Government Medical College

Abstract Gestational trophoblastic disease ( GTD ) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow‐up with human chorionic gonadotropin ( hCG ) is essential for early diagnosis of gestational trophoblastic neoplasia ( GTN ). The duration of hCG monitoring varies depending on histology type and regression rate. Low‐risk GTN ( FIGO Stages I– III : score <7) is treated with single‐agent chemotherapy but may require additional agents; although scores 5–6 are associated with more drug resistance, overall survival approaches 100%. High‐risk GTN ( FIGO Stages II – III : score >7 and Stage IV ) is treated with multiple agent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent resistant tumors.

Cellulose is a linear biopolymer which is composed of nanofibrils, thus having a large surface area. This low-cost, low-density, high-specific-surface-area, easily processable polymer is found in nature in the form of plants, bacteria and tunicates. Cellulose has outstanding characteristics including low cytotoxicity, biocompatibility, good mechanical properties, high chemical stability, and cost effectiveness which make them suitable candidates for biomedical applications. The manipulation of cellulose at nanoscale resulted in nanocellulose having exceptional physicochemical properties. Therefore, cellulose nanocomposite is a fascinating area of research which has applications in biomedical fields like wound healing, bone tissue engineering, three dimensional printing, drug carriers, medical implants etc. This review is mainly focused on the developments in the generation of cellulose nanocomposites and their potential applications in the biomedical field.

Gestational trophoblastic disease (GTD) is a group of uncommon conditions associated with abnormal pregnancy. Histologically, it includes the benign partial and complete hydatidiform mole, invasive and metastatic mole, as well as the malignant choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT). Molar pregnancies may develop persistent elevated serum human chorionic gonadotropin (hCG) levels after evacuation (complete mole 15%−20%, partial mole 0.1%−5% [1–3]), with a chance of progression to choriocarcinoma that may require treatment. Together with the malignant forms of GTD these are grouped under gestational trophoblastic neoplasia (GTN). Molar pregnancy is more common in some parts of Asia, with reported incidence rates as high as 2 per 1000 pregnancies [4,5] compared with Europe and North American where the incidence is usually reported to be less than 1 per 1000 pregnancies [6,7]. However, the incidence of molar pregnancy seems to be decreasing in Asian countries, possibly related to improvements in the economy and diet as well as a decrease in birth rates [4]. The incidence of choriocarcinoma is difficult to estimate because of its rarity and trouble in clinically distinguishing postmolar choriocarcinoma from invasive mole owing to lack of histologic biopsy material. Although choriocarcinoma has been reported to affect approximately 1 in 40 000 to 9 in 40 000 pregnancies [3], the incidence rates have been declining. PSTT and ETT are rarer than choriocarcinoma. Histologically, complete mole has florid cistern formation, trophoblastic proliferation, and absence of fetal parts. In contrast, such histological features are less marked in partial mole and fetal parts are present, such as fetal cells [8]. Hydropic spontaneous abortion may mimic the appearance of partial mole. Cytogenetics can help to differentiate complete mole from partial mole and hydropic spontaneous abortion. Typically, complete mole is diploid and has 46,XX chromosomes with both Xs from paternal origin whereas partial mole is triploid with maternal and paternal genetic origin. Hydropic spontaneous abortion normally has 46,XX or XY from both parents. Immunohistochemical staining of p57Kip2, which is an imprinted gene, can help to show the presence of maternal genes and enable complete mole to be excluded [8,9]. Rarely, invasive and metastatic moles can be diagnosed by removal of the uterus or a metastatic lesion. Choriocarcinoma is a malignant tumor with absence of chorionic villi, abnormal syncytiotrophoblast and cytotrophoblast, necrosis, and hemorrhage. It may invade the uterus and surrounding organs and it is common to have distant spread, particularly to the lung, but it may also involve the liver, spleen, kidneys, bowels, and brain [8]. PSTT arises from the mononuclear intermediate trophoblast on the maternal side of the placental bed invading the myometrium. It has variable size and appearance, may be tan or yellowish with foci of necrosis, and on average is about 5 cm in size. Tumor cells have irregular nuclear membranes, hyperchromatic nuclei, and dense eosinophilic to amphophilic cytoplasm. Chorionic villi are absent. Tumor cells are strongly and extensively reactive to human placental lactogen (hPL) but only focally reactive to hCG. It has to be differentiated from the benign exaggerated placental site reaction where the Ki67 index is lower [8]. ETT is a lesion of chorionic-type intermediate trophoblast. It usually appears as a discrete, hemorrhagic, solid, and cystic lesion. It may be found in the fundus, lower uterine segment, or endocervix, or even the broad ligament. Histologically, islands of intermediate trophoblastic cells are surrounded by extensive necrosis and associated with a hyaline-like matrix. The tumor is focally immunoreactive to hPL, hCG, cytokeratin, and inhibin-alpha. It can be differentiated from PSTT by positive p63 immunostaining. ETT may coexist with choriocarcinoma or PSTT [10–12]. Emerging data indicate that atypical placental site nodules (APSN) can co-exist and/or preceded ETT and PSTT, suggesting that at least APSN cannot be regarded as benign [13]. The most common presentation of a hydatidiform mole is abnormal vaginal bleeding in pregnancy. With the advent of ultrasound assessment of early pregnancy complications, molar pregnancy is usually diagnosed during the first trimester. Hence, the previous classical presentations of hyperemesis gravidarum, hyperthyroidism, pre-eclampsia, pulmonary trophoblastic embolization, and uterine size larger than dates are rarely seen nowadays. The typical snow storm appearance of complete mole may not be seen in early first trimester complete mole. Absence of fetal parts, cystic appearance of the placenta, and deformed gestational sac may indicate early molar pregnancy. Hence, some molar pregnancies are only diagnosed on histological examination after dilation and curettage for a spontaneous abortion. Postmolar GTN is usually diagnosed by hCG surveillance. Patients are generally asymptomatic. At the 2000 FIGO Gynecology Oncology Committee meeting the definition of postmolar GTN based on hCG-level changes, histology, and specific investigations was agreed upon (Boxes 1 and 2) [14]. For monitoring of GTN, an hCG assay that can detect all forms of hCG, such as beta-hCG, core hCG, C-terminal hCG, nicked-free beta, beta core, and preferably the hyperglycosylated forms, should be used; these are different from those used for a routine pregnancy test. A persistent low hCG level should be followed up, after exclusion of false positives due to heterophile antibodies, as some may progress to GTN with rising hCG level [15,16]. As only about 50% of GTN follows molar pregnancy, the rest can occur after a spontaneous abortion, ectopic pregnancy, or a term pregnancy where no hCG monitoring would be recommended. Therefore, clinical presentations vary from abnormal vaginal bleeding; bleeding from metastatic sites in the abdomen, lung, or brain; pulmonary symptoms; and neurological signs from spine or brain metastasis [3]. GTN should be considered in the differential diagnosis of patients with unusual presentations and serum hCG should be performed as part of the workup of such patients. Suction evacuation of molar pregnancy should be carried out by an experienced gynecologist, especially if the uterus is larger than 16 weeks gravid size and ideally under ultrasound guidance. The risk of heavy bleeding can be reduced with use of oxytocics given after dilation and the onset of suction curettage. If there is no persistent bleeding, second evacuation is usually not needed. Hysterectomy is rarely indicated unless there is a co-existing indication. Follow-up with hCG monitoring is essential for early diagnosis of postmolar GTN. Recent data show that GTN rarely occurs after the hCG has spontaneously returned to normal and hence contraception for only 6 months rather than 1 year is now recommended [3,17]. Termination of pregnancy is not indicated if accidental pregnancy occurs during surveillance after the hCG level has returned to normal. Also, data now show that it is safe to recommend oral contraceptives [18]. The risk of recurrence is low (0.6%–2%) after one molar pregnancy, although much increased after consecutive molar pregnancies [19–21]. Mutations in NLRP7 and KHDC3L have been reported in women with recurrent molar pregnancy [22–24]. Molar pregnancy rarely co-exists with a normal pregnancy. The diagnosis is usually made on ultrasound. Although there is a high risk of spontaneous abortion, about 40% result in live births without significantly increasing the risk of GTN [25]. Hence, in the absence of complications and normal genetic and ultrasound findings, pregnancy can be allowed to proceed. Treatment of GTN is generally by chemotherapy. The best regimen to use depends on stage and classification. In the 2000 FIGO staging and classification (Tables 1 and 2), a risk score of 6 and below is classified as low risk and above 6 is considered high risk. Patients with low-risk GTN should be treated with one of the single-agent methotrexate or actinomycin D protocols listed in Box 3. The Cochrane Review in 2012, including 513 patients in five randomized controlled trials, showed that actinomycin D (Act-D) appeared to be superior to methotrexate (MTX) (risk ratio [RR] 0.64; 95% confidence interval, [CI] 0.54−0.76) [26]. Methotrexate was associated with significantly more treatment failure than actinomycin D (RR 3.81; 95% CI, 1.64−8.86). A further trial is ongoing, comparing not only efficacy, but toxicity and quality of life of pulsed actinomycin D and multiday methotrexate regimens [27]. Chemotherapy should be changed to the alternative single agent if there has been a good response to the first agent but the hCG level plateaus above normal during treatment or if toxicity precludes an adequate dose or frequency of treatment. If there is an inadequate response to the initial single agent, a significant elevation in hCG level, development of metastasis, or resistance to sequential single-agent chemotherapy, multi-agent chemotherapy as for high-risk disease should be initiated [2]. Studies in the UK showed that if the hCG level is less than 100 IU/L or 300 IU/L, change to single-agent Act-D gives a good response [2,28,29]; otherwise, multiple agents need to be used. After the hCG level has returned to normal, consolidation with 2–3 more cycles of chemotherapy will decrease the chance of recurrence. The overall complete remission rate is close to 100% [2,30]. Multiple agent chemotherapy regimens are used to treat high-risk GTN. The most commonly used is EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) (Table 3), although the Cochrane Database review [31] failed to conclude what combination was best. The complete remission rate was approximately 85% and the five-year overall survival rate was 75%−90%. However, patients with liver and/or brain metastasis have poorer outcomes [32–34]. Among the high-risk group as defined by the FIGO staging and classification, a subgroup with a score greater than or equal to 12 as well as patients with liver, brain, or extensive metastases did poorly when treated with first-line multiple agent chemotherapy [35]. For those with massive disease, starting with standard chemotherapy may cause severe marrow suppression leading to bleeding, septicemia, and even multiple organ failure. This may be avoided by starting with a lower dose and a less intensive regimen, such as etoposide 100 mg/m2 and cisplatin 20 mg/m2 on days 1 and 2, repeated weekly for 1–3 weeks, before starting the usual chemotherapy regimen [36]. For those patients with liver or brain metastases or a very high-risk score, EP (etoposide and platinum)/EMA or another more intensive chemotherapy regimen (Table 4), rather than EMA, may yield a better response and outcome. Such regimens can also be used in treating relapse or progressive disease while on first-line chemotherapy. For such high-risk patients, a longer consolidation with four cycles of chemotherapy should be considered. In patients with brain metastases, an increase in the methotrexate infusion to 1 g/m2 will help the drug cross the blood brain barrier and intrathecal methotrexate 12.5 mg can be given at the time of CO when EMA-CO is used. Some centers may give whole brain radiotherapy 3000 cGy in 200 cGy daily fractions concurrent with chemotherapy or use stereotactic radiation to treat brain metastases. Surgery may have an important role in the management of GTN. Hysterectomy can be considered in uncontrolled uterine bleeding, although it can often be avoided with the use of uterine artery embolization. Laparotomy may be needed to stop bleeding in organs such as the liver, gastrointestinal tract, kidneys, and spleen. Neurosurgery is needed if there is bleeding into the brain or increased intracranial pressure. In patients with an isolated drug-resistant tumor, removal of isolated cranial or pulmonary nodules or hysterectomy can improve survival. Radiotherapy has a limited role in GTN, except in treatment of brain metastasis, although its efficacy compared with intrathecal methotrexate is controversial [33,37]. Both PSTT and ETT are less chemosensitive than choriocarcinoma. Hysterectomy is the primary mode of treatment in most cases. However, if fertility preservation is desired, especially in a localized lesion, conservative management such as uterine curettage, hysteroscopic resection, and chemotherapy may be considered. Fertility preservation is not suitable in diffuse lesions. EP-EMA is the most commonly used chemotherapy. Interval from antecedent pregnancy of more than 48 months seems to be the most significant adverse prognostic factor. After treatment of GTN, frequent monitoring of hCG for at least 12 months with reliable contraception is essential for surveillance of relapse. Future fertility, pregnancy, and offspring are not affected, although psychosocial and sexual counseling may be needed for some patients. The authors have no conflicts of interest to declare. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract This paper is an extension of the well known rank order clustering algorithm for group technology problems. The ROC method is analysed and its main drawbacks are identified. The present method uses the ROC algorithm in conjunction with a block and slice method for obtaining a set of intersecting machine cells and non-intersecting part families. Then a hierarchical clustering method is applied based on a measure of association among pairs of machine cells. Clustering is terminated when all the surviving cells are non-intersecting or when a single group is formed. In the latter case, the number of cells is determined on the basis of a suitable decision criterion and the bottleneck machines are identified at the appropriate hierarchical level in the clustering process.

SUMMARY Block diagonalization of binary matrices is a primary step in the design of cellular production systems. ‘Grouping efficiency’ which is a weighted average of two measures that consider the voids in the diagonal blocks and exceptional elements in the off-diagonal blocks was the only criterion available to measure the goodness of block diagonal forms. The present work critically analyses this function and brings out its shortcomings, the most severe of them being its low discriminating power. A simple and elegant function has been derived in its place. The new function called grouping efficacy obviates all the defects of the earlier function while retaining the requisite properties. The mathematical properties of the function have been analysed and the function values compared with those of grouping efficiency in the case of well-structured and ill-structured data sets.

BACKGROUND: Nipah Virus (NiV) is a highly fatal emerging zoonotic virus and a potential threat to global health security. Here we describe the characteristics of the NiV outbreak that occurred in Kerala, India, during May-June 2018. METHODS: We used real-time reverse transcription polymerase chain reaction analysis of throat swab, blood, urine, and cerebrospinal fluid specimens to detect NiV. Further, the viral genome was sequenced and subjected to phylogenetic analysis. We conducted an epidemiologic investigation to describe the outbreak and elucidate the dynamics of NiV transmission. RESULTS: During 2-29 May 2018, 23 cases were identified, including the index case; 18 were laboratory confirmed. The lineage of the NiV responsible for this outbreak was closer to the Bangladesh lineage. The median age of cases was 45 years; the sex of 15 (65%) was male. The median incubation period was 9.5 days (range, 6-14 days). Of the 23 cases, 20 (87%) had respiratory symptoms. The case-fatality rate was 91%; 2 cases survived. Risk factors for infection included close proximity (ie, touching, feeding, or nursing a NiV-infected person), enabling exposure to droplet infection. The public health response included isolation of cases, contact tracing, and enforcement of hospital infection control practices. CONCLUSION: This is the first recorded NiV outbreak in South India. Early laboratory confirmation and an immediate public health response contained the outbreak.

AIMS: There are limited contemporary data on the presentation, management, and outcomes of acute coronary syndrome (ACS) admissions in India. We aimed to develop a prospective registry to address treatment and health systems gaps in the management of ACSs in Kerala, India. METHODS AND RESULTS: We prospectively collected data on 25 748 consecutive ACS admissions from 2007 to 2009 in 125 hospitals in Kerala. We evaluated data on presentation, management, and in-hospital mortality and major adverse cardiovascular events (MACE). We created random-effects multivariate regression models to evaluate predictors of outcomes while accounting for confounders. Mean (SD) age at presentation was 60 (12) years and did not differ among ACS types [ST-segment myocardial infarction (STEMI) = 37%; non-STEMI = 31%; unstable angina = 32%]. In-hospital anti-platelet use was high (>90%). Thrombolytics were used in 41% of STEMI, 19% of non-STEMI, and 11% of unstable angina admissions. Percutaneous coronary intervention rates were marginally higher in STEMI admissions. Discharge medication rates were variable and generally suboptimal (<80%). In-hospital mortality and MACE rates were highest for STEMI (8.2 and 10.3%, respectively). After adjustment, STEMI diagnosis (vs. unstable angina) [odds ratio (OR) (95% confidence interval = 4.06 (2.36, 7.00)], symptom-to-door time >6 h [OR = 2.29 (1.73, 3.02)], and inappropriate use of thrombolysis [OR = 1.33 (0.92, 1.91)] were associated with higher risk of in-hospital mortality and door-to-needle time <30 min [OR = 0.44 (0.27, 0.72)] was associated with lower mortality. Similar trends were seen for risk of MACE. CONCLUSION: These data represent the largest ACS registry in India and demonstrate opportunities for improving ACS care.

BACKGROUND: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. METHODS: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18-22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. FINDINGS: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87-1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. INTERPRETATION: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. FUNDING: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.

Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow-up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histological type and regression rate. Low-risk GTN (FIGO Stages I-III: score <7) is treated with single-agent chemotherapy but may require additional agents; although scores 5-6 are associated with more drug resistance, overall survival approaches 100%. High-risk GTN (FIGO Stages II-III: score ≥7 and Stage IV) is treated with multiagent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent treatment-resistant tumors.

RATIONALE: Interstitial lung disease (ILD) is a heterogeneous group of acute and chronic inflammatory and fibrotic lung diseases. Existing ILD registries have had variable findings. Little is known about the clinical profile of ILDs in India. OBJECTIVES: To characterize new-onset ILDs in India by creating a prospective ILD using multidisciplinary discussion (MDD) to validate diagnoses. METHODS: Adult patients of Indian origin living in India with new-onset ILD (27 centers, 19 Indian cities, March 2012-June 2015) without malignancy or infection were included. All had connective tissue disease (CTD) serologies, spirometry, and high-resolution computed tomography chest. ILD pattern was defined by high-resolution computed tomography images. Three groups independently made diagnoses after review of clinical data including that from prompted case report forms: local site investigators, ILD experts at the National Data Coordinating Center (NDCC; Jaipur, India) with MDD, and experienced ILD experts at the Center for ILD (CILD; Seattle, WA) with MDD. Cohen's κ was used to assess reliability of interobserver agreement. MEASUREMENTS AND MAIN RESULTS: A total of 1,084 patients were recruited. Final diagnosis: hypersensitivity pneumonitis in 47.3% (n = 513; exposure, 48.1% air coolers), CTD-ILD in 13.9%, and idiopathic pulmonary fibrosis in 13.7%. Cohen's κ: 0.351 site investigator/CILD, 0.519 site investigator/NDCC, and 0.618 NDCC/CILD. CONCLUSIONS: Hypersensitivity pneumonitis was the most common new-onset ILD in India, followed by CTD-ILD and idiopathic pulmonary fibrosis; diagnoses varied between site investigators and CILD experts, emphasizing the value of MDD in ILD diagnosis. Prompted case report forms including environmental exposures in prospective registries will likely provide further insight into the etiology and management of ILD worldwide.

The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development.

Background: Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial tumor. Despite modern therapies, it is still fatal with tremendously poor prognosis with a median survival of 14 months. Even though mean survival and progression-free survival (PFS) are considered as primary response measure, it is important to assess the effects of therapies on disease burden and health-related quality of life (HRQoL). Changes in quality of life (QoL) indicates the impact of cytotoxic therapy and may aid in defining response in the absence of quantifiable endpoints like tumor regression. The objective was to assess 2-year survival and quality of life in GBM patients who underwent primary surgery followed by chemo-radiotherapy and 6-month adjuvant chemotherapy with temozolomide. Materials and methods: Single-institution retrospective study of 60 patients of GBM from 2015 to 2017. Data regarding patient factors, disease factors, and treatment factors were collected and survival was calculated. Results: 60 patients with GBM were analyzed, male to female ratio was 1.6:1. Patients most commonly presented with headache. Most common tumour site is the frontal lobe. The median overall survival (OS) was 10 months. The 1-year and 2-year survival rates were 30% and 6.7%, respectively. Compared to before surgery patients have showed improved emotional, social and role functioning in Post radiotherapy period. There was a decrease in symptoms like pain, headache and seizures. Conclusions: OS and QoL in GBM patients remains poor despite constant research and studies. Maximum safe resection followed by adjuvant temozolomide has shown improvement in OS. Post-surgery and adjuvant radiotherapy patients have shown a decrease in symptoms and better QoL.

BACKGROUND: Examining the knowledge, attitude, perceptions and practices (KAP) of the medical students regarding antibiotic resistance (ABR) and use can help us in devising suitable educational interventions for them, tailored according to their earlier held knowledge, beliefs, capabilities and experience. METHODS: A cross sectional, questionnaire based survey was conducted among the second year medical students of a teaching hospital, whereby their KAP regarding antibiotic use and resistance was assessed by using a five point Likert scale, whose responses ranged from 'strongly agree' to 'strongly disagree,' 'always' to 'never and 'very important' to 'unimportant'. The data was analyzed by using simple descriptive statistics. Wherever it was relevant, the Chi-square test was used to determine any significant difference. RESULTS: The response rate was 100 per cent. The number of respondents who agreed that ABR was an important and a serious public health issue in our teaching hospital (n= 66, 68 per cent), was significantly less (p < 0.001) as compared to the number of respondents who agreed that ABR was an important and a serious issue which the country (n = 86, 88.65 per cent) and the world (n = 88, 90.7 per cent) were facing. Only 77.3 per cent (n= 75) of the respondents were aware that bacteria were not responsible for causing colds and flu, while the remaining 22.7 per cent (n = 22) were not knowledgeable about this fact. More than 80 per cent rated the adverse effect profile of the antibiotic and the risk of a superinfection as the important factors which deserved consideration. Cost of the antibiotic was considered to be an important factor deserving consideration by only 56.7 percent (n=55) of the participants. CONCLUSIONS: Our survey revealed that most of the students were aware of the antimicrobial resistance and its consequences. The only concern was their casual attitude regarding the antibiotic use. Further educational interventions are necessary to improve their understanding and perceptions on antibiotic resistance, as well as their attitude towards antibiotic use.

Yoga originated in India more than 5,000 years ago and is a means of balancing and harmonizing the body, mind, and emotions. Yoga practice is useful in the management of various lifestyle diseases, including type 2 diabetes. Psycho-neuro-endocrine and immune mechanisms are involved in the beneficial effects of yoga on diabetes. Incorporation of yoga practice in daily life helps to attain glycaemic control and reduces the risk of complications in people with diabetes. In this review, we briefly describe the role of various yoga practices in the management of diabetes based on evidence from various clinical studies.

BACKGROUND: Periodontology is a fast-evolving field with newer insights into traditional periodontal diagnosis. Advances in periodontal disease diagnostic research are moving toward methods whereby periodontal risk can be identified and quantified by objective measures such as biomarkers. OBJECTIVES: The aim of this study was to evaluate malondialdehyde (MDA) levels in whole saliva of patients with chronic periodontitis. MATERIALS AND METHODS: Whole saliva samples were collected from 85 patients: 30 patients with chronic periodontitis, 25 with gingivitis, and 30 periodontally healthy controls. To determine the clinical condition of each subject, the gingival index and clinical attachment level were measured. The salivary MDA levels were determined spectrophotometrically. RESULTS: < 0.005) were detected in patients with periodontitis compared to the healthy controls. There was no statistically significant difference in the salivary MDA levels between patients with gingivitis and healthy controls. CONCLUSIONS: Higher salivary MDA levels seem to reflect increased oxygen radical activity during periodontal inflammation. Thus, MDA can be used as a marker of oxidative stress in patients with periodontitis.

BACKGROUND: There are no recent data on prevalence of coronary artery disease (CAD) in Indians. The last community based study from Kerala, the most advanced Indian state in epidemiological transition, was in 1993 that reported 1.4% definite CAD prevalence. We studied the prevalence of CAD and its risk factors among adults in Kerala. METHODS: In a community-based cross sectional study, we selected 5167 adults (mean age 51 years, men 40.1%) using a multistage cluster sampling method. Information on socio-demographics, smoking, alcohol use, physical activity, dietary habits and personal history of hypertension, diabetes, and CAD was collected using a structured interview schedule. Anthropometry, blood pressure, electrocardiogram, and biochemical investigations were done using standard protocols. CAD and its risk factors were defined using standard criteria. Comparisons of age adjusted prevalence were done using two tailed proportion tests. RESULTS: The overall age-adjusted prevalence of definite CAD was 3.5%: men 4.8%, women 2.6% (p < 0.001). Prevalence of any CAD was 12.5%: men 9.8%, women 14.3% (p < 0.001). There was no difference in definite CAD between urban and rural population. Physical inactivity was reported by 17.5 and 18% reported family history of CAD. Other CAD risk factors detected in the study were: overweight or obese 59%, abdominal obesity 57%, hypertension 28%, diabetes 15%, high total cholesterol 52% and low level of high density lipoprotein cholesterol 39%. Current smoking was reported only be men (28%). CONCLUSION: The prevalence of definite CAD in Kerala increased nearly three times since 1993 without any difference in urban and rural areas. Most risk factors of CAD were highly prevalent in the state. Both population and individual level approaches are warranted to address the high level of CAD risk factors to reduce the increasing prevalence of CAD in this population.

BACKGROUND: There is a considerable lack of scientific estimate of psychiatric morbidity among Indian prisoners. OBJECTIVE: The objective of the following study is to study the prevalence of psychiatric morbidity among prisoners. SETTINGS AND DESIGN: A cross-sectional study at District Jail, Kozhikode, Kerala. MATERIALS AND METHODS: A total of 255 prisoners who were inmates during the period from mid-April to mid-July 2011 participated in the study. The study subjects included both male and female remand or convict prisoners. Socio-demographic data, clinical history and criminological history were collected from each individual. Psychiatric morbidity was assessed using MINI-Plus. STATISTICAL ANALYSIS: Done by using SPSS version 16 (SPSS Inc, Chicago, USA). RESULTS: A total of 175 subjects (68.6%) had a current mental illness. Substance use disorder was the most common diagnosis (47.1%). Antisocial personality disorder was diagnosed in 19.2%, adjustment disorder in 13.7%, mood disorder in 4.3% and psychosis in another 6.3% of prisoners. A high rate of a current psychiatric disorder was seen in male (69.7%) prisoners. A significant association was noticed for the different nature of crimes with psychiatric diagnoses and previous imprisonment. Nearly 4% of prisoners reported a moderate to high suicide risk. CONCLUSION: Mental health problems among prisoners were quite high. Mentally ill prisoners are at high risk for repeated incarceration. The increased rate of psychiatric disorders should be a concern for mental health professionals and the policy makers.

Some studies suggest that periodontal diseases increase the risk of oral cancer, but contradictory results also exist. Inadequate control of confounders, including life course exposures, may have influenced prior findings. We estimate the extent to which high levels of periodontal diseases, measured by gingival inflammation and recession, are associated with oral cancer risk using a comprehensive subset of potential confounders and applying a stringent adjustment approach. In a hospital-based case-control study, incident oral cancer cases (N = 350) were recruited from two major referral hospitals in Kerala, South India, from 2008 to 2012. Controls (N = 371), frequency-matched by age and sex, were recruited from clinics at the same hospitals. Structured interviews collected information on several domains of exposure via a detailed life course questionnaire. Periodontal diseases, as measured by gingival inflammation and gingival recession, were evaluated visually by qualified dentists following a detailed protocol. The relationship between periodontal diseases and oral cancer risk was assessed by unconditional logistic regression using a stringent empirical selection of potential confounders corresponding to a 1% change-in-estimates. Generalized gingival recession was significantly associated with oral cancer risk (Odds Ratio = 1.83, 95% Confidence Interval: 1.10-3.04). No significant association was observed between gingival inflammation and oral cancer. Our findings support the hypothesis that high levels of periodontal diseases increase the risk of oral cancer.

The drug-excipient compatibility studies were carried out with the possible excipients viz. Tween 80, Carbopol 940, chitosan, sodium alginate, and polycaprolactone (PCL) for their possible use in the formulation of eugenol loaded nanoemulsion gels and nanoparticles. The eugenol-excipient compatibility studies were carried out by visual observations, differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), and high-performance thin-layer chromatography (HPTLC). No notable change was observed in the samples on visual observation. From the results of the DSC studies, to a much extent, it was assumed that eugenol was not subjected to any interaction with the selected excipients for the proposed nanoemulsion gel and nanoparticles. But in some cases viz. polycaprolactone and Carbopol, though not to a significant level, slight deviation of the nature and position of the endothermic peaks of eugenol were observed. The results of the IR spectroscopy confirmed the compatibility of eugenol with Tween 80, Carbopol 940, chitosan, sodium alginate, and polycaprolactone. The retention factor of the HPTLC densitogram peaks for all the physical mixtures was well within the retention factor (Rf) value range observed for pure eugenol. The study results confirmed that eugenol is compatible with the selected excipients for the development of nanoemulsion gels and nanoparticles.

There is a paucity of health policy relevant data for chronic liver disease from India, impeding formulation of an interventional strategy to address the issue. A prospective, multicentric study to delineate the etiology and clinical profile of chronic liver disease in India is reported here. A centrally coordinated and monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and analyzed. Eleven hospitals from different parts of India participated. Data were uploaded into a web based proforma and monitored by a single centre according to a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383) attending the eleven participating hospitals of India had liver disease. 65807 (24·68%) were diagnosed for the first time (new cases). Of these, 13014 (19·77%, median age 43 years, 73% males) cases of chronic liver disease were finally analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34·3% of 4413) was the commonest cause of cirrhosis while Hepatitis B (33·3%) was predominant cause of chronic liver disease in general and non-cirrhotic chronic liver disease (40·8% out of 8163). There was significant interregional differences (hepatitis C in North, hepatitis B in East and South, alcohol in North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause of chronic liver disease. Hepatitis B (46·8% of 438 cases) was the commonest cause of hepatocellular Cancer.11·7% had diabetes. Observations of our study will help guide a contextually relevant liver care policy for India and could serve as a framework for similar endeavor in other developing countries as well.