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Tumour budding is an established prognostic factor in various solid tumours, including colorectal cancers and oral squamous cell carcinomas. However, its role is unclear and needs to be defined for squamous cell carcinoma of the lung (LSCC). Hence, we conducted a systematic review and meta-analysis investigating the prognostic role of tumour budding in LSCC. PubMed, Embase and Scopus were searched for peer-reviewed literature investigating the association between tumour budding and survival outcomes or clinicopathological variables in LSCC. The primary outcomes were pooled estimates for overall and recurrence-free survival with hazard ratio (HR) as the effect measure. The association between tumour budding and clinicopathological parameters was also investigated. Of 243 studies, nine were included, comprising 2546 patients. An increased risk of death [HR = 1.76, 95% confidence interval (CI) = 1.50-2.05, P < 0.00001] and recurrence (HR = 1.37, 95% CI = 1.12-1.68, P = 0.003) was evident in patients with high-grade tumour budding. Sensitivity and subgroup analyses revealed consistent results. Pathological stage II, lymph node metastasis, lymphovascular and pleural invasion were associated with high-grade tumour budding. Tumour budding is a new and promising prognostic factor in patients with LSCC. However, pervasive heterogeneity and publication bias reduces the credibility of these findings and the applicability of tumour budding in clinical practice. Future studies are required to standardise reporting on tumour budding in LSCC., (© 2022 John Wiley & Sons Ltd.)

Background: Human papillomavirus (HPV) is a sexually transmitted infection and a causative agent of cervical cancer. It is common in adolescent girls and young women, and the majority of infections are transient and asymptomatic. In Botswana, there are currently no data on the HPV prevalence against which the impact of prophylactic HPV vaccines can be measured., Objectives: To establish a baseline HPV prevalence in an unvaccinated cohort of young women., Methods: Women aged ≥18 years were recruited from the University of Botswana between September 2016 and May 2020. Demographic and behavioural characteristics of participants were collected. Subsequently, cervicovaginal swabs were obtained and tested for HPV using polymerase chain reaction-restriction fragment length polymorphism. We determined the prevalent HPV types, and evaluated the risk factors associated with HPV positivity., Results: A total of 978 young women were recruited. Overall, there were 589 (60.2%) participants with HPV infection and 12 (1.2%) with HIV. The median (interquartile range) age of the study participants was 19 (18 - 20) years. Multivariate logistic regression analysis showed that significant factors associated with HPV positivity were sexual activity (adjusted odds ratio (aOR) 2.06; 95% confidence interval (CI) 1.49 - 2.63; p&lt;0.001), number of sex partners ≥3 (aOR 2.10; 95% CI 1.39 - 3.18; p&lt;0.001), and smoking (aOR 2.00; 95% CI 1.26 - 3.20; p=0.004)., Conclusion: Our results demonstrate for the first time the prevalence of HPV in unvaccinated young women in Botswana. We found a high prevalence of HPV infection, with statistical differences with different risk factors. This finding supports the need for HPV vaccination strategies for females prior to sexual debut to reduce the future burden of cervical cancer in Botswana.

Objectives: To estimate the association between chronic hypertension and perinatal mortality and to evaluate the extent to which risks are impacted by preterm delivery., Design: Cross-sectional analysis., Setting: United States, 2015-18., Population: Singleton births (20-44 weeks of gestation)., Exposure: Chronic hypertension, defined as elevated blood pressure diagnosed before pregnancy or recognised before 20 weeks of gestation., Main Outcomes and Measures: We derived the risk of perinatal mortality in relation to chronic hypertension from Poisson models, adjusted for confounders. The impacts of misclassification and unmeasured confounding were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association., Results: Of the 15 090 678 singleton births, perinatal mortality rates were 22.5 and 8.2 per 1000 births in chronic hypertensive and normotensive pregnancies, respectively (adjusted risk ratio 2.05, 95% CI 2.00-2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although causal mediation analysis revealed that most of the association of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term and late term gestations, suggesting that a planned early term delivery at 37-38 6/7  weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84-90%) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension, were preventable., Conclusions: Chronic hypertension is associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates., Tweetable Abstract: Maternal chronic hypertension is associated with increased risk for perinatal mortality, largely driven by preterm birth., (© 2021 John Wiley & Sons Ltd.)

Cervical cancer is one of the most common cancers in developing nations. It has had a tremendous impact on the lifetime of millions of women over the last century and continues to do so. In this collaborative clinicians' review, we highlight the incidence, treatment and clinical outcomes of cervical cancer in low-income (LICs) and low- and middle-income countries (LMICs) across Asia, South America, South Africa and Eastern Europe. With the cervical cancer burden and locally advanced cancers being high, the majority of LICs/LMICs have been striving to adhere to optimal evaluation and treatment guidelines. However, the huge gap in resource availability, rural versus urban disparity and access to resources have led to poor compliance to evaluation, treatment and post-treatment rehabilitation. To mitigate the overwhelming numbers, various treatment strategies like neoadjuvant chemotherapy, hypofractionation radiation schedules (both external and brachytherapy) have been attempted with no major success. Also, the compliance to concurrent chemoradiation in various regions is a major challenge. With the burden of advanced cancers, the lack of palliative care services and their integration in cancer care is still a reality., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

In 2020, the World Health Organization launched a major initiative to eliminate cervical cancer globally. The initiative is built around the three key pillars of human papillomavirus (HPV) vaccination, cervical screening and treatment, with associated intervention targets for the year 2030. The '90-70-90' targets specify that 90% of adolescent girls receive prophylactic HPV vaccination, 70% of adult women receive a minimum twice-in-a-lifetime cervical HPV test and 90% receive appropriate treatment for preinvasive or invasive disease. Modelling has shown that if these targets are met, the elimination of cervical cancer, defined as fewer than four cases per 100 000 women per annum, will be achieved within a century. Many high-income countries are well positioned to eliminate cervical cancer within the coming decades, but few have achieved '90-70-90' and many challenges must still be addressed to deliver these critical interventions effectively. This review considers the current status of cervical cancer control in relation to each of the three elimination pillars in high-income countries and discusses some of the developments that will assist countries in reaching these ambitious targets by 2030., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Study Objective: To explore the effect of the diagnosis of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome on affected Malaysian women., Design: Qualitative study with a quantitative component., Setting: Pediatric and adolescent gynecology unit at Universiti Kebangsaan Malaysia Medical Centre, Malaysia., Participants: Twelve women with MRKH., Interventions: Face-to-face interview and short questionnaire., Main Outcome Measures: Thematic analysis was used to understand participants' experiences., Results: There were 7 themes identified: (1) delayed diagnoses; (2) doctors' roles and attitudes; (3) gender identity; (4) family and society's response; (5) reaction toward infertility; (6) managing sexual intimacy; and (7) coping mechanisms. Several participants consulted their physicians regarding their primary amenorrhea at an opportunistic setting. When they were referred to the gynecologists, they were dismayed at the lack of information given. The term, "MRKH" plays an important role to ease information-seeking. Participants felt that the doctors were insensitive toward them. Mental illness is a significant complication of MRKH. All participants acknowledged that infertility was the hardest part of the condition. The importance of blood lineage affects their outlook on childbearing options. Some were afraid of sexual intimacy and worried that they would not be able to satisfy their partners. Participants gained support and bonded with their counterparts in the MRKH support group., Conclusion: A multidisciplinary approach including medical, psychological, and social support is essential for the management of MRKH. Adequate information and sexual education plays the utmost importance in preventing social-related complications of MRKH., (Copyright © 2021 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

The recently discovered flat electronic bands and strongly correlated and superconducting phases in magic-angle twisted bilayer graphene (MATBG) 1,2 crucially depend on the interlayer twist angle, θ. Although control of the global θ with a precision of about 0.1 degrees has been demonstrated 1-7 , little information is available on the distribution of the local twist angles. Here we use a nanoscale on-tip scanning superconducting quantum interference device (SQUID-on-tip) 8 to obtain tomographic images of the Landau levels in the quantum Hall state 9 and to map the local θ variations in hexagonal boron nitride (hBN)-encapsulated MATBG devices with relative precision better than 0.002 degrees and a spatial resolution of a few moiré periods. We find a correlation between the degree of θ disorder and the quality of the MATBG transport characteristics and show that even state-of-the-art devices-which exhibit correlated states, Landau fans and superconductivity-display considerable local variation in θ of up to 0.1 degrees, exhibiting substantial gradients and networks of jumps, and may contain areas with no local MATBG behaviour. We observe that the correlated states in MATBG are particularly fragile with respect to the twist-angle disorder. We also show that the gradients of θ generate large gate-tunable in-plane electric fields, unscreened even in the metallic regions, which profoundly alter the quantum Hall state by forming edge channels in the bulk of the sample and may affect the phase diagram of the correlated and superconducting states. We thus establish the importance of θ disorder as an unconventional type of disorder enabling the use of twist-angle gradients for bandstructure engineering, for realization of correlated phenomena and for gate-tunable built-in planar electric fields for device applications.

The lack of radiotherapy linear accelerators (linacs) in low- and middle-income countries (LMICs) has been recognised as a major barrier to providing quality cancer care in these regions, together with a shortfall in the number of highly qualified personnel. It is expected that additional challenges will be faced in operating precise, high-technology radiotherapy equipment in these environments, and anecdotal evidence suggests that linacs have greater downtime and higher failure rates of components than their counterparts in high-income countries. To guide future developments, such as the design of a linac tailored for use in LMIC environments, it is important to take a data-driven approach to any re-engineering of the technology. However, no detailed statistical data on linac downtime and failure modes have been previously collected or presented in the literature. This work presents the first known comparative analysis of failure modes and downtime of current generation linacs in radiotherapy centres, with the aim of determining any correlations between linac environment and performance. Logbooks kept by radiotherapy personnel on the operation of their linac were obtained and analysed from centres in Oxford (UK), Abuja, Benin, Enugu, Lagos, Sokoto (Nigeria) and Gaborone (Botswana). By deconstructing the linac into 12 different subsystems, it was found that the vacuum subsystem only failed in the LMIC centres and the failure rate in an LMIC environment was more than twice as large in six of the 12 subsystems compared with the high-income country. Additionally, it was shown that despite accounting for only 3.4% of the total number of faults, linac faults that took more than 1 h to repair accounted for 74.6% of the total downtime. The results of this study inform future attempts to mitigate the problems affecting linacs in LMIC environments., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: The present study was carried out for comparative evaluation of case-based learning (CBL) aided with WhatsApp and didactic lectures (DL) while teaching a pathology topic to second-year medical students. In addition, the acceptability of WhatsApp as an aid to CBL was assessed., Material and Methods: After obtaining informed consent, 70 second-year Bachelor of Medicine and Bachelor of Surgery (MBBS) students were exposed to six sessions of CBL aided by case scenarios for one set of topics of anemia posted on WhatsApp groups. This was followed by six sessions of DL for separate set of topics in anemia. The multiple-choice questions (MCQ) test scores obtained pre and postintervention, of CBL and DL sessions, were compared to paired t-test (within the groups) and Student's t-test (between the groups). Categorical data were analyzed using Chi-square (χ 2 ) test. Student's self-administered questionnaires and focus group discussions (FGDs) were used to collect student perceptions and analyzed quantitatively, as well as qualitatively., Results: The mean MCQ scores obtained postintervention in CBL topics were significantly higher compared to DL (22.78 ± 2.99 vs 17.78 ± 3.35; P < 0.001). Students perceived that CBL enhanced their curiosity; hence, the acquired knowledge through various resources was retained better. It enhanced their analytical skills and interest in learning pathology. In FGDs, the students appreciated the use of WhatsApp as an aid to CBL for its ease of sharing scenario-related additional information and prior discussions among themselves in chat groups at their convenience., Conclusion: CBL aided by WhatsApp helped students acquire knowledge, discuss and learn actively, score more, and retain better than DL. Using WhatsApp as a platform helped them to interact at their ease and seek guidance from their mentors without resistance and hesitation., Competing Interests: None

Background: LupusPRO is a SLE specific patient reported outcomes measure developed and validated in the USA. This study aimed to validate the Hindi version of LupusPRO in systemic lupus erythematosus (SLE) patients in India., Methods: Disease activity and damage were assessed using SELENA-SLEDAI and SLICC/ACR damage Index respectively. Demographic and clinical features were recorded. The Hindi Version of LupusPRO and 36-Item Short Form Health Survey (SF-36) were administered for assessment of quality of life. Depression, anxiety and fatigue were assessed using Patient Health Questionnaire 9 (PHQ9), Generalized Anxiety Disorder 7 (GAD7) and Fatigue Severity Scale (FSS) respectively. Internal consistency reliability, test-retest reliability, convergent and discriminant validity (against corresponding domains of the SF-36, fatigue, depression and anxiety), criterion validity (against disease activity and damage) and known group validity were tested., Results: A total of 144 (140 females) patients with SLE with a mean age of 32.48 ± 7.26 years participated in the study. The median (interquartile range) SELENA SLEDAI was 2 (5.5). The internal consistency reliability of the LupusPRO domains was >0.7 for most domains (except for lupus symptoms, lupus medication, procreation and social support).We noted good convergent validity of LupusPRO domains with corresponding domains of SF-36, pain vitality with fatigue (FSS) and emotional health domain with depression (PHQ9) and anxiety (GAD7). Criterion validity of lupus symptoms with disease activity was observed. Known group validity of the LupusPRO domains with patient reported health status was observed. Confirmatory factor analysis showed a good fit., Conclusion: The Hindi LupusPRO has fair psychometric properties among Indian patients with SLE.

Despite the advances in the primary prevention of cervical cancer, there is an absolute increase in the incidence of cervical cancer as a result of an increase in world population. A vast majority of patients in low and low-middle income countries continue to present at a locally advanced stage, necessitating treatment with chemoradiation and brachytherapy. There is a dearth of equipment and trained professionals for the treatment of cervical cancer, especially in low and low-middle income countries. There is an urgent need to improve treatment availability and develop better treatments. Worldwide trends, however, reveal a low number of therapeutic and innovative research trials in cervical cancer. The present article elucidates the existing challenges and provides solutions to improve outcomes. The proposed strategies hinge on strengthening collaborations for global advocacy., (Copyright © 2019 The Royal College of Radiologists. All rights reserved.)

Objective: To evaluate the positive aspects of caregiving and its correlates (socio-demographic and clinical variables, caregiver burden, coping, quality of life, psychological morbidity) in the primary caregivers of patients with bipolar affective disorder (BPAD)., Methods: A total of 60 primary caregivers of patients with a diagnosis of BPAD were evaluated on the Scale for Positive Aspects of Caregiving Experience (SPACE) and the Hindi version of Involvement Evaluation Questionnaire, Family Burden Interview Schedule (FBIS), modified Hindi version of Coping Checklist, shorter Hindi version of the World Health Organization Quality of Life (WHOQOL-BREF), and Hindi translated version of 12-item General Health Questionnaire (GHQ-12)., Results: Caregivers of patients with BPAD had the highest mean score in the SPACE domain of Motivation for caregiving role (2.45), followed by Caregiver satisfaction (2.38) and Caregiving personal gains (2.20). The mean score was the lowest for the domain of Self-esteem and social aspect of caring (2.01). In terms of correlations, age of onset of BPAD had a negative correlation with various domains of SPACE. The mean number of total lifetime affective and depressive episodes correlated positively with Self-esteem and social aspect of caring. Caregiver satisfaction correlated negatively with FBIS domains of Disruption of routine family activities, Effect on mental health of others, and subjective burden. Coercion as a coping mechanism correlated positively with domains of Caregiving personal gains, Caregiver satisfaction, and the total score on SPACE. Three (Physical health, Psychological health, Environment) out of 5 domains of the WHOQOL-BREF correlated positively with the total SPACE score. No association was noted between GHQ-12 and SPACE scores., Conclusion: Positive caregiving experience in primary caregivers of patients with BPAD is associated with better quality of life of the caregivers.

Objective: To assess the positive aspects of caregiving and its correlates among caregivers of patients with dementia., Methods: A total of 55 primary caregivers of patients with dementia were invited to complete the Scale for Positive Aspects of Caregiving Experience (SPACE), Coping Checklist, Social Support Questionnaire, and World Health Organization Quality of Life-BREF version. Caregivers were also assessed by a clinician using the Burden Interview Schedule. Patients were assessed using the Hindi Mental State Examination and Instrumental Activities of Daily Living Scale., Results: The mean SPACE domain score was highest for motivation for caregiving role (2.63) followed by caregiver satisfaction (2.54), caregiving personal gains (2.4), and self-esteem and social aspect of caring (2.23). More educated caregivers scored significantly lower in the self-esteem and social aspect of caring. Married caregivers had a higher mean score in the motivation for caregiving role. There were some correlations between subjective burden and various SPACE domains, but the total objective burden score had no correlation with the SPACE. Higher use of avoidance coping was associated with a positive caregiving experience. Stronger social support was associated with higher score in the motivation for caregiving role. Higher level of caregiver burden in various domains was associated with lower motivation for caregiving. Caregiver satisfaction was associated with better quality of life for caregivers in terms of the environment., Conclusions: A positive caregiving experience for primary caregivers of patients with dementia is associated with both objective and subjective burdens, avoidance coping, and perceived social support.

CYP1A1 gene is involved in estrogen metabolism, and previously, we have reported association of variant rs2606345 with altered anti-epileptic drugs (AED) response in North Indian women with epilepsy (WWE). The present study aims to replicate the pharmacogenetic association, perform functional characterization and study its distribution within ethnically diverse Indian population. The variant was genotyped in 351 patients to assess the pharmacogenetic association and 552 healthy individuals belonging to 24 different ethnic groups to examine the distribution in Indian population. We observed significant overrepresentation of 'A' allele and 'AA' genotype in poor responders in WWE at Bonferroni-corrected significance levels. The recessive allele was found to lower the promoter activity by ~70-80% which was further substantiated by thermally less stable hairpin formed by it (ΔT m =7 °C). Among all ethnic groups, west Indo-European (IE-W-LP2) subpopulation showed highest genotypic frequency of the variant making women from this community more prone to poor AED response. Our results indicate that rs2606345 influences drug response in WWE by lowering CYP1A1 expression.

Background: There is limited information about the challenges of cancer management and attempts at improving outcomes in Africa. Even though South and North Africa are better resourceds to tackle the burden of breast cancer, similar poor prognostic factors are common to all countries. The five-year overall Survival rate for breast cancer patients does not exceed 60% for any low and middle-income country (LMIC) in Africa. In spite of the gains achieved over the past decade, certain characteristics remain the same such as limited availability of breast conservation therapies, inadequate access to drugs, few oncology specialists and adherence to harmful socio-cultural practices. This review on managing breast cancer in Africa is authored by African oncologists who practice or collaborate in Africa and with hands-on experience with the realities., Methods: A search was performed via electronic databases from 1999 to 2016. (PubMed/Medline, African Journals Online) for all literature in English or translated into English, covering the terms "breast cancer in Africa and developing countries". One hundred ninety were deemed appropriate., Results: Breast tumors are diagnosed at earlier ages and later stages than in highincome countries. There is a higher prevalence of triple-negative cancers. The limitations of poor nursing care and surgery, inadequate access to radiotherapy, poor availability of basic and modern systemic therapies translate into lower survival rate. Positive strides in breast cancer management in Africa include increased adaptation of treatment guidelines, improved pathology services including immuno-histochemistry, expansion and upgrading of radiotherapy equipment across the continent in addition to more research opportunities., Conclusion: This review is an update of the management of breast cancer in Africa, taking a look at the epidemiology, pathology, management resources, outcomes, research and limitations in Africa from the perspective of oncologists with local experience.

Closing the gap in cancer care within low- and middle-income countries and in indigenous and geographically isolated populations in high-income countries requires investment and innovation. This is particularly true for radiotherapy, for which the global disparity is one of the largest in healthcare today. New models and paradigms and non-traditional collaborations have been proposed to improve global equity in cancer control. We describe recent initiatives from within the radiation oncology community to increase access to treatment, build the low- and middle-income countries' radiation oncology workforce, mobilise more professionals from within high-income countries and raise awareness of the global need for equitable cancer care., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Aim: This study aimed to screen the patients with various malignancies for the presence of depressive disorders and anxiety disorder using standardized rating scales., Materials and Methods: Five hundred and thirty-four (n = 534) patients attending the radiotherapy outpatient services completed the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 (GAD-7) Questionnaire., Results: About half (n = 248; 46.4%) of the patients had psychiatric morbidity either in the form of depressive disorder or in the form of GAD. Higher stage of malignancy (from early, advanced to metastasis) was associated with higher prevalence of depressive disorder and GAD. The presence of psychiatric morbidity, especially anxiety disorder, was associated with being from low socioeconomic status., Conclusion: The present study suggests that psychiatric morbidity in the form of depressive and anxiety disorders is very common among patients with malignancies. Accordingly, there is a need for close liaison between oncologists and mental health professionals to improve the outcome of patients with various malignancies.

Objective: Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia., Methods: The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed., Results: A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults., Conclusion: Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, with many women initially presenting during adolescence. Diagnosis during this period is particularly challenging, yet many emphasize the importance of an early diagnosis given the long-term metabolic and reproductive health consequences associated with the syndrome. The objective of this study was to review the current literature to determine whether the diagnostic label 'PCOS' is necessary to effectively manage adolescent girls presenting with features of the syndrome. A literature search was conducted (PubMed, Medline, Informit Health and the Cochrane Database of Systematic Reviews) identifying papers addressing the diagnosis and management of PCOS during adolescence. Articles were selected based on date of publication, relevance of material and the quality of evidence presented. A total of 427 papers were screened, with 40 of these selected from the initial search. A subsequent 154 were included from manual review of reference lists from key papers identified in the initial search. Current guidelines recommend treating the individual manifestations of PCOS. In doing so, there is good evidence identifying that this approach adequately targets the underlying metabolic and reproductive changes associated with the syndrome. This suggests that providing a diagnostic label of PCOS is not actually necessary to effectively manage adolescent girls with features of this syndrome., (© 2015 World Obesity.)

En1, Nr2f1, Gpc4, Sfrp2, Shox2, Tbx15 and Thbd are among the genes involved in development process of an organism in a number of tissues, in particular adipose tissue. Considering the involvement of isobutyl-methyl-xanthine (IBMX), indomethacin, dexamethasone (DEX), triiodothyronine (T3), and insulin in adipocyte differentiation, we propose that these differentiation-inducing agents may regulate differentiation in brown adipose tissue through a developmental process. Stromavascular cells isolated from interscapular brown fat of mice were cultured in DMEM-LG medium. Proliferating brown preadipocytes were differentiated in the presence of IBMX, indomethacin, DEX, T3 and insulin. Pref1 (marker of proliferation stage) and uncoupling protein 1 (UCP1, marker for differentiation stage) were upregulated during proliferation and differentiation, respectively. Relative expression of Pref1, UCP1 and developmental genes was determined in different stages of adipogenesis. En1, Gpc4, Nr2f1, Sfrp2 and Shox2 were upregulated during differentiation. Differentiation of preadipocytes in the absence of IBMX, indomethacin, and DEX resulted in drastic reduction in fat accumulation in differentiated adipocytes with simultaneous decrease in En1, Gpc4, Nr2f1, Sfrp2, Shox2 and Tbx15 gene expression. T3 upregulated the expression of En1, Gpc4, Sfrp2 and Tbx15 genes during differentiation and downregulated Shox2 expression as compared to proliferated state. Insulin upregulated the expression of Shox2.

Ethnic and regional variations have been found in the pharmacological treatment response. Though many efficacy studies have been conducted in India for antipsychotic treatment modalities of schizophrenia, there is a lack meta-analytic data of the existing literature from India. This study aimed to conduct a systematic review and meta-analysis of the antipsychotic treatment trials of schizophrenia in the Indian context. All controlled trials from India evaluating the clinical efficacy of antipsychotics in patients with schizophrenia were evaluated and 28 trials were included in the metanalysis. Effect sizes were computed using Cohen's 'd' and risk of bias was evaluated. Meta analysis revealed superiority of first generation antipsychotics over placebo (mean effect size of 1.387, confidence interval of 1.127 to 1.648). Second generation antipsychotics were marginally better than first generation antipsychotics (effect size 0.106, confidence intervals 0.009 to 0.204). There was improvement in the methodology of the trials over time (Kendall tau=0.289, P=0.049), though no statistically significant increase in trial duration and sample size was noted. There is lack of data on long term efficacy of antipsychotic in schizophrenia from India. First generation antipsychotics have demonstrated benefits over placebo in patients with schizophrenia in the Indian context, though marginally lesser than second generation ones.

Objective: To evaluate the prescription pattern of antidepressants in patients with medical co-morbidity from major psychiatric centres in Asia., Methods: The Research on Asian Psychotropic Prescription Pattern for Antidepressants (REAP-AD 2013) collected data from 42 psychiatric centres in 10 Asian countries and regions. Antidepressant prescriptions of 2320 patients with various psychiatric disorders were evaluated. Of these, 370 patients who had specified medical co-morbidities formed the study cohort., Results: Escitalopram (20%) and mirtazapine (20%) were the most commonly prescribed antidepressants in patients with medical co-morbidity followed by sertraline (16%), trazodone (15%), and paroxetine (12%). Overall, more than half (52%; 247/476) of prescriptions comprised selective serotonin reuptake inhibitors. Slightly less than two-thirds (63%; n = 233) of patients received at least 1 selective serotonin reuptake inhibitor. In addition, 79% of patients were prescribed only 1 antidepressant. The mean number of antidepressants used per patient was 1.25 (standard deviation, 0.56). There were subtle differences in the most preferred antidepressant across medical illnesses such as diabetes mellitus, liver dysfunction, acid peptic disease, and cerebrovascular disease. Differences were also seen in prescription patterns across different countries., Conclusion: Although selective serotonin reuptake inhibitors formed the bulk of antidepressant prescriptions in the presence of medical co-morbidity, mirtazapine was also commonly used in the presence of medical co-morbidities. Specified medical morbidities do influence the selection of antidepressants.

Purpose: To correlate the structure of the macula, as measured by spectral-domain optical coherence tomography (SD-OCT) and function, as measured by microperimetry (MAIA) in patients with retinitis pigmentosa (RP) and relatively good visual acuity., Design: Prospective, cross-sectional, non-intervention study., Subjects: Patients with RP., Methods: Thirty patients with RP and good central visual acuity were identified. Each patient underwent SD-OCT of the macula and microperimetry. The images were overlaid using the custom-designed software. The retinal sensitivity by microperimetry was correlated with corresponding retinal thickness, as measured by the SD-OCT. ELM, COST, and IS/OS junction were scored as intact, disrupted, or absent., Main Outcome Measures: Comparing the retinal sensitivity on the MAIA with various measurements on the SD-OCT., Results: The retinal sensitivity on the MAIA showed a significant correlation with total retinal thickness and outer retinal thickness on the SD-OCT. There was no association with either the inner retinal thickness or the choroidal thickness. ORT showed a statistically significant correlation with the anatomical classification of ELM (r=-0.76, P<0.001), IS/OS (r=-0.800, P<0.001), and COST (r=-0.733, P<0.001)., Conclusion: This study determined that there was a high correlation of the structure and function of the central macula in patients with RP. These studies are important to establish surrogate markers that can be used as end points for various tests in future therapeutic clinical trials.

Objective: To study the prevalence and incidence of seizures in patients prescribed clozapine., Methods: The treatment records of 222 patients commenced on clozapine were retrospectively reviewed during the period of January 2007 to June 2014 to evaluate the prevalence of seizures before and after starting clozapine., Results: The majority of patients commenced on clozapine were male (65%), single (65%), and unemployed (57%). The mean (± standard deviation) dose of clozapine was 277.9 ± 102.5 mg/day. A history of seizure was present in 6 patients who were also prescribed antiepileptic medication; of these 6 patients, only 1 case had recurrence of seizure while taking clozapine due to poor compliance with ongoing antiepileptic medication. The incidence rate of new-onset seizure with clozapine was 6% (12/216). Most patients who developed seizures were male, aged between 24 and 41 years, and had a long duration of illness (≥ 10 years). The risk of seizure was associated with the dose of clozapine used: 3% (5/159) with dose up to 300 mg/day, 8% (4/49) with 325 to 500 mg/day, and 38% (3/8) in those receiving > 500 mg/day. More than half of the patients (7/12) who developed seizures while prescribed clozapine were managed with reduction in the dose of clozapine. In one-third of cases (4/12) an antiepileptic medication was added and in 1 case, clozapine was stopped. All patients who continued on clozapine remained seizure-free at follow-up that ranged from 6 months to 4 years., Conclusion: The incidence of seizures with clozapine was 6% and the risk of seizures increased with higher doses.