Osteopontin: A Key Multifaceted Regulator in Tumor Progression and Immunomodulation.

The tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cells, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs is crucial for enhancing treatment outcome and reducing the burden of toxicity. In this review, we have provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we dissected the signaling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancements in the roles of splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSC enhancement, immunomodulation, metastasis, chemoresistance and metabolic reprogramming, and further suggests that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.

Nickel-Catalyzed Alkene Isomerization to Access Bench-Stable Enamines and Their [3 + 2] Annulation.

Enamines are difficult to prepare on the bench due to their instability, which results in side reactions, decompositions, poor yields, etc. Herein, we developed a simple and effective method for making bench-stable enamines using a very low amount of nickel catalyst loading. The deuterium exchange, competitive reaction, and radical clock experiment have all been found to favor the ionic mechanism of this alkene isomerization. Scale-up and [3 + 2] annulation reaction of enamines with activated cyclopropane to deliver cyclopentane derivatives have shown the value of this method in organic synthesis.

Hindi translation and cultural adaptation of the quality of recovery score-40 (QoR-40 score): A validation study.

Background and Aims: The quality of recovery (QoR)-40 score has been used worldwide and validated in many surgical cohorts to assess global patient recovery. We aim to translate and culturally adapt the QoR-40 score into Hindi and test the validity and reliability of the translated version in patients undergoing cancer surgery. Methods: The translation of the QoR-40 questionnaire was based on the forward and backward translation methods. Patients filled out the translated version of the QoR-40 preoperatively, on the third postoperative day in the morning (POD3) and the evening. The reliability of the translated questionnaire was checked for internal consistency, test-retest reliability and split-half reliability. Construct validity was assessed with a correlation coefficient value between the total QoR-40 score, visual analogue scale (VAS) for pain and total length of hospital stay. Content validity was evaluated for feasibility and understanding. Results: The questionnaire was completed by 350 patients. The correlation coefficient r for repeatability was 0.21, the split-half test was 0.92, and Cronbach's alpha was 0.82. The correlation between QoR-40 on POD3 with VAS score and length of stay was -0.35 and -0.67, respectively. The average time to complete the questionnaire was 3.8 minutes; 90% of the respondents found the translated questionnaire easy to understand, and 92% of the patients related the questions to their recovery. Conclusion: The Hindi translation of the QoR-40 questionnaire is a valid and reliable version of the original questionnaire in English to assess the QoR in Hindi-speaking patients after cancer surgery.

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.

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.

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.

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.

Gender reassignment surgery - a narrative overview of anaesthetic considerations and implications.

The twenty-first century, with its transforming ideology and rising acceptance, is witnessing an increased number of transgender people applying for gender reassignment surgery (GRS). The procedure of GRS is a lengthy and complex one involving the active collaboration of multiple disciplines including psychology, psychiatry, family medicine, plastic surgery, endocrinology, otolaryngology, urology, gynaecology, maxillofacial surgery, and anaesthesiology. The considerable paucity of literature regarding the management of patients presenting for GRS places health care providers at a disadvantage. It is imperative to cautiously regard the specific medical, emotional, social, and economic concerns regarding these patients. Health care providers need to be trained well to deal empathetically with such patients. The present literature about GRS deals mainly with the surgeon's perspective, while the anaesthetist's approach remains hazy. This is because GRS imposes the need for anaesthesiologists to search for better and more efficient modes of anaesthesia so as to improve prognosis and minimize the associated morbidity. Anaesthetists should understand the associated psychological aspects and effects of hormone therapy while performing an extensive and informative pre-operative evaluation to formulate an effective strategy. Providing the optimal modes for anaesthesia and keeping a cautious watch for complications along with timely intervention in the advent of the same comprise the approach for high-quality anaesthetic care. This review aims to provide a detailed overview of significant considerations and competent peri-operative outcomes in patients presenting for GRS.

Proportion of CD34+CD38-CD123+ Leukemia Stem Cells at Diagnosis Varies in ELN Risk Groups and an Emerging Novel Marker for Prognosticating the Intermediate Risk patients of Acute Myeloid Leukemia: A Prospective Study.

The proportion of CD34 + CD38 - CD123 + leukemia stem cells (LSCs) at diagnosis of Acute Myeloid Leukemia (AML) correlated with induction remission (IR), relapse free survival and overall survival in few studies. Prospectively bone marrows of AML patients were immunophenotyped for CD34 + CD38 - CD123 + LSCs at baseline using sequential gating, relevant clinical and laboratory data collected and clinical outcomes were studied.The patients (n = 47) were risk stratified as favorable risk, intermediate risk and adverse risk. The percent of LSCs at baseline in favorable risk group (mean = 13.06%) was significantly less than the adverse (mean = 34.8%, p = 0.027) and the intermediate risk group (mean = 53.2%, p = 0.001). On further analysis, 12 patients attaining IR in intermediate risk group had significantly less LSCs than 15 in non-IR group (mean = 21.18%; range 3-85.6% vs mean = 73.85%; range 12.1-97.9%, p = 0.0002). Of all 47 patients, the proportion of LSCs at baseline was significantly less in those achieving IR (p = 0.024) and correlated with time to response (TTR) (rs = 0.432). Thus to conclude, the proportion of CD34 + CD38 - CD123 + LSCs at diagnosis is less in the favorable than the intermediate and adverse risk groups and is  an emerging novel marker for predicting remission in the prognostically diverse intermediate risk group.

Clinico-Hematological Profile of Paroxysmal Nocturnal Hemoglobinuria in Indian Patients: FLAER Flow Cytometry Based Experience from an Indian Tertiary Care Centre.

PNH is a rare disease with wide spectrum of intra-vascular hemolysis and thrombosis to sub-clinical PNH clones. We aimed to study the clinico-hematological profile and clone size on granulocytes and monocytes of PNH patients classified as per International PNH Interest Group recommendations. A retrospective analysis of clinico-hematological profile of 112 PNH clone positive patients by FLAER based flow cytometry between January and September 2017 done and classified into classical PNH, PNH with aplastic anemia or myelodysplastic syndrome (PNH-AA/MDS) and sub-clinical PNH clones (PNH-sc). Of 112 patients, majority were PNH-sc (62) followed by PNH-AA/MDS (34) and classical PNH (16). The commonest clinical feature was anemia in all 3 groups followed by jaundice (87.5%) in classical PNH and fever in PNH-AA/MDS (64.7%) and PNH-sc (48.4%). Thrombosis was present in 25% (4/16) classical PNH and 2.9% (1/34) of PNH-AA/MDS. The mean hemoglobin, reticulocyte count and LDH was higher in classical PNH. Bone marrow was predominantly hypercellular in classical PNH (11/16) and hypocellular in PNH-AA/MDS (31/34) and PNH-sc (50/62) with dyserythropoiesis predominantly in PNH-AA/MDS (83.8%) and PNH-sc (74.1%). Marrow iron was reduced in 62.2% classical PNH contrary to increased in PNH-BMF (58%) and PNH-sc (91%). The mean clone size in PNH-sc was significantly lower with > 50% in 16.2% patients. Three patients with MDS-MLD and MDS-MLD-RS in PNH-sc had > 80% clone on granulocytes and monocytes. Most PNH patients in Indian setting are PNH-sc with significantly lower clone, however, a clone size > 50% is not uncommon in Indian PNH-sc.

Comparison of CRP and procalcitonin for etiological diagnosis of fever during febrile neutropenia in hematology patients- an experience from a tertiary care center in Northern India.

INTRODUCTION: Febrile neutropenia is a common cause in morbidity and mortality during treatment of hematological neoplasms. METHODS: Subjects included all cases admitted under hematology department with febrile neutropenia from February to June 2018. Each febrile episode was investigated by standard investigations (Blood culture, Chest x ray etc.); Procalcitonin (PCT) and c reactive protein (CRP) was sent at fever onset 0, 24, 48 h, day 7 and day 14. RESULTS: Data was analyzed for 52 febrile episodes in 50 patients. PCT cut off value at 24 h of ≤1.2 ng/ml had a sensitivity and specificity of 62.5% and 87.5% for discriminating Invasive fungal infection (IFI) and Microbiologically documented infection (MDI) (p = 0.033). PCT had a negative predictive value of 70% for the diagnosis of IFI as compared to MDI. CRP cut off >160 mg/dl at 48 h was suggestive of fever due to fungal infection with a sensitivity of 100%, specificity of 48%, PPV of 33.3% and NPV of 100%. CRP at 24 and 48 h of fever was useful to distinguish non-infectious causes of fever from infectious causes. CONCLUSION: PCT at 24 h and CRP at 48 h was useful in identifying fungal infection. CRP was a better marker when compared to PCT for identifying disease fever.

Pediatric myelofibrosis: WHO 2024 update on myeloproliferative neoplasms calling?

OBJECTIVES: Pediatric myelofibrosis is a rare entity with the largest reported series of 19 cases. We describe here the clinicopathological spectrum and outcomes of 15 cases of pediatric myelofibrosis. METHODS: Case files of myelofibrosis of patients less than 18 years were retrieved from January 2016 to January 2019, and patients with idiopathic myelofibrosis after exhaustive work-up were studied. Their clinicopathological profiles were studied and then followed up for resolution and malignant transformation. RESULTS: Of the 15 cases of idiopathic myelofibrosis, transfusion-dependent anemia (14/15) was most common presentation. Only one patient showed leukoerythroblastosis with dacryocytes. Myeloid hyperplasia was seen in 13 of 15 patients and megakaryocytic hyperplasia in 10 patients. Dysmegakaryopoiesis was seen in 8 of 15 patients, and only three had small loose megakaryocytic clustering. None showed hyperchromatic megakaryocytes, intrasinusoidal hematopoiesis, or osteosclerosis. One patient with trisomy 8 tested positive for JAK2V617F. Bone marrow biopsy was hypercellular in 13, and 8 had world health organization (WHO) MF-3 fibrosis. None of the patients developed malignancy, one had spontaneous resolution, and one patient required allogenic stem cell transplant. CONCLUSIONS: Pediatric myelofibrosis is a distinct entity from primary myelofibrosis in adults and merits mention in the WHO manual as a distinct entity.

Anesthetic considerations and goals in robotic pediatric surgery: a narrative review.

The morphosis from open surgeries to minimally invasive procedures is in greater part owing to the development of robotics. There has been a hiking popularity of robotic assistance for surgeries in recent years. Though a minimally invasive approach for surgery, it poses major challenges for an anesthesiologist that compound further for pediatric patients. The need of the hour for an anesthesiologist is to have a scrupulous knowledge and understanding of the associated anatomical and physiological considerations in case of pediatric patients. Major anesthetic concerns include restricted patient access, physiologic changes of pneumoperitoneum and different operative positions, risk of hypothermia, efficient fluid and peri-operative pain management. Timely anticipation, cautious observation for peri-operative complications and quick intervention to manage the same are warranted to provide high-quality anesthetic care. This simply implies that as robotic surgery plans to stretch up-to zenith, anesthesiologists shall strive to ace their part in robotic pediatric anesthesia as well. With an efficient and dynamic teamwork, robotic-assisted surgeries hold the potential to turn wonders for the future of surgery.

Outcomes of paroxysmal nocturnal hemoglobinuria in the pediatric age group in a resource-constrained setting.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal stem cell disorder. Eculizumab and bone marrow transplantation are disease-modifying treatments for PNH but may not be readily available in resource-constrained settings. Of 52 pediatric patients with PNH, 20 had classical PNH and 32 had PNH/aplastic anemia (PNH/AA). Median time to diagnosis was 30 months in classical PNH patients. Renal failure was present in four patients (20%). Six (30%) achieved complete response, 10 (50%) achieved partial response with androgens in classical PNH. Two underwent allogenic stem cell transplantation. In the PNH/AA group, 16 (50%) were in CR and seven (21%) were in PR with anti-thymocyte globulin ± cyclosporine.

Comparison of in chemico skin sensitization methods and development of an in chemico skin photosensitization assay.

Chemical substances that induce an allergic response in skin upon contact are called skin allergens or sensitizers, while chemical substances that elicit an allergic response only in presence of light are called photoallergens or photo sensitizers. The Direct Peptide Reactivity Assay (DPRA, OECD N° 442C, 2015) and the Amino Acid Derivative Reactivity Assay (ADRA) are in chemico assays used to discriminate between allergens and non-allergens. The DPRA and the ADRA, respectively, monitor the depletion of model peptides and modified amino acids induced by crosslinking with test chemicals. In the current study we compared these two assays and analyzed their suitability to predict skin sensitization potential of several chemical substances.  In order to study the combined effect of a chemical compound and UV light, we modified DPRA (photo-DPRA) as well as ADRA (photo-ADRA) by introduction of a photo-irradiation parameter. Analysis using photo-DPRA and photo-ADRA correctly distinguished known photoallergens from non-photoallergens. Upon irradiation, photoallergens selectively showed higher depletion of model peptides or modified amino acids. Thus, photo-DPRA and/or photo-ADRA can serve as non-animal in vitro methods for the identification and assessment of photoallergens/ photosensitizers.

Carbohydrates and polyphenolics of extracts from genetically altered plant acts as catalysts for in vitro synthesis of silver nanoparticle.

Eco-friendly biosynthetic approach for silver nanoparticles production using plant extracts is an exciting advancement in bio-nanotechnology and has been successfully attempted in nearly 41 plant species. However, an established model plant system for systematically unraveling the biochemical components required for silver nanoparticles production is lacking. Here we used Arabidopsis thaliana as the model plant for silver nanoparticles biosynthesis in vitro. Employing biochemical, spectroscopic methods, selected mutants and over-expressor plants of Arabidopsis involved in pleotropic functions and sugar homeostasis, we show that carbohydrates, polyphenolics and glyco-proteins are essential components which stimulated silver nanoparticles synthesis. Using molecular genetics as a tool, our data enforces the requirement of sugar conjugated proteins as essentials for AgNPs synthesis over protein alone. Additionally, a comparative analysis of AgNPs synthesis using the aqueous extracts of some of the plant species found in a brackish water ecosystem (Gracilaria, Potamogeton, Enteromorpha and Scendesmus) were explored. Plant extract of Potamogeton showed the highest potential of nanoparticles production comparable to that of Arabidopsis among the species tested. Silver nanoparticles production in the model plant Arabidopsis not only opens up a possibility of using molecular genetics tool to understand the biochemical pathways and components in detail for its synthesis.

Decline in seminal quality in Indian men over the last 37 years.

BACKGROUND: Since the first report of a decline in semen quality in 1974, there have been several reports of similar declines across populations. Despite some scattered reports of declining semen quality in the Indian sub-continent, comprehensive studies analyzing semen quality over the last few decades have not been undertaken. We undertook the present study to investigate the temporal trend in semen parameters in Indian populations over a period of 37 years (1979-2016). METHODS: Publications providing semen analysis details for fertile and infertile men from the Indian sub-continent were collected by a thorough literature search. Semen quality data for 6466 normal fertile or presumptive normal men (from 119 studies/data sets) and 7020 infertile men (from 63 studies/data sets) published between 1979 and 2016 were retrieved. We undertook systematic review and quantitative analysis of mean sperm count, motility, normal morphology and other available parameters. Data were analyzed to estimate semen parameters reference values for Indian men and to assess temporal trends in infertile, fertile and all subjects. RESULTS: Seminal quality shows a decreasing temporal trend and the decrease is higher in infertile than fertile males. In pooled analysis for all individuals, significant (p < 0.05 or < 0.001) declines in sperm concentration and normal morphology are observed; however, isolated analysis for each group shows declines without statistical significance. The mean (± SD) semen volume, sperm concentration, total motility, rapid linear progressive motility, normal sperm morphology and sperm viability for Indian fertile men are 2.88 ± 0.77 ml, 81.08 ± 29.21 million/ml, 66.37 ± 10.95%, 52.64 ± 15.78%, 56.68 ± 20.23% and 72.63 ± 8.31%, respectively, whereas in infertile these are 3.07 ± 1.27 ml, 37.94 ± 26.41 million/ml, 40.22 ± 13.76%, 26.79 ± 15.47%, 36.41 ± 21.66% and 55.25 ± 11.99%, respectively. The mean seminal parameter values were significantly lower (p < 0.001) in infertile as compared to fertile men, except semen volume. CONCLUSIONS: Semen parameters in Indian men have declined with time and the deterioration is quantitatively higher in the infertile group. The study also provides reference values for semen parameters in Indian men.