Spectrum of Rare and Novel Indel Mutations Responsible for ß Thalassemia in Eastern India.

There is limited data available regarding the clinical utility of routine molecular diagnosis of ß Thalassaemia in addition to HPLC-based screening in low resource settings. The current study highlights the caveats of an HPLC-based screening compared to the inclusion of genetic confirmation as a second-tier test and its implications in terms of genotype-phenotype correlation. A prospective, institution-based, observational study was conducted at the Department of Paediatric Medicine, including 103 children aged up to 12 years. Five common mutations for ß Thalassemia and the HbE mutation in the HBB gene were tested by a two-tiered approach using multiplex ARMS PCR and PCR RFLP methods respectively. Sanger sequencing of all three exons of the HBB gene was performed in all negative cases. Sequencing revealed many rare pathogenic mutations like c.316-106 C > G (dbSNP: 34,690,599); Hb Kairouan (c.92G > C); c.33 C > A (dbSNP rs35799536); c.47G > A (dbSNP rs63750783); c.51delC (HbVar ID 799); c.[93-2 A > C] and c.118 C > T (HbVar ID 845). We detected a novel Pathogenic M_000518.5(HBB):c.164_168delinsGGCATCA (p.Val55fs) mutation in a heterozygous state which was reported in the ClinVar database with accession ID VCV000590977.2. We also encountered several cases of silent carrier on HPLC and de novo occurrence of mutation. We conclude that the multiplex touchdown ARMS PCR methodology employed in the present study provides a low-cost solution for molecular diagnostics of Β Thalassaemia. The problem of silent carriers in HPLC is significant enough to rethink if we need supplemental genetic testing in the couple when one of the partners is a carrier. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01098-w.

Characterization of the internal working-life exposome using minimally and non-invasive sampling methods - a narrative review.

During recent years, we are moving away from the 'one exposure, one disease'-approach in occupational settings and towards a more comprehensive approach, taking into account the totality of exposures during a life course by using an exposome approach. Taking an exposome approach however is accompanied by many challenges, one of which, for example, relates to the collection of biological samples. Methods used for sample collection in occupational exposome studies should ideally be minimally invasive, while at the same time sensitive, and enable meaningful repeated sampling in a large population and over a longer time period. This might be hampered in specific situations e.g., people working in remote areas, during pandemics or with flexible work hours. In these situations, using self-sampling techniques might offer a solution. Therefore, our aim was to identify existing self-sampling techniques and to evaluate the applicability of these techniques in an occupational exposome context by conducting a literature review. We here present an overview of current self-sampling methodologies used to characterize the internal exposome. In addition, the use of different biological matrices was evaluated and subdivided based on their level of invasiveness and applicability in an occupational exposome context. In conclusion, this review and the overview of self-sampling techniques presented herein can serve as a guide in the design of future (occupational) exposome studies while circumventing sample collection challenges associated with exposome studies.

Transforming growth factor beta orchestrates PD-L1 enrichment in tumor-derived exosomes and mediates CD8 T-cell dysfunction regulating early phosphorylation of TCR signalome in breast cancer.

Tumor cells promote immune evasion through upregulation of programmed death-ligand 1 (PD-L1) that binds with programmed cell death protein 1 (PD1) on cytotoxic T cells and promote dysfunction. Though therapeutic efficacy of anti-PD1 antibody has remarkable effects on different type of cancers it is less effective in breast cancer (BC). Hence, more details understanding of PD-L1-mediated immune evasion is necessary. Here, we report BC cells secrete extracellular vesicles in form of exosomes carry PD-L1 and are highly immunosuppressive. Transforming growth factor beta (TGF-ß) present in tumor microenvironment orchestrates BC cell secreted exosomal PD-L1 load. Circulating exosomal PD-L1 content is highly correlated with tumor TGF-ß level. The later also found to be significantly associated with CD8+CD39+, CD8+PD1+ T-cell phenotype. Recombinant TGF-ß1 dose dependently induces PD-L1 expression in Texos in vitro and blocking of TGF-ß dimmed exosomal PD-L1 level. PD-L1 knocked down exosomes failed to suppress effector activity of activated CD8 T cells like tumor exosomes. While understanding its effect on T-cell receptor signaling, we found siPD-L1 exosomes failed to block phosphorylation of src family proteins, linker for activation of T cells and phosphoinositide phospholipase Cγ of CD8 T cells more than PD-L1 exosomes. In vivo inhibition of exosome release and TGF-ß synergistically attenuates tumor burden by promoting Granzyme and interferon gamma release in tumor tissue depicting rejuvenation of exhausted T cells. Thus, we establish TGF-ß as a promoter of exosomal PD-L1 and unveil a mechanism that tumor cells follow to promote CD8 T-cell dysfunction.

The Potentials and Pitfalls of Using Adult Stem Cells in Cancer Treatment.

Stem cells play a pivotal role in the developmental stages of an organism and in adulthood as well. Therefore, it is not surprising that stem cells constitute a focus of extensive research. Indeed, several decades of stem cell research have tremendously increased our knowledge on the mechanistic understandings of stem cell biology. Interestingly, revealing the fundamental principles of stem cell biology has also fostered its application for therapeutic purposes. Many of the attributes that the stem cells possess, some of which are unique, allow multifaceted exploitation of stem cells in the treatment of various diseases. Cancer, the leading cause of mortality worldwide, is one of the disease groups that has been benefited by the potentials of therapeutic applications of the stem cells. While the modi operandi of how stem cells contribute to cancer treatment are many-sided, two major principles can be conceived. One mode involves harnessing the regenerative power of the stem cells to promote the generation of blood-forming cells in cancer patients after cytotoxic regimens. A totally different kind of utility of stem cells has been exercised in another mode where the stem cells can potentially deliver a plethora of anti-cancer therapeutics in a tumor-specific manner. While both these approaches can improve the treatment of cancer patients, there exist several issues that warrant further research. This review summarizes the basic principles of the utility of the stem cells in cancer treatment along with the current trends and pinpoints the major obstacles to focus on in the future for further improvement.

Oxidative cyanation of 2-oxindoles: formal total synthesis of (±)-gliocladin C.

Efficient oxidative direct cyanations of 3-alkyl/aryl 2-oxindoles using Cyano-1,2-BenziodoXol-3(1H)-one (CBX) (2a) have been reported under 'transition metal-free' conditions to synthesize a wide variety of 3-cyano 3-alkyl/aryl 2-oxindoles sharing an all-carbon quaternary center under additive-free conditions. The application of this process is shown by the formal total synthesis of (±)-gliocladin C (11c) in a few steps.

Screening for Hypertension in Asymptomatic Individuals in India: An Expert Consensus Statement.

INTRODUCTION: Hypertension (HTN) is a rapidly growing epidemic in India. It is no larger restricted to older adults as more young Indians are being diagnosed with HTN. Despite its significant prevalence, the awareness, treatment, and control of HTN remain low in India. Thus, early diagnosis is essential to control HTN and prevent future complications. Screening for HTN can help identify undiagnosed and asymptomatic HTN, and thereby the early use of interventions to control the blood pressure (BP). However, no comprehensive guidelines have been established for effective HTN screening in asymptomatic individuals in an Indian setting. OBJECTIVE: To provide consensus recommendations for hypertension screening in India. CONSENSUS RECOMMENDATIONS: Screening for HTN can provide more effective control of HTN and reduce the complications. Experts recommended that the initial age at screening should be 18 years. In individuals at a high risk of HTN, targeted screening can be undertaken. BP measurement using an electronic BP recorder (with at least two readings) are required for identifying HTN during screening. In asymptomatic adults with BP <130/85 mmHg and BP of 130-139/85- 89 mmHg, rescreening should be conducted every 3-5 years and at least every year, respectively. Screening for HTN can be cost effective even when universal screening of the entire population is undertaken. CONCLUSION: The consensus recommendations would increase the awareness of HTN screening. Screening for HTN can provide more effective control of HTN and reduce the complications.

Clinical Profile and Therapeutic Response of Scrub Typhus in Children: A Recent Trend from Eastern India.

OBJECTIVE: The aim of this study was to assess the clinico-laboratory parameters, complications and therapeutic responses in children with scrub typhus in Eastern India. MATERIALS AND METHODS: In this prospective, observational study, all children (age, <12 years) with suspected scrub typhus with a compatible clinical scenario were enrolled consecutively over six months. Cases confirmed by means of a positive IgM serology or a positive Weil-Felix reaction (OXK = 1/80 or above) were administered enteral doxycycline (4.5 mg/kg/day). RESULTS: Out of 94 recruited children, 61 had confirmed scrub typhus (mean age = 6.1 years, M:F = 1.1:1) with or without complications and having a considerably higher incidence of neurological presentation (meningoencephalistis n = 21, 34.4%). The most frequent manifestations included vomiting (n = 39, 63.9%), abdominal pain (n = 33, 54.1%), lymphadenopathy (n = 36, 59%), hepatosplenomegaly (n = 32, 52.5%), pedal edema (n = 32, 52.5%) and eschar formation (n = 30, 49.2%). Low hemoglobin levels, leukocytosis, thrombocytopenia, hypoalbuminemia, hyponatremia, increased liver enzymes and increased C-reactive protein were associated with delayed defervescence (>48 h). CONCLUSION: Scrub meningoencephalitis, with a notably higher incidence, showed favorable therapeutic response. Prompt and empiric doxycycline therapy could be lifesaving.

Transition-Metal Free Oxidative Alkynylation of 2-Oxindoles with Ethynylbenziodoxolone (EBX) Reagents.

We report an efficient direct alkynylations of 3-alkyl/aryl 2-oxindoles employing ethynyl-1,2-benziodoxol-3(1H)-one (EBX) to afford a wide variety of 3-alkynyl-3-alkyl/aryl 2-oxindole under transition-metal free condition. In addition to activated carbonyl compounds viz. 2-oxindole-3-alkylcarboxylates, this direct alkynylations protocol works efficiently on 3-alkyl/aryl 2-oxindols as well thereby widening the scope even further. Eventually, a Pd(0)-catalyzed asymmetric decarboxylative allylation of few products is shown to furnish synthetically viable enantioenriched 2-oxindoles with C-3 quaternary stereocenters.

Articulatin-D induces apoptosis via activation of caspase-8 in acute T-cell leukemia cell line.

Leukemia is among the most aggressive and prevalent human malignant carcinoma. Chemotherapy is the preferred therapeutic strategy; however, recurrence of cancer and non-selective cytotoxicity are the major concerns. Unlike synthetic chemotherapeutic agents, mistletoe ribosome-inactivating protein (RIP) displays anti-tumor function in various types of cancers. However, its effect on leukemia cells is little explored. In this study, we assessed the impact of Viscum articulatum RIP (Articulatin-D) on the survival of acute T-cell leukemia cells and the involved molecular and cellular mechanisms. Cell proliferation assay showed that Articulatin-D suppressed the viability of leukemia cells selectively. We further confirmed that the elevation of mitochondrial membrane potential and exposure of phosphatidylserine are the early events of apoptosis induction in Articulatin-D-treated Jurkat cells. Subsequently, we found that Articulatin-D treatment induces apoptosis in Jurkat cells in a time- and concentration-dependent manner. In conclusion, we provided evidence that Articulatin-D efficiently activates caspase-8 involved in extrinsic pathway of apoptosis induction, which ultimately results in caspase-3-dependent DNA fragmentation of Jurkat cells. Further evaluation of Articulatin-D in cell culture and animal models may provide novel information on selective cytotoxicity to acute T-cell leukemia and its involvement in targeting tumor cell survival pathways.

Exercise and eating habits among urban adolescents: a cross-sectional study in Kolkata, India.

BACKGROUND: Unhealthy eating and lack of exercise during adolescence culminated into earlier onset and increasing burden of atherosclerotic cardiovascular diseases (CVDs) worldwide. Among urban Indian adolescents, prevalence of these risk factors of CVD seemed to be high, but data regarding their pattern and predictors was limited. To address this dearth of information, a survey was conducted among urban adolescent school-students in Kolkata, a highly populated metro city in eastern India. METHODS: During January-June, 2014, 1755 students of 9th-grade were recruited through cluster (schools) random sampling. Informed consents from parents and assents from adolescents were collected. Information on socio-demographics, CVD-related knowledge and perception along with eating and exercise patterns were collected with an internally validated structured questionnaire. Descriptive and regression analyses were performed in SAS-9.3.2. RESULTS: Among 1652 participants (response rate = 94.1%), about 44% had poor overall knowledge about CVD, 24% perceived themselves as overweight and 60% considered their general health as good. Only 18% perceived their future CVD-risk and 29% were engaged in regular moderate-to-vigorous exercise. While 55% skipped meals regularly, 90% frequently consumed street-foods and 54% demonstrated overall poor eating habits. Males were more likely to engage in moderate-to-vigorous exercise [adjusted odds ratio (AOR) = 3.40(95% confidence interval = 2.55-4.54)] while students of higher SES were less likely [AOR = 0.59(0.37-0.94)]. Males and those having good CVD-related knowledge were more likely to exercise at least 1 h/day [AOR = 7.77(4.61-13.07) and 2.90(1.46-5.78) respectively]. Those who perceived their future CVD-risk, skipped meals more [2.04(1.28-3.25)] while Males skipped them less [AOR = 0.62(0.42-0.93)]. Subjects from middle class ate street-foods less frequently [AOR = 0.45(0.24-0.85)]. Relatively older students and those belonging to higher SES were less likely to demonstrate good eating habits [AOR = 0.70(0.56-0.89) and 0.23(0.11-0.47) respectively]. A large knowledge-practice gap was evident as students with good CVD-related knowledge were less likely to have good eating habits [AOR = 0.55(0.32-0.94)]. CONCLUSIONS: CVD-related knowledge as well as eating and exercise habits were quite poor among adolescent school-students of Kolkata. Additionally, there was a large knowledge-practice gap. Multi-component educational interventions targeting behavioral betterment seemed necessary for these adolescents to improve their CVD-related knowledge, along with appropriate translation of knowledge into exercise and eating practices to minimize future risk of CVDs.

Global Urine Metabolomics in Patients Treated with First-Line Tuberculosis Drugs and Identification of a Novel Metabolite of Ethambutol.

Population level variation of drug metabolism phenotype (DMP) has great implications in treatment outcome, drug-related side effects, and resistance development. In this study, we used a gas chromatography-time of flight-mass spectrometry (GC-TOF-MS)-based untargeted urine metabolomics approach to understand the DMP of a tuberculosis (TB) patient cohort (n= 20) from Tripura, a state in the northeastern part of India. Urine samples collected at different postdose time points (2 h, 6 h, 12 h, 24 h, 36 h, and 48 h) from these newly diagnosed TB patients receiving first-line anti-TB drugs were analyzed, and we have successfully detected three of the four first-line drugs,viz, isoniazid (INH), ethambutol (ETB), and pyrazinamide (PZA). The majority of their known metabolites, acetyl-isoniazid (AcINH), isonicotinic acid (INA), isonicotinuric acid (INTA), 2,2'-(ethylenediimino)-dibutyric acid (EDBA), 5-hydroxypyrazinamide (5OH-PZA), pyrazinoic acid (POA), and 5-hydroxypyrazinoic acid (5OH-POA), were also detected. Analyzing the variation in abundances of drugs and their known metabolites and calculating the metabolic ratios in these samples, we offer comprehensive DMP information on this small patient cohort that represents Tripura, India. The majority (75%) of these patients are found to be slow acetylators of INH. The average metabolic ratios of POA/PZA and 5OH-POA/POA are 3.16 ± 3.03 and 6.09 ± 6.15, respectively. Employing correlation analysis of the metabolomics metadata and a manual prediction of drug catabolism, we have proposed 2-aminobutyric acid (AABA) as a novel metabolite of ETB. These observations indicate the usefulness of GC-MS-based metabolomics to characterize the DMP at a population level and also to identify novel drug metabolites.

Synthesis of 2-Oxindoles Sharing Vicinal All-Carbon Quaternary Stereocenters via Organocatalytic Aldol Reaction.

An organocatalytic enantioselective aldol reaction using paraformaldehyde as C1-unit has been developed for the synthesis of 2-oxindoles sharing vicinal all-carbon quaternary stereocenters. The methodology is eventually employed in the formal total synthesis of (+)-folicanthine (1b).

Tube formation in the first trimester placental trophoblast cells: Differential effects of angiogenic growth factors and fatty acids.

The study aims to investigate whether cytosolic fatty acid-binding protein-4 (FABP4) is involved in angiogenic growth factors- and fatty acid-induced tube formation in first trimester placental trophoblast cells, HTR8/SVneo. We determined the tube formation both at basal as well as stimulated levels in the absence and presence of inhibitors of FABP4 and VEGF signaling pathways. Basal level of tube formation was maximally reduced in the presence of 50 µM of FABP4 inhibitor compared with those by VEGF signaling pathway inhibitors (rapamycin, L-NAME, and p38 MAP kinase inhibitor). Whereas docosahexaenoic acid, 22:6n-3 (DHA)-, and VEGF-induced tube formation was maximally inhibited by p38 MAP kinase inhibitor (63.7 and 34.5%, respectively), however, leptin-induced tube formation was inhibited maximally by FABP4 inhibitor (50.7%). ANGPTL4 and oleic acid (OA)-induced tube formation was not blocked by any of these inhibitors. The FABP4 inhibitor inhibited cell growth stimulated by DHA, leptin, VEGF, and OA (P < 0.05) but was not affected by ANGPTL4. VEGF, leptin, and OA also increased FABP4 protein level in these cells, though the uptake of fatty acids by these cells was not affected by the presence of FABP4 inhibitor. Our data demonstrate that FABP4 may be involved in part in the basal level, and stimulated tube formation by VEGF, DHA, and leptin, whereas it has little or no effect in ANGPTL4- and OA-induced tube formation in these cells. Thus, FABP4 may play a differential role in fatty acids and angiogenic growth factors-mediated tube formation in the first trimester trophoblast cells in vitro.

Deregulated tyrosine-phenylalanine metabolism in pulmonary tuberculosis patients.

Metabolic profiling of biofluids from tuberculosis (TB) patients would help us in understanding the disease pathophysiology and may also be useful for the development of novel diagnostics and host-directed therapy. In this pilot study we have compared the urine metabolic profiles of two groups of subjects having similar TB symptoms and categorized as active TB (ATB, n = 21) and non-TB (NTB, n = 21) based on GeneXpert test results. Silylation, gas chromatography mass spectrometry, and standard chemometric methods were employed to identify the important molecules and deregulated metabolic pathways. Eleven active TB patients were followed up on longitudinally for comparative urine metabolic profiling with healthy controls (n = 11). A set of 42 features qualified to have a variable importance parameter score of > 1.5 of a partial least-squares discriminate analysis model and fold change of > 1.5 at p value < 0.05 between ATB and NTB. Using these variables, a receiver operating characteristics curve was plotted and the area under the curve was calculated to be 0.85 (95% CI: 0.72-0.96). Several of these variables that represent norepinephrine, gentisic acid, 4-hydroxybenzoic acid, hydroquinone, and 4-hydroxyhippuric acid are part of the tyrosine-phenylalanine metabolic pathway. In the longitudinal study we observed a treatment-dependent trend in the urine metabolome of follow-up samples, and subjects declared as clinically cured showed similar metabolic profile as those of asymptomatic healthy subjects. The deregulated tyrosine-phenylalanine axis reveals a potential target for diagnostics and intervention in TB.

The interplay between glucose and fatty acids on tube formation and fatty acid uptake in the first trimester trophoblast cells, HTR8/SVneo.

The study aims to investigate the impacts of hyperglycemia in the presence of fatty acids on early placentation processes that involves tube formation, cellular growth and proliferation, and metabolic activities of the first trimester trophoblast cells. Effects of maternal circulatory glucose levels that mimic physiological (5.5 mM), pre-diabetic (11 mM) and diabetic (≥25 mM) phenotypes on tube formation (as a measure of angiogenesis in vitro), cellular viability and proliferation, fatty acid uptake and expression of genes associated with invasion, angiogenesis and fatty acid metabolism were examined using HTR8/SVneo cells. Glucose (25 mM) induced tube formation, viability, and proliferation of the first trimester trophoblast cells, HTR8/SVneo. Tube formation was, however, disintegrated in the presence of high glucose (40 mM) which was partially protected by eicosapentaenoic acid, 20:5n-3 (EPA) and docosahexaenoic acid, 22:6n-3 in vitro. Glucose (25 mM)-mediated induction in tube formation was favored by increased cellular uptake of [(14)C]EPA (p < 0.05). Treatment of HTR8/SVneo cells with glucose (25 mM) significantly increased mRNA and protein level of matrix metalloproteinase-9 (MMP9) (p < 0.05). In addition, glucose (25 mM) stimulated the expression of fatty acid binding protein-4, FABP4, and plasma membrane fatty acid binding protein, FABPpm, in these cells (p < 0.05). Glucose-stimulated tube formation in a 'concentration-dependent' manner, and this may involve activation of several factors that include MMP9 and fatty acid uptake and metabolism.

Concise total syntheses of (±)-mesembrane and (±)-crinane.

A straightforward and unified strategy to access Amaryllidaceae alkaloids comprising a cis-3a-aryloctahydroindole scaffold has been developed. The strategy features Eschenmoser-Claisen rearrangement of allylalcohol as a key step for the installation of all-carbon quaternary stereocenters present in these alkaloids. The consequent iodolactonization-reduction-oxidation sequence beautifully assembles the advanced intermediate keto-aldehyde 10a, b in synthetically viable yields. The methodology has been successfully applied in the efficient syntheses of (±)-mesembrane (1a) and (±)-crinane (2a).

Investigation of gender-specific exhaled breath volatome in humans by GCxGC-TOF-MS.

Exploring gender-specific metabolic differences in biofluids provides a basic understanding of the physiological and metabolic phenotype of healthy subjects. Many reports have shown gender-specific metabolome profiles in the urine and serum of healthy subjects; however, limited studies focusing on exhaled human breath are available in the literature. In this study, we profiled the exhaled breath (~450 mL) volatile organic compounds (VOCs) of 47 healthy volunteers (age: 19-47; 23 male (M) and 24 female (F)) using a multidimensional gas chromatography and mass spectrometry and employed chemometric analysis to identify gender-specific VOCs. Eleven exhaled breath VOCs were identified from both uni and multivariate analysis from a training set (M = 15, F = 15) that could differentiate the genders within a healthy population. A partial least-squares discriminate analysis (PLS-DA) model built using these putative markers showed high accuracy in predicting (area under the receiver operating characteristic curve >0.9) a hold out/test sample set (n = 17). The outcomes of this report open up new avenues to undertake larger studies to elucidate the association of exhaled breath metabolites with gender-specific disease phenotypes and pharmacokinetics in the future.

AI-based disease category prediction model using symptoms from low-resource Ethiopian language: Afaan Oromo text.

Automated disease diagnosis and prediction, powered by AI, play a crucial role in enabling medical professionals to deliver effective care to patients. While such predictive tools have been extensively explored in resource-rich languages like English, this manuscript focuses on predicting disease categories automatically from symptoms documented in the Afaan Oromo language, employing various classification algorithms. This study encompasses machine learning techniques such as support vector machines, random forests, logistic regression, and Naïve Bayes, as well as deep learning approaches including LSTM, GRU, and Bi-LSTM. Due to the unavailability of a standard corpus, we prepared three data sets with different numbers of patient symptoms arranged into 10 categories. The two feature representations, TF-IDF and word embedding, were employed. The performance of the proposed methodology has been evaluated using accuracy, recall, precision, and F1 score. The experimental results show that, among machine learning models, the SVM model using TF-IDF had the highest accuracy and F1 score of 94.7%, while the LSTM model using word2vec embedding showed an accuracy rate of 95.7% and F1 score of 96.0% from deep learning models. To enhance the optimal performance of each model, several hyper-parameter tuning settings were used. This study shows that the LSTM model verifies to be the best of all the other models over the entire dataset.

CSI clinical practice guidelines for dyslipidemia management: Executive summary.

Dyslipidemias are the most important coronary artery disease (CAD) risk factor. Proper management of dyslipidemia is crucial to control the epidemic of premature CAD in India. Cardiological Society of India strived to develop consensus-based guidelines for better lipid management for CAD prevention and treatment. The executive summary provides a bird's eye-view of the 'CSI: Clinical Practice Guidelines for Dyslipidemia Management' published in this issue of the Indian Heart Journal. The summary is focused on the busy clinician and encourages evidence-based management of patients and high-risk individuals. The summary has serialized various aspects of lipid management including epidemiology and categorization of CAD risk. The focus is on management of specific dyslipidemias relevant to India-raised low density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol (non-HDL-C), apolipoproteins, triglycerides and lipoprotein(a). Drug therapies for lipid lowering (statins, non-statin drugs and other pharmaceutical agents) and lifestyle management (dietary interventions, physical activity and yoga) are summarized. Management of dyslipidemias in oft-neglected patient phenotypes-the elderly, young and children, and patients with comorbidities-stroke, peripheral arterial disease, kidney failure, posttransplant, HIV (Human immunodeficiency virus), Covid-19 and familial hypercholesterolemia is also presented. This consensus statement is based on major international guidelines (mainly European) and expert opinion of lipid management leaders from India with focus on the dictum: earlier the better, lower the better, longer the better and together the better. These consensus guidelines cannot replace the individual clinician judgement who remains the sole arbiter in management of the patient.