sociodemographic and anthropometric indicators. Methods A multi-center cross-sectional study was conducted across India. Participants in the age groups of 6 to 11 years (group 1) and 12 to 16 years (group 2) were selected from randomly chosen schools from each center. Data on socio economic status, anthropometric measures was collected. Blood samples were collected for biochemical analysis of micronutrients. Point estimates and 95% confidence intervals was used to assess the prevalence of deficiencies. Associations were observed using chi square, student t test and ANOVA test. Results From April 2019 to February 2020, 2428 participants (1235 in group 1 and 1193 group 2) were recruited from 60 schools across ten cites. The prevalence of calcium and iron deficiency was 59.9% and 49.4% respectively. 25 Hydroxy Vitamin D deficiency was seen in 39.7% and vitamin B12 in 33.4% of subjects. Folate, Selenium and Zinc were deficient in 22.2%, 10.4% and 6.8% of subjects respectively. Vitamin A deficiency least (1.6%). Anemia was prevalent in 17.6% subjects and was more common among females. Conclusion One or more micronutrient deficiencies are found in almost one half of school going children in urban area. Hence efforts must be made to combat these on priority. Trial registration number CTRI/2019/02/017783.

Ionizing radiation (IR) therapy is a major cancer treatment modality and an indispensable auxiliary treatment for primary and metastatic cancers, but invariably results in debilitating organ dysfunctions. IR-induced depletion of neural stem/progenitor cells in the subgranular zone of the dentate gyrus in the hippocampus where neurogenesis occurs is considered largely responsible for deficiencies such as learning, memory, and spatial information processing in patients subjected to cranial irradiation. Similarly, IR therapy-induced intestinal injuries such as diarrhea and malabsorption are common side effects in patients with gastrointestinal tumors and are believed to be caused by intestinal stem cell drop out. Hematopoietic stem cell transplantation is currently used to reinstate blood production in leukemia patients and pre-clinical treatments show promising results in other organs such as the skin and kidney, but ethical issues and logistic problems make this route difficult to follow. An alternative way to restore the injured tissue is to preserve the stem cell pool located in that specific tissue/organ niche, but stem cell response to ionizing radiation is inadequately understood at the molecular mechanistic level. Although embryonic and fetal hypersensity to IR has been very well known for many decades, research on embryonic stem cell models in culture concerning molecular mechanisms have been largely inconclusive and often in contradiction of the in vivo observations. This review will summarize the latest discoveries on stem cell radiosensitivity, highlighting the possible molecular and epigenetic mechanism(s) involved in DNA damage response and programmed cell death after ionizing radiation therapy specific to normal stem cells. Finally, we will analyze the possible contribution of stem cell-specific chromatin’s epigenetic constitution in promoting normal stem cell radiosensitivity.

This chapter describes the methods of isolation of mouse periosteal progenitor cells. There are three basic methods utilized. The bone grafting method was developed utilizing the fracture healing process to expand the progenitor populations. Bone capping methods requires enzymatic digestion and purification of cells from the native periosteum, while the Egression/Explant method requires the least manipulation with placement of cortical bone fragments with attached periosteum in a culture dish. Various cell surface antibodies have been employed over the years to characterize periosteum derived progenitor cells, but the most consistent minimal criteria was recommended by the International Society for Cellular Therapy. Confirmation of the multipotent status of these isolated cells can be achieved by differentiation into the three basic mesodermal lineages in vitro.

This chapter describes the methods of isolation of mouse periosteal progenitor cells. There are three basic methods utilized. The bone grafting method was developed utilizing the fracture healing process to expand the progenitor populations. Bone capping methods requires enzymatic digestion and purification of cells from the native periosteum, while the Egression/Explant method requires the least manipulation with placement of cortical bone fragments with attached periosteum in a culture dish. Various cell surface antibodies have been employed over the years to characterize periosteum derived progenitor cells, but the most consistent minimal criteria was recommended by the International Society for Cellular Therapy. Confirmation of the multipotent status of these isolated cells can be achieved by differentiation into the three basic mesodermal lineages in vitro.

Unintended outcomes of cancer therapy include ionizing radiation (IR)-induced stem cell depletion, diminished regenerative capacity, and accelerated aging. Stem cells exhibit attenuated DNA damage response (DDR) and are hypersensitive to IR, as compared to differentiated non-stem cells. We performed genomic discovery research to compare stem cells to differentiated cells, which revealed Phosphoprotein phosphatase 2A (PP2A) as a potential contributor to susceptibility in stem cells. PP2A dephosphorylates pATM, γH2AX, pAkt etc. and is believed to play dual role in regulating DDR and apoptosis. Although studied widely in cancer cells, the role of PP2A in normal stem cell radiosensitivity is unknown. Here we demonstrate that constitutively high expression and radiation induction of PP2A in stem cells plays a role in promoting susceptibility to irradiation. Transient inhibition of PP2A markedly restores DNA repair, inhibits apoptosis, and enhances survival of stem cells, without affecting differentiated non-stem and cancer cells. PP2Ai-mediated stem cell radioprotection was demonstrated in murine embryonic, adult neural, intestinal, and hematopoietic stem cells.

Summary Dynamic spatiotemporal modification of chromatin around DNA damage is vital for efficient DNA repair. Normal stem cells exhibit an attenuated DNA damage response (DDR), inefficient DNA repair, and high radiosensitivity. The impact of unique chromatin characteristics of stem cells in DDR regulation is not yet recognized. We demonstrate that murine embryonic stem cells (ES) display constitutively elevated acetylation of histone H3 lysine 9 (H3K9ac) and low H3K9 tri-methylation (H3K9me3). DNA damage-induced local deacetylation of H3K9 was abrogated in ES along with the subsequent H3K9me3. Depletion of H3K9ac in ES by suppression of monocytic leukemia zinc finger protein (MOZ) acetyltransferase improved ATM activation, DNA repair, diminished irradiation-induced apoptosis, and enhanced clonogenic survival. Simultaneous suppression of the H3K9 methyltransferase Suv39h1 abrogated the radioprotective effect of MOZ inhibition, suggesting that high H3K9ac promoted by MOZ in ES cells obstructs local upregulation of H3K9me3 and contributes to muted DDR and increased radiosensitivity., Highlights • Embryonic stem cells show impaired H3K9 deacetylation at DNA DSB sites • Downregulation of MOZ-dependent H3K9ac improves ATM activation in stem cells • MOZ knockdown protects embryonic stem cells from radiation-induced cell death • MOZ suppression-mediated radioprotection is dependent on methyltransferase Suv39h1, H3K9 acetylation is high in stem cells, but requires downregulation at DNA damage sites. Sharma and colleagues show inefficient H3K9 deacetylation and tri-methylation in embryonic stem cells and establish H3K9 acetyltransferase MOZ as a potential therapeutic target to improve ATM activation and stem cell survival after DNA damage induction.

Visual gait assessment is a cost-effective clinical method to assess post-stroke gait deviations. The Rivermead Visual Gait Assessment (RVGA) is a one such measure that assesses the kinematic aspect of the gait deviations in stroke. However, the available information on psycho-clinocometric properties of the measure is not adequate.To establish reliability and validity of RVGA using walking-videos of the post-stroke subjects.Design: Observational study.A rehabilitation institute Participants: A convenience sample of 40 chronic stroke patients.RVGA, Fugl-Meyer assessment (lower extremity), 10-m walk test, Time up and go test, and Berg balance scale (BBS).Walking was video-taped from the anterior aspect, posterior aspect, affected side, and less-affected side. After coding the tapes, a research staff member provided them to four different raters in a random order. Each rater scored the coded video on the RVGA data collection sheet twice: one at the baseline and another after 1 month to eliminate any recollection of the initial assessment.The findings exhibit that there was good-to-excellent agreement between the scores of the raters and also between the assessments (correlation coefficient = 0.94 to 0.95; P0.001). The measure also exhibits acceptable validity when correlated with scores of BBS (r = 0.4; P0.001).Video-based RVGA is a reliable and valid tool to assess gait-related impairment in post-stroke hemiparesis. This cost-effective measure may be incorporated in the clinical and research practice to discern and quantify complex phenomenon of the gait deviation. RVGA may be considered as a useful tool, especially in developing countries where expensive gait analyzer is usually not available.

Objective To investigate whether methotrexate (MTX) administered orally to rheumatoid arthritis (RA) patients in split doses at 2–3 days’ interval, would result in equal or better efficacy, tolerability and compliance, without increasing toxicity compared to single weekly dose given orally or parenterally. Materials and methods One hundred and thirty-five patients fulfilling the American College of Rheumatology (ACR) 2010 criteria for RA, on 7.5 mg of MTX weekly orally, with the Simplified Disease Activity Index (SDAI) > 11 were enrolled for a 24-week period. Patients were randomly divided into three groups and were given MTX: Group 1 7.5 mg twice or thrice weekly orally, Group 2 15 mg or 22.5 mg in a single dose weekly orally and Group 3 15 mg or 22.5 mg in a single dose weekly as an intramuscular injection. The primary outcomes were low disease activity (LDA) and mean change in SDAI at week 24, whereas secondary outcomes included remission, adverse events and compliance. Results At week 24, adherence to treatment was maximum in Group 1, 69% (P = 0.09). In intention-to-treat analysis at 24 weeks, Group 1, 49%, Group 2, 36% and Group 3, 47% achieved LDA (P = 0.4). There was significant difference in mean change in SDAI at week 24 from baseline (P = 0.008) among the groups. Group 3 patients were more uncomfortable with the mode of administration of MTX (P = 0.003). There was no significant difference in adverse events. Conclusion Oral split doses of MTX are better than an oral single dose and similar to parenteral MTX in terms of efficacy.

Objectives To correlate and compare serum levels of procalcitonin (PCT) and C-reactive protein (CRP) in children with severe and very severe community acquired pneumonia (CAP), as defined by World Health Organization (WHO) and also had radiological abnormalities consistent with pneumonia. Methods This was a cross-sectional study, done in a tertiary care teaching hospital in north India. Included were children aged between 2 months and 5 years, hospitalized for CAP. Definitions of WHO for diagnosing severe and very severe pneumonia have been used as gold standard. Written informed consent was obtained from parents. Those, who have wheeze, fever more than 14 days, and severe malnutrition, were excluded. For estimations of serum PCT and CRP levels, commercially available enzymes linked fluorescent assay and enzymes linked immune-sorbent assay kits were used, respectively. Results From June 2013 to September 2013, fifty cases were recruited, among which 56% (n=28/50) and 44% (n=22/50) were very severe pneumonia and severe pneumonia, respectively. In cases of very severe pneumonia and severe pneumonia, mean serum PCT levels were 17.65±18.9ng/ml and 0.93±2.91ng/ml (p=0.01) and mean serum CRP levels were 85.25±17.83mg/dl and 56.50±23.13mg/dl (p≤0.01), respectively. Serum PCT and CRP levels were positively linearly correlated (r=0.45). Using serum PCT levels >2ng/ml and serum CRP levels >60mg/dl, cut-off for differentiating very severe and severe pneumonia, the sensitivity was same (92.9%), but specificity of PCT was higher (86.4%) than CRP (63.6%). Area under receiver operating characteristics (ROC) curves was 0.923 and 0.837 for serum PCT and CRP, respectively. Conclusion Serum PCT and CRP are positively linearly correlating with each other and PCT has better differentiating ability between very severe and severe pneumonia than CRP.

Objectives To study the prevalence of rheumatic musculoskeletal symptoms in rural and urban areas of Lucknow. Method The survey was carried out in a cluster of rural (n = 5118) and urban (n = 5053) communities of Lucknow through a door-to-door survey. Demographic data were collected and subjects with musculoskeletal pain (MSK pain) were identified. A Hindi adapted version of the Community Oriented Program for the Control of Rheumatic Diseases questionnaire was used. Trained community volunteers completed the questionnaire. Results Present and past MSK pain was the most common self-reported problem in urban areas (34.1%), while it was the third most common self-reported problem in rural areas (15.1%), after abdominal pain and cough. Females (214.9 and 419.5 per 1000) were more affected than males (118.8 and 265.2 per 1000) in rural and urban areas, respectively. Point prevalence of MSK pain (pain in last week) was higher in urban areas (28.2%) compared to rural areas (14.1%). In rural as well as urban areas, knee (rural: 49.3%, urban: 50.6%) and spine (rural: 56%, urban: 43.6%) were highly reported pain sites. Fatigue ([n] rural: 328, urban: 368) weakness ([n] rural: 310, urban: 324) and anorexia ([n] rural: 84, urban: 142) were most common systemic symptoms reported by urban as well as rural people. Urethritis/balanitis and ulcers in the mouth were the most common other symptoms reported by people in both the areas. Conclusion MSK pain is a predominant health problem of both rural and urban areas. Sex-adjusted prevalence is higher among females than males. Knee and back were highly prevalent pain sites in both rural and urban areas of Lucknow.

Objectives To study the distribution of various rheumatological diseases in rural and urban areas of Lucknow, India. Method A study using adapted a Community Oriented Program for the Control of Rheumatic Diseases scheme was carried out in a cluster of rural (n = 5118) and urban (n = 5053) communities through a door-to-door survey. Trained community volunteers completed the questionnaires. Patients with musculoskeletal pain (MSK pain) were clinically evaluated by a physician. X-ray examinations and blood investigations were also done. Diagnosis was made according to International Classification of Diseases-9 classification system. Results Among persons reporting MSK pain in rural areas, high prevalence of osteoarthritis (OA) knee (35%) was observed followed by fibromyalgia (32.1%), backache (28.4%), non-specific pain (NSP) (20.7%) and rheumatoid arthritis (RA) (1.2%). In urban area, OA knee (36.3%) and backache (36.6%) were found highly prevalent, followed by fibromyalgia (11.1%), NSP (10.9%) and neck pain (7.4%). In urban areas among MSK pain patients, prevalence of RA was only 1.6%. Age-adjusted analysis among urban people showed backache complaints begin early (>20 years) than rural people. Significantly higher numbers of Knee OA complaints emerged among urban people than rural in the age group 21-60 years. Projected population prevalence of knee OA was 44.9 and 106.07/1000 in rural and urban areas, respectively. Further projected population prevalences of fibromyalgia, backache, RA and NSP in rural and urban areas are 41.2 and 32.4, 36.5 and 106.6, 1.56 and 4.74, 26.0 and 32.0 per 1000, respectively. Conclusion OA knee, fibromyalgia, backache and NSP are predominant health problems of both areas. Female preponderance was observed in all rheumatological diseases in both the areas.

Introduction: Oral cancer is the sixth most common form of cancer reported globally which includes lip, tongue, mouth, and throat. Developing countries face several challenges to identify and remove potential risk factors. Chewing tobacco/pan masala is considered to be the most potential risk factor for oral precancerous lesions and oral cancer. Objective: To study the clinical-epidemiological profile of oral cancer cases and potential risk factor associated with it. Materials and Methods: This is cross-sectional study which includes all major tertiary hospital in Lucknow district. Five hundred and eight cases of oral cancer reported in all major tertiary hospitals in Lucknow district during 2013–2016. Study Variable: Clinicoepidemiological characteristics of oral cancer cases. Statistical Analysis: percentages, proportions. Results: Out of 508 cases, majority of the subjects included in the study belonged to 18–75 years age group. Reported cases of oral cancer in males were higher as compared to females. Most of the subjects belonged to lower middle and upper lower socioeconomic group. It was found that 199 (39.2%) subjects consumed smokeless tobacco. Buccal mucosa was the common site of oral cancer being present in 50.4% of the subjects. Histopathologically, 256 cases of buccal mucosa, 17 cases of lip, 33 cases of alveolar region, 16 cases of mandible region, 156 cases of tongue region, 7 cases of gingival buccal sulcus region, and 23 cases of palate were diagnosed as oral squamous cell carcinoma. Conclusion: In the present study, the most affected site was buccal mucosa (50.4%), tongue (30.7%), and other diagnosis was

AIM Several studies have shown that colchicine exhibits an improvement in the symptoms of knee osteoarthritis (OA) but its effect on disease progression is unknown. To clarify the mechanism of action this study was done to see if colchicine prevents degradation of collagen fiber network in OA by studying serum cartilage oligomeric matrix protein (COMP) levels, a marker of cartilage turnover, over a period of 1 year. METHODS Seventy-five patients received colchicine plus paracetamol and 75 received placebo alone for the same time period. Serum COMP assays were done at baseline, 2 months and 1 year by enzyme-linked immunosorbent assay. These markers were compared between visits using repeated measures analysis of variance. RESULTS Serum COMP levels in the paracetamol-alone group did not show significant change between baseline and 2 months; however, there was a significant increase in serum COMP levels from 2 months to 1 year, suggesting increased uncoupling of proteoglycans from collagen and disease progression. No such change was seen in the colchicine group, signifying lack of progression of disease in this group. CONCLUSION Colchicine may act as a disease-modifying agent in OA.