Adventitious rooting in response to long-term cold: a possible mechanism of clonal growth in alpine perennials.

Arctic alpine species experience extended periods of cold and unpredictable conditions during flowering. Thus, often, alpine plants use both sexual and asexual means of reproduction to maximize fitness and ensure reproductive success. We used the arctic alpine perennial Arabis alpina to explore the role of prolonged cold exposure on adventitious rooting. We exposed plants to 4°C for different durations and scored the presence of adventitious roots on the main stem and axillary branches. Our physiological studies demonstrated the presence of adventitious roots after 21 weeks at 4°C saturating the effect of cold on this process. Notably, adventitious roots on the main stem developing in specific internodes allowed us to identify the gene regulatory network involved in the formation of adventitious roots in cold using transcriptomics. These data and histological studies indicated that adventitious roots in A. alpina stems initiate during cold exposure and emerge after plants experience growth promoting conditions. While the initiation of adventitious root was not associated with changes of DR5 auxin response and free endogenous auxin level in the stems, the emergence of the adventitious root primordia was. Using the transcriptomic data, we discerned the sequential hormone responses occurring in various stages of adventitious root formation and identified supplementary pathways putatively involved in adventitious root emergence, such as glucosinolate metabolism. Together, our results highlight the role of low temperature during clonal growth in alpine plants and provide insights on the molecular mechanisms involved at distinct stages of adventitious rooting.

Exsanguinated to death by a perforated duodenal ulcer: Masquerader apprehended on autopsy.

ABSTRACT: Gastroduodenal perforation commonly due to spontaneous perforation of a pre-existing peptic ulcer is a surgical emergency. On laparotomy, approximately 60%-70% perforations are duodenal and 15%-20% gastric. The most prevalent etiology are Helicobacter pylori infection in 65%-70% and non-steroidal anti-inflammatory drugs (NSAIDS) abuse in 30%-50% cases depending on the prevalence of H. pylori infection. We report here the autopsy findings in a 29-year-old male who collapsed suddenly in the emergency room of our hospital after a bout of massive hematemesis.

Gene editing improves endoplasmic reticulum-mitochondrial contacts and unfolded protein response in Friedreich's ataxia iPSC-derived neurons.

Friedreich ataxia (FRDA) is a multisystemic, autosomal recessive disorder caused by homozygous GAA expansion mutation in the first intron of frataxin (FXN) gene. FXN is a mitochondrial protein critical for iron-sulfur cluster biosynthesis and deficiency impairs mitochondrial electron transport chain functions and iron homeostasis within the organelle. Currently, there is no effective treatment for FRDA. We have previously demonstrated that single infusion of wild-type hematopoietic stem and progenitor cells (HSPCs) resulted in prevention of neurologic and cardiac complications of FRDA in YG8R mice, and rescue was mediated by FXN transfer from tissue engrafted, HSPC-derived microglia/macrophages to diseased neurons/myocytes. For a future clinical translation, we developed an autologous stem cell transplantation approach using CRISPR/Cas9 for the excision of the GAA repeats in FRDA patients' CD34+ HSPCs; this strategy leading to increased FXN expression and improved mitochondrial functions. The aim of the current study is to validate the efficiency and safety of our gene editing approach in a disease-relevant model. We generated a cohort of FRDA patient-derived iPSCs and isogenic lines that were gene edited with our CRISPR/Cas9 approach. iPSC derived FRDA neurons displayed characteristic apoptotic and mitochondrial phenotype of the disease, such as non-homogenous microtubule staining in neurites, increased caspase-3 expression, mitochondrial superoxide levels, mitochondrial fragmentation, and partial degradation of the cristae compared to healthy controls. These defects were fully prevented in the gene edited neurons. RNASeq analysis of FRDA and gene edited neurons demonstrated striking improvement in gene clusters associated with endoplasmic reticulum (ER) stress in the isogenic lines. Gene edited neurons demonstrated improved ER-calcium release, normalization of ER stress response gene, XBP-1, and significantly increased ER-mitochondrial contacts that are critical for functional homeostasis of both organelles, as compared to FRDA neurons. Ultrastructural analysis for these contact sites displayed severe ER structural damage in FRDA neurons, that was undetected in gene edited neurons. Taken together, these results represent a novel finding for disease pathogenesis showing dramatic ER structural damage in FRDA, validate the efficacy profile of our FXN gene editing approach in a disease relevant model, and support our approach as an effective strategy for therapeutic intervention for Friedreich's ataxia.

VagiBIOM Lactobacillus suppository improves vaginal health index in perimenopausal women with bacterial vaginosis: a randomized control trial.

Bacterial vaginosis (BV) can cause vaginal dysbiosis that may influence general vaginal health and pregnancy complications. Balancing vaginal microbiome using Lactobacillus spp. may be a new way to prevent and treat mild BV. We conducted a randomized, double-blind, placebo-controlled pilot study aimed at evaluating the effect of the product VagiBIOM, a multi-Lactobacillus vaginal suppository, on peri- and premenopausal women with BV in restoring vaginal pH and overall vaginal health by resetting the vaginal microbiome composition. Sixty-six peri- and premenopausal women with BV symptoms were randomized with a 2:1 ratio to be treated with VagiBIOM or placebo suppositories. Vaginal pH, VAS itching score, total Nugent score, and vaginal health index (VHI) were measured. Vaginal microbiome changes before and after the treatment were analyzed by 16S rRNA sequencing and bioinformatics analysis. After 4 weeks of intervention with VagiBIOM or a placebo, the mean score for vaginal pH, VAS itching, and total Nugent score was significantly decreased from the baseline. Compared to the baseline scores, the VHI scores improved significantly following 28-day intervention (p < 0.001). Our results revealed two Lactobacillus species, L. hamsteri, and L. helveticus, as indicator species occurring differentially in the VagiBIOM-treated group. Furthermore, the regression and species network analyses revealed significant bacterial associations after VagiBIOM treatment. Lactobacillus hamsteri was positively associated with the Nugent score and negatively associated with vaginal pH. L. iners and L. salivarius were positively and inversely associated with VHI. As is typical, Bacteroides fragilis was positively associated with vaginal pH and negatively associated with the Nugent score. Interestingly, the Lactobacillus spp. diversity improved after VagiBIOM treatment. The VagiBIOM suppository treatment for peri- and premenopausal women with BV significantly relieved vaginal itching by decreasing vaginal pH and Nugent scores and improving the overall VHI after 4 weeks' intervention. This effect was primarily the result of VagiBIOM improving vaginal Lactobacillus diversity.Trial Registration ClinicalTrials.gov registration: NCT05060029, first registration 09/28/2021: Title: A Pilot Study to Evaluate the Efficacy and Safety of Lactobacillus Species Suppositories on Vaginal Health and pH.

Primary extranodal lymphomas: five-year experience from a tertiary care center of North India.

BACKGROUND: Primary extranodal lymphomas (pENL) are lymphomas with minimal nodal involvement and dominant extranodal disease. We aimed to study the prevalence and clinicopathological characteristics of pENL presenting at our center over 5 years from January 2015 to January 2020. METHODS: This is a cross-sectional study of pENL patients in which relevant clinical and laboratory data was collected including demography, site, stage, international prognostic index-revised, imaging findings, hematological, and biochemical parameters and comorbidities including underlying immunodeficiency. The paraffin blocks were subjected to routine hematoxylin and eosin stain and immunohistochemistry with standard lymphoma panel. RESULTS: Of 341 lymphomas, 73 (21.4%) were pENL with commonest site being gastrointestinal tract (31.5%) followed by head and neck (23.2%) and soft tissues (9.6%). Diffuse large B-cell lymphoma (DLBCL) (39.7%) was the commonest histological type (germinal center type-48%, nongerminal center-52%) followed by marginal zone lymphomas (MZL) (23.3%) and primary CNS lymphoma (8.2%). Primary breast lymphoma, primary bone marrow lymphoma, and follicular lymphoma constituted 4.1, 5.4, and 4.1% of pENL, respectively. There was a case of high grade B cell lymphoma of ileum with features intermediate between DLBCL and Burkitt. Other unusual pENL were anaplastic DLBCL of tonsils, DLBCLs of bone marrow with M band, MZL of base of tongue, Richter's transformation of tonsillar small lymphocytic lymphoma, and follicular lymphoma presenting as pericardial mass. Of 12 cases of T-non-Hodgkin lymphoma, commonest were mycosis fungoides (4/12) followed by mediastinal T-lymphoblastic lymphoma (2/12) and peripheral T-cell lymphoma (2/12). CONCLUSION: pENL has unique clinical presentation depending on the location with site-specific distribution of histological subtypes.

Rescue of Alzheimer's disease phenotype in a mouse model by transplantation of wild-type hematopoietic stem and progenitor cells.

Alzheimer's disease (AD) is the most prevalent cause of dementia; microglia have been implicated in AD pathogenesis, but their role is still matter of debate. Our study showed that single systemic wild-type (WT) hematopoietic stem and progenitor cell (HSPC) transplantation rescued the AD phenotype in 5xFAD mice and that transplantation may prevent microglia activation. Indeed, complete prevention of memory loss and neurocognitive impairment and decrease of ß-amyloid plaques in the hippocampus and cortex were observed in the WT HSPC-transplanted 5xFAD mice compared with untreated 5xFAD mice and with mice transplanted with 5xFAD HSPCs. Neuroinflammation was also significantly reduced. Transcriptomic analysis revealed a significant decrease in gene expression related to "disease-associated microglia" in the cortex and "neurodegeneration-associated endothelial cells" in the hippocampus of the WT HSPC-transplanted 5xFAD mice compared with diseased controls. This work shows that HSPC transplant has the potential to prevent AD-associated complications and represents a promising therapeutic avenue for this disease.

Anaphylaxis spares no drug: A report of diclofenac-induced anaphylaxis mimicking post-laparoscopy respiratory complication.

Peri-anesthetic anaphylaxis is a rare but grave problem. After receiving informed consent for publication, we discuss the case of a female patient posted for laparoscopic cholecystectomy who developed an anaphylactic reaction to intravenous diclofenac, mimicking post-laparoscopy respiratory complication in the perioperative period. A 45-year-old, American Society of Anesthesiologists physical status (ASA-PS) I, female patient was posted for laparoscopic cholecystectomy under general anesthesia (GA). The procedure took 60 minutes and concluded uneventfully. In the post-anesthesia care unit, the patient complained of respiratory difficulty. Even after the supplemental oxygen and in absence of any significant finding on respiratory examination, the patient soon developed severe cardiorespiratory collapse. On evaluation, administration of intravenous diclofenac a few minutes before the event was suspected as the trigger for this anaphylactic response. The patient responded to the injection of adrenaline, and her post-surgical progress over the next two days was uneventful. The retrospective tests done for confirming diclofenac hypersensitivity were found to be positive. No drug, however safe, should be given blindly without proper observation and monitoring. The course of development of anaphylaxis can range from a few seconds to minutes and hence, the earliest recognition and prompt action can be the only deciding factor between life and death for such patients.

Species-specific transcriptional reprogramming during adventitious root initiation.

Adventitious roots or shoot-borne roots transdifferentiate from cells close to vascular tissues after cell reprogramming, which is associated with increased transcriptional activity. Recently, Garg et al. provided a genome-wide landscape of transcriptional signatures during the early stages of adventitious root initiation in rice and showed that conserved transcription factors acquire species-specific function.

Hemophagocytic Lymphohistiocytosis in Erythema Nodosum Leprosum: Case Report of an Unusual Conundrum.

Hemophagocytic lymphohistiocytosis (HLH) and erythema nodosum leprosum (ENL) result from a complex agent-host interaction and form a continuum of the same spectrum. A 30-year-old multi-gravida presented at 36 weeks gestation with fever and erythematous raised lesions over the face and upper and lower limbs after defaulting treatment for borderline lepromatous leprosy. Skin biopsy confirmed ENL, hence multi-drug therapy (MDT) and oral steroids were restarted. However, her condition worsened and she developed icterus, periorbital puffiness, pleural effusion, ascites and splenomegaly. Laboratory investigations showed pancytopenia, conjugated hyperbilirubinemia, transaminitis, elevated lactate dehydrogenase, hypertriglyceridemia, hyperferritinemia and hypofibrinogenemia. Dapsone was stopped on the suspicion of dapsone hypersensitivity but hyperbilirubinemia progressed. Diagnosis of HLH was clinched after bone marrow aspirate showed florid hemophagocytosis and subsequently, intravenous immunoglobulin (2 g/kg) over 5 days and dexamethasone were administered. The patient improved gradually with normalization of laboratory parameters and restarted MDT. This case depicts a rare and potentially catastrophic complication of ENL and emphasizes a vigil for HLH syndrome in such cases.

Prevention of mortality in acute lung injury induced by oleic acid: Application of polyherbal decoction (bronco T).

Acute lung injury (ALI) is a lethal respiratory disorder; directed uncontrolled inflammation, sloughing of the alveolar cells and their diffusion, and altered cardiorespiratory parameters with a global mortality rate of 40%. This study was designed to assess the preventive effect of a polyherbal decoction (Bronco T, 1.5 g/kg b. w.) on cardiorespiratory variables in oleic acid-induced ALI in rats. Oleic acid increases the level of neutrophil infiltration leading to pulmonary edema and alters the cardiorespiratory dynamics. The adult male rats were surgically cannulated and treated with intravenous oleic acid (0.38 ml/kg b. w.) to establish the ALI model. Bronco T was pre-administered orally 3 hours before oleic acid. The biophysical, histological, biochemical, and molecular effects were compared with dexamethasone (5 mg/kg b. w. i. p.). The animals were randomly divided into control, lethal, standard, and treatment groups. Respiratory frequency (RF), heart rate (HR), and mean arterial pressure (MAP) were recorded on a computerized chart recorder; arterial blood sample was collected to determine PaO2/FiO2, TNF-α, and MPO. Lipid peroxidation, superoxide dismutase, and catalase activity were evaluated to measure oxidative stress in bronchoalveolar lavage. Additionally, the pulmonary water content, COX-2 expression and histological examination were determined in the lung. A molecular docking study of the active phytoconstituent of BT obtained from HR-LCMS analysis against reported targets (IL-6, COX-2, TNFα, MPO and ENaC) of ALI was carried out. The B.T. pretreatment prevents mortality in comparison to the oleic acid group. It protects the lungs and heart from the detrimental effect of oleic acid, on par with dexamethasone. COX-2 mRNA expression was significantly down-regulated in the treatment group. The reduced level of TNF-α, MPO, SOD and catalase supported the protective effect of B.T. The in silico study revealed strong binding interaction between the phytoconstituent (Galangin 3- [galactosyl-(1-4)-rhamnoside and Beta solamarine] of BT and the reported target. The B.T. pre-administration attenuates the oleic acid-induced mortality and cardiorespiratory toxicity.

Airway management training program for nurses via online course in COVID-19 preparedness.

BACKGROUND: Nursing officers are an integral component of any medical team. They participate in taking care of basic airway management and assist in advanced airway management, specifically amidst the current coronavirus disease 2019 (COVID-19) pandemic. AIM: To assess the efficacy of a standardized web-based training module for nurses in preparedness to fight against COVID-19. METHODS: The training was held in three sessions of 1 h each, consisting of live audio-visual lectures, case scenarios, and skill demonstrations. The sequence of airway equipment, drug preparation, airway examination, and plans of airway management was demonstrated through mannequin-based video-clips. RESULTS: Pre- and post-test scores as well as objective structured clinical examination scores were analyzed using Student's t-test and the Likert scale was used for feedback assessment. It was found that the mean score out of the total score of 20 was 8.47 ± 4.2 in the pre-test, while in the post-test it was 17.4 ± 1.8 (P value < 0.001). The participants also felt self-reliant in executing the roles of airway assistant (63.3%) and drug assistant (74.3%). Fear of self-infection with COVID-19 was also high, as 66% of participants feared working with the patient's airway. CONCLUSION: Amidst this COVID-19 emergency, when the health care systems are being persistently challenged, training of nursing staff in the safe conduct of airway management can ensure delivery of life-saving treatment.

Post-synthetic modification of graphene quantum dots bestows enhanced biosensing and antibiofilm ability: efficiency facet.

Graphene quantum dots (GQDs) are a luminescent class of carbon nanomaterials with a graphene-like core structure, possessing quantum confinement and edge effects. They have gained importance in the biological world due to their inherent biocompatibility, good water dispersibility, excellent fluorescence and photostability. The improved properties of GQDs require the logical enactment of functional groups, which can be easily attained through post-synthetic non-covalent routes of modification. In this regard, the present work has for the first time employed a simple one-pot post-modification method utilizing the salt of amino caproic acid, an FDA approved reagent. The adsorption of the modifier on GQDs with varying weight ratios is characterized through DLS, zeta potential, Raman, absorption and fluorescence spectroscopy. A decrease of 20% in the fluorescence intensity with an increase in the modifier ratio from 1 to 1000 and an increased DLS size as well as zeta potential demonstrate the efficient modification as well as higher stability of the modified GQDs. The modified GQDs with a high weight ratio (1 : 100) of the modifier showed superior ability to sense dopamine, a neurotransmitter, as well as competent biofilm degradation ability. The modified GQDs could sense more efficiently than pristine GQDs, with a sensitivity as low as 0.06 µM (limit of detection) and 90% selectivity in the presence of other neurotransmitters. The linear relationship showed a decrease in the fluorescence intensity with increasing dopamine concentration from 0.0625 µM to 50 µM. Furthermore, the efficiency of the modified GQDs was also assessed in terms of their antibiofilm effect against Staphylococcus aureus. The unmodified GQDs showed only 10% disruption of the adhered bacterial colonies, while the modified GQDs (1 : 100) showed significantly more than 60% disruption of the biofilm, presenting the competency of the modified GQDs. The unique modifications of GQDs have thus proven to be an effective method for the proficient utilization of zero-dimensional carbon nanomaterials for biosensing, bioimaging, antibacterial and anti-biofilm applications.

Impact of Nano Preparation of Phytoconstituents in Medulloblastoma.

The conventional cancer treatment strategies from chemotherapy to surgery often lead to inadequate results which in some cases lead to relapsing of the tumor being treated. Medulloblastoma witness 30% relapse rate which is universally fatal among children. Although the treatment of primary medulloblastoma is well established including surgical excision, postsurgical irradiation, and, more recently, chemotherapy, there is no established treatment for its recurrence. Despite efforts to improve its therapy, frequent long-haul survivors have been recorded in the world's medical literature. In this book chapter, we have attempted to focus light on the nano preparation of phytoconstituents as an alternative approach as it has advantage of providing better bioavailability of the compound in terms of crossing the blood-brain barrier and an additional benefit in terms of limited adverse effects of the natural product over the traditional chemotherapeutic approaches. In recent times, biological methods or green approaches in the case of plants have received immense attention due to its safety and lack of contamination in the process. In this chapter, we will explore some plant products that have been incorporated into nanocarriers to improve their bioavailability in this tumor treatment.

Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants - Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) - a molecular docking study.

COVID-19 (Coronavirus disease 2019) is a transmissible disease initiated and propagated through a new virus strain SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) since 31st December 2019 in Wuhan city of China and the infection has outspread globally influencing millions of people. Here, an attempt was made to recognize natural phytochemicals from medicinal plants, in order to reutilize them against COVID-19 by the virtue of molecular docking and molecular dynamics (MD) simulation study. Molecular docking study showed six probable inhibitors against SARS-CoV-2 Mpro (Main protease), two from Withania somnifera (Ashwagandha) (Withanoside V [10.32 kcal/mol] and Somniferine [9.62 kcal/mol]), one from Tinospora cordifolia (Giloy) (Tinocordiside [8.10 kcal/mol]) and three from Ocimum sanctum (Tulsi) (Vicenin [8.97 kcal/mol], Isorientin 4'-O-glucoside 2″-O-p-hydroxybenzoagte [8.55 kcal/mol] and Ursolic acid [8.52 kcal/mol]). ADMET profile prediction showed that the best docked phytochemicals from present work were safe and possesses drug-like properties. Further MD simulation study was performed to assess the constancy of docked complexes and found stable. Hence from present study it could be suggested that active phytochemicals from medicinal plants could potentially inhibit Mpro of SARS-CoV-2 and further equip the management strategy against COVID-19-a global contagion. HighlightsHolistic approach of Ayurvedic medicinal plants to avenge against COVID-19 pandemic.Active phytoconstituents of Ayurvedic medicinal plants Withania somnifera (Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) predicted to significantly hinder main protease (Mpro or 3Clpro) of SARS-CoV-2.Through molecular docking and molecular dynamic simulation study, Withanoside V, Somniferine, Tinocordiside, Vicenin, Ursolic acid and Isorientin 4'-O-glucoside 2″-O-p-hydroxybenzoagte were anticipated to impede the activity of SARS-CoV-2 Mpro.Drug-likeness and ADMET profile prediction of best docked compounds from present study were predicted to be safe, drug-like compounds with no toxicity.Communicated by Ramaswamy H. Sarma.

Efficacy of interventional treatment strategies for managing patients with cervicogenic headache: a systematic review.

Cervicogenic headache (CeH) is caused by the disorder of the cervical spine and its anatomical structures. Patients who fail to respond to conservative therapies can undergo interventional treatment. The purpose of this review is to describe the various interventions and compare their relative efficacies. Although a few reviews have been published focusing on individual interventions, reviewing studies on other available treatments and establishing the most efficacious approach is still necessary. We performed a systematic review of studies available on the various interventions for CeH. The PubMed, Embase, and Cochrane databases were searched for literature published between January 2001 and March 2021. Based on the inclusion criteria, 23 articles were included. Two reviewers independently extracted the data from the studies and summarized them in a table. Eleven of twenty-three studies evaluated the effect of radiofrequency ablation (RFA), 5 evaluated occipital nerve blocks, 2 each for facet joint injections and deep cervical plexus blocks, and 1 study each evaluated atlantoaxial (AA) joint injections, cervical epidural injection, and cryoneurolysis. Most of the studies reported pain reduction except 2 studies on RFA. In conclusion, based on the available literature, occipital nerve blocks, cervical facet joint injection, AA joint injection, deep cervical plexus block, cervical epidural injection may be reasonable options in refractory cases of CeH. RFA was found to have favorable long-term outcomes, while better safety has been reported with pulsed therapy. However, our review revealed only limited evidence, and more randomized controlled trials are needed to provide more conclusive evidence.

In silico screening of Pueraria tuberosa (PTY-2) for targeting COVID-19 by countering dual targets Mpro and TMPRSS2.

COVID-19 pandemic was started in Wuhan city of China in December 2019; immensely affected global population. Herein, an effort was made to identify potential inhibitors from active phytochemicals of Pueraria tuberosa (PTY-2) via molecular docking study. Our study showed five potential inhibitors (Robinin, Genistin, Daidzin, Hydroxytuberosone, Tuberostan) against Mpro and five inhibitors (Robinin, Anhydrotuberosin, Daidzin, Hydroxytuberosone, Stigmasterol) against TMPRSS2. Out of these, Robinin, Daidzin and Hydroxytuberosone were common inhibitors for Mpro and TMPRSS2. Among these, Robinin showed the highest binding affinity, therefore, tested for MD simulation runs and found stable. ADMET analysis revealed the best-docked compounds are safe and follow the Lipinski Rule of Five. Thus, it could be suggested that phytochemicals of PTY-2 could serve as potential inhibitors for COVID-19 targets.Communicated by Ramaswamy H. Sarma.

Inherited and acquired thrombophilia in women of Indian ethnicity with recurrent pregnancy loss: An observational study from North India.

OBJECTIVES: The spectrum of thrombophilia in women with recurrent pregnancy loss (RPL) is different in Indian ethnicity as reported by few studies. We aimed to study the prevalence of thrombophilia in RPL patients referred to hematology department of a tertiary centre. MATERIAL AND METHODS: This is an observational study of 112 RPL patients with no apparent cause after extensive workup for non-hematological causes. The investigations performed were routine coagulogram, APLA workup, plasma homocysteine, MTHFRC677T polymorphisms, Protein C, free Protein S, Anti-thrombin III levels, test for Activated Protein C resistance (APC-R) ,Factor V Leiden and Prothrombin gene G20210A mutation. RESULTS: Of 112 patients, at least one thrombophilia was identified in 70.5% and combined thrombophilia in 12.5% patients. Hyperhomocysteinemia (30.4%) and APLA (25.9%) were the commonest thrombophilia whereas anticoagulant defects were seen in 12.5% of the population. Protein C deficiency (5.35%) was the commonest anticoagulant defect followed by APCR (3.6%). Mutational analysis revealed MTHFRC677T polymorphism in 20.5% whereas Factor V Leiden heterozygous in 1.8% patients. None of the patients had homozygous Factor V Leiden or Prothrombin gene G20210A mutation. Hyperhomocysteinemia, MTHFRC677T and Protein C deficiency were more associated with early pregnancy losses whereas Protein S deficiency, Factor V Leiden and APLA caused both early and late losses. Patients with greater number of losses were positive for homozygous MTHFRC677T, factor V Leiden and APLA. CONCLUSION: The approach to investigating Indian women with RPL should be based on the prevalence of thrombophilia which is unique to Indian ethnicity.