BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George’s Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (?3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of “BRCAness” in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP- ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

COVID-19, the novel coronavirus 2019: current updates and the future

COVID-19 is a new strain that has not been previously identified in humans. It is large, enveloped, single-stranded RNA virus. The clinical features range from the common cold to more severe diseases i.e., MERS and SARS. Incubation period ranges between 1-12.5 days (median 5-6 days). As on 07 March, 2020 total confirmed cases are 1,01,927 with 3486 deaths in 93 countries/territories/areas. The various lab tests for COVID-19 virus are NAAT, serological testing, viral sequencing and viral culture. Many aspects of this virus is still not understood. The authors in this article describe studies to know the pathogenesis as well as immunological response with use of animal methods. Authors also discuss genetic engineering, evaluation of activation and inflammatory activity of myeloid cells during pathogenic human coronavirus, etc. that can help in prevention and treatment of COVID-19 in near future.

Escitalopram add-on in stable Schizophrenia with subsyndromal depression

Background: Significant proportion of the patients of schizophrenia suffer from subsyndromal symptomatic depressive symptoms (SSD) which not only add to the burden of disease but also to the already pre-existing challenges of living with this serious mental illness. Many psychiatrists prescribe antidepressants to patients with schizophrenia who have subsyndromal symptomatic depressive symptoms but data regarding SSD in schizophrenia is meagre. Aim was to study the effect of addition of Escitalopram on psychopathology, cognition and functioning in patients with stable schizophrenia having subsyndromal depressive symptoms and to compare these parameters with patients treated with antipsychotics alone.Methods: The study was a prospective, 8-week randomized double-blind placebo-controlled trial. Seventy four patients who fulfilled the diagnostic criteria of Schizophrenia on the basis of the ICD10-DCR, adjudged to be stable clinically and not requiring any increase in dose of antipsychotic medication over the last eight weeks were recruited into the study. The patients randomly received either Antipsychotics with add-on Escitalopram (10 mg/day) or Antipsychotics with placebo for 8 weeks. The patients were assessed using the HAM-D, CDRS, PANSS, SCoRS, SOFAS and CGI scores at the end of 8 weeks. Patients were also assessed for adverse events at baseline, week 4 and week 8.Results: A total of sixty-six patients who completed the study were analyzed. The HAM-D, CDRS and PANSS score showed significantly better cognition and functioning in the patients of add-on Escitalopram group when compared with the placebo group. There was no significant difference between the two groups in terms of observed side effects.Conclusions: Escitalopram addition to the standard anti-psychotic treatment of schizophrenia, in patients having subsyndromal depressive symptoms, results in better cognition and improved functioning.

Intrauterine platelet rich plasma versus injection G-CSF for treatment of thin endometrium in infertility

Background: For success in IVF treatment, it is essential that the patient has a responsive endometrium together with many other factors. Inspite of numerous treatments available today for growth of endometrium, there is lack of any ideal drug or protocol for increasing endometrial thickness. The study is an attempt to evaluate the role of two drugs for increasing endometrial growth before embryos transfers.Methods: This study is a retrospective cohort study including 50 patients with previously diagnosed as thin endometrium patients who may or may not have failed previous cycles of IVF. Patients were randomly divided into two groups. First group-Group A (n=25) are patients randomly selected to undergo intrauterine PRP instillation for increase in endometrial thickness before embryo transfer. Second group-Group B (n=25) are randomly selected from a retrospective cohort of thin endometrium to take injection GCSF  as intrauterine infusion (total dose 300mcg) on day of trigger or day 11 of cycle followed by 60 units subcutaneously after embryo transfer. The difference in endometrial thickness during transfer and the pregnancy outcomes were compared.Results: Injection GCSF was found to be more effective than intrauterine PRP in improving endometrial thickness in patients with thin endometrium with a p-value of <0.0001.  It was found that the chemical and clinical pregnancy rates were comparable as the p values were 0.77 and 0.37 respectively and hence statistically not significant. Although patients given injection GCSF had a slightly higher clinical pregnancy rate (44%) as compared to patients given intrauterine PRP which was 28%. All other variables were comparable.Conclusions: In the study it was proven that injection GCSF, is more effective for the treatment of thin endometrium patients as compared to intrauterine PRP infusion. Though the clinical and chemical pregnancy rates were comparable, a higher percentage of women were clinically pregnant in the group given injection GCSF.  Intrauterine PRP can also be a good alternative for thin endometrium.  More studies and RCTS are needed for comparison to prove the effectiveness of these drugs for treatment of thin endometrium.

A short term evaluation of effect on serum urea, creatinine and potassium levels with use of angiotensin II receptor blockers (olmesartan or telmisartan) in stage 1 hypertensive patients

Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) are being used as first line agents for the treatment of hypertension in haemodialysis patients as well as in the general population. Serious hyperkalemia is common in patients with end-stage renal disease, and is observed in about 10% of haemodialysis patients. Although many research have been done so far to compare the antihypertensive efficacy of ARBs, but such studies to evaluate the effect on serum urea, creatinine and potassium levels are not so common in North India region.Methods: In this open label, prospective, randomized study, we evaluated the effect on serum urea, creatinine and potassium levels with use of ARB’s (olmesartan or telmisartan) in stage 1 hypertensive patients (JNCVII). 60 patients were randomized in to two groups. The odd numbers will be allotted olmesartan 20 mg (group A) and even numbers to telmisartan 40 mg (group B). Impacts on serum urea, creatinine and potassium levels were evaluated after 12 weeks.Results: Our results indicates that there was no statistically significant alterations in mean serum creatinine, blood urea and in mean serum potassium levels compared to baseline within the two groups as well as when mean of both groups were compared, olmesartan showed a better reduction in blood pressure as compared to telmisartan.Conclusions: Olmesartan showed a better reduction in blood pressure with similar effects in biochemical parameters as telmisartan.

The Bethesda system for reporting of thyroid cytopathology and its category wise management

Background: Fine-needle aspiration cytology (FNAC) of thyroid is a rapid diagnostic test for thyroid nodules. The Bethesda system classifies thyroid FNAC into six categories. Each category is linked to a malignancy risk and has recommended clinical management. The aim of this study was to analyze the thyroid cytology smears by Bethesda system and to assess the frequency of various categories and to correlate it previous published studies. Category wise management is also discussed in detail.Methods: A total of 388 thyroid FNAC samples were examined from January 2017 to June 2018 in the Department of Pathology, in Medanta- The Medicity Gurugram.Results: A total of 388 cases were reported according to Bethesda system of reporting. Categories were as follows: I (14.69%), II (61.85%), III (11.34%), IV (2.57%), V (2.660%), VI (4.91%) nodules.Conclusions: The Bethesda System for reporting thyroid cytopathology proved to be an excellent reporting system and it puts clinician and the cytopathologist on the same page and easier to communicate regarding diagnosis.

A Cross Sectional Study of Drug Utilization Pattern in Indoor Patients of Tertiary Care Teaching Hospitals in Central India

OBJECTIVE: To evaluate the pattern of drug utilization with special focus on the use of antimicrobials. METHODS: Single day hospital-wide point prevalence survey was conducted to assess drug utilization pattern.  Information regarding age, gender, occupation, income group, diagnosis, patient’s present/past medical history, treatment, any adverse drug reactions, and investigations were recorded in a proforma. Drug utilization pattern was evaluated using quality indicators of drug use recommended by WHO. RESULTS: A total of 77 patients were included, 62% male and 38% female. Maximum number of patients was admitted for infectious diseases (34%). Pantoprazole was most commonly prescribed drug & ceftriaxone was most commonly prescribed antibiotic. The average number of drugs prescribed per encounter was 4.87.  Oral route was the most preferred route. Percentage of drugs prescribed by generic name was 42.44%. Percentage of drugs prescribed from essential medical list was 49.33%. Multivitamins & non steroidal anti-inflammatory drugs (NSAIDS) were most commonly prescribed fixed dose combination in our study.  CONCLUSION: Majority of drugs were prescribed by oral route. Essential medical list and updated guidelines were available in the hospital. Poly-pharmacy, over use of proton-pump inhibitors & multivitamins was areas of concern. Prolonged and irrational use of antibiotics for surgical prophylaxis was noted in surgical indoor patients. There was underutilization of microbiological facilities.

Fresh versus frozen embryo transfer: a retrospective cohort study

Background: Elective frozen embryo transfer (FET), has recently increased significantly with improvements in cryopreservation techniques. Observational studies and randomized controlled trials suggested that the endometrium in stimulated cycles is not optimally prepared for implantation; risk of ovarian hyperstimulation syndrome reduced and pregnancy rates increased following FET and perinatal outcomes are less affected after FET. However, the evidence is not unequivocal and recent randomised control trials challenge the use of elective FET for the general IVF population. Pregnancy rates were analysed in a cohort of patients undergoing embryo transfers.Methods: This was a retrospective cohort study of patients who underwent embryo transfers from April 2018 to March 2019 at study centre in Surat.175 cycles of embryo transfers (119 fresh and 56 frozen) were included in the study. Outcomes measured were positive pregnancy, clinical pregnancy and ongoing clinical pregnancy rates achieved in the IVF-ET cycles.Results: There were no statistically significant differences between positive pregnancy rate (54.6% versus 60.7%, Odds ratio (OR) 0.78; 95% Confidence Interval (CI) 0.41-1.49), clinical pregnancy rate (48.73% versus 57.14%, OR 0.52; 95% CI 0.1- 2.64) and ongoing clinical pregnancy rate  (45.38% versus 51.78% OR 1.4; 95% CI 0.29 - 6.67) in fresh ET and FET cycles, respectively, p < 0.05 was considered statistically significant for all measures.Conclusions: Despite the observed higher rates of positive biochemical, clinical and ongoing clinical pregnancy per transfer in the FET cohort, these did not reach statistical significance. Thus, both transfer strategies are reasonable options, although there is a trend favouring the freeze-all strategy.

Historic migration to South Asia in the last two millennia: A case of Jewish and Parsi populations

The South Asian populations have a mosaic of ancestries likely due to the interactions of long-term populations of the landmassand those of East and West Eurasia. Apart from prehistoric dispersals, there are some known population movements to India. Inthis study, we focussed on the migration of Jewish and Parsi populations on temporal and spatial scales. The existence of Jewishand Parsi communities in India are recorded since ancient times. However, due to the lack of high-resolution genetic data, theirorigin and affiliation with other Indian and non-Indian populations remains shrouded in legends. Earlier genetic studies onpopulations of Indian Jews have found evidence for a minor shared ancestry of Indian Jews with Middle Eastern (Jews)populations, whereas for Parsis, the Iranian link was proposed. Recently, in our high-resolution study, we were able to quantifythe admixture dynamics of these groups, which has suggested a male-biased admixture. Here, we added the newly availableancient samples and revisited the interplay of genes and cultures. Thus, in this study we reconstructed a broad genetic profile ofIndian Jews and Parsis to paint a fine-grained picture of these ethnic groups.

Case reports for embryo banking: for women who want their own

Out of the many challenges in management of female factor infertility, poor responders and low response to stimulation in aged and even younger women, seems to be a common problem. It is very difficult to offer one particular management strategy or treatment protocol for optimum outcome in this group of women of poor responders. In a low resource set up, IVF (In vitro Fertilization) specialist doctors usually face a challenge in treating women with poor/ low ovarian reserve as ovum / gamete donation is considered as a taboo in various sections of society even today. Hence women insist on having an offspring of "their own" and vehemently deny ovum / gamete donations. In this article we discuss 2 cases of poor ovarian reserve retrospectively, who underwent multiple cycles of controlled ovarian hyperstimulation for embryo banking and ultimately achieved pregnancy. Both patients achieved pregnancy with the method of embryo banking. Embryo banking should be considered and discussed. Various articles have discussed the advantages and disadvantages of embryo banking or even oocytes accumulation. The advantages of this technique is patients with poor/low ovarian reserve get a chance to be pregnant with their own oocytes and also have a chance for vitrification of residual embryos. Another advantage in such patients is that the embryos can undergo PGS (Preimplantation Genetic Screening) techniques in cases of suspected genetic disorders. The disadvantage in a low resource set up like India is the cost of the treatment. Nevertheless, embryo banking and accumulation of oocytes should be given as an option for treatment of poor/ low ovarian reserve and could be considered as a ray of hope for all future mothers hoping for a child of "their own".

Torsion of Appendix Epiploicae as a Cause of Abdominal Pain in Postpartum Period – A Rare Case Report

Torsion of an epiploic appendix is a little or difficult to diagnose initially is a rare surgical entity which is capable of mimicking different pathologies. Less than 200 cases of torsion of appendices epiploicae have been reported in literature. Till date, none in my knowledge has been in postpartum period. We report the first case in gynecological literature of a normal delivery being complicated by this rare entity. We present our experience in a 38-year-old pregnant female patient.

Anaplastic Lymphoma Kinase (ALK) Gene Rearrangement Detection Using Fluorescene In-Situ Hybridization (FISH) In Lung Cancer Prognostication

Lung cancer is a leading cause of cancer related death worldwide. It is increasing at a very fast rate in both men and women. Some significant mutations occurring at molecular level in lung adenocarcinoma, like ALK, EGFR, KRAS, MET, and, ALK (anaplastic lymphoma kinase) gene mutations for an ALK encoded transmembrane receptor tyrosine kinase domain and subsequently participating in the progression of Non-Small Cell Lung Adenocarcinoma (NSCLC). Some fusion partner genes involved in this process are EML-4, KLC1, KIF5B and TFG. The ALK-EML-4 rearrangement is the second most common oncogenic mutation in the nonsmall cell lung adenocarcinoma. There is 3-7% ALK mutation occurring in early or never-smokers in accompanying NSCLC. The NSCLC with ALK gene mutation generally do not have EGFR or KRAS gene mutation which are also molecular markers, which get mutated in cancer. For the detection of ALK mutation in NSCLC, different types of techniques like Fluorescence in situ Hybridization (FISH), Immunohistochemistry (IHC) and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) are being used. On the basis of sensitivity and specificity, FISH is gold standard in detecting the mutation when compared with other methodologies like IHC and RT- PCR. However in the Indian setting, FISH is more expensive and hence not available everywhere. In this review the efficacy of these different techniques in detecting ALK mutation and the detailed interpretation of results obtained with FISH has been discussed. For the treatment of ALK/MET mutated NSCLC patients an orally administered drug, crizotinib drug (tyrosine kinase inhibitor) has been approved by Food and Drug Administration (FDA) of United States. Highly sensitive and specific techniques are used for the detection of ALK gene mutation in NSCLC patients which have to be given for crizotinib treatment.

A study on pre-XDR & XDR tuberculosis & their prevalent genotypes in clinical isolates of Mycobacterium tuberculosis in north India.

Background & objectives: Pre-extensively drug resistant (pre-XDR) and extensively drug resistant tuberculosis (XDR-TB) have been areas of growing concern, and are posing threat to global efforts of TB control. The present study was planned to study the presence of pre-XDR and XDR Mycobacterium tuberculosis and their genotypes in clinical isolates obtained from previously treated cases of pulmonary TB. Methods: A total of 219 isolates obtained from previously treated cases of pulmonary TB were subjected to first-line (streptomycin, isoniazid, rifampicin and ethambutol) and second-line (ofloxacin, kanamycin, capreomycin and amikacin) drug susceptibility testing on solid Lowenstein-Jensen medium by proportion method. Genotyping was done for pre-XDR and XDR-TB isolates using 12 loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats (MIRU-VNTR). Results: Multi-drug resistance was observed in 39.7 per cent (87/219) isolates. Pre-XDR and XDR M. tuberculosis isolates amongst 87 multi-drug resistant (MDR) TB isolates were 43 (49.4%) and 10 (11.4%), respectively. Two most dominant genotypes among pre-XDR and XDR M. tuberculosis isolates were Beijing and Delhi/CAS types. Interpretation & conclusions: Resistance to second-line anti-tubercular drugs should be routinely assessed in areas endemic for TB. Similar genotype patterns were seen in pre-XDR and XDR-TB isolates. Beijing and Delhi/CAS were predominant genotypes.

Bilateral gemination of maxillary permanent incisors: a case report

Developmental dental disorders may be due to anomalies in tooth number, size, shape and structure. Gemination and fusion are anomalies of shape with close similarity but with different etiology. Gemination and fusion are anomalies of shape with close similarity but with different etiology. The etiology of germination is not fully understood environmental factors such as trauma, vitamin deficiencies, systemic diseases and certain genetic predisposition have been suggested as possible causes. A 9 year old male patient reported to the department of pedodontics and preventive dentistry Dr R Ahmed Dental College & Hospital with the chief complaint of unaesthetic upper front teeth on clinical examination. It was found that the upper central incisors were markedly large in size with buccolingual grooves present partially separating two halves of crown. The incisors were caries free and there was no history of pain or any discomfort. Since the roots were not completely formed the patient was kept on follow up for the treatment to be delivered.

Modified Root Submergence Technique for Pontic Site Development in Maxillary Anterior Region.

Extraction of tooth leads to alveolar ridge resorption, which is more pronounced in the 1st year after extraction. Ridge resorption results in loss of interdental papillae and creation of unesthetic black triangles. Root submergence technique (RST) is a procedure where the tooth is decoronated and submerged at or below the alveolar bone level. The goal of the technique is to maintain the attachment complex of the tooth, which will prevent the alveolar bone resorption at the site with maintained soft tissue profile resulting in better esthetic results. The present case describes a relatively bloodless and minimally invasive modified RST that can be implemented in routine clinical practice with the predictable esthetic outcome.

Left atrial ball thrombus with acute mesenteric ischemia: Anesthetic management and role of transesophageal echocardiography.

A 62 year old female with severe mitral stenosis, large left atrial ball thrombus and acute mesenteric ischemia emergently underwent mitral valve replacement, left atrial clot removal and emergency laparotomy for mesenteric ischemia. Peri‑operative management issues, particularly, the anesthetic challenges and the role of transesophageal echocardiography are discussed.

Chemistry and bioactivities of essential oils of some Ocimum species：an overview

Essential oils of different species of the genus Ocimum are natural flavouring materials of commercial importance. The data given in current literature are pertaining to the chemical composition of essential oils of different Ocimum species viz., Ocimum basilicum Linn. (alt. Ocimum basilicum var. minimum, Ocimum basilicum var. purpurience), Ocimum campechianum Mill., Ocimum canum Sims. (Ocimum americanum), Ocimum citriodorum, Ocimum gratissimum Linn., Ocimum kilimandscharicum Linn., Ocimum micranthum Willd., Ocimum sanctum Linn., (alt. Ocimum tenuiflorum Linn.), Ocimum selloi Benth., Ocimum trichodon, Ocimum utricifolium from different geographical regions. A considerable difference in chemical composition of a particular species is found, which may be due to their occurrence in different eco-climatic zones and changes in edaphic factors. Attention is also focused on the biological properties of Ocimum oils which are related to their various interesting applications as antimicrobial, antioxidant, repellent, insecticidal, larvicidal, nematicidal and therapeutic (anti-inflammatory, antinociceptive, antipyretic, antiulcer, analgesic, anthelmintic, anticarcinogenic, skin permeation enhancer, immunomodulatory, cardio-protective, antilipidemic) agents.

Endometrial thickness as a test for endometrial cancer in women with abnormal postmenopausal and perimenopausal vaginal bleeding & its histopathological correlation.

Introduction: The menopausal & perimenopausal age are characterized by a deficiency of progesterone and relative hyperestrogenism leading to increased risk of carcinoma endometrium. Transvaginal ultrasonography is used to evaluate the thickness of endometrium in perimenopausal & postmenopausal women presenting with abnormal bleeding per vaginum & its histopathological classification was done. Material & Methods: This retrospective study was carried out in R D Gardi Medical College and Hospital, Ujjain. Seventy five cases were selected from May 2010 - May 2012 and studied in respect to age,parity,socio-economic status, and endometrial thickness in women with abnormal bleeding per vaginum & its relation to histopathology findings of endometrium obtained through D & C. Results:Out of seventy five cases, 49(65.5%) were in perimenopausal age group, and 26(34.5%) in postmenopausal age group. Endometrial thickness greater than 12mm was in 73.4% of perimenopausal and 25.3% of postmenopausal women. In perimenopausal women with abnormal bleeding,histopathology showed‘Benign Hyperplasia’in 51%, ‘Proliferative endometrium’in 26.5%, ‘Secretary endometrium’ in 4.08%, ‘Atrophic endometrium’ in 2.04%, ‘Atypical Hyperplasia’ in 10.2%, andcarcinoma in 6.12%.Whereas in postmenopausal women, Atypical Hyperplasia in 11.4%, carcinoma in 46.12%,benign hyperplasia in 7.6%, proliferative endometrium in 15.33%, secretary endometrium in 7.69%, and atrophic in 11.4%. Conclusion: In majority endometrial thickness by TVS may be helpful in planning investigation protocol and further management.

R659X mutation in the MLH1 gene in hereditary non-polyposis colorectal cancer (HNPCC) in an Indian extended family.

Background & objective: Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome), is a genetically heterogeneous disorder that is believed to account for 2–10 per cent of all the colorectal cancer cases. The disease follows autosomal dominant inheritance pattern with high penetrance (85%) and younger age of onset when compared to patients with sporadic tumours. HNPCC is associated with germ-line mutations in the DNA mismatch repair (MMR) genes namely MLH1, MSH2, MSH6, and PMS2. The present study was aimed at analyzing mismatch repair gene(s) in an extended Indian family satisfying the Amsterdam criteria, and extending the analysis to general population to estimate frequency of the mutations/polymorphisms observed. Methods: A total 12 members of the HNPCC family were studied for genetic investigation. Ethnically matched 250 normal individuals were also included as controls to study the observed mutations/ polymorphisms at population level. Results: The analysis resulted in identification of a 1975C>T mutation in exon 17, resulting in substitution of arginine residue with stop codon at codon 659. 655A>G substitution was also observed, resulting in replacement of isoleucine with valine at codon 219. Similar analysis on 250 ethnically matched control subjects revealed complete absence of R659X mutation, while I219V variant was found in 9.8 per cent of the controls. Interpretation & conclusion: R659X mutation correlates with disease phenotype, and 655A>G locus is highly polymorphic. Our study suggested that R659X substitution was prime cause for the disease phenotype in this family. I219V substitution is a polymorphism having no association with the disease onset or segregation. The family members harbouring this mutation were advised to be under regular medical surveillance.