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There is increasing evidence that dsyregulated epigenetic mechanisms of gene expression are involved in the pathogenesis of attention deficit hyperactivity disorder (ADHD). This review presents a comprehensive summary of the current state of research on the role of epigenetics in the pathogenesis of ADHD. The potential role of epigenetic drugs in the treatment of ADHD is also reviewed. Several studies suggest there are epigenetic abnormalities in preclinical models of ADHD and in ADHD patients. Regarding DNA methylation many studies have reported DNA hypermethylation. There is evidence that there is increased histone deacetylation in ADHD patients. Abnormalities in the expression of microRNAs (miRNAs) in ADHD patients have also been found. Some currently used drugs for treating ADHD, in addition to their more well established mechanisms of action, have been shown to alter epigenetic mechanisms of gene expression. Clinical trials of epigenetic drugs in patients with ADHD are reporting favorable results. These data suggest that abnormal epigenetic mechanisms of gene expression may be involved in the pathogenesis of ADHD. Drugs acting on epigenetic mechanisms may be a potential new class of drugs for treating ADHD.

Objective To determine the prevalence and study the association of ovarian, uterine, and breast cancers with endometriosis. Methods A cross-sectional study of all women with a tissue-proven diagnosis of endometriosis postoperatively in a tertiary care hospital between January 1, 2010, and December 31, 2019, was conducted to determine the prevalence of coexistent malignancy. Patient details were obtained from electronic clinical records. Univariate analysis followed by multivariate analysis was done to find independent risk factors associated with malignancy. Results Out of 800 patients, 104 (13.0%) were found to have coexistent malignancy: ovarian (50, 6.2%); endometrial (33, 4.1%); synchronous ovarian and endometrial (7, 0.9%); and breast (14, 1.8%). Increasing age (odds ratio [OR] 1.13; 95% confidence interval [CI] 1.09-1.16), higher levels of cancer antigen 125 (CA 125) (OR 1.002; 95% CI 1.001-1.005), postmenopausal status (OR 6.2; 95% CI 2.0-19.2), duration of endometriosis over 5 years (OR 4.7; 95% CI 2.5-9.0), and endometriomas larger than 8 cm (area under the curve 0.83) were predictive of coexistent malignancy. Conclusion Endometriosis is associated with an increased risk of ovarian, endometrial, and breast malignancy. Increasing age, postmenopausal status, higher levels of CA 125, larger endometrioma, and long-standing disease are predictive risk factors.

Human papillomavirus (HPV) vaccination offers an excellent prospect for the primary prevention of cervical cancer. The bivalent and quadrivalent vaccines are both available in India. The nonavalent vaccine is licensed but not yet available. However, there still remain controversies regarding the vaccination of older women, immunocompromised females and other special groups. To provide recommendations for HPV vaccination in India. The Federation of Obstetric and Gynecological Societies of India (FOGSI) convened an expert group on cervical cancer prevention to formulate good clinical practice recommendations (GCPR) with respect to vaccine efficacy and safety, target groups, optimal timing and dosing schedules. HPV vaccines are licensed for females aged 9-45 years in India and have been seen to be safe and effective. FOGSI recommends HPV vaccination of all girls15 years of age as the best target group, in whom two-doses at an interval of 6 months, extendable to 18 months, are recommended. Three-doses are recommended in girls15 years of age, immunocompromised persons and sexual assault survivors. Older women and women with abnormal screening results may be vaccinated with an understanding that vaccination does not protect against already acquired infections and screening has to continue. Single-dose vaccination results are promising. Increased awareness is required to reduce vaccine hesitancy. HPV vaccination should be the priority to achieve the elimination of cervical cancer. The introduction of affordable HPV vaccines and reduced dose schedules will improve coverage.

The global increase in cancer burden is a challenge for countries with scarce resources. Amongst all the malignancies, gynaecological cancer still continues to have a high incidence and prevalence leading to significant morbidity and mortality. While a multipronged strategy of decreasing the gynaecological cancer burden is a global priority, one of the key strategies to decrease the morbidity and mortality is to train gynaecological oncology specialists. Most of the developed nations have an established gynaecologic oncology training programme in the form of a well-designed curriculum and skill training. However, in developing countries where the actual disease burden of these cancers is highest, such focused training programmes have only started emerging and evolving over the past two decades. While it is a positive step to initiate such training programmes in a country like India, there are still gaps in the uniformity of curriculum and training. Also, exposure to modern practices in gynaecologic oncology surgery, chemotherapy and technology in radiation oncology, especially brachytherapy, is still insufficient in many centres. This review discusses some of the challenges and opportunities in the still evolving programmes for training gynaecologic oncologists in India.

Primary peritoneal carcinoma (PPC) at presentation often masquerades as epithelial ovarian carcinoma (OC) but behaves different with respect to treatment response, recurrence patterns and has inferior outcomes. The objective of this study is to compare the clinicopathological features and survival outcomes of PPC and OC.Prospectively maintained database of patients presenting to the gynecologic oncology department at a tertiary hospital was reviewed between 1st January 2010 and 31st December 2020. A comparative analysis of high-grade serous stage III/IV PPC and OC was done. Demographics, treatment details, complications and survival outcomes were collected from electronic medical records.151 OC and 69 PPC patients were included. A higher proportion of women with PPC had reduced performance status prior to hysterectomy with salpingo-oophorectomy, a shorter symptom to treatment interval, and large volume ascites. A significantly lower number of women with PPC (4.3 vs. 46.1%; Plt; 0.001) underwent primary cytoreduction, had a lower median surgical complexity score (3 vs. 4; Plt; 0.001) but higher recurrence rates (66.7 vs. 47.0%; P = 0.041) as compared to the patients with OC. The median progression-free survival (PFS) was 18 (15-20) months in PPC and 23 (17-28) months in OC patients (log-rank P = 0.034), while the median overall survival (OS) was similar (44 vs. 48 months; log-rank P = 0.696). The presence of extraperitoneal disease and interval cytoreduction was associated with shorter PFS. Suboptimal cytoreduction and delay in adjuvant chemotherapy beyond 6 weeks post-surgery was associated with reduced OS.PPC is an aggressive disease with lower PFS compared to OC. Commonly presenting with large volume carcinomatosis, it is not amenable for primary cytoreduction, making the usage of neoadjuvant chemotherapy a common practice and pragmatic approach.

Background: The rapid and major advances being made in epigenetics are impacting pharmacology, giving rise to new sub-disciplines in pharmacology, pharmacoepigenetics, the study of the epigenetic basis of variation in response to drugs; and pharmacoepigenomics, the application of pharmacoepigenetics on a genome-wide scale. Methods: This article highlights the following aspects of pharmacoepigenetics and pharmacoepigenomics: epigenetic therapy, the role of epigenetics in pharmacokinetics, the relevance of epigenetics to adverse drug reactions, personalized medicine, drug addiction, and drug resistance, and the use of epigenetic biomarkers in drug therapy. Results: Epigenetics is having an increasing impact on several areas of pharmacology. Conclusion: Pharmacoepigenetics and pharmacoepigenomics are new sub-disciplines in pharmacology and are likely to have an increasing impact on the use of drugs in clinical practice.

Aims: Cervical cancer is one of the leading causes of cancer among women, worldwide. HIV-positive women tend to have persistent infection and infection with multiple human papillomavirus (HPV) types. There is a need for affordable HPV DNA tests as viable alternatives to the existing costly commercial assays. The aim of the study was to establish PGMY-CHUV reverse hybridization assay as a cost-effective tool for HPV genotyping. Study Design: This was a prospective study conducted in a tertiary care centre from March 2011 to July 2012. Subjects and Methods: Fifty cervical brush samples from HIV-infected women and 43 WHO reference samples were tested by both the CHUV assay and linear array (LA). Results: The CHUV assay in comparison to the LA showed a sensitivity of 91%, specificity of 52% and a moderate agreement for all samples that were compared. However, most high-risk HPV types were identified amongst the clinical samples, and the entire range of genotypes in the WHO reference panel was detected. Statistical Analysis: The accuracy indices such as sensitivity, specificity, positive predictive value and negative predictive value were calculated. The level of agreement (kappa value) between the two assays was also calculated. Conclusion: The CHUV assay had an acceptable sensitivity, but it lacked specificity for HPV detection. Despite the lower rates of detection of multiple infections from clinical samples, better results were obtained with the WHO reference samples and the ability of the assay to identify the entire range of genotypes suggests that it can be an efficient tool for genotyping.

To assess the relevance of enlarged cardiophrenic lymph nodes (CPLN) seen on staging CT of ovarian cancer patients. Retrospective cohort study of consecutive patients with primary ovarian malignancy who underwent staging CT between 2013 and 2016. Images were reviewed by two radiologists in consensus. Enlarged CPLN was defined as a short axis diameter ≥ 7 mm. Clinical and imaging findings; management decisions; outcome of cytoreductive surgery and survival were compared between patients with and without enlarged CPLN on staging CT. Enlarged CPLN were found in 42 patients (41.5%) and was significantly associated with higher radiological PCI (p = 0.002); large volume upper abdominal disease (p = 0.001); enlarged lesser omental, periportal and supra-renal para-aortic lymph nodes (p ≤ 0.05); unfavorable sites of disease involvement (p

Enhanced recovery protocols consist of a bundle of concepts including early feeding, opioid-sparing multimodal pain management, and euvolemia, with the overarching goal of hastening postoperative recovery. Enhanced recovery after surgery has been shown to reduce hospital length of stay, reduce costs, and decrease perioperative opioid requirements in benign and oncologic gynecologic surgery. Interventions without supporting evidence of benefit, such as the use of mechanical bowel preparation, routine use of nasogastric tubes and surgical drains, caloric restriction, routine use of intravenous opioid analgesics, and over-vigorous intravenous hydration should be discouraged to improve broader endpoints such as patient satisfaction and overall recovery. Successful implementation requires engagement from a multidisciplinary team including surgeons, anesthesiologists, nurses, and pharmacists.

There is increasing evidence that changes in epigenetic mechanisms of gene expression are involved in the pathogenesis of mood disorders. Such evidence stems from studies conducted on postmortem brain tissues and peripheral cells or tissues of patients with mood disorders. This article describes and discusses the epigenetic changes in the mood disorders (major depressive disorder and bipolar disorder) found to date. The article also describes and discusses preclinical drug trials of epigenetic drugs for treating mood disorders. In addition, nonrandomized and randomized controlled trials of nutritional drugs with effects on epigenetic mechanisms of gene expression in patients with major depressive disorder and bipolar disorder are discussed. Trials of epigenetic drugs and nutritional drugs with epigenetic effects are showing promising results for the treatment of mood disorders. Thus, epigenetic drugs and nutritional drugs with epigenetic effects could be useful in the treatment of patients with these disorders.

Background: The Indian HIPEC registry is a self-funded registry instituted by a group of Indian surgeons for patients with peritoneal metastases (PM) undergoing surgical treatment. This work was performed to • Evaluate outcomes of cytoreductive surgery ± HIPEC in patients enrolled in the registry. • Identify operational problems. Methods: A retrospective analysis of patients enrolled in the registry from March 2016 to September 2017 was performed. An online survey was performed to study the surgeons’ attitudes and existing practices pertaining to the registry and identify operational problems. Results: During the study period, 332 patients were enrolled in 8 participating centres. The common indication was ovarian cancer for three centres and pseudomyxoma peritonei for three others. The median PCI ranged from 3 to 23. A CC-0/1 resection was obtained in 94.7%. There was no significant difference in the morbidity (p = .25) and mortality (p = .19) rates between different centres. There was a high rate of failure-to-rescue (19.3%) patients with complications and the survival in patients with colorectal PM was inferior. A lack of dedicated personnel for data collection and entry was the main reason for only 10/43 surgeons contributing data. The other problem was the lack of complete electronic medical record systems at all centres. Conclusions: These results validate existing practices and identify country-specific problems that need to be addressed. Despite operational problems, the registry is an invaluable tool for audit and research. It shows the feasibility of fruitful collaboration between surgeons in the absence of any regulatory body or funding for the project.

Background and Objectives. Angioleiomyoma is a benign perivascular neoplasm commonly involving subcutaneous tissue of extremities, head, and trunk region. They rarely involve the female genital tract. This study analyses clinicopathological features of 6 cases of uterine angioleiomyoma. Methods. Routine sections of 6 cases were reviewed and immunohistochemical markers namely muscle-specific actin, h-caldesmon, desmin, CD10, WT-1, HMB-45, and melan-A were done. Results. Of the 6 cases, 4 cases had tumor involving the corpus and 2 cases had tumor in the cervix. Grossly, all tumors had a whorled and congested cut surface. Microscopic examination of all the cases revealed circumscribed neoplasms composed of interlacing fascicles of benign perivascular smooth muscle cells with evenly distributed slit-like blood vessels (solid variant) along with vessels exhibiting thick muscular walls with swirling pattern (venous variant). In only 2 cases many dilated vessels were seen (cavernous variant). Immunohistochemically, all cases were positive for muscle-specific actin, h-caldesmon, and desmin. All cases were negative for CD10 and WT-1 ruling out endometrial stromal tumor and were negative for HMB-45 and melan-A ruling out perivascular epithelioid cell tumor (both endometrial stromal tumor and perivascular epithelioid cell tumor have prominent vessels but have different histomorphology). In all cases, surgical excision was curative and there were no intraoperative or postoperative complications. Follow-up of all the cases has been unremarkable. Conclusion. As the World Health Organization has not included angioleiomyoma in the classification of mesenchymal tumors of uterine corpus and cervix, we recommend that it should be included in the classification.

Bipolar disorder (BD) is a common psychiatric disorder which can be devastating to affected patients, if not adequately treated. Although effective drugs are presently available for treating BD, many patients do not respond adequately. There are also problems with the current management of patients with this disorder: drug-resistant BD, rapid-cycling BD and cognitive decline in BD patients despite drug therapy. In this context, new and more effective drugs will be valuable in the clinical management of BD patients.This article discusses the potential of the use of epigenetic drugs in the management of BD. Although several classes of epigenetic drugs are under investigation, at present, most attention is focused on two classes of epigenetic drugs: DNA methyltransferase inhibitors and histone deacetylase inhibitors (HDACis). Several preclinical drug trials of HDACis for the treatment of BD have been conducted.HDACis have shown promising results in preclinical studies of BD. However, the currently available HDACis suffer from acting non-specifically on HDAC isozymes. More isozyme-specific HDACis are likely to have greater efficacy and less toxicity than the current HDACis. It is suggested that efforts should be made to develop such HDACis. Once such HDACis with adequate ability to cross the blood-brain barrier become available, investigators could consider proceeding to clinical trials of HDACis for the treatment of BD.

Cognitive disorders are an important group of disorders affecting the brain for which currently used drugs are often of low efficacy and mainly of symptomatic value. There is increasing evidence suggesting that epigenetic changes in gene expression underlie cognitive disorders. Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs, that reverse epigenetic changes in gene expression. At present most work on epigenetic drugs focuses on two types of drugs: histone deacetylase (HDAC) inhibitors, and drugs targeting DNA methylation. This article describes the role of epigenetic drugs in treating cognitive disorders, focusing on Alzheimer's disease, Huntington's disease, and Parkinson's disease. Epigenetic drugs may improve the clinical management of patients with cognitive disorders.

Background: Epigenetics refers to the study of heritable changes in gene expression not involving changes in DNA sequence and is presently an active area of research in biology and medicine. There is increasing evidence that epigenetics is involved in the pathogenesis of psychiatric disorders. Aims and Methods: Several studies conducted to date have suggested that psychosocial factors act by modifying epigenetic mechanisms of gene expression in the brain in the pathogenesis of psychiatric disorders. Such studies have been conducted both on brain tissues and also using peripheral tissues as substitutes for brain tissues. This article reviews such studies. Results and Conclusion: Epigenetic mechanisms of gene expression in the brain appear to link one individual with another in the context of social psychiatry. Epigenetics appears to be of major importance to the field of social psychiatry.

DNA methylation is a major epigenetic mechanism that leads to inhibition of gene transcription and is known to be involved in the pathogenesis of cancer. The effectors of DNA methylation are DNA methyltransferases (DNMTs) that catalyze either de novo or maintenance methylation of hemimethylated DNA after DNA replication. DNA methylation patterns in cancer are distorted, with three ways by which DNA methylation contributes to cancer: hypomethylation of the cancer genome, focal hypermethylation of the promoters of tumour suppressor genes, and direct mutagenesis. Drugs that inhibit DNMTs are proving to be useful in the treatment of cancer with a few such drugs approved for clinical use. These drugs include nucleoside inhibitors, non-nucleoside inhibitors, oligonucleotides, and noncoding RNAs that target messenger RNAs of genes encoding DNMTs. The major value of DNMT inhibitors could be that at low doses they can induce the re-expression of aberrantly silenced tumour suppressor genes, allowing cancer cells to revert to a normal phenotype and/or reacquire cellular pathways needed for cell cycle regulation and apoptosis induction. They could also be useful in combination with other anticancer drugs.

Hypothesis:Assessment of the prevalence and type distribution of human papillomavirus (HPV) in squamous cell carcinomas (SCC) of the cervix across India was undertaken to estimate the impact of available prophylactic HPV-L1 vaccines in the country and to find out additional types that might be needed to be incorporated in second-generation vaccines.Methods:High-risk (HR) HPVs were genotyped from 667 histopathologically confirmed cases of SCC from 6 different centers representing 4 regions across India: Advanced Centre for Treatment, Research and Education in Cancer, Mumbai; All India Institute of Medical Sciences, New Delhi; Cancer Foundation of India, Kolkata; Christian Medical College, Vellore; Kidwai Memorial Institute of Oncology, Bangalore; and Regional Cancer Center, Thiruvananthapuram. Human papillomaviruses in tumor biopsies were analyzed by Xcytonscreen HPV based on PGMY09/11 multiplex polymerase chain reaction and reverse dot blot assay.Results:Overall viral prevalence across India was not different; 92.1% of 667 cases harbored HPV; 8% were negative. Infection with single HR type was seen in 86.8%: predominant types being HPV-16 followed by HPV-18, -45, -73, -31, -56, -52, -58, -59, -33, -68, -51, -35, -26, and -39. Human papillomavirus types 16/18-positive fraction formed 79.6%; other types comprised 12.4%.Conclusions:Prophylactic HPV-16/18-L1 vaccines would provide greater than 75% protection against SCC in India. Ranking and frequencies of non-16/18 types were different from earlier reports. Hence, considering the possibility of promotion of persistence of nonvaccine types in the vaccinees due to original antigenic sin and the lack of organized screening programs in India, a broad-based vaccine approach would be appropriate.

Objective. HPV infection is a necessary but insufficient cause of cervical cancer. The significance of HPV DNA in blood however is debatable because of variable detection rates due to the differences in the methodology used. The aim of this study was to detect and quantitate HPV 16 and 18 plasma viremia in women with cervical neoplasia. Methods. HPV DNA was detected in cervical tissue using consensus PGMY primers and genotyped using reverse line blot hybridization. HPV 16 and 18 quantitation in tissue and detection and quantitation in plasma was performed using sensitive real time PCRs targeting E6/E7 region of HPV 16/18 genome respectively. Results were correlated with viral loads in corresponding tissue and with clinical disease stage. Results. Viremia was detected in 56.4% of HPV 16 positive women and 20% of HPV 18 positive women. The prevalence of HPV 16 DNA in plasma increased with advancing disease stage ( p =0.001), although HPV 16 absolute plasma viral load was not significantly associated with advancing disease stage ( p =0.281). There was no correlation between absolute plasma viral load and viral load in corresponding cervical tissue (Spearman's rho=0.184, p =0.187). The prevalence of HPV 18 viremia and absolute HPV 18 plasma viral load were not associated with advancing disease stage ( p =0.620, p =0.508). Conclusion. The presence of HPV 16 in plasma is a marker of advancing cervical disease.

Objective: Human papillomavirus (HPV) contributes to the development of cervical cancer. We hypothesize that HPV DNA and messenger RNA (mRNA) levels may be associated with increasing stages of cervical cancer. Materials and Methods: In this study, we measured DNA and mRNA viral loads of the most common high-risk HPV-16 and HPV-18 in cervical biopsy tissue of women with cervical neoplasia using real-time polymerase chain reaction. Results: Median HPV-16 and HPV-18 DNA viral loads were 58,342 copies and 71,367 per 5000 cells, respectively. We found that HPV-16 and HPV-18 DNA levels did not correlate with advancing tumor stage (P = 0.977 and P = 0.263). Messenger RNA transcripts were detected in 81 (86%) of HPV-16 DNA-positive women and in 16 (84.2%) of HPV-18-positive women. Median HPV-16 and HPV-18 transcript copy numbers were 5964 and 6158, respectively. In women with squamous cell carcinoma, HPV-16 mRNA loads showed an increasing but not statistically significant trend with advancing disease stage (ρ = 0.231, P = 0.058). Conclusions: We conclude that HPV mRNA levels and not DNA levels may be associated with advancing stages of cervical cancer.

OBJECTIVES: The hypothesis to be tested was that the prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasia would be significantly higher in HIV seropositive women as compared with seronegative controls. Secondary aims were to determine the risk factors for HPV and cervical intraepithelial neoplasia and the HPV types in HIV-positive women. MATERIALS AND METHODS: A cross-sectional study of women 18 to 49 years old was done. Seventy-five women who were HIV seropositive and 58 seronegative women of whom 27 had HIV-positive partners participated in the study. A Pap smear and a cervical swab for HPV were done. Women with Pap smear abnormality underwent colposcopy and large loop excision procedures if indicated. RESULTS: Ten (13.3%) HIV-positive women had high-grade squamous intraepithelial lesion as compared with 2 (3.4%) seronegative women (odds ratio [OR] 4.3; 95% CI = 0.9-41.7; p =.048). Among the HIV-positive women 28 (37.3%) had high-risk HPV whereas only 9 (15.5%) had high-risk HPV among seronegative women (OR 3.2; 95% CI = 1.3-8.3; p =.009). Among women who were positive for high-risk HPV the HIV-positive women were significantly more likely to have more than 1 HPV type (OR 7.4; 95% CI = 1.4-43.7; p =.005). Women who had coitus at less than 18 years of age were more likely to have high-risk HPV infection (OR 2.9; 95% CI = 1.2-6.2; p =.013) even after controlling for HIV status. CONCLUSIONS: HIV-positive women have a higher risk for multiple HPV infections as compared with seronegative women. Behavioral factors dominate HIV in determining HPV infections and resultant cervical neoplasia.

Summary Study of hantavirus infections in India is in its early stages. As early symptoms of hantavirus disease can be non-specific and the diagnosis confirmed only by laboratory testing, use of appropriate diagnostic tools is important. To improve the diagnosis of hantavirus infections in India, commercial ELISA systems followed by indirect immunofluorescence assays were used to detect anti-hantavirus IgM and IgG in samples from patients with acute febrile illness. Of 347 patients tested, 5.2% showed serological evidence of hantavirus infection. Sequences obtained from patients showing molecular evidence of hantavirus infection were related to Hantaan virus. In the absence of μ-capture ELISA, we recommend the use of combination testing systems in areas non-endemic for hantavirus infections. In India there is an increased risk of rodent-borne infections and the differential diagnosis of undifferentiated febrile illness should include hantavirus infection.

Objective To determine if human papillomavirus (HPV) DNA in pelvic lymph nodes or plasma of women with early-stage cervical cancer is a marker for recurrence. Materials and methods Twenty-eight women undergoing radical hysterectomy for cervical cancer stage IB had HPV DNA testing in cervical tissue, plasma, and the largest lymph nodes. Human papillomavirus genotyping was done by restriction fragment length polymorphism/line blot assay. Human papillomavirus quantitation was performed with specific primers for types 16 and 18. Women were followed up to determine recurrence of disease. Results Human papillomavirus DNA was detected in cervical tumor tissue from all the women. Twenty-two women had genotype 16, 5 women had HPV18, and 1 had type 31. Human papillomavirus viral load in cervical biopsies significantly correlated with the viral loads in the lymph nodes (r = 0.97; p = 0). Nine women had nodal metastasis, but only 3 of them had HPV DNA in lymph nodes. Recurrence was seen in 4 women, of whom 3 had tumor in the lymph nodes at initial surgery and none had HPV. Conclusions Human papillomavirus DNA can be detected in lymph nodes even when they are not obviously involved by tumor metastasis. This study did not show plasma or lymph node HPV DNA to be a prognostic marker.

Schizophrenia is an important psychiatric disorder for which effective drugs are available. However, there are problems with current drug therapy of schizophrenia in that some patients do not respond adequately. Moreover, some patients show treatment resistance and some patients show cognitive decline despite treatment. Hence new and effective drugs will be useful for the treatment of this disorder. Since there is increasing evidence that epigenetic mechanisms of gene expression are defective in schizophrenia, drugs that correct epigenetic defects, epigenetic drugs, could be useful in the treatment of this disorder. This paper discusses preclinical epigenetic models for screening epigenetic drugs for schizophrenia. It also discusses how such models could be useful for the discovery and development of such drugs.

Purpose: Emergence of drug resistance following HIV prophylaxis has an important impact on ART program. Objective: To investigate the emergence of drug resistance in HIV-1 infected pregnant women. Materials and Methods: Fifty-three HIV-1 infected pregnant women who had received 4-12 weeks of antenatal AZT followed by Nevirapine during delivery and Combivir [AZT + 3TC] for 1 week postpartum (group-1, n = 48) or who come at the time of delivery and received Nevirapine followed by Combivir for 1 week (group-2, n = 5) were recruited. Samples were collected prior to the start of the prophylaxis and 5-8 weeks postpartum. In addition, a third sample was collected between 26-65 weeks postpartum from 7 women. Amplification of HIV-1 pol gene and drug resistance analysis was done. Result: Two (3.8%) women in group-1 showed transmitted drug resistance and they continued to show this even at 6 weeks postpartum. One (2%) woman from group-1 showed a mutation after 6-8 weeks of prophylaxis. Among the samples collected between 26-65 weeks postpartum, 3/7 (43%) showed mutations and all these women belong to group-1. Women belonging to group-2 didn′t show mutation prior to or following prophylaxis. Conclusion: In contrast to the available data among pregnant women with ART prophylaxis, our data showed reduced frequency of mutations following 5-8 weeks of postpartum but an emergence of mutation later (26-65 weeks). The addition of Combivir with the single dose Nevirapine during delivery and the early stage of the disease with higher CD4 counts could be the reasons for this.

Objective: The aim of this study was to assess long-term effects for women following the use of magnesium sulphate for pre-eclampsia. Design: Assessment at 2-3 years after delivery for women recruited to the Magpie Trial (recruitment in 1998-2001, ISRCTN 86938761), which compared magnesium sulphate with placebo for pre-eclampsia. Setting: Follow up after discharge from hospital at 125 centres in 19 countries across five continents. Population: A total of 7927 women were randomised at the follow-up centres. Of these women, 2544 were not included for logistic reasons and 601 excluded (109 at a centre where

In a cross-sectional study performed between June 2001 and November 2003, the HPV 16 E6 gene of 50 women with cervical neoplasia and 20 cytologically normal women (‘controls’) was sequenced following amplification by PCR. The 350T to G variant was seen in 35 (70%) of 50 patients' isolates while it was seen in only 3 (15%) of the 20 isolates from the ‘controls’. The higher occurrence of the 350G variant among the patients was statistically significant (P

Background: HPV DNA has been detected in metastatic tumour and HPV plasma viraemia may indicate a poor prognosis and a high risk for metastasis. Objective: Detection of HPV DNA in plasma of patients with cervical carcinoma. Study design: A cross-sectional study was done, wherein cervical biopsies and plasma samples were collected from 58 women with invasive cervical carcinoma, 10 women with cervical intraepithelial neoplasia (CIN) and 30 control women in the same age range. Polymerase chain reaction (PCR) was employed to detect the presence of HPV DNA. Samples positive for HPV DNA were typed by restriction fragment length polymorphism (RFLP). To confirm that the HPV sequence in plasma was identical to that in tissue, sequencing was done on all the paired plasma and tissue samples. Results: All the 30 paired cervical tissue and plasma samples from the controls were negative for HPV DNA. HPV DNA was detectable in cervical tissues of 55 (94.8%) of 58 patients with invasive cervical carcinoma and in all 10 patients (100%) with CIN and in eight (11.8%) of the total 68 plasma samples from patients. All eight plasma samples were from women with invasive cervical carcinoma with three each in stages IIIB and IV and one each in stages IIB and IB, respectively. Of the eight positive samples, seven were typed as HPV-16 and 1 as HPV-58. HPV types detected in cervical tissue and plasma pairs from these eight patients correlated as revealed by RFLP and sequencing. A patient with stage IB cancer had detectable HPV DNA in the external iliac lymph node, removed at Wertheims hysterectomy, which was histopathologically free of tumour. The HPV type in the node, was the same as that present in the paired tissue and plasma sample. Conclusions: HPV DNA is detectable in the plasma of patients with advanced cervical cancer.

Objectives. Specific nucleotide variations in the E2 DNA sequence were looked for in samples with an intact human papillomavirus (HPV) 16 episomal E2 DNA. Methods. Ninety-two women, 76 with invasive cervical carcinoma and 16 with cervical intraepithelial neoplasia (CIN) were recruited. HPV DNA typing was performed by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Intact episomal E2 DNA of HPV 16 was detected by PCR. Important nucleotide variations in samples with amplifiable E2 DNA were detected by RFLP. Nucleotide sequencing was performed on representative samples to confirm RFLP findings. Results. A total of 89 (96.7%) women were positive for HPV DNA. Of these, 56 (63%) were positive for HPV 16, and of these, 38 (68%) were positive for intact episomal HPV 16 E2 DNA while 18 (32%) were negative. Samples with intact episomal HPV 16 E2 DNA sequences were grouped into four different digestion profiles I to IV based on RFLP patterns. Digestion patterns revealed absence of any sequence variations in samples with digestion profile I and presence of a 2983 A-G variation in those with profile II. Samples with digestion profiles III and IV revealed three variations in the hinge region (3516 C-A, 3538 A-C, 3566 T-G) and two in the DNA binding domain (3684 C-A, 3694 T-A) of the E2 sequence. Sequencing performed on representative samples confirmed RFLP findings. Conclusions. PCR-RFLP helped in the identification of important HPV 16 E2 sequence variations, circumventing the need for sequencing. The presence of the nucleotide variations in positions that could alter the biological and immunological functions of the E2 protein combined with its increased occurrence in this study bring out the importance of these variations.

OBJECTIVE: To determine the prevalence of physical violence during pregnancy and the factors associated with it. DESIGN: A population-based, multicentre, cross sectional household survey. SETTING: Rural, slum and urban non-slum areas of Bhopal, Chennai, Delhi, Lucknow, Nagpur, Trivandrum and Vellore, in India. PARTICIPANTS: A total of 9938 women who were 15 to 49 years of age and living with a child younger than 18 years old. METHODS: Probability proportionate to size sampling of households was performed in three strata. Trained field workers administered a structured questionnaire. Women who reported domestic violence were asked about violence during pregnancy. Outcome variables included six violent behaviours: slap, hit, kick, beat, use of weapon and harm in any other way. Moderate to severe violence was defined as experience of any one or more of the following behaviours: hit, beat or kick. Odds ratios were calculated for risk and protective factors of violence during pregnancy using logistic regression. MAIN OUTCOME MEASURES: Physical spousal violence. RESULTS: The lifetime experience, during pregnancy, of being slapped was 16%, hit 10%, beat 10%, kicked 9%, use of weapon 5% and harmed in any other way 6%. Eighteen percent of women experienced at least one of these behaviours and 3% experienced all six. The overall prevalence of moderate to severe violence during pregnancy was 13%. Logistic regression showed that the factors determining whether a woman experienced moderate to severe violence during pregnancy were: husband accusing wife of an affair (OR 7.1; 95% CI 5.1 to 9.8), dowry harassment (OR 4.1; 95% CI 2.8 to 6.1), husband having an affair (OR 3.7; 95% CI 2.8 to 4.8), husband being regularly drunk (OR 3.2; 95% CI 2.6 to 4.1), low education of husband (OR 2.8; 95% CI 1.4 to 5.6), substance abuse by husband (OR 2.6; 95% CI 1.3 to 5.5), no social support (OR 1.8; 95% CI 1.1 to 3.0), three or more children (OR 1.6; 95% CI 1.2 to 2.1) and household crowding (OR 1.1; 95% CI 1.0 to 1.2). CONCLUSION: In this study, 12.9% of women experienced moderate to severe physical violence during pregnancy. Suspicion of infidelity, dowry harassment, husband being regularly drunk and low education of husband were the main risk factors for violence during pregnancy. Language: en

The objective of the study was to determine the community prevalence of genital syndromes in women and evaluate the syndromic management of vaginal discharge in this setting. A representative sample for the state of Tamilnadu was chosen using probability proportional to size cluster technique. Thirty clusters were selected from three districts. Demographic, sexual behaviour, risk factors, clinical and laboratory data were collected from the selected population using a structured questionnaire. Direct smear examination for Trichomonas vaginalis, culture for Neisseria gonorrhoeae and Haemophilus ducreyi, serological tests for syphilis (RPR and TPHA), hepatitis B (Hbs Ag ELISA), IgM and IgG antibodies to HSV2 (Novum diagnostics, Germany) and PCR test for detection of C. trachomatis from urine were done. There were 1157 women in the selected population. On examination, vaginal discharge was the most common genital syndrome (38.4%). The sensitivity, specificity, positive and negative predictive value of vaginal discharge as a marker for STD in women was found to be 43.3%, 61.6%, 10.7% and 91.1%, respectively. We concluded that treatment on the basis of syndromic management would result in over-treatment of 90% of women with vaginal discharge.

This study was an attempt to determine the prevalence and significant risk factors associated with severe psychological violence in 6 WorldSAFE sites. The respondents were 3975 women aged 15-49 years and residing in selected urban areas in Chile, Egypt, the Philippines and India. Using a standard instrument translated locally, psychological violence was measured using items indicating the following domains: verbal abuse, fear and separation. A woman who had experienced severe psychological violence had admitted that she had experienced any of the above-mentioned behaviors '3 or more times' in her lifetime (lifetime prevalence) or with her current partner during the past 12 months (current prevalence). The results showed a lifetime prevalence of severe psychological violence ranging from 10.5% of women in Egypt to about 50% in Chile and Trivandrum, India. Verbal abuse was most common among the different behavioral indicators. A woman's mental health status and partner alcohol use were found to be the common significant risk factors. Recommendations were made to facilitate efforts to address severe psychological violence in developing countries.

Background: The viral transforming genes E6 and E7 of human papillomavirus (HPV) 16 cause the degradation of tumor suppressor proteins. Expression of these oncoproteins increases following the integration of viral DNA into the host cell, resulting in the disruption of the E2 open reading frame (ORF). Aim: To detect and correlate HPV-16 oncogene transcripts and HPV-16 E2 DNA in cervical biopsies obtained from women (n = 68) with cervical neoplasia. Methods: HPV-16 E6/E7 transcript and HPV-16 E2 DNA detection was performed on the cervical biopsies of 42 women positive for HPV-16 (36 with invasive cervical carcinoma and 6 with cervical intraepithelial neoplasia [CIN]). PCR was used to detect HPV DNA in cervical biopsies then restriction fragment length polymorphism (RFLP) was used to type the HPV DNA. Reverse-transcription (RT)-PCR for HPV-16 E6/E7 oncogene mRNA transcripts and a PCR to detect the HPV-16 E2 DNA was performed on HPV-16-positive samples. Results: HPV-16 E6/E7 mRNA transcripts were not detected in any of the CIN I or II biopsies, but were detected in all cases of CIN III and invasive cancer in different combinations (E6 alone, E6*I, E6*I/E6*II, E6/E6*I/ E6*II) except for one patient with stage IIB cancer treated with radiotherapy. The incidence of episomal E2 DNA was high in this study with 52.4% of the samples positive for episomal E2. It was even detected in patients with advanced stage cancer with 50%, 42%, and 66.6% of samples positive in stages IIB, IIIB, and IV, respectively. Discussion: HPV-16 E6/E7 mRNA oncogene transcripts, in various combinations, were uniformly detectable in the majority of the high-grade cervical lesions examined. Intact episomal E2 DNA was seen in a high proportion of samples, even from advanced cervical lesions. Conservation of the E2 gene with concomitant expression of viral oncogenes in advanced cervical lesions may point to alternate mechanisms, other than integration, bringing about the enhanced expression of E6/E7 mRNA. Conclusions: This study suggests that the detection of the HPV-16 oncogene transcripts could serve as an indicator for assessing the prognosis of patients on radiotherapy. The majority of HPV-16-positive cervical neoplastic lesions are transcriptionally active and express the oncogene transcripts. The increased occurrence of intact HPV-16 episomal E2 DNA in advanced lesions further substantiates the fact that the disruption of E2 ORF is not mandatory for increased oncogene expression. Thus, this study underscores the significance of investigating alternative mechanisms of oncogene expression in HPV-16.

There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses the potential use of epigenetic drugs in the treatment of MS, focusing on DNMTi and HDACi. Preclinical drug trials of DNMTi and HDACi for the treatment of MS are showing promising results. Epigenetic drugs could improve the clinical management of patients with MS.

Objective To determine the effect of a nicorandil congener, SG-209 on the myometrium. Study design Isolated strips of myometrium, from nine women who underwent hysterectomy, were made to contract with 55 mM KCl before and after incubation with three concentrations of SG-209 (1.5, 3.0 and 10 μM). The mean height of contraction and the area under the curve were analysed using a non-parametric test. Results At a 10 μM concentration, SG-209 significantly decreased the mean area under the curve from 10.8 to 2.5 cm 2 ( p Conclusion SG-209 significantly relaxes the human non-pregnant myometrium. Along with its congener, nicorandil, it may be useful in clinical conditions that require uterine relaxation.

We measured the impact of hypertensive disorders in pregnancy (chronic hypertension, pregnancy-induced hypertension, and eclampsia) on birthweight, gestational duration, and small-for-gestational-age births. We employed a retrospective cohort design using North Carolina birth certificate data for the years 1988-1990, with the analyses based on nearly 300,000 pregnancies. Women noted to have eclampsia during pregnancy had a substantially greater risk of delivering very-low-birthweight infants (birthweight < or = 1,499 gm; risk difference (RD) = 6.7%) and moderately-low-birthweight infants (1,500-2,499 gm; RD = 14.6%), and very preterm (gestational age < 33 weeks; RD = 7.1%) and moderately preterm (33-36 weeks; RD = 9.3%) births, compared with women without hypertension. Corresponding risk differences for these outcomes were 1.9% and 5.1% for very low and moderately low birthweight, and 1.6% and 3.0% for very preterm and moderately preterm for women with chronic hypertension. Risk differences were of similar magnitude for women with pregnancy-induced hypertension for these outcomes. Hypertensive disorders in pregnancy were associated with small-for-gestational-age infants, with risk differences of 5.1%, 3.5%, and 9.2% for chronic hypertension, pregnancy-induced hypertension, and eclampsia, respectively. The patterns of risk were similar for preterm births due to spontaneous onset of labor and those due to other precipitating events. We observed similar patterns for black and white women. Control for confounders through multivariable logistic regression models did not alter the observed patterns. In spite of the limited data quality, we found that hypertensive disorders in pregnancy substantially increase the risk of low birthweight, preterm births, and small-for-gestational-age births.

Objectives: To determine the pattern of intrauterine growth and the gestation at birth of Indian fetuses. Method: One hundred twenty consecutive women who had reliable menstrual histories, low-risk pregnancies and who were booked for delivery at the Christian Medical College Hospital, Vellore, before 20 weeks' gestation were recruited to the study. Ultrasound fetal biometry was carried out at 4-weekly intervals from 20 weeks and at weekly intervals after 36 weeks until delivery. Results: Growth patterns of fetal biparietal diameter and femur length were comparable to those reported in Western populations. However there was a lag in growth of abdominal circumference (AC) after 28 weeks in comparison with that reported in Western populations. The median gestation at delivery following spontaneous labor was 39 weeks. No association was observed between rate of growth of AC and gestation at birth. Conclusion: Slowing of growth of the fetal AC after 28 weeks and a shorter length of gestation result in the birth of smaller babies in this ethnic group. The implications of these findings are discussed.

There is evidence suggesting that the primary (idiopathic) mental disorders are due to epimutations involving genes that determine the structure of the brain. Although in the past it has been suggested that the genes underlying the primary mental disorders may be unidentifiable, recent developments in neuroscience suggest otherwise. This paper outlines various epigenetic strategies that may help identify the genes underlying these disorders.

Summary This study was conducted to determine whether the atypical opioid analgesic tramadol inhibits the contractility of isolated non-pregnant human myometrium. Ten strips of non-pregnant human myometrium stimulated with 55 mm potassium chloride (KCl) were treated with three concentrations (30, 100 and 300 μm) of tramadol to test for any inhibitory effect of tramadol. The effects of concurrent administration of the s adrenoceptor antagonist propranolol (1 μm), the guanylyl cyclase and nitric oxide synthase inhibitor methylene blue (20 μm) and the opioid receptor antagonist naloxone (100 μm) with tramadol were also studied. Tramadol caused a concentration-dependent inhibition of KCl-induced myometrial contractility, which was statistically significant at all three concentrations of tramadol used. Propranolol significantly reversed the inhibitory effect of 100 μm tramadol on KCl-induced myometrial contractility but not that of 300 μm tramadol. Neither methylene blue nor naloxone reversed the inhibitory effect of tramadol on KCl-induced myometrial contractility. These results suggest that tramadol inhibits KCl-induced contractility of isolated human myometrium. They also suggest that tramadol relaxes the myometrium due to stimulation of s1 adrenoceptors. However, the concentrations of tramadol required to relax the myometrium were high and likely to be attained at toxic doses, rather than therapeutic doses, of tramadol.

There is increasing evidence that epigenetics plays a major role in the pathogenesis of the idiopathic mental disorders. This article comments on the role of epigenetics in the pharmacotherapy, psychotherapy and nutritional management of these disorders.There are two classes of epigenetic drugs undergoing trials for treating the idiopathic mental disorders: DNA methyltransferase and histone deacetylase inhibitors. These drugs may fulfil the need for newer and more effective drugs for treating these disorders. Psychotherapy could exert its therapeutic effect in idiopathic mental disorders through epigenetic mechanisms. As nutrients like folic acid and vitamin B(12) can influence an individual's epigenome, especially early in life, abnormal intakes of such agents may be involved in the pathogenesis of the idiopathic mental disorders. Hence, adequate emphasis should be given to such factors in an individual's nutrition, especially early in life. Nutrients such as L-methylfolate and S-adenosylmethionine may also be useful in nutritional therapy of these disorders.Epigenetics plays a key role in the pathogenesis of the idiopathic mental disorders. Due emphasis should be given to epigenetic mechanisms in the pharmacotherapy, psychotherapy and nutritional management of these disorders.

Objective: To study the effect of the extraamniotic Foley catheter as a cervical ripening agent prior to induction of labor. Method: A descriptive study was carried out on 187 patients who had labor induced following cervical ripening with the extraamniotic Foley catheter. There were 99 nulliparas and 88 multiparas whose labor outcomes were analyzed separately. Results: The mean change in the modified Bishop score was 3.7 for nulliparas and 3.3 for multiparas. The induction-delivery interval was 8.7 h for nulliparas and 5.5. h for multiparas. Conclusion: The Foley catheter was found to be an effective agent for cervical ripening in both primiparas and multiparas and its use was not associated with any complications.

Objective This study aims to determine the incidence, timing, and risk factors of clinical venous thromboembolism. Methods A cohort of patients who had major gynecologic cancer surgery between 1998 and 2008 was identified. Secondarily, a nested case–control design wherein patients who had clinical VTE within 90days after surgery were considered cases. Controls were matched on age, race, surgery date, and cancer site. Risk factors were evaluated for VTE within 90days, and late VTE between 8 and 90days. Results We identified 4158 women, 18years or older, without a history of recent thrombosis. We observed 126 cases of clinical VTE within 90days of surgery (incidence 4%) of which 96 (76%) occurred after post-operative day 7. In a multivariable model including age, ASA, BMI, race, and site of cancer, only ovarian cancer was a significant predictor for VTE within 90days (HR 2.8; 95% CI 1.6, 5.0). In the nested case–control study, we identified hospital stay≥5days (OR 2.8; 95% CI 1.5, 5.1) and prior VTE (OR 2.6; 95% CI 1.1, 6.1) as significant risk factors for VTE within 90days. Only hospital stay ≥5days (OR 2.5; 95% CI 1.3, 4.7) was significantly associated with late VTE between 8 and 90days. Conclusion In gynecologic cancer patients, over 75% of VTE are detected more than 7days after surgery. Patients with ovarian cancer, prolonged hospitalization, or a history of VTE are at highest risk of developing clinical VTE. Such patients would be optimal candidates for clinical trials evaluating extended VTE prophylaxis.

This study investigated the ability of the antihypertensive drug minoxidil to inhibit potassium chloride (KCl)-induced contractility of the isolated human myometrium. Twelve strips of myometrium obtained from 12 patients who underwent hysterectomy were triggered to contract with 55 mM KCl before and after incubation with 3 concentrations (1, 3 and 10 microM) of minoxidil. The percent inhibition by minoxidil on the extent of contraction, and the area under the contractile curve of KCl-induced contraction of the myometrial strips was determined. Furthermore, the effect of 10 microM glibenclamide on the inhibition generated by 3 microM minoxidil on KCl-induced contractility was studied. It was found that minoxidil produced a concentration-dependent inhibition of KCl-induced contractility of the myometrium and that glibenclamide reversed this inhibitory effect. These results suggest that the inhibitory effect of minoxidil on isolated human myometrium contractility may prove useful in clinical conditions requiring relaxation of the myometrium.