Search for Baryon Number Violation in Top Quark Production and Decay Using Proton-Proton Collisions at sqrt[s]=13 TeV.

A search is presented for baryon number violating interactions in top quark production and decay. The analysis uses data from proton-proton collisions at a center-of-mass energy of 13 TeV, collected with the CMS detector at the LHC with an integrated luminosity of 138 fb^{-1}. Candidate events are selected by requiring two oppositely charged leptons (electrons or muons) and exactly one jet identified as originating from a bottom quark. Multivariate discriminants are used to separate the signal from the background. No significant deviation from the standard model prediction is observed. Upper limits are placed on the strength of baryon number violating couplings. For the first time the production of single top quarks via baryon number violating interactions is studied. This allows the search to set the most stringent constraints to date on the branching fraction of the top quark decay to a lepton, an up-type quark (u or c), and a down-type quark (d, s, or b). The results improve the previous bounds by 3 to 6 orders of magnitude based on the fermion flavor combination of the baryon number violating interactions.

Differentially expressed microRNAs in biochemically characterized FrieswalTM crossbred bull semen.

In addition to the transmission of paternal genome, spermatozoa also carry coding as well as noncoding microRNAs (miRNAs) into the female oocyte during the process of biological fertilization. Based on RNA deep sequencing, a total 28 number of differentially expressed miRNAs were cataloged in categorized FrieswalTM crossbred (Holstein Friesian X Sahiwal) bull semen on the basis of conception rate (CR) in field progeny testing program. Validation of selected miRNAs viz. bta-mir-182, bta-let-7b, bta-mir-34c and bta-mir-20a revealed that, superior bull semen having comparatively (p < .05) lower level of all the miRNAs in contrast to inferior bull semen. Additionally, it was illustrated that, bta-mir-20a and bta-mir-34c miRNAs are negatively (p < .01) correlated with seminal plasma catalase (CAT) activity and glutathione peroxidase (GPx) level. Interactome studies identified that bta-mir-140, bta-mir-342, bta-mir-1306 and bta-mir-217 can target few of the important solute carrier (SLC) proteins viz. SLC30A3, SLC39A9, SLC31A1 and SLC38A2, respectively. Interestingly, it was noticed that all the SLCs were significantly (p < .05) expressed at higher level in superior quality bull semen and they are negatively correlated (p < .01) with their corresponding miRNAs as mentioned. This study may reflect the role of miRNAs in regulating few of the candidate genes and thus may influence the bull semen quality traits.

Trends of Infectious Disease Markers Among Healthy Blood Donors In Northern India: A Ten Year Study.

OBJECTIVE: Transfusion transmitted infection (TTI) is a major hazard for blood transfusion. The present retrospective chart review was undertaken to study the demographic profile and TTI trends among blood donors to see impact of interventions on blood safety. METHODS: Data of donors and TTI screening results from 2010 to 2019 were analyzed. Degree of significance was determined by Chi square test. RESULTS: Out of 1,68,570 donors, 33,227 (19.7%) were voluntary and 1,35,343 (80.3%) were replacement with 2.8% females and 54% belonging to the age group 18-29 years. Voluntary donation increased by only 3% in ten years and total reactivity rate was 1.6%. The reactive rate for all infections was 0.8% in volunteer donors and 1.95% in replacement donors (p-value < 0.001). The prevalence of HBsAg, HCV, HIV and syphilis showed a significant decline from 2010 to 2014. Of the donors who were reactive for HBV, 8.7% were missed by ELISA but detected by NAT. Donor reactivity for malaria remained the same in this period. CONCLUSION: Newer strategies and effort to increase voluntary donation helping the general public adopt a healthy lifestyle is urgently needed in India. Higher prevalence of TTI among replacement donors is substantiated by this study. Role of counseling of donors cannot be overemphasized. Utility of malaria screening for blood donors needs to be reexamined by evaluating evidences from other blood banks. A rational policy approach, based on a careful assessment of epidemiological data, cost effectiveness analysis, and opinion of stakeholders is necessary for universal adoption of NAT.

Use of geographical information systems (GIS) in assessing ecological profile, fish community structure and production of a large reservoir of Himachal Pradesh.

The present study demonstrates the spatial analysis and mapping of fish and different measures of environmental parameters and fish diversity of Pong reservoir, Himachal Pradesh, using Kriging spatial interpolation methods for geographical information system mapping. Seasonal data on environmental parameters, potential fish habitat and fish diversity was collected from lentic (dam), lentic (reservoir), transitional and lotic zone of the reservoir.. Important environmental parameters like water temperature, dissolved oxygen, electrical conductivity, water depth and transparency showed variations across the different zones of the reservoir. The sediment of the reservoir was sandy clay loam in nature as per texture analysis. Fish species richness, Shannon index and evenness index showed a similarity of the lotic and lentic (reservoir) zones of the reservoir. Six potential fish breeding grounds were identified in the reservoir indicating high conservation significance. The analysis of data showed a declining trend in fish production from 456.9 tonnes during the decade 1976-1987 to 347.91 tonnes during 2009-2020. The factors like anthropogenic climate change, predation of a stocked fish juvenile by water birds, undersized fish stocking and unscientific management are the probable reasons for the decreasing fish production. The spatial variation pattern of the water spread area, environmental parameters, fish catch and potential fish breeding grounds depicted in the GIS platform can be used as an important information base by the policy makers for fisheries management. The stocking of large size fish as a stocking material and adequate protection of the potential fish breeding grounds are the key advisories for the sustainable enhancement of fisheries as well as conservation.

A novel approach for estimation of aboveground biomass of a carbon-rich mangrove site in India.

Mangroves can play a crucial part in climate change mitigation policies due to their high carbon-storing capacity. However, the carbon sequestration potential of Indian mangroves generally remained unexplored to date. In this study, multi-temporal Sentinel-1 and 2 data-derived variables were used to estimate the AGB of a tropical carbon-rich mangrove forest of India. Ensemble prediction of multiple machine learning algorithms, including Random Forest (RF), Gradient Boosted Model (GBM), and Extreme Gradient Boosting (XGB), were used for AGB prediction. The multi-temporal dataset was used in two different ways to find the most suitable method of using them. The results of the analysis showed that the modeling field measured AGB with individual date data values results in estimates with root mean square errors (RMSE) ranging from 149.242 t/ha for XGB to 151.149 t/ha for the RF. Modeling AGB with the average and percentile metrics of the multi-temporal image stack improves the prediction accuracy of AGB, with RMSE ranging from 81.882 t/ha for the XGB to 74.493 t/ha for the RF. The AGB modeling using ensemble prediction showed further improvement in accuracy with an RMSE of 72.864 t/ha and normalized RMSE of 11.38%. In this study, the intra-seasonal variation of Sentinel-1 and 2 data for mangrove ecosystems was explored for the first time. The variations in remotely sensed variables could be attributed mainly to soil moisture availability and rainfall in the mangrove ecosystem. The efficiency of Sentinel-1 and 2 data-derived variables and ensemble prediction of machine learning models for Indian mangroves were also explored for the first time. The methodologies established in this study can be used in the future for accurate prediction and repeated monitoring of AGB for mangrove ecosystems.

SGLT2-inhibition and Vascular Euphoria a Reconciliation of Vascular Health and Disease Homeostasis.

The concept of SGLT2-inhibition, once regarded as a non-physiological approach to glycemia control, now finds a foundational relevance in risk-modification for cardiovascular, kidney, and metabolic outcomes, spanning beyond type-2 diabetes. Major studies have proven meaningful improvements in various clinical outcomes, with different SGLT2-i agents. Apart from glycosuria, SGLT2-inhibition is associated with several patho-physiological effects, which may contribute to the clinical benefits seen with these agents. This narrative review is an attempt to appraise the different patho-physiological effects mediated by SGLT2-inhibition, based on contemporary evidence. The review classifies these effects in the acronym of EUPHORIA, and grades the possible relevance of each effect, in improving clinical outcomes.

Rationale, study design and methodology of the LANDMARC trial: a 3-year, pan-India, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

AIM: India contributes towards a large part of the worldwide epidemic of diabetes and its associated complications. However, there are limited longitudinal studies available in India to understand the occurrence of diabetes complications over time. This pan-India longitudinal study was initiated to assess the real-world outcomes of diabetes across the country. METHODS: The LANDMARC study is the first prospective, multicentre, longitudinal, observational study investigating a large cohort of people with type 2 diabetes mellitus across India over a period of 3 years. The primary objective of this ongoing study is to determine the proportion of people developing macrovascular diabetes complications over the duration of the study (36 months ± 45 days) distributed over seven visits; the secondary objective is to evaluate microvascular diabetes complications, glycaemic control and time-to-treatment adaptation or intensification. Overall, 6300 participants (aged 25-60 years) diagnosed with type 2 diabetes for at least 2 years will be included from 450 centres across India. Data will be recorded for baseline demographics, comorbidities, glycaemic measurements, use of anti-hyperglycaemic medications and any cardiovascular or other diabetes-related events occurring during the observational study period. CONCLUSIONS: The LANDMARC study is expected to reveal the trends in complications associated with diabetes, treatment strategies used by physicians, and correlation among treatment, control and complications of diabetes within the Indian context. The findings of this study will help to identify the disease burden, emergence of early-onset complications and dose titration patterns, and eventually develop person-centred care and facilitate public health agencies to invest appropriate resources in the management of diabetes. (Trial Registration No: CTRI/2017/05/008452).

Cardiovigilance.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality across the globe. Prevention and management of the CVD pandemic calls for concerted action on part of all health care professionals, as well as other concerned stakeholders. We call for cardiovigilance in healthcare and define it as "the action or state of keeping careful watch, to prevent, screen, diagnose and manage cardiovascular disease (CVD) in a timely and appropriate manner". We expand upon the concept of cardiovigilance, describe its utility, and suggest various taxonomic rubrics to simplify its practice.

SCAR marker for Phytophthora nicotianae and a multiplex PCR assay for simultaneous detection of P. nicotianae and Candidatus Liberibacter asiaticus in citrus.

AIMS: This study aimed to develop a random amplified polymorphic DNA (RAPD)-based sequence characterized amplified region (SCAR) marker for species-specific detection of Phytophthora nicotianae, a global plant pathogen. Another objective was to develop a multiplex PCR assay for simultaneous detection of P. nicotianae and huanglongbing-causing bacterium, Candidatus Liberibacter asiaticus (CaLas) in citrus roots using the developed SCAR marker and a previously published 16SrDNA-based CaLas-specific primer set. METHODS AND RESULTS: The RAPD primer, OPA4, amplified a specific fragment of c. 400 bp only in P. nicotianae isolates. The fragment was eluted, purified, cloned and sequenced. One set of SCAR primers (SCAR4F/SCAR4R1), developed from the sequence information of the fragment, was found specific to P. nicotianae and produced an amplicon of 330 bp size, and was found non-specific to the five Phytophthora species (P. citrophthora, P. palmivora, P. lacustris, P. boehmeriae and P. insolita) and five other pathogens (Mycosphaerella citri, Alternaria alternata, Septobasidium pseudopedicillatum, Phytopythium vexans and Colletotrichum gloeosporioides) isolated from the citrus agroecosystem. The sensitivity of the primer pair was 5 pg µl-1 of mycelial DNA. Furthermore, the specific SCAR primers coupled with a previously reported CaLas-specific primer set were used effectively in developing a multiplex PCR assay to detect P. nicotianae and CaLas simultaneously in root tissues of citrus plants. CONCLUSIONS: A rapid method using a RAPD-based SCAR marker for the detection of P. nicotianae was developed. Furthermore, a multiplex PCR assay was established for simultaneous detection of P. nicotianae and CaLas in citrus roots. SIGNIFICANCE AND IMPACT OF THE STUDY: A RAPD-SCAR marker-based detection system and the one-step multiplex PCR method developed in this study can be applied to index citrus trees infected (individually or conjointly) with P. nicotianae and CaLas. The present technique developed would also be useful in monitoring disease epidemiology and phytosanitary surveillance.

HbA1C in Management of Type II Diabetes Mellitus: A Cross-sectional Survey of Indian Physicians.

OBJECTIVES: Hemoglobin A1C (HbA1C) estimation is the standard and commonly used method for diagnosis and monitoring of diabetes therapy. We conducted a questionnaire based survey to understand the Indian physician's adherence to HbA1C for effectively managing Type 2 diabetes mellitus (T2DM) patients and its influence on the decision making process. METHODS: A validated questionnaire comprising of 10 questions was administered to physicians/endocrinologists at the 44th Annual Conference of RSSDI-2016, Hyderabad. The questions of the survey were designed to understand average cutoff HbA1C level for physicians to start the mono-therapy or combination therapy with or without insulin along with preferred class of Oral anti-diabetic drugs (OAD) in Indian T2DM patients. RESULTS: 41% physicians selected HbA1C level in between 7.0-7.4% to start mono-therapy while 94.5% chose metformin as the first line OAD. In metformin uncontrolled patients, 56.8% responders chose to start a DPP4 inhibitor. To initiate dual therapy 42.9% responders chose HbA1c level of 8.0-8.4% while for triple therapy 37.1% responders selected HbA1c level of 9.0-9.4%. CONCLUSION: This survey shows the management patterns of T2DM patients by Indian physicians are in line with western guidelines especially AACE. Though guidelines do not offer stringent recommendation on first/second add-on class of OADs, DPP4i emerged as preferred choice for mono-therapy in metforminintolerant patients and as first add-on in patients uncontrolled on metformin alone.

Clinical Benefits of Fixed Dose Combinations Translated to Improved Patient Compliance.

Pharmacotherapy with fixed dose combination (FDC) drugs is becoming popular as evidence-based clinical guidelines recommend using multiple therapeutic agents in complex regimens for many chronic diseases including type 2 diabetes mellitus (T2DM). FDC formulations have unique advantages such as complementary mechanism of action, synergistic effects, better tolerability, elongated product life-cycle management, and cost savings. Polypharmacy is a frequent problem in T2DM patients having hypertension, dyslipidemia, and other comorbidities. Use of FDCs is a rational approach for achieving optimal therapeutic benefits while minimizing pill-burden. Greater convenience with decreased pill-burden leads to improved adherence, resulting in superior clinical outcomes and greater cost-effectiveness. However, the general guidance for the clinical development and approval of FDC drugs in India is not much standardized. For rationale approval, the central and state regulators must harmonize their procedures for licensing FDCs. Because regulatory approval of FDCs is based on bioavailability data, similar to the way generic medications are approved, the lack of prospective, randomized controlled trials directly comparing FDCs with their component drugs administered as separate pills should not be considered a limitation to their use. Nevertheless, all new and existing FDC products should be subjected to submission of longterm safety surveillance through closely monitored national level postmarketing studies.

Expert Group Consensus Opinion: Role of Anti-inflammatory Agents in the Management of Type-2 Diabetes (T2D).

Diabetes is a major public health emergency of the 21st century. Results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study have found prevalence of diabetes and prediabetes in India to be as high as 7.3% and 10.3%, respectively with nation-wide projection of 77.2 million people with prediabetes and 69.2 million with diabetes. It is well established that insulin resistance (IR) and islet ß-cell failure are the two major features of T2D Multiple mechanisms including glucotoxicity, lipotoxicity, oxidative stress, endoplasmic reticulum stress, formation of amyloid deposits in the islets, etc. have been hypothesized to participate in the pathology of the disease. In the concluding decade of the last century, numerous studies - prospective and cross-sectional, have confirmed the role of chronic low-grade inflammation as a pathogenetic factor of T2D. It has been shown that increased levels of various inflammatory markers and mediators including fundamental markers like white blood cell count, C-reactive protein (CRP) to the more specific circulating cytokines like, interleukin-6 (IL-6), IL-1ß, plasminogen activator inhibitor-1 (PAI-1), etc. correlate with incident T2D. Based on the robust evidence implying the role of inflammation in T2D pathogenesis, several studies have proven that the proinflammatory cytokines play a central role in the development of microvascular diabetic complications such as nephropathy, retinopathy, and neuropathy. Inflammation in T2D causes accelerated atherosclerosis which predisposes to CVD, the leading cause of mortality in these patients. Recently there is a considerable increase in the interest among the researchers about anti-inflammatory therapies in the setting of chronic disorders such as T2D and CV diseases. In a multi-country study conducted in Asia, approximately 50% of Indian respondents had poor diabetes control. Most patients initially respond to sulfonylurea and/or metformin, and later these agents lose their effectiveness with time. Therapeutic option in patients uncontrolled on two-drug combination therapy is either to add third oral drug or insulin. However, use of insulin is limited due to its high cost and poor compliance. Majority of new treatment options like GLP1 agonists, insulin analogs and SGLT2 inhibitors are costly considering they are still under patent. The thiazolidinedione class of drugs is associated with adverse effects like fluid retention and weight gain that may result in or exacerbate edema and congestive heart failure. Thus there is a need for a safe and inexpensive treatment option for the management of uncontrolled T2D. Considering the role of inflammation in T2D pathogenesis, the drug should not only have antihyperglycemic effects but also reduce inflammatory burden thus reducing the progression and complications of T2D. The current interest is apparently directed towards drugs targeting inflammation acting at different stages of the inflammatory cascade. In the recently published CANTOS study, canakinumab, a selective, high-affinity, fully human monoclonal antibody which inhibits IL-1ß, has no consistent long-term benefits on HbA1c. Other selective inhibitors like anakinra (IL-1 receptor antagonist) and etanercept (TNF inhibitor) too have yielded modest effects on glycemic parameters and insulin sensitivity. However, hydroxychloroquine (HCQ), a broad anti-inflammatory agent has been shown to reduce HbA1c by 0.87%. Hydroxychloroquine (HCQ) is considered as one of the safest disease modifying anti-rheumatic drug, used widely for the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The effect of HCQ in preventing development of diabetes in patients with chronic inflammatory diseases was highlighted in a prospective observational study of 4905 adults with rheumatoid arthritis and no diabetes with 21.5 years of follow-up. Patients who took HCQ for more than 4 years had a significant 77% lower risk of diabetes compared with non users of HCQ (RR, 0.23; 95% CI, 0.11-0.50). Taking cue from this study highlighting the anti-diabetic effect of HCQ, pioneering research studies evaluating these effects of HCQ were conducted in India. In 2014, hydroxychloroquine 400 mg got DCGI approval as an adjunct to diet and exercise to improve glycemic control of patients on metformin, sulfonylurea combination in Type 2 diabetes.

Textural pattern classification for oral squamous cell carcinoma.

Despite being an area of cancer with highest worldwide incidence, oral cancer yet remains to be widely researched. Studies on computer-aided analysis of pathological slides of oral cancer contribute a lot to the diagnosis and treatment of the disease. Some researches in this direction have been carried out on oral submucous fibrosis. In this work an approach for analysing abnormality based on textural features present in squamous cell carcinoma histological slides have been considered. Histogram and grey-level co-occurrence matrix approaches for extraction of textural features from biopsy images with normal and malignant cells are used here. Further, we have used linear support vector machine classifier for automated diagnosis of the oral cancer, which gives 100% accuracy.

Adipose tissue polyunsaturated fatty acids and metabolic syndrome among adult parents and their children.

BACKGROUND AND AIMS: Polyunsaturated fatty acids (PUFA) may play a role in the etiology of the metabolic syndrome (MetS). The aim of the study was to examine the associations of adipose tissue PUFA biomarkers with MetS among parents and children in Mesoamerica. METHOD AND RESULTS: We conducted a cross-sectional study among 468 parents and 201 children aged 7-12 y from the capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica, and Belize, and Tuxtla Gutiérrez in Mexico. We measured PUFA biomarkers in gluteal adipose tissue by gas chromatography. In adults, MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III definition. In children, we created an age- and sex-standardized metabolic risk score using abdominal circumference, the homeostasis model of insulin resistance, blood pressure, serum HDL cholesterol, and triglycerides. We estimated prevalence ratios of MetS and mean differences in metabolic score across quartiles of PUFA using multivariable-adjusted Poisson and linear regression models, respectively. Among adults, MetS was associated with low alpha-linolenic acid (ALA), high eicosapentaenoic acid (EPA), and low gamma-linolenic acid (GLA). It was linearly, positively associated with dihomo-gamma-linolenic acid (DGLA) and estimated Δ6-desaturase (D6D) activity. Among children, the metabolic score was positively associated with docosapentaenoic acid (DPA), DGLA, and D6D activity. CONCLUSIONS: Among Mesoamerican adults, MetS prevalence is inversely associated with adipose tissue ALA and GLA, and positively associated with EPA, DGLA, and the D6D index. Among children, metabolic risk score is positively associated with DPA, DGLA, and the D6D index.

Functional proteomic analysis of crossbred (Holstein Friesian × Sahiwal) bull spermatozoa.

Male infertility is one of the prime concerns of dairy cattle production. The study was designed to find out differentially expressed proteins in categorized crossbred (Holstein Friesian × Sahiwal) bull semen to serve as potential biomarkers for male infertility. Frozen crossbred bull semen with satisfactory phenotypic records were defined as "good" and "poor" based on their fertility rates. A total of 1,547 proteins were detected in bull spermatozoa using liquid chromatography-mass spectrometer (LC-MS/MS) analysis. Results revealed that 558 (36.1%) and 653 (42.2%) proteins were expressed to good and poor quality bull spermatozoa, respectively. A total of 336 proteins (21.7%) were reported to be unique for both good and poor quality bull semen, and among the common proteins, 224 (66.7%) and 112 (33.3%) were up- and downregulated in good and poor quality categorized bull semen, respectively. Gene Ontology analysis of global proteomes identified different signalling pathways, and most of them were related to cellular motility, immune systems as well as cellular metabolisms. The distinctive presence of some of the proteins may provide an insight into the molecular mechanistic role played by these proteins in crossbred bull infertility.

Indian College of Physicians (ICP) Position Statement on Pharmacovigilance.

Pharmacovigilance is the art and science of detection, understanding and prevention of adverse drug reactions and not merely a critical analysis of prescriptions and errors. This field starts with reporting by clinicians of a suspected adverse drug reaction (ADR) to the pharmacologist followed by joint causality analysis and ends at the application of new information by a clinician for benefit of patients. There are a number of ways, which can be utilised for reporting adverse effects using pen and paper format to software applications for smart phones. Varied types of activities spreading from systematic reviews to the mechanistic evaluation of ADR can be performed under the umbrella of pharmacovigilance. It is of utmost importance for clinicians to understand how to identify, communicate and understand adverse effects of drugs with an aim to prevent harm to patients.

Indian College of Physicians Position Statement: Addictive Disorders Among Persons with Diabetes Mellitus.

OBJECTIVES: Migraine, a common primary headache disorder which can be severely disabling, associated with poor health-related quality of life (HRQoL) amongst affected patients. The present study was performed to provide adequate clinical data on migraine and the management practices in India. MATERIAL AND METHODS: A cross-sectional study was designed to assess disease burden, HRQoL, symptom profile, management trends and comorbidities associated with migraine patients across ten centres in India. This study assessed HRQoL using Migraine Specific Quality of life (MSQ) and Migraine Disability Assessment Scores (MIDAS) questionnaire. Categorical variables were summarized as frequency, and percentage and continuous variables as mean and standard deviation respectively. RESULTS: A total of 705 patients were enrolled with a mean age of 35.2 years. Hypertension (7.0%) was the highest co-morbid illness associated with migraine. A higher MSQ score was observed in females as compared to males (39.3±12.4 and 37.4±11.6) while MIDAS showed a comparable score (27.7±47.6 and 27.2±35.4). Majority of migraine patients were unemployed (61.6%) and in profession, females had poor HRQoL than males by MIDAS and MSQ. Majority of patients had pulsating, bilateral attacks for the duration of 4h to 72 h. Paracetamol (47.1%) and propranolol (50.9%) was most commonly prescribed drugs for acute attack and prophylaxis, respectively. CONCLUSION: The quality of life was superior in males as compared to females amongst migraine patients in India. Hypertension was the commonest comorbidity associated with migraine. KEY MESSAGES: Migraine is associated with substantial disability with higher prevalence in females and older people (age >40 years). NSAIDs and propanol was widely prescribed drug in acute attacks and prophylaxis of migraine respectively. Cardiovascular diseases, diabetes mellitus and anxiety were common comorbidities associated with migraine.

Association of Physicians of India: Position Statement on Role of Chirally Pure Molecules in Clinical Practice.

Chirally pure molecules or enantiomers are non-superimposable mirror images of each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure molecules (single enantiomers) are important in the field of drug discovery as the drug targets such as enzymes and receptors are enantioselective in nature. Clinical studies have demonstrated that chirally pure drugs exhibit different pharmacokinetic and metabolic profiles, reduced adverse events, improved safety profiles and similar therapeutic activity at lowered drug dosage as compared with the racemate in many therapeutic areas. However, since there is a low level of awareness on the advantages of chirally pure molecules among clinicians, pharmacists and patients in India, the Association of Physicians of India (API) developed this position statement to increase awareness on the concept of chirality and the associated advantages of using chirally pure drugs in certain therapeutic areas to maximize patient outcomes. This includes the clinical evidence associated with single enantiomers such as S-metoprolol, S-amlodipine, esomeprazole, escitalopram, levobupivacaine, cisatracurium, S-etodolac, dexketoprofen, levofloxacin in terms of efficacy and safety as compared with their racemates. In addition, the API also provides some tactical recommendations for clinicians, pharmacists, patients, regulatory body and pharmaceutical companies to increase awareness on chirally pure drugs and puts forth the need for expedited availability of chirally pure drugs in the Indian market.

Publish and flourish: Take the road less travelled!

Scientific research and publications are essential for advancement of medical knowledge. The perceived need for 'publications' in medical journals, has increased substantially in view of the recently mandated requirement of original research publications in indexed journals to ensure career progression in academic institutions. There has been an unprecedented rise in the number of standalone journals and publishers, ready to process manuscripts on priority with almost guaranteed publication, at a cost. Many of these publishers have questionable credibility and could be regarded as 'predatory'. It is imperative for a concerted and broad based initiative to foster awareness creation among students at the post-graduate level and for faculty of medical colleges and research institutions. We need to adopt stringent measures to curtail this scourge of predatory publishing. It is advisable for researchers to take the road less travelled, and publish in 'reputed' and 'accepted' journals to flourish. This article aims to bring focus on to the present situation in the scientific publication arena in the Indian context, highlight emerging threats and suggest possible remedies.

Mesenchymal stromal cells for cartilage repair in osteoarthritis.

Treatment for articular cartilage damage is quite challenging as it shows limited repair and regeneration following injury. Non-operative and classical surgical techniques are inefficient in restoring normal anatomy and function of cartilage in osteoarthritis (OA). Thus, investigating new and effective strategies for OA are necessary to establish feasible therapeutic solutions. The emergence of the new discipline of regenerative medicine, having cell-based therapy as its primary focus, may enable us to achieve repair and restore the damaged articular cartilage. This review describes progress and development of employing mesenchymal stromal cell (MSC)-based therapy as a promising alternative for OA treatment. The objective of this review is to first, discuss how in vitro MSC chondrogenic differentiation mimics in vivo embryonic cartilage development, secondly, to describe various chondrogenic differentiation strategies followed by pre-clinical and clinical studies demonstrating their feasibility and efficacy. However, several challenges need to be tackled before this research can be translated to the clinics. In particular, better understanding of the post-transplanted cell behaviour and learning to enhance their potency in the disease microenvironment is essential. Final objective is to underscore the importance of isolation, storage, cell shipment, route of administration, optimum dosage and control batch to batch variations to realise the full potential of MSCs in OA clinical trials.