Synthesis of amide derivatives of 3-aryl-3H-benzopyrans as osteogenic agent concomitant with anticancer activity.

The present study reports a series of 3-aryl-3H-benzopyran-based amide derivatives as osteogenic agents concomitant with anticancer activity. Six target compounds viz 22e, 22f, 23i, and 24b-d showed good osteogenic activity at 1 pM and 100 pM concentrations. One of the potential molecules, 24b, effectively induced ALP activity and mRNA expression of osteogenic marker genes at 1 pM and bone mineralization at 100 pM concentrations. These molecules also presented significant growth inhibition of osteosarcoma (MG63) and estrogen-dependent and -independent (MCF-7 and MDA-MB-231) breast cancer cells. The most active compound, 24b, inhibited the growth of all the cancer cells within the IC50 10.45-12.66 µM. The mechanistic studies about 24b showed that 24b induced apoptosis via activation of the Caspase-3 enzyme and inhibited cancer cell migration. In silico molecular docking performed for 24b revealed its interaction with estrogen receptor-ß (ER-ß) preferentially.

Selenocysteine vs Cysteine: Tuning the Derivatization on Benzenesulfonyl Moiety of a Triazole Linked Dansyl Connected Glycoconjugate for Selective Recognition of Selenocysteine and the Applicability of the Conjugate in Buffer, in Serum, on Silica Gel, and in HepG2 Cells.

A dansyl derivatized triazole linked glucopyranosyl conjugate ((NO2)L) has been synthesized and characterized and was used in the present study. The conjugate (NO2)L releases a fluorescent product upon reaction by Cys-SeH in aqueous PBS buffer by exhibiting a ∼210-fold fluorescence enhancement even in the presence of 20 other amino acids with a minimum detection limit of (1.5 ± 0.2) × 10(-7) M. The selectivity of the Cys-SeH to (NO2)L was further proven by extending the fluorescence study to different other selenium compounds. The role of para-nitrobenzenesulfonyl (pNBS) center in (NO2)L in the selective recognition of Cys-SeH was confirmed when the fluorescence emission studies were carried out using five different derivatizations possessing two NO2, five fluoro, two fluoro, one fluoro, and no fluoro groups. The nucleophilic substitution reaction of Cys-SeH on (NO2)L has been clearly demonstrated on the basis of (1)H NMR, ESI-MS, and absorption spectroscopy, and the heat changes were monitored by isothermal titration calorimetry. The application potential of (NO2)L has been demonstrated by studying its selectivity toward Cys-SeH in aqueous PBS buffer, in bovine serum, and on the silica gel surface that lead to minimum detection limits of (25 ± 2), (80 ± 5), and (168 ± 16) ppb, respectively. The biological applicability of (NO2)L for Cys-SeH was further demonstrated in HepG2 cells by fluorescence microscopy. Thus, (NO2)L is aqueous soluble and a biologically acceptable probe for Cys-SeH.

Comparative performance of four single extreme outlier discordancy tests from Monte Carlo simulations.

Using highly precise and accurate Monte Carlo simulations of 20,000,000 replications and 102 independent simulation experiments with extremely low simulation errors and total uncertainties, we evaluated the performance of four single outlier discordancy tests (Grubbs test N2, Dixon test N8, skewness test N14, and kurtosis test N15) for normal samples of sizes 5 to 20. Statistical contaminations of a single observation resulting from parameters called δ from ±0.1 up to ±20 for modeling the slippage of central tendency or ε from ±1.1 up to ±200 for slippage of dispersion, as well as no contamination (δ = 0 and ε = ±1), were simulated. Because of the use of precise and accurate random and normally distributed simulated data, very large replications, and a large number of independent experiments, this paper presents a novel approach for precise and accurate estimations of power functions of four popular discordancy tests and, therefore, should not be considered as a simple simulation exercise unrelated to probability and statistics. From both criteria of the Power of Test proposed by Hayes and Kinsella and the Test Performance Criterion of Barnett and Lewis, Dixon test N8 performs less well than the other three tests. The overall performance of these four tests could be summarized as N2≅N15 > N14 > N8.

Significance of Nestin and CD133 as cancer stem cell markers in diffuse glioma and association with p53 expression and IDH status.

BACKGROUND: Recent evidence suggests that the tumor stem cells that are responsible for the pathogenesis of gliomas have similar properties to those of neural stem cells. We have studied two of the most consistently expressed stem cell markers in gliomas, i.e., CD133 and Nestin, and compared them with respect to p53 expression and IDH status. OBJECTIVES: To assess the level of expression of Nestin and CD133, and identify a correlation among various grades of diffuse glioma with IDH status and expression of p53. MATERIALS AND METHODS: A cross-sectional retrospective study with 102 subjects for the expression of cancer stem cell markers; CD133 and Nestin and the correlation of their expression with that of p53 and IDH1 status in adult diffuse glioma. The study was conducted in the Departments of Pathology and Neurosurgery. The expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded sections. The scoring of expression of CD133 and Nestin was adapted from Zhang et al. The scoring for p53 was adopted from Aruna et al. Results: The diffuse gliomas were graded based on WHO into grade II (30.3%), grade III (28.4%), and grade IV (41.3%). Among WHO grade IV, 59.4% were primary, and 40.4% were secondary glioblastomas. 73% of the diffuse gliomas were IDH mutant, and p53 showed an overall expression of 76.4%. The expression of CD133 and Nestin were compared with the increasing grades of diffuse gliomas, which, when plotted on ROC curves, had AUCs of 0.6806 and 0.6119, respectively. Their expression showed a positive correlation with the IDH status of the tumor. CONCLUSIONS: Cancer stem cell markers CD133 and Nestin are expressed in diffuse glioma and have a higher expression with increasing WHO grade of malignancy. These cancer stem cell markers have shown significant association with the IDH-1 mutant status of diffuse gliomas. Hence, it can be inferred that diffuse gliomas with a higher expression of CD133 and Nestin have a poorer prognosis. Further, these cancer stem cell markers may be used as therapeutic targets in the future.

Tuberculoma of the Cavernous Sinus and Meckel's Cave in a Child.

Tuberculous infection of the cavernous sinus and Meckel's cave is extremely rare. In this report, we describe a patient with tuberculoma of the cavernous sinus and Meckel's cave, extending to the petrous apex. The patient underwent microsurgical excision of the lesion and antitubercular chemotherapy resulting in a good outcome. We describe the diagnostic difficulties and review the relevant literature.

Opportunistic Fonsecaea pedrosoi brain abscess in a patient with non-cirrhotic portal fibrosis-induced hypersplenism--a novel association.

Non-cirrhotic portal fibrosis, a common cause of splenomegaly in tropical countries, can lead to hypersplenism and pancytopenia. Hypersplenism in this setting has not been associated with opportunistic infections. We describe a patient with hypersplenism secondary to non-cirrhotic portal fibrosis who developed a Fonsecaea pedrosoi brain abscess and succumbed to the illness despite aggressive management.

Serum Levels of Netrin-4 and Its Association With Hepatocellular Carcinoma: Results From a Case-Control Study.

BACKGROUND: Angiogenesis plays a vital role in the progression of hepatocellular carcinoma (HCC) by contributing to tumor growth and metastasis. Netrin-4 (NTN4) is a secreted glycoprotein that regulates angiogenesis and maintains endothelial homeostasis. There were no studies found focusing on the value of NTN4 as a serum biomarker for the diagnosis and prognosis of HCC. In this study, we aimed to investigate the systemic expression of NTN4 in patients with HCC. We also explore the association of NTN4 with major clinicopathological and biochemical characteristics of HCC. METHODS: A total of 116 patients with HCC and 44 healthy volunteers were recruited in this case-control study. Clinical characteristics and liver function parameters were recorded among the study subjects. The levels of α-fetoprotein (AFP) were quantified in patients with HCC. The serum levels of NTN4 (pg/ml) were estimated by enzyme-linked immunosorbent assay (ELISA). RESULTS: The median NTN4 levels were significantly decreased in patients with HCC when compared to control subjects (p < 0.0001). There was no difference between NTN4 levels in AFP-positive patients and AFP-negative patients (p = 0.39). Of note, NTN4 levels were significantly decreased in HCC patients with metastasis (p < 0.02) and portal vein invasion (p < 0.04). Further, NTN4 levels were significantly reduced in HCC patients with Child-Pugh C score (p < 0.05). The receiver operating characteristic curve for serum levels of NTN4 in the HCC group and control group was generated. At a cut-off of 30 pg/ml, the sensitivity and specificity for NTN4 were 80% and 82%, respectively, with an AUC of 0.894. CONCLUSIONS: Low levels of NTN4 were associated with increased tumor aggressiveness and metastasis in HCC. Estimation of circulating NTN4 has prognostic value as a minimally invasive biomarker in HCC. Future studies might shed the role of NTN4 in the development of HCC.

Hepatic Expression of NTN4 and Its Receptors in Patients with Hepatocellular Carcinoma.

BACKGROUND: Angiogenesis contributes to hepatocellular carcinoma (HCC) progression by promoting tumor growth and metastasis. Netrin-4 (NTN4) is a secreted glycoprotein that has been reported to control angiogenesis and preserve endothelial homeostasis. Macrovascular invasion of the portal vein, referred to as portal vein invasion (PVI) is associated with poor prognosis in HCC patients. In this work, we sought to understand more about the systemic and hepatic level expression of NTN4 and its receptors in HCC patients with and without portal vein invasion. METHODS: A total of 154 patients with HCC, and 90 healthy volunteers were recruited in this case-control study. Patients with HCC were further subdivided into those with portal vein invasion (PVI) (n=68), and those without portal vein invasion (NPVI) (n=86). Clinical characteristics and liver function parameters were recorded among the study subjects PVI and NPVI. The serum levels of NTN4 (pg/ml) were estimated by ELISA. HCC tissues and normal non-tumorous liver tissues (controls) were collected for gene expression analysis of NTN4 and its receptors. RESULTS: ALT, ALP, and GGT levels were significantly elevated in the serum of HCC patients with PVI compared to NPVI and control subjects. Systemic NTN4 was significantly reduced in both PVI and NPVI patients compared to control subjects. At the tissue level, the hepatic NTN4 followed a similar trend with significantly lower mRNA expression in both patients with PVI and NPVI compared to control subjects. CONCLUSIONS: Systemic and hepatic NTN4 levels were reduced in both PVI and NPVI subjects. The hepatic expression of NTN4 receptors Neogenin and UNC5B were markedly elevated in patients with HCC with PVI compared to NPVI. Future experimental studies might shed the role of NTN4 and its receptors in the development of PVI in HCC.

A study on H-score threshold for p16ink4a immunoperoxidase expression in squamous cell tumours of oral cavity.

Background: Validity of various detection methods used are likely contributing factor to this wide variation of prevalence of HPV (0-73%) by using GP5/GP6/MY09/MY11 (L1) primer. PCR is a sensitive method but does not identify transcriptionally active High-risk Human papillomavirus and also does not indicate whether the virus is isolated from malignant tumour cells and non-neoplastic cells. P16ink4a Immunohistochemistry is a highly sensitive and Cost-effective surrogate marker for transcriptionally active high-risk HPV for oral cancer. Objective The aim of the present study was to evaluate the H-SCORE of p16 expression in the surface epithelial tumour sites of a large cohort of squamous cell carcinoma (SCC), severe dysplasia (SD). we sought to determine whether the p16 algorithm is reliable in Oral cavity SCC and severe dysplasia (SD). Materials and Methods: This study used Immunohistochemistry in archival Formalin-fixed paraffin embedded specimens for assessment of p16 protein expression, cytoplasmic and nuclear staining intensity was categorized based on score (range, 0-3) and presence of tumour cell staining (0-100%). Results: The majority of positive cases had low H-score of p16 staining except 3/161 (1.8%) cases of tongue SCC had positive for p16 with diffuse moderate staining with ≥2 scores. There were no significant differences in the distribution of demographic, exposure and histopathological characteristics between patients with and without P16 expression. Conclusion: The present study demonstrated that p16 expression is a reliable HPV marker in the lateral border of the tongue with tonsil involvement but no other sites of the oral cavity. Further p16 IHC detection is required in large cohort of all sites of tongue squamous cell carcinoma studies to validate the marker of HPV.

Role of pro-angiogenic marker galectin-3 in follicular neoplasms of thyroid.

The role of pro-angiogenic marker galectin-3 (GAL-3) was examined in differential diagnosis of follicular neoplasms of thyroid into histological subsets of follicular adenoma (FA), follicular carcinoma (FC) and follicular variant of papillary thyroid carcinoma (FVPTC). The study included 22 cases from January 2006 to June 2011 comprising of FA (n = 12), FC (n = 3) and FVPTC (n = 7). Immunohistochemical evaluation of GAL-3 was performed on representative histologic sections from the resected thyroid specimens. The proportion of stained cells and intensity of staining in tumor blood vessels were evaluated. GAL-3 expression showed that angiogenesis was prominent in malignancy (FC and FVPTC) and negative in non-neoplastic thyroid parenchyma and benign condition (FA). GAL-3 expression was found to differentiate benign from malignant follicular neoplasms. Focal and diffuse positivity for GAL-3 was found to be associated with FC and FVPTC respectively, thus GAL-3 can be used as a immunohistochemical marker in the differential diagnosis of follicular neoplasms of thyroid based on the type of expression. Limitation of this study was relatively less number of cases studied; however, this data need to be corroborated in larger cohort.

Loading and Release of Quercetin from Contact-Drawn Polyvinyl Alcohol Fiber Scaffolds.

Polymeric drug releasing systems have numerous applications for the treatment of chronic diseases and traumatic injuries. In this study, a simple, cost-effective, and scalable method for dry spinning of crosslinked polyvinyl alcohol (PVA) fibers is presented. This method utilizes an entangled solution of PVA to form liquid bridges that are drawn into rapidly drying fibers through extensional flow. The fibers are crosslinked by a one-pot reaction in which glyoxal is introduced to the PVA solution prior to contact drawing. Failure analysis of fiber formation is used to understand the interplay of polymer concentration, glyoxal concentration, and crosslinking time to identify appropriate formulations for the production of glyoxal-crosslinked PVA fibers. The small molecule quercetin (an anti-inflammatory plant flavonoid) can be added to the one-pot reaction and is shown to be incorporated into the fibers in a concentration-dependent manner. Upon rehydration in an aqueous medium, the glyoxal-crosslinked PVA fiber scaffolds retain their morphology and slowly degrade, as measured over the course of 10 days. As the scaffolds degrade, they release the loaded quercetin, reaching a cumulative release of 56 ± 6% of the loaded drug after 10 days. The bioactivity of the released quercetin is verified by combining quercetin-loaded fibers with contact-drawn polyethylene oxide-type I collagen (PEO-Col) fibers and monitoring the growth of PC12 cells on the fibers. PC12 cells readily attach to the PEO-Col fibers and display increased nerve growth factor-induced elongation and neurite formation in the presence of quercetin-loaded PVA fibers relative to substrates formed from only PEO-Col fibers or PEO-Col and PVA fibers without quercetin.

Multi-pin contact drawing enables production of anisotropic collagen fiber substrates for alignment of fibroblasts and monocytes.

Type I collagen is the most abundant protein in the human body and is known to play important roles in numerous biological processes including tissue morphogenesis and wound healing. As such, it is one of the most frequently used substrates for cell culture, and there have been considerable efforts to develop collagen-based cell culture substrates that mimic the structural organization of collagen as it is found in native tissues, i.e., collagen fibers. However, producing collagen fibers from extracted collagen has been notoriously difficult, with existing methods providing only low throughput production of collagen fibers. In this study, we prepared collagen fibers using a highly efficient, bio-friendly, and cost-effective approach termed contact drawing, which uses an entangled polymer fluid to aid in fiber formation. Contact drawing technology has been demonstrated previously for collagen using highly concentrated dextran solutions with low concentrations of collagen. Here, we show that by replacing dextran with polyethylene oxide (PEO), high collagen content fibers may be readily formed from mixtures of soluble collagen and PEO, a polymer that readily forms fibers by contact drawing at concentrations as low as 0.5%wt. The presence of collagen and the formation of well-ordered collagen structures in the resulting fibers were characterized by attenuated total reflectance Fourier-transform infrared spectromicroscopy, Raman spectromicroscopy, and fluorescence microscopy. Corresponding to well-ordered collagen, the mechanical properties of the PEO-collagen fibers approximated those observed for native collagen fibers. Growth of cells on aligned PEO-collagen fibers attached to a polydimethyl siloxane support was examined for human dermal fibroblast (WS1) and human peripheral leukemia blood monocyte (THP-1) cell lines. WS1 and THP-1 cells readily attached, displayed alignment through migration and spreading, and proliferated on the collagen fiber substrate over the course of several days. We also demonstrated the retrieval of viable cells from the PEO-collagen fiber substrates through enzymatic digestion of the collagen substrate with collagenase IV.

Gastric adenocarcinoma presenting with multiple skeletal muscle metastases.

A 42-year-old man presented to the gastroenterology clinic with features of gastric outlet obstruction, significant weight loss, anaemia, ascites, and pain in the lower back and left thigh. CT scan of the abdomen and pelvis showed wall thickening in the antropyloric region of the stomach and enhancing soft tissue lesion in the left psoas and right gluteal region. Gastroscopy revealed a circumferential growth in the antrum and pylorus of the stomach, and biopsy from the growth was reported as moderately differentiated adenocarcinoma. Positron emission tomography-CT scan showed multiple skeletal muscle metastases all over the body. Fine-needle aspiration cytology and immunohistochemistry from the psoas lesion confirmed metastatic adenocarcinoma deposits. He underwent antropyloric stenting for his obstructive symptoms and received supportive care, finally succumbed to his illness after 6 weeks.

A statistically coherent robust multidimensional classification scheme for water.

Serious limitations of the existing water classification schemes prompted us to propose a new statistically coherent water nomenclature system. An extensive database of ionic charge-balanced concentrations of 8 elements (4 cations Ca, Mg, Na, and K; and 4 anions SO4, Cl, HCO3, and CO3), in 46,292 multivariate outlier-free simulated samples, was used for training the multidimensional classification system. The initial assignment for 16 classes was achieved from the greater molar concentration concept of each cation and anion, called the Greater molar conc model. Seven hybrid log-ratios (hlr) from 8 elemental concentrations were used for linear discriminant analysis (LDA) and canonical analysis to propose 16 multidimensional discriminant functions from the 7 hlr model. The LDA and canonical analysis were also performed on the initial molar concentrations of 7 elements, without any log-transformation, which was designated as the 7 M conc model. The robustness of these three classification systems (7 hlr, 7 M conc, and Greater molar conc) was tested against analytical uncertainty propagation and mineral-water interaction effects. The 7 hlr model, due to its higher robustness, was considered as the best option for the nomenclature of the 16 types of water. From the probability concept, it was possible to identify hybrid water types, along with the basic or primary types of water. Our water classification scheme (7 hlr model under the "basic+hybrid" option) can classify as many as 256 different classes of water. Due to the clearly high complexity of the proposed classification scheme, we developed a new online computer program WaterMClaSys_LDA (Water Molar Classification System from Linear Discriminant Analysis) available at our web portal http://tlaloc.ier.unam.mx, for use by anyone after registration and log-in. The usefulness of the new classification scheme is illustrated by applications to groundwater, lake water, and geothermal water samples from South India, Mongolia, and western Turkey, respectively.

Surface-Functionalized Poly(Ether Sulfone) Composite Hollow Fiber Membranes with Improved Biocompatibility and Uremic Toxins Clearance for Bioartificial Kidney Application.

Bioartificial kidney (BAK) is attracting the focus of the research community. In this study, the efficacy of surface-functionalized poly(ether sulfone)-TPGS-graphene oxide composite hollow fiber membranes as a promising material for the single extracorporeal unit for BAK application was evaluated. The cytotoxicity was examined using human primary renal proximal tubular epithelial cells (hPTCs), and the removal of uremic toxins (urea, creatinine, phosphate, and lysozyme) from the toxin-spiked goat blood was measured. The surface-functionalized polymer composite membranes acted as a biocompatible material for attachment and proliferation of hPTCs, which was confirmed by microscopy studies, proliferation, and activity assays. The functional activity of these renal cells over this biocompatible membrane was also maintained. Remarkably, the functionalized composite membranes showed removal of urea (46.4 ± 3.5%), creatinine (52.2 ± 3.9%), phosphate (35.5 ± 2.7%), and lysozyme (11.2 ± 0.8%) from the toxin-spiked goat blood. Therefore, these obtained results showed that the surface-functionalized poly(ether sulfone)-TPGS-graphene oxide composite hollow fiber membranes are suitable for BAK application.

Sister Mary Joseph Nodule as an Initial Presentation of Pancreatic Adenocarcinoma.

Sister Mary Joseph (SMJ) nodule is a metastatic umbilical nodule seen in primary tumors of the gastrointestinal or genitourinary tract. The stomach and colon are the common gastrointestinal cancers associated with SMJ nodule. The pancreas is a rare primary site for umbilical metastasis. Moreover, malignant umbilical nodules as the first presentation in pancreatic cancer is rare. Pancreatic adenocarcinoma that metastasizes to umbilicus usually arise from the body or tail of the pancreas. The presence of SMJ nodule usually indicates poor prognosis. Umbilical nodule is a simple physical finding to the presence of an advanced intra-abdominal malignancy. Although rare, pancreatic cancer should be considered as one of the primary sites in such a situation.

Pathological abnormalities in splenic vasculature in non-cirrhotic portal hypertension: Its relevance in the management of portal hypertension.

BACKGROUND: Portal hypertension (PH) is associated with changes in vascular structure and function of the portosplenomesenteric system (PSMS). This is referred to as portal hypertensive vasculopathy. Pathological abnormalities of PSMS has been described in the literature for cirrhotic patients. Raised portal pressure and hyperdynamic circulation are thought to be the underlying cause of this vasculopathy. In view of this, it is expected that pathological changes in splenic and portal vein similar to those reported in cirrhotic patients with PH may also be present in patients with non-cirrhotic PH (NCPH). AIM: To investigate pathological abnormalities of splenic vein in patients with NCPH, and suggest its possible implications in the management of PH. METHODS: A prospective observational study was performed on 116 patients with NCPH [Extrahepatic portal vein obstruction (EHPVO): 53 and non-cirrhotic portal fibrosis (NCPF): 63] who underwent proximal splenorenal shunt (PSRS), interposition shunt or splenectomy with devascularization in JIPMER, Pondicherry, India, a tertiary level referral center, between 2011-2016. All patients were evaluated by Doppler study of PSMS, computed tomography porto-venogram and upper gastrointestinal endoscopy. An acoustic resonance forced impulse (ARFI) scan and abdomen ultrasound were done for all cases to exclude cirrhosis. Intraoperative and histopathological assessment of the harvested splenic vein was performed in all. The study group was divided into delayed and early presentation based on the median duration of symptoms (i.e. 108 mo). RESULTS: The study group comprising of 116 patients [77 (66%) females and 39 (34%) males] with NCPH had a median age of 22 years. Median duration of symptoms was 108 mo. The most common presentation in both EHPVO and NCPF patients was upper gastrointestinal bleeding (hematemesis and melena). The ARFI scan revealed a median score of 1.2 (1.0-1.8) m/s for EHPVO and 1.5 (0.9-2.8) m/s for NCPF. PSRS was performed in 84 patients (two of whom underwent interposition PSRS using a 10 mm Dacron graft); splenoadrenal shunt in 9; interposition mesocaval shunt in 5; interposition 1st jejunal to caval shunt in 1 patient and devascularization with splenectomy in 17 patients. Median pre-splenectomy portal pressure was 25 (range: 15-51) mm Hg. In 77% cases, the splenic vein was abnormal upon intraoperative assessment. Under macroscopic examination, wall thickening was observed in 108 (93%), venous thrombosis in 32 (28%) and vein wall calcification in 27 (23%) cases. Upon examination under a surgical magnification loupe, 21 (18%) patients had intimal defects in the splenic vein. Histopathological examination of veins was abnormal in all cases. Medial hypertrophy was noted in nearly all patients (107/116), while intimal fibrosis was seen in 30%. Ninety one percent of patients with intimal fibrosis also had venous thrombosis. Vein wall calcification was found in 22%, all of whom had intimal fibrosis and venous thrombosis. The proportion of patients with pathological abnormalities in the splenic vein were significantly greater in the delayed presentation group as compared to the early presentation group. CONCLUSION: Pathological changes in the splenic vein similar to those in cirrhotic patients with PH are noted in NCPH. We recommend that PH in NCPH be treated as systemic and pulmonary hypertension equivalent in the gastrointestinal tract, and that early aggressive therapy be initiated to reduce portal pressure and hemodynamic stress to avoid potential lethal effects.

Indian Academy of Cytologists National Guidelines for Cytopathology Laboratories for Handling Suspected and Positive COVID-19 (SARS-CoV-2) Patient Samples.

COVID-19, caused by the SARS-CoV-2 virus, has been declared a pandemic by the World Health Organization. This scenario has impacted the way we practice cytopathology. Cytology laboratories receive fresh and potentially infectious biological samples including those from the respiratory tract, from COVID-19 positive or suspected patients. Hence, the Indian Academy of Cytologists thought it necessary and fit to bring forth appropriate guidelines starting from transportation, receipt, processing, and reporting of samples in the COVID-19 era. The guidelines are prepared with the aim of safeguarding and protecting the health care personnel including laboratory staff, trainees and cytopathologists by minimizing exposure to COVID-19 so that they remain safe, in order to able to provide a continuous service. We hope that these national guidelines will be implemented across all cytopathology laboratories effectively.

Enhancing early detection of neurological and developmental disorders and provision of intervention in low-resource settings in Uttar Pradesh, India: study protocol of the G.A.N.E.S.H. programme.

INTRODUCTION: Around 9% of India's children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants <5 months. In addition, children with developmental delay, intellectual disabilities, late detected genetic disorders or autism spectrum disorder show abnormal general movements (GMs) during infancy. General Movement Assessment in Neonates for Early Identification and Intervention, Social Support and Health Awareness (G.A.N.E.S.H.) aims to (1) provide evidence as to whether community health workers can support the identification of infants at high-risk for neurological and developmental disorders and disabilities, (2) monitor further development in those infants and (3) initiate early and targeted intervention procedures. METHODS: This 3-year observational cohort study will comprise at least 2000 infants born across four districts of Uttar Pradesh, India. Community health workers, certified for GMA, video record and assess the infants' GMs twice, that is, within 2 months after birth and at 3-5 months. In case of abnormal GMs and/or reduced MOSs, infants are further examined by a paediatrician and a neurologist. If necessary, early intervention strategies (treatment as usual) are introduced. After paediatric and neurodevelopmental assessments at 12-24 months, outcomes are categorised as normal or neurological/developmental disorders. Research objective (1): to relate the GMA to the outcome at 12-24 months. Research objective (2): to investigate the impact of predefined exposures. Research objective (3): to evaluate the interscorer agreement of GMA. ETHICS AND DISSEMINATION: G.A.N.E.S.H. received ethics approval from the Indian Government Chief Medical Officers of Varanasi and Mirzapur and from the Ramakrishna Mission Home of Service in Varanasi. GMA is a worldwide used diagnostic tool, approved by the Ethics Committee of the Medical University of Graz, Austria (27-388 ex 14/15). Apart from peer-reviewed publications, we are planning to deploy G.A.N.E.S.H. in other vulnerable settings.

Preoperative cytodiagnosis of cystic pleomorphic adenoma with squamous metaplasia and cholesterol crystals: a case report.

BACKGROUND: Pleomorphic adenoma with extensive squamous metaplasia and cystic change may cause diagnostic confusion both in cytology and histopathology, which stresses the need for a guarded approach while interpreting such lesions. CASE: A 50-year-old man presented with a submandibular swelling of 6 months' duration. Routine fine needle aspiration (FNA) yielded mucoid fluid, mixed with whitish particles. Cytologic smears revealed fibromyxoid connective tissue fragments, epithelial cell clusters exhibiting squamous metaplasia, clumps of keratin material, few multinucleated giant cells, a large number of cholesterol crystals and scattered cyst macrophages in a thin proteinaceous background. The cystic nature of the swelling caused some degree of diagnostic dilemma; however, ultimately, a cytologic diagnosis of "pleomorphic adenoma with squamous metaplasia and cystic change" was offered, which was confirmed by subsequent histopathologic examination. CONCLUSION: Our case emphasizes the need for a cautious and systematic approach in the cytologic and histopathologic interpretation of cystic pleomorphic adenoma with metaplastic epithelial changes. Cholesterol crystals found in the aspirate material of our case is a rare finding in pleomorphic adenoma.