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Lp-PLA2 is an enzyme encoded by the PLA2G7 gene located at chromosome 6p12-21, which is included in different signal transduction pathways. The potential of serum levels of Lp-PLA2 as a marker of inflammation quantifying cardio-metabolic risk, renal impairment and oxidative stress has been explored in earlier studies. It has also been used in chronic obstructive pulmonary disease, hepatic disease, metabolic conditions and exercise tolerance. Additionally, it shows promising evidence for the assessment of risk for certain cardiovascular conditions in otherwise seemingly healthy individuals. COVID-19 has affected life and the economy globally. The identification of biomarkers to assess the sickness and treatment plan is the need of the hour. This review summarizes the pathophysiological inter-relationship between serum levels of Lp-PLA2 and COVID-19. The authors hypothesize that the estimation of Lp-PLA2 levels may help in the early identification of risk and thus may play a beneficial role in the proactive management of COVID-19.

Background: In bipolar disorder (BD), depression is the most difficult-to-treat dimension and available evidence suggests that add-on supraphysiological doses of levothyroxine may be an effective augmenting agent. Aim: This systematic review has been conducted to evaluate the efficacy and safety of supraphysiologic doses of levothyroxine in bipolar depression in adults. Methods: After a comprehensive literature search on MEDLINE/PubMed, Scopus, Cochrane databases and International Clinical Trial Registry Platform (ICTRP), reviewers extracted data from eight relevant articles. PRISMA guidelines were followed in the selection, analysis and reporting of findings. Quality assessment was done using the risk of bias assessment and a random effects model was used to estimate effect size. Meta-analysis could not be done due to the lack of randomized, placebo-controlled trials and adequate data. A systematic review was done on eight studies and analysis on the pre–post change in Hamilton depression rating scale score (HDRS) was done for six studies. Results: The random model analysis of pooled effects showed a standardized mean difference of HDRS score by 2.62 (95% CI: 2.21–3.04; p Conclusion: Add-on supraphysiological dose of levothyroxine has a potential role in attenuating depressive symptoms in bipolar depression, especially in therapy-resistant BD. PROSPERO Registration Number: CRD42020218456.

Rationale Mitochondrial dysfunctions have emerged as new biological hypothesis and therapeutic target for bipolar disorder. This network meta-analysis has been done to evaluate the comparative efficacy of mitochondrial agents in bipolar depression. Methods After a comprehensive literature search on PubMed/MEDLINE, Cochrane databases, and International Trials Registry Platform, efficacy data were extracted from 15 randomized controlled trials. Random-effects meta-analysis was done following both frequentist and Bayesian approaches to pool the effects across the interventions. A network graph was built, relative effects of interventions in respect to one another and placebo were calculated, and treatments were ranked as per P- and SUCRA scores. Change in depression rating score was the primary outcome. Data was entered in contrast level and arm level for frequentist and Bayesian approaches, respectively. Results Amongst mitochondrial agents, N-acetylcysteine (NAC) was shown to have the highest probability of being the best treatment, followed by coenzyme Q10 and combination therapy of alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) as depicted by P- and SUCRA scores. In the Bayesian approach, none of the treatments had better efficacy than placebo, but in the frequentist approach, NAC (effect estimate: - 1.18 (95% CI: - 2.05; - 0.31)) was significantly better than placebo. Conclusion Methodically, there may be a difference of magnitude in frequentist and Bayesian approaches, but the direction of effect and ranking probabilities do not differ. We conclude that none of the existing mitochondrial agents showed better efficacy than placebo in bipolar depression regarding depression rating scores.

Purpose During the first few months of the COVID-19 outbreak, healthcare workers (HCW) faced levels of personal risk, emotional distress, and professional strain not seen in their lifetimes. This study described how these stressors influenced various aspects of their sleep patterns. Methods From May 19 to June 20, 2020, an electronic, cross-sectional survey was administered to a convenience sample of in- and outpatient HCW in a large, nonprofit healthcare system. Respondents described the pandemic’s initial impact on personal and professional life and various sleep dimensions: regularity, efficiency, duration, timing, quality, and daytime sleepiness. Results Two hundred seven providers responded, representing 17 different healthcare roles. Most (82%) were women with a median age of 39 years (IQR1–3, 31–53). A majority of respondents (81%) worked in an inpatient setting, with half (46%) primarily on the “frontline.” Approximately one-third of respondents (37%) were physicians and one-quarter (28%) were nurses. Overall, 68% of HCW reported at least one aspect of sleep worsened during the beginning of the pandemic; the most impacted were daytime sleepiness (increased in 43%) and sleep efficiency (worse in 37%). After adjusting for COVID exposure and burnout, frontline providers had twofold higher odds of poor pandemic sleep, aOR 2.53, 95%CI 1.07–5.99. Among frontline providers, physicians were fivefold more likely to develop poor pandemic sleep compared to nurses (OR 5.73, 95%CI 1.15–28.57). Conclusions During the initial wave of COVID-19, a majority of HCW reported a decline in sleep with an increase in daytime sleepiness and insomnia. Frontline workers, specifically physicians, were at higher risk. Supplementary Information The online version contains supplementary material available at 10.1007/s11325-021-02515-9.

Epilepsy treatment is challenging because of multiple impediments like lack of efficacy of monotherapy, adverse drug reactions, and different comorbidities. Add-on therapy to first-line antiepileptics may be the option to overcome therapeutic hurdles. The present randomized, double-blind, add-on placebo-controlled clinical trial was conducted to evaluate the effect of add-on melatonin in the treatment of generalized epilepsy with generalized onset motor seizure in adults. The control group (n = 52) received add-on placebo, and the test group (n = 52) received add-on melatonin (3 mg/day) with valproate (20 mg/kg in two divided doses). Clinical evaluation of seizure frequency, Chalfont-National Hospital seizure severity scale (NHS3), Pittsburgh sleep quality index (PSQI), quality of life in epilepsy inventory, Epworth sleepiness scale (ESS), and biochemical estimation of serum neuron-specific enolase (NSE) and glutathione reductase were done at baseline and compared with follow-up at 8 weeks. Among 104 patients randomized [mean (SD) age of 27.6 (11.5); 84 (80.8%) male], 88 (84.6%) completed the trial. The responder rate and seizure-free rate in the test group were significantly (p = 0.006 and 0.034) higher than the control group. There was a significantly higher reduction in the frequency of seizures (p = 0.016) and NHS3 (-2.39; 95%CI: -4.56 to -0.21; p = 0.032) in the test group compared to the control group. Similarly, improvement in PSQI (-1.40; 95%CI: -2.64 to -0.15; p = 0.029) was significantly better in the test group. There was no significant difference in the change in ESS (p = 0.621) and quality of life scoring (p = 0.456) between the study groups. The decrease in serum NSE was significantly higher with the test group compared to the control group (-2.01; 95% CI: -3.74 to -0.27; p = 0.024). Add-on melatonin increased serum glutathione reductase significantly (p = 0.038), but there was no significant difference between the groups (p = 0.685). Add-on melatonin with valproate for generalized epilepsy with generalized onset motor seizures in adults can achieve a significantly better clinical outcome by reducing the seizure frequency, severity and attaining a better seizure-free rate in comparison to the control group.

Antibiotic prophylaxis is commonly given to all patients undergoing cochlear implant surgery. However, currently, there is no consensus if pro- phylactic usage of antibiotics in cochlear implantation accords any benefit and if the duration of such use varies according to the surgeon's experience or institutional preference. A systematic review was conducted to gather evidence on ideal duration for antibiotic prophylaxis rec- ommended for patients undergoing cochlear implantation. We registered the protocol in the International Prospective Register of Systematic Reviews (CRD42021235079) and reported the systematic review following the Preferred Reporting Items for Systematic Reviews and Meta- Analysis statement. Of the 278 screened articles, 6 full-text original articles satisfied the inclusion criteria and were included. There were a total of 2081 participants in these 6 retrospective studies and all studies except 1 included both adult and pediatric populations. Antibiotic therapy was given as intervention, either as single dose or multiple doses, and compared with other group(s) receiving either no antibiotic prophylaxis or a different duration of prophylaxis. Three studies did not find any significant difference between infection rates when a different duration of antibiotic prophylaxis was given, while 2 studies found a single dose to be more efficacious, and yet another study concluded that a longer dura- tion of antibiotic prophylaxis was more beneficial. Based on the available data, the ideal duration of post-operative antibiotic therapy to be given after cochlear implant surgery could not be defined. However, administrating a single dose of intraoperative antibiotic seems to be the most consistent practice so far.

Alpha lipoic acid is known to reverse NMDA receptor hypofunction in addition to dopamine receptor blockade activity. It also enhances neurotrophic factors and has antioxidant potential. These properties combined together may be beneficial for treatment-resistant schizophrenia (TRS).This study evaluates the effect of alpha lipoic acid (ALA) on psychopathological scores (positive, negative, cognitive), neurotrophic factors and oxidative stress in TRS.A pilot randomized double-blind placebo-controlled parallel design trial was conducted in 20 patients with TRS. After initial screening, participants were randomized into test (add-on ALA) and control (add-on placebo) groups. After recruitment, clinical evaluations with scale for assessment of positive symptoms and negative symptoms (SAPS and SANS), schizophrenia cognitive rating scale (SCoRS), UKU side effect rating scale were done. Serum levels of BDNF, MDA, and GSH were estimated. Patients were followed up for 8 weeks, and clinical and biochemical evaluations were repeated. Adherence to medication was evaluated at follow-up.A significantly greater improvement was found in SANS score in the test group when compared to control (Mann-Whitney U = 17.0; p = 0.021), whereas there was no significant improvement in SAPS score (Mann-Whitney U = 41.5; p = 0.780). A significant increase in BDNF levels was observed in the control group when compared to ALA (U = 20.0; p = 0.041). No significant differences were found between the test and control groups in serum MDA (U = 30.0; p = 0.221), serum GSH (U = 40.0; p = 0.683), and medication adherence rating scale (MARS) scores (U = 44.0; p = 0.934).ALA supplementation improved psychopathology and decreased oxidative stress in patients with TRS. This study thus shows the potential of adjunctive ALA in TRS.The study was prospectively registered in Clinical Trial Registry of India (CTRI/2020/03/023707 dated 02.03.2020).

The outbreak of coronavirus disease 2019 (Covid-19) severely impacted global health and economic status. The native receptor-ligand interaction of Angiotensin-converting enzyme 2 (ACE2) and S protein induces host cell pathogenesis via immunosuppression.The emerging evidence reports the sex disparity in Covid-19 induced mortality rate which affects abundantly men population. Although the biological interaction of Covid-19 with receptor upregulates the viral genome protein interactions and initiates the predictive multiorgan failure followed by acute kidney injury (AKI) in Covid-19 infected male population.Besides, the knowledge and lessons learned from the study depict that cellular and molecular links may explain the risk and severity of Covid-19 and AKI in the male population and lead to management of Covid-19 induced AKI. Therefore, this review explored the pathways associated with the pathogenesis of two diseased conditions with sex disparity.

Serotonin-dopamine activity modulators (SDAMs) have been approved as an adjunctive treatment to antidepressants in patients with inadequate response. These drugs have been proposed to have a beneficial effect on cognition, sleep-related problems, and other affective symptoms in patients with depression. Previous studies have shown inconsistent evidence and have not reported a pooled effect of the 2 drugs of this class: aripiprazole and brexpiprazole. This meta-analysis evaluated the effect of augmentation with SDAM drugs in patients with major depression. The meta-analysis protocol was made as per Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines and registered in the International Prospective Register of Ongoing Systematic Reviews. The PubMed/MEDLINE, Cochrane Clinical Trial registry, and EudraCT databases were searched with prespecified search terms. A random-effects meta-analysis was performed using the meta package in R software. Fifteen studies were included in this meta-analysis. The random-effects model analysis observed a pooled effect of 1.55 (95%CI, 1.32-1.84; prediction interval, 0.95-2.55, z = 5.19 [P.0001]) for remission between the SDAM and placebo groups. A pooled effect of 1.58 (95%CI, 1.37-1.83; prediction interval, 1.00-2.51, z = 6.34 [P .0001]) for adverse events and 0.72 (95%CI, 0.48-1.08; prediction interval, 0.46-1.12; z = -1.58 [P = .113]) for serious adverse events was observed. No significant publication bias was noticed. The quality of the evidence was rated as high. Adjunct SDAM increased remission in patients and had no significant effect on serious adverse events compared to placebo. Therefore, we conclude that SDAM drugs can be an effective and safe antidepressant augmentation strategy in patients with major depressive disorder.

Plants consistently synthesize and accumulate medically valuable secondary metabolites which can be isolated and clinically tested under in vitro conditions. An advancement with such important phytochemical production has been recognized and utilized as herbal drugs. Bioactive andrographolide (AGL; C20H30O5) isolated from Andrographis paniculate (AP) (Kalmegh) is a diterpenoid lactones having multifunctional medicinal properties including anti-manic, anti-inflammatory, liver, and lung protective. AGL is known for its immunostimulant activity against a variety of microbial infections thereby, regulating classical and alternative macrophage activation, Ag-specific antibody production during immune disorder therapy. In vitro studies with AGL found it to be effective against multiple tumors, neuronal disorders, diabetes, pneumonia, fibrosis, and other diverse therapeutic misadventures. Generally, virus-based diseases like ZIKA, influenza A virus subtype (H1NI), Ebola (EBOV), Dengue (DENV), and coronavirus (COVID-19) epidemics have greatly increased scientific interest and demands to develop more effective and economical immunomodulating drugs with minimal side effects. Trials and in vitro pharmacological studies with AGL and medicinally beneficial herbs might contribute to benefit the human population without using chemical-based synthetic drugs. In this review, we have discussed the possible role of AGL as a promising herbal-chemo remedy during human diseases, viral infections and as an immunity booster.

Monotherapy with triptans in acute migraine is ineffective in many patients and contraindicated in certain cardiovascular diseases where alternative therapeutic options are necessary to explore. This meta-analysis has evaluated the efficacy and safety of lasmiditan for the treatment of acute migraine in adults. After performing a literature search on MEDLINE/PubMed, Scopus, Cochrane databases, and International Clinical Trial Registry Platform, reviewers assessed eligibility and extracted data from 4 relevant articles. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed in the selection, analysis, and reporting of findings. A random-effects model was used to estimate effect size. Quality assessment was done using the risk of bias assessment tool and meta-regression for probable variables affecting effect size. Subgroup analysis was done depending on the dose of lasmiditan. Lasmiditan use was associated with a significantly higher percentage of patients with pain freedom (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.72-2.39; P < .00001), sustained pain freedom (OR, 1.93; 95%CI, 1.55-2.39; P

The combination of an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor having different biological targets has become an integral part of the treatment of pulmonary arterial hypertension; however, several clinical studies have reported conflicting results. The objective of this meta-analysis was to evaluate the effect of an endothelin receptor antagonist and phosphodiesterase-5 inhibitor combination in pulmonary arterial hypertension. After performing a comprehensive literature search in MEDLINE, Cochrane and the International Clinical Trial Registry Platform, reviewers assessed eligibility and extracted data from seven relevant articles (publications till December 2018). PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed in the selection, analysis and reporting of findings. The odds ratio and mean difference were calculated to estimate the difference in clinical worsening, 6-minute walking distance, pulmonary vascular resistance and N-terminal pro-brain natriuretic peptide between the groups. Quality assessment was performed using the risk of bias assessment tool and a meta-regression for probable variables affecting effect size. The random-effect model analysis revealed an odds ratio of 0.56 [95% confidence interval (CI) 0.41–0.76; p = 0.0002] for clinical worsening, mean difference of 15.64 (95% CI 2.67–28.61; p = 0.02) for 6-minute walking distance, − 1.66 (95% CI − 3.82 to 0.50; p = 0.13) for pulmonary vascular resistance and − 21.04 (95% CI − 26.87 to − 15.22; p

Neurotrophic factors like Brain-Derived Neurotrophic Factor (BDNF), Neurotrophin 3 (NT3) and Nerve Growth Factor (NGF), play a role in neuroplasticity and neurogenesis contributing to the pathogenesis of schizophrenia. The objective of the present study was to investigate and compare the effect of olanzapine and lurasidone on the change in serum neurotrophins in patients with schizophrenia. The present study was a randomized, open-label, active-controlled, parallel design clinical trial. After randomization baseline evaluations of serum BDNF, NGF, NT3, Positive and Negative Syndrome Scale (PANSS) scoring, Social and Occupational Functioning Assessment Scale (SOFAS) scoring of 101 unmedicated schizophrenia patients were done. Patients were reassessed after 6 weeks of monotherapy with olanzapine or lurasidone. Serum BDNF increased after treatment with both the drug groups but rise with olanzapine was found to be significantly higher (916.22; 95 %CI: 866.07 to 966.37; p 0.001) in comparison to lurasidone. Increase in levels NGF and NT3 was also observed but there was no significant difference between the groups (NGF: 2.32; CI: 3.54 to -3.53; p = 0.57 and NT3: 0.99; CI: 2.11 to 0.14; p = 0.086). The difference in improvement in PANSS and SOFASS with both the drugs was not statistically significant. Both the drugs alleviate the symptoms of schizophrenia but olanzapine was better tolerated. Our findings suggest that increase in serum BDNF with olanzapine monotherapy is significantly higher than that with lurasidone but there is no significant difference in change in serum NGF and NT3. TRIAL REGISTRATION: ClinicalTrials.gov identifier: (NCT03304457).

We compared the labour pattern in the active phase of labour, defined at 4 cm versus 6 cm cervical dilatation, in a South Asian population. This was a prospective observational study where 500 low risk nulliparous women were recruited. Our aim was to study, the average labour pattern curve of all parturients. Mean duration of the active phase from 4 to 10 cm was 5.12 ± 2.10 hours and from 6 to 10 cm was 2.79 ± 1.72 hours. The 95th percentile values suggests that it takes 5-6 hours to progress from 4 to 6 cm and again 5-6 hours from 6 to 10 cm. The minimum labour progression rate can be as low as 0.5 cm/hour with vaginal delivery (VD) still being achieved. The slope of labour curve steepens after 6 cm, suggesting 6 cm as the onset of the active phase. Allowing labour to continue for a longer period before 6 cm of cervical dilation may reduce the rate of unnecessary intrapartum intervention and caesarean section (CS) for labour dystocia.Impact StatementWhat is already known on this subject? Friedman's definitions of normal labour and abnormal labour are widely accepted in current obstetric practises. Friedman's normal dilatation rate of 1 cm/h that is universally accepted is becoming questionable in our current obstetric population because of escalating rates of unnecessary labour interventions like oxytocin augmentation and CS.What the results of this study add? The rule of 1 cm/hour of labour progression cannot be applied to every woman and inappropriate interventions should be withheld until labour progression does falls below 0.5 cm/hour.What the implications are of these findings for clinical practice and/or further research? Six centimetres rather than 4 cm of cervical dilatation is a more appropriate landmark for the start of the active phase. Allowing labour to continue for a longer period before 6 cm of cervical dilation may reduce the rate of unnecessary intrapartum interventions and CS for labour dystocia.

Background Lacunae exist in understanding the underlying etiology in majority of recurrent pregnancy loss (RPL) cases. Given the significance of regulated immune-modulation in pregnancy, and the central role of pro-inflammatory TNF-α plays in it; this study targeted to appraise the significance of TNF-α profile in RPL pathogenesis in an ethnically distinct population from Assam, India. Methods Term delivery, medically terminated pregnancy (MTP) and RPL cases (based on ASRM criteria) were enrolled with no anatomical and chromosomal abnormalities or pathological infections; and blood and/or placenta/product of conceptus (POC) tissue samples were collected with informed consent. Serum level and tissue level TNF-α expression profile were screened using specific molecular tools, and was correlated with TNF-α −308 G/A genotype; for its association with RPL predisposition. Results A significant gestation specific increase in serum TNF-α levels was observed in MTP cases (19.932 ± 4.407 pg/mL) compared to term delivery subjects (p = 0.001), while a comparable levels were observed with RPL cases (22.709 ± 5.833 pg/mL) (p = 0.646). A site specific (POC) increased expression was observed in RPL compared to MTP cases at both at transcript (6.37 ± 3.714 folds) and protein levels. The TNF-α -308 variant genotype was associated with increased predisposition to RPL (OR = 1.721) compared to MTP as well as significantly increased serum TNF-α levels (p = 0.017); especially in subjects with a homozygous TNF-α -308 A/A genotype. Conclusion Our data emphasizes on the importance of site specific TNF-α expression levels in RPL pathogenesis in the studied population, and underlines its importance in screening, clinical stratification, and therapeutics by molecular targeting using TNF-α inhibitors.

Smoking is the leading cause of morbidity and mortality in different non-communicable diseases, and cessation leads to immense health benefits. The present network meta-analysis has been conducted to evaluate and compare the effects of available pharmacological interventions for smoking cessation in adults. A standard meta-analysis protocol was developed and after performing a comprehensive literature search on MEDLINE/PubMed, Cochrane databases, and International Clinical Trials Registry Platform, reviewers extracted data from 97 randomized controlled trials. PRISMA guidelines were followed in data extraction, analysis and reporting of findings. Random effects Bayesian network meta-analysis was done to pool the effects across the interventions. Network graph was built, and for closed triangles in the network graph, node splitting analysis was performed. The primary outcome measure was self-reported biochemically verified smoking abstinence at six months. The number of participants achieving continuous abstinence was reported. Data for the number of participants reporting at least one adverse event was also extracted, if available. Combination of nicotine receptor agonist and nicotine replacement therapy had a significant odd of 4.4 (95%CrI:2.2-8.7), bupropion and nicotine receptor agonist 4.0 (95%CrI:2.1-7.7), bupropion and nicotine replacement therapy 3.8 (95%CrI:2.3-6.2), combination nicotine replacement therapy has an odd of 2.6 (95%CrI:1.8-3.8), and nicotine receptor agonist had a significant odd of 2.7 (95%CrI:2.3-3.2) when compared to placebo (moderate quality of evidence) for continuous abstinence at 6 months. When compared with behavioural therapy, the odds ratio of interventions was not statistically significant. Combination of nicotine receptor agonist and nicotine replacement therapy has the highest probability of being the best treatment for abstinence from smoking.

Targeted anti-IL-1β therapy may be a valuable option for the management of gouty arthritis. The present meta-analysis has evaluated the effect of canakinumab, an anti-IL-1β monoclonal antibody in gouty arthritis. A standard meta-analysis protocol was developed and after performing a comprehensive literature search in MEDLINE, Cochrane, and International Clinical Trial Registry Platform (ICTRP), reviewers assessed eligibility and extracted data from three relevant articles. A random-effects model was used to estimate the pooled effect size as the mean difference in Visual Analouge Scale (VAS) score, serum hsCRP, serum Amyloid A, and risk ratio for global assessment between the groups. Quality assessment was done using the risk of bias assessment tool and summary of findings was prepared using standard Cochrane methodology with GradePro GDT. Treatment with canakinumab showed a mean reduction of VAS score by 14.59 mm [95% CI − 19.42 to − 9.77], serum hsCRP by 15.36 mg/L [95% CI 1.62–29.11], serum Amyloid A by 67.18 mg/L [95% CI 17.06–117.31], and improvement in patient global assessment (RR = 1.478; 95% CI 1.29–1.67) and physician global assessment (RR = 1.44; 95% CI 1.28–1.61). The probability that future studies may have a mean difference in VAS score less than zero has been calculated to be 27.3% using a cumulative distribution function (CDF) calculator. This meta-analysis shows the beneficial effect of canakinumab over triamcinolone by reducing VAS score, serum hsCRP, serum amyloid A, and improvement in global assessments in acute gouty arthritis.

Worldwide, many newborns die in the first month of life, with most deaths happening in low/middle-income countries (LMICs). Families’ use of evidence-based newborn care practices in the home and timely care-seeking for illness can save newborn lives. Postnatal education is an important investment to improve families’ use of evidence-based newborn care practices, yet there are gaps in the literature on postnatal education programees that have been evaluated to date. Recent findings from a 13 000+ person survey in 3 states in India show opportunities for improvement in postnatal education for mothers and families and their use of newborn care practices in the home. Our survey data and the literature suggest the need to incorporate the following strategies into future postnatal education programming: implement structured predischarge education with postdischarge reinforcement, using a multipronged teaching approach to reach whole families with education on multiple newborn care practices. Researchers need to conduct robust evaluation on postnatal education models incorporating these programee elements in the LMIC context, as well as explore whether this type of education model can work for other health areas that are critical for families to survive and thrive.

Patients with schizophrenia are at higher risk of cardiovascular morbidity and mortality than healthy individuals. This study was conducted to compare the effect of lurasidone and olanzapine on cardiometabolic parameters in unmedicated patients with schizophrenia. The present study was a randomized open-label, parallel design, active-controlled clinical trial. After recruitment and randomization of 101 patients, a baseline assessment was done by PANSS, SOFAS, lipid profile, fasting blood glucose, HbA1c, serum insulin and serum hs-CRP. HOMA-IR, atherogenic index, coronary risk index and cardiovascular risk indices were calculated as derived parameters. Patients received either lurasidone 80 mg or olanzapine 10 mg as monotherapy and followed up after 6 weeks. There was a significant increase in fasting blood glucose (p < 0.001), HbA1c (p < 0.001) and serum insulin (p < 0.001) after 6 weeks of therapy in both the treatment groups but the difference between the groups was not significant (FBS, p = 0.209; HbA1c, p = 0.209; serum insulin, p = 0.720). Olanzapine showed worsening of lipid profile (p < 0.001) while the same improved with lurasidone (p < 0.001) and the difference between the groups was found to be significant (p < 0.001). Serum HDL level decreased in both the treatment groups (olanzapine, p < 0.001; lurasidone, p < 0.001) but the difference between the groups was not significant (p = 0.333). There was an increase in hs-CRP levels in both the treatment groups (olanzapine, p < 0.001; lurasidone, p < 0.001) with no significant difference between them (p = 0.467). Atherogenic index, coronary risk index and cardiovascular risk index increased significantly in the olanzapine group as compared with the lurasidone group (p < 0.001). Lurasidone showed a favourable effect on lipid profile and cardiovascular risk indices over olanzapine. However, long-term studies are needed to establish and generalize the findings. ClinicalTrials.gov NCT03304457

The aim of this article is to understand the pros and cons of various methods involved in first-in-human (FIH) dose calculation and act decisively in dose escalations when calculating the maximum tolerated dose. We reviewed early phase clinical trials for methods of FIH dose and dose-escalation steps and discuss them in line with existing guidelines. We also reviewed the clinical trial registry to recognize trends in trial registration in recent years and after a massive failure in a few trials. Phase 1 trials of TGN 1412 and BIA10-2474 would always be remembered as catastrophes for pharmaceutical development plans. Quite often than not, healthy human volunteers are the guinea pigs in this stage of drug development. And, the most important aspect of designing an early phase study is deciding upon the dose to be started with, apart from the selection of cohort and escalation steps. The common principles used for FIH dose calculation include no observed adverse effect level, minimum anticipated biological effect level, pharmacologically active dose, pharmacokinetic/pharmacodynamic approach, and similar drug comparison approach. Early phase clinical trials are basically foundation stones on which lies the entire onus of the later stages of development. Deciding FIH dose is a crucial step that necessitates the incorporation of detailed data from the preclinical stages and application of the most conservative approach for the safety/benefit of the volunteers in these studies.

Smoking tobacco is the major hazard for lung cancer in Indian subcontinent especially men, compare to woman where, other important risk factors such as air pollutions are responsible. So, the aim of the study is to compare chronic smokers (CS) and non-smokers living in areas with air quality categorized as poor (AQI 201-300) or moderate (AQI 101-200). We measured the expression of non-small cell lung cancer (NSCLC) biomarkers;. IDH1, CEA, Cyfra21-1, and TPA through quantitative Real-Time PCR (qRT-PCR) and compared the levels of upregulation of the transcripts in stage IIIa NSCLC over control benign tissues among the smoking and AQI settings. Though the all biomarkers were significantly up-regulated in tumor tissues compared to control benign tissues, the fold change increase of IDH1 and CEA was highest in CS-poor/moderate AQI, followed by non-smokers-poor AQI and non-smokers moderate AQI. This indicates the aggressiveness and poor prognosis in CS living in either poor or moderate AQI areas. The level of Cyfra21-1 was lower in in the CS groups in comparison to non-smokers in the poor AQI area. This suggest higher Lung Squamous cell carcinoma histology in non-smokers living areas with poor AQI. Hence, we conclude that poor air quality can be as injurious for lung cancers as chronic smoking.

The role of sodium benzoate, an NMDA receptor enhancer, in schizophrenia has been evaluated in a few clinical trials, but results are contradictory and inconclusive. The present meta-analysis has evaluated the efficacy and safety of add-on sodium benzoate for the treatment of schizophrenia.After performing a literature search on MEDLINE/PubMed, Scopus, Cochrane databases and International Clinical Trial Registry Platform, reviewers assessed eligibility and extracted data from four relevant articles. PRISMA guidelines were followed in the selection, analysis, and reporting of findings. The random-effect model was used to estimate effect size. Quality assessment was done using the risk of bias assessment tool, and sensitivity analysis was done in case of high heterogeneity.Add-on sodium benzoate can improve positive symptoms of schizophrenia significantly (MD: -1.87; 95%CI: -3.25 to -0.48; p = 0.008) but had no significant favourable effect on negative symptoms (p = 0.84), general psychopathology (p = 0.49), and total PANSS score (p = 0.19) over the control. There was no significant improvement in GAF (p = 0.43), CGI (p = 0.58), cognitive function (p = 0.46) and quality of life (p = 0.73). Extrapyramidal symptoms were significantly higher (MD: 0.39; 95% CI:0.19-0.60; p = 0.0002) in the sodium benzoate group in comparison to the control group; however, there was no significant difference in respect to other adverse events.Sodium benzoate can improve the positive symptoms of schizophrenia without any beneficial effect on other symptomatology, cognition, quality of life and functioning. Further studies are needed to evaluate long-term efficacy, safety and use in specific subgroups of patients.

Chronic lymphocytic leukemia is a disease with up-regulated expression of the transmembrane tyrosine-protein kinase ROR1, a member of the Wnt/planar cell polarity pathway. In this study, we identified COBLL1 as a novel interaction partner of ROR1. COBLL1 shows clear bimodal expression with high levels in chronic lymphocytic leukemia patients with mutated IGHV and approximately 30% of chronic lymphocytic leukemia patients with unmutated IGHV. In the remaining 70% of chronic lymphocytic leukemia patients with unmutated IGHV, COBLL1 expression is low. Importantly, chronic lymphocytic leukemia patients with unmutated IGHV and high COBLL1 have an unfavorable disease course with short overall survival and time to second treatment. COBLL1 serves as an independent molecular marker for overall survival in chronic lymphocytic leukemia patients with unmutated IGHV. In addition, chronic lymphocytic leukemia patients with unmutated IGHV and high COBLL1 show impaired motility and chemotaxis towards CCL19 and CXCL12 as well as enhanced B-cell receptor signaling pathway activation demonstrated by increased PLCγ2 and SYK phosphorylation after IgM stimulation. COBLL1 expression also changes during B-cell maturation in non-malignant secondary lymphoid tissue with a higher expression in germinal center B cells than naive and memory B cells. Our data thus suggest COBLL1 involvement not only in chronic lymphocytic leukemia but also in B-cell development. In summary, we show that expression of COBLL1, encoding novel ROR1-binding partner, defines chronic lymphocytic leukemia subgroups with a distinct response to microenvironmental stimuli, and independently predicts survival of chronic lymphocytic leukemia with unmutated IGHV.

Neuron-specific enolase (NSE) is the most investigated biomarker in the context of epilepsy and brain damage. The present study was conducted to investigate the change in serum NSE in patients with focal seizure and the effect of carbamazepine and oxcarbazepine on serum NSE. The present study is a randomized, open-label, parallel design clinical trial (ClinicalTrials.gov Identifier: NCT02705768) conducted on 60 patients of focal seizure. After recruitment, detailed history, clinical evaluations including Chalfont-National Hospital seizure severity scale (NHS3), Quality of Life in Epilepsy Inventory (QOLIE-31) and serum NSE estimation were done at baseline. Thirty healthy volunteers were recruited for a baseline evaluation of serum NSE. After randomization, one group received tablet oxcarbazepine and another group received tablet carbamazepine. At 4 weeks follow-up, all the parameter were reassessed. Serum NSE level was found to be significantly increased in patients with focal seizure in comparison to healthy volunteers. In both drug groups, serum NSE decreased significantly but the reduction in carbamazepine group (1.43; 95%CI: 0.18-2.67; p=0.025) was significantly higher than oxcarbazepine group.NHS3 score, score in all seven domains of QOLIE-31 and final QOLIE-31 score improved significantly in both the groups. In conclusion, serum NSE increases in the patients with focal seizure within 48h of a seizure episode. Therapy with carbamazepine and oxcarbazepine can decrease serum NSE level but the reduction is significantly higher with carbamazepine. Therapy with both the drugs can decrease the severity of epilepsy and improve the quality of life but adverse events were more with carbamazepine.

Background Hysterosalpingography (HSG) is a useful screening test for the evaluation of female infertility. Laparoscopy has proven role in routine infertility work up but role of hysteroscopy in an infertile patient with normal HSG for additional information is a subject of debate. Hysteroscopy permits direct visualization of the cervical canal and the uterine cavity and thereby helping in the evaluation of shape, and cavitary lesion.Objective To detect uterine abnormalities in infertile women by various approaches i.e. HSG and hysteroscopy and evaluating the role of combining hysteroscopy with laparoscopy for the evaluation of tubo-uterine factor for primary infertility.Method One twenty eight infertile women were evaluated and HSG was performed as a basic test for evaluation of tubes and uterine cavity. Women were subjected to combined laparoscopic and hysteroscopic examination on evidence of HSG abnormalities. In absence of any HSG abnormality, women were subjected to ovulation induction for three to six months and if they did not conceive during this period they were undertaken for combined laparo-hysteroscopic evaluation.Result The positive predictive value of HSG for detecting the intrauterine abnormalities was 70% among 126 patients where the hysteroscopy could be performed successfully. The diagnostic accuracy of HSG for intrauterine abnormalities revealed false negative rate of 12.96%. The most frequent pathologies encountered by laparoscopy were tubal and/or peritoneal and were found in 68% (87/128) of women. Total 64.06% infertile women had some abnormality on laparoscopy. This detection rate has been increased from 64.06% to 71.86% on including the concomitant hysteroscopy.Conclusion HSG is a good diagnostic modality to detect uterine as well as tubal abnormalities in infertile patient. HSG and hysteroscopy are complementary to each other and whenever the patient is undertaken for diagnostic laparoscopy for the infertility, hysteroscopy should be combined to improve the detection rate of abnormalities especially in communities where there is enormous risk of pelvic infection.

The sleep and circadian rhythm disruptions in schizophrenia are attributed to a decrease in nocturnal melatonin level which may worsen if treated with conventional sedative drugs. This study was planned to evaluate the effects of add-on ramelteon on sleep and circadian rhythm disturbances in schizophrenia. A randomized, rater-blinded clinical trial was conducted on 120 patients with schizophrenia. Patients were categorized into predominantly positive (PG) or negative (NG) symptoms depending on Positive and Negative Syndrome Scale (PANSS) scoring, and then they were randomized into control (haloperidol/risperidone) or test (add-on ramelteon) groups. After recruitment, baseline serum melatonin, serum AANAT, urinary melatonin and Pittsburgh Sleep Quality Index (PSQI) were evaluated. Patients were reassessed after 4 weeks of therapy with antipsychotics with or without ramelteon. A significantly greater increase in night-time melatonin level (PG: 10·19; 95%CI: 1·42 to 18·97; p = 0·024; NG: 18·74; 95%CI: 8·48 to 29·0; p = 0·001), decrease in PSQI scores (PG: −1·57; 95%CI: −2·59 to −0·55; p = 0·003; NG: −2·49; 95%CI: −4·59 to −0·39; p = 0·021), increase in urinary melatonin (PG: 0·20; 95% CI: 0·056 to 0·35; p = 0·008; NG :0·15; 95% CI: 0·01 to 0·29; p = 0·034), increase in serum AANAT (PG: 4·61; 95%CI: 1·34 to 7·87; p = 0·007; NG:3·46; 95%CI: 1·30 to 5·63; p = 0·002) and improvement in PANSS score were found in patients receiving add-on ramelteon. The increase in serum melatonin and decrease in PSQI score were greater with predominantly negative symptom group in comparison to positive symptom group. Ramelteon may be considered as an add-on therapy with antipsychotic drugs for sleep and circadian rhythm disturbances in schizophrenia.

Background The neurotrophic hypothesis of depression has been mostly studied with a focus on brain-derived neurotrophic factor (BDNF) leading to lack of data on non-BDNF neurotrophins (NTs). The aim of this study was to evaluate the effect of antidepressant drugs on changes in serum nerve growth factor (NGF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Methods A prospective cohort study was conducted on 105 patients with depression who were subgrouped to the group 1 (mild and moderate depression without somatic syndrome treated with sertraline), group 2 (mild and moderate depression with somatic syndrome treated with dosulepin), and group 3 (severe depression without psychotic symptoms treated with venlafaxine). At baseline, the severity of depression (Montgomery-Asberg Depression Rating Scale [MADRS]), serum NGF, NT-3, and NT-4 were estimated. Thirty-five healthy volunteers were recruited as controls for a baseline comparison of NTs. All patients were followed up after 6 weeks to evaluate the changes in NT levels and correlate it with the change in MADRS scores. Results At baseline, NT levels were significantly lower in patients with depression in comparison with healthy control. In group 1, serum NGF, NT-3, and NT-4 level were found to increase significantly after treatment, whereas changes in groups 2 and 3 were statistically not significant. Montgomery-Asberg Depression Rating Scale score and serum NGF at baseline had an inverse relation (r = -0.648), whereas the change in MADRS score in sertraline group had a positive correlation (r = 0.86) with the change of serum NGF. Conclusions Monotherapy with sertraline increased the level of non-BDNF NTs; however, treatment with dosulepin and venlafaxine did not produce any significant changes in patients with depression.

Retrospective analysis has already shown correlation between severe Chronic Periodontitis (CP) cases with human papiloma virus (HPV). Hence, we aimed to explore deep-seated infected granulation tissue removed during periodontal flap surgery procedures for residential bacterial species between HPV+ and HVP- CP cases, which may serve as good predisposition marker for oral cancer. All CP-granulation samples showed the prominence ofFirmicutes, Proteobacteria, andBacteroidetesphyla with an abundance of gram negative anaerobes, exceptStreptococcus. In Beta diversity nonmetric multidimensional scaling plot, the random distribution of species was observed between HPV+ and HPV- CP granulation-samples. However, an abundance ofCapnocytophaga ochraceawas observed in HPV+ CP samples (pPorphyromonas endodontalis,Macellibacteroides fermentas,Treponema phagedenis, andCampylobacter rectusspecies were highly abundant in HPV- CP samples (p

The Aetiology of Neonatal Infection in South Asia (ANISA) study is being carried out at 5 sites across Bangladesh, India and Pakistan, generating in-depth information on etiologic agents in the community setting. Pregnancies are identified, births are registered and young infants are followed up to 59 days old with regular assessments for possible serious bacterial infection following a generic protocol. Specimens are collected from suspected cases. This article describes the challenges in implementing the generic ANISA protocol and modifications made to accommodate the Odisha site, India.Primary challenges in implementing the protocol are the large geographic area, with a population of over 350,000, to be covered; assessing young infants at home and arranging timely transport of sick young infants to study hospitals for physician confirmation of illness; and specimen collection and treatment. A large workforce is deployed in a 3-tier system in the field, while clinical, microbiology, laboratory and data management teams collaborate dynamically. Mobile phones with text message capability, integration with the Odisha State government's health system, involvement of local communities and strict monitoring at different levels have been critical in addressing these challenges.This article describes the challenges and modalities adopted to collect complex and accurate data on etiology, timing of disease and associated factors for community-acquired neonatal infections. Attention to local culture and customs, training and employing community level workers and supervisors, involving existing government machinery, using technology (cell phones), and uninterrupted systematic monitoring are critical for implementing such complex protocols that aim to collect population-based data to drive policy.

Environmental pharmacology is the knowledge, study and the methods implemented for amalgamating the presence of pharmaceutical products and their metabolites in the environment. Pharmaceutical and house care products and their metabolites gain access to the environment through various means and affect the flora and fauna and modulate the ecosystem. The effect on wildlife, biofilms and human are being studied to gain knowledge of sources and causations. Potential risks of development of acute and chronic toxicity, carcinogenicity, interference with hormone and immune systems and drug resistance are of major concern. They may alter the genome and can affect future generations leaving them vulnerable to disease. There are regulations in good manufacturing practices and disposal which take into account the environmental risks but the knowledge for stakeholders and their implementation is very restricted. Ecopharmacology and ecopharmacovigilance are propagators of green healthcare. A strategy towards human health risk assessment and ecotoxicological hazard evaluation must be developed and risk minimization measures to be sought for and applied.

The genetic association of Hypospadias-risk studies has been conducted in Caucasians, Chinese-Han populations and few in Indian populations. Although no comprehensive approach has been followed to assess genetic involvement in the severity of the disorder. The study evaluated to establish the correlation between genotyped SNPs/CNVs and Hypospadias-severity by an association in a total 30 SNPs in genes related to sex hormone-biosynthesis and metabolism; embryonic-development and Phospholipase-D-signalling pathways on 138 surgery-confirmed hypospadias-cases from North-India (84 Penile and 28 cases of Penoscrotal-Hypospadias compared against 31 cases of Glanular+Coronal), and analyzed and identified copy number variants (CNVs) in four Familial samples (18 members) and three paired-sporadic cases (6 samples) using array-based comparative-genomic-hybridization and validated in 32 Hypospadias samples by TaqMan assay. Based on Odds Ratio at 95% CI, Z Statistic and Significance Levels, STS gene-rs17268974 was associated with Penile-Hypospadias and 9-SNPs (seven-SNPs (rs5934740; rs5934842; rs5934913; rs6639811; rs3923341; rs17268974; rs5934937) of STS gene; rs7562326-SRD5A2 and rs1877031-STARD3 were associated with Penoscrotal-Hypospadias. On aggregate analysis with p

S100B, a cytokine produced by astrocytes, has been studied as a biomarker of glial and neuronal damage in epilepsy. The present study investigated the reliability of serum S100B as a biomarker and the effect of carbamazepine and oxcarbazepine on serum S100B in patients with focal seizure. The present randomized, open-label, active-controlled, parallel design clinical trial (NCT02705768) conducted on 60 patients with focal seizure. After recruitment, clinical evaluations were performed including Chalfont-National Hospital seizure severity scale (NHS3), Quality of Life in Epilepsy Inventory (QOLIE-31) and serum S100B was estimated. Thirty healthy individuals were recruited for evaluation of serum S100B at baseline only. After randomization, the study groups received either tablet oxcarbazepine or tablet carbamazepine. At follow-up after 2 weeks, clinical status was checked and at 4 weeks, NHS3 and QOLIE-31 were scored along with serum S100B level estimation. Serum S100B level in patients with focal seizure increased significantly in comparison to healthy volunteers. The decrease in serum S100B was significantly higher with carbamazepine group (0.004; 95% CI 0.001–0.006; p = 0.01) over oxcarbazepine group. In logistic regression analysis, there was an increase in the log odds of 0.17 for focal seizure positivity against healthy controls if S100B level increases by 1 pg and area under curve obtained by ROC analysis was 0.96 (p

Smoking has been associated with increased risk of periodontitis. The aim of the present study was to compare the periodontal disease severity among smokers and nonsmokers which may help in better understanding of predisposition to this chronic inflammation mediated diseases. We selected deep-seated infected granulation tissue removed during periodontal flap surgery procedures for identification and differential abundance of residential bacterial species among smokers and nonsmokers through long-read sequencing technology targeting full-length 16S rRNA gene. A total of 8 phyla were identified among which Firmicutes and Bacteroidetes were most dominating. Differential abundance analysis of OTUs through PICRUST showed significant (p>0.05) abundance of Phyla-Fusobacteria (Streptobacillus moniliformis); Phyla-Firmicutes (Streptococcus equi), and Phyla Proteobacteria (Enhydrobacter aerosaccus) in nonsmokers compared to smokers. The differential abundance of oral metagenomes in smokers showed significant enrichment of host genes modulating pathways involving primary immunodeficiency, citrate cycle, streptomycin biosynthesis, vitamin B6 metabolism, butanoate metabolism, glycine, serine, and threonine metabolism pathways. While thiamine metabolism, amino acid metabolism, homologous recombination, epithelial cell signaling, aminoacyl-tRNA biosynthesis, phosphonate/phosphinate metabolism, polycyclic aromatic hydrocarbon degradation, synthesis and degradation of ketone bodies, translation factors, Ascorbate and aldarate metabolism, and DNA replication pathways were significantly enriched in nonsmokers, modulation of these pathways in oral cavities due to differential enrichment of metagenomes in smokers may lead to an increased susceptibility to infections and/or higher formation of DNA adducts, which may increase the risk of carcinogenesis.

Summary We previously developed a mass spectrometry-based method, dynamic organellar maps, for the determination of protein subcellular localization and identification of translocation events in comparative experiments. The use of metabolic labeling for quantification (stable isotope labeling by amino acids in cell culture [SILAC]) renders the method best suited to cells grown in culture. Here, we have adapted the workflow to both label-free quantification (LFQ) and chemical labeling/multiplexing strategies (tandem mass tagging [TMT]). Both methods are highly effective for the generation of organellar maps and capture of protein translocations. Furthermore, application of label-free organellar mapping to acutely isolated mouse primary neurons provided subcellular localization and copy-number information for over 8,000 proteins, allowing a detailed analysis of organellar organization. Our study extends the scope of dynamic organellar maps to any cell type or tissue and also to high-throughput screening., Graphical Abstract, Highlights • High-resolution organellar maps with label-free quantification (LFQ) • High-throughput organellar maps with TMT-based multiplexing • Deep mapping of EGF-induced protein localization changes with SILAC, LFQ, and TMT • A quantitative spatial proteome from mouse primary neurons, Dynamic organellar maps previously provided a proteomic method for capturing protein subcellular localization changes in cultured cells. Itzhak et al. have now adapted the approach to a universal format, extending the method to all cell types. Application to primary mouse neurons provides spatial and quantitative information for more than 8,000 proteins.

The planar cell polarity (PCP) pathway is a conserved pathway that regulates cell migration and polarity in various contexts. Here we show that key PCP pathway components such as Vangl2, Celsr1, Prickle1, FZD3, FZD7, Dvl2, Dvl3, and casein kinase 1 (CK1)-ϵ are upregulated in B lymphocytes of patients with chronic lymphocytic leukemia (CLL). Elevated levels of PCP proteins accumulate in advanced stages of the disease. Here, we show that PCP pathway is required for the migration and transendothelial invasion of CLL cells and that patients with high expression of PCP genes, FZD3, FZD7, and PRICKLE1, have a less favorable clinical prognosis. Our findings establish that the PCP pathway acts as an important regulator of CLL cell migration and invasion. PCP proteins represent an important class of molecules regulating pathogenic interaction of CLL cells with their microenvironment. Cancer Res; 73(5); 1491–501. ©2012 AACR.

Recurrence of fistula is one of the very common complications of fistula repair. The disease has immense psychosomatic effect on the patients due to continuous leakage of urine. Management of recurrent vesico-vaginal fistula (VVF) repair poses a challenge to surgeons.Group I-12 patients with recurrent VVF, having robotic repair from August 2006 to June 2008, were included in the present study. Group II-20 patients matched in all possible parameters with recurrent VVF having open surgical repair in the past were taken as controls. Patients in both the groups were evaluated by assessing relevant clinical details; performing urine routine examination and culture, renal function test, three swab test, ultrasonogram-kidney, ureter, and bladder radiograph, intravenous urogram (to look for upper tract and rule out uretero-vaginal fistula), and urethro-cystoscopy. The details were retrospectively recorded from the case sheets.In group I, 100% were successfully managed as compared with 90% in group II, but it was not statistically significant (p0.05). Mean blood loss was significantly less (p0.05) in group I compared with group II (mean 88 vs. 170 mL). The mean hospital stay also was significantly less (p0.05) in group I in comparison with group II (mean 3.1 vs. 5.6 days). None of the patients had complications in group I compared with group II, but it was not significant.The present study suggests that robotic VVF repair is a better option for recurrent fistulas in view of its reduced morbidity, without compromising the results.

Purpose Based on copy number alterations and transcriptional profiles, the posterior fossa tumors (medulloblastoma (MB), ependymoma and pilocytic astrocytoma) have been classified into various subgroups. The study design was aimed to identify and catalog genome-wide copy number alterations and differential gene expression in different types of North-Indian pediatric posterior fossa tumors and matched control tissue through Molecular Inversion Probe (MIP) Based and Human Transcriptome Array. Experimental design MIP based OncoScan Array and Human Transcriptome Array 2.0 were used to molecularly-categorize histopathologically and immunohistochemically proven tumor samples on the basis of copy number variations and altered gene expression patterns and/or alternative splicing events. Results Based on molecular, histopathological/immunohistochemical and age-dependent factors MB was subgrouped into group-3 MB, Wnt and SHH; ependymoma into balanced, numerical and structural/anaplastic; and pilocytic astrocytoma was stratified age-dependently. Compared with the vermis tissue of MB, the vermis tissue of ependymoma showed higher levels of gain and losses compared with their counter tumor parts implicating metastasis within the confined region. Group-3 MB and anaplastic ependymoma represented highest differentially expressed genes both at gene and exon levels in the CN altered regions compared with other subgroups of MB and ependymoma respectively. Conclusion This multiomics approach based molecular characterization of posterior fossa tumors together with clinical and histopathological factors may help us in the area of personalized medicine.

Background: ω–3 fatty acids have beneficial effects in chronic inflammatory diseases that are characterized by accumulation of leukocytes and leukocyte-mediated tissue injury. Accumulation of leukocytes occurs, in part, due to pro-inflammatory responses in endothelial cells, such as increase in expression of leukocyte adhesion receptors and chemokines, such as MCP-1 and IL-8. Methods: ω–3 fatty acids, such as EPA, are highly polyunsaturated and readily undergo auto-oxidation. We studied the effect of oxidized EPA and unoxidized (native) EPA on leukocyte-glomerular endothelial cell interactions using adhesion assays, ELISA assays and transmigration assays. We used electrophoresis mobility shift assays to determine the effect of oxidized and unoxidized EPA on cytokine-induced nuclear factor-ĸB (NF-ĸB) activation. Results: Oxidized EPA but not unoxidized EPA dose-dependently inhibits cytokine-induced leukocyte adhesion receptors on glomerular endothelial cells, which correlates with inhibition of leukocyte-glomerular endothelial cell interactions. Oxidized EPA but not unoxidized EPA inhibits cytokine-induced glomerular endothelial and mesangial cell expression of MCP-1, and to a lesser extent IL-8. Transmigration assays show that oxidized EPA but not unoxidized EPA inhibits leukocyte transmigration across glomerular endothelial cells. Oxidized EPA but not unoxidized EPA potently inhibited cytokine-induced activation of NF-ĸB in glomerular endothelial and mesangial cells. Conclusions: These studies show that the beneficial effects of fish oil in chronic inflammatory diseases, including IgA nephropathy, may result from the inhibitory effects of oxidized ω–3 fatty acids on pro-inflammatory events in endothelial cells via inhibition of NF-ĸB activation.

Objective— The aim of this study was to determine the effects of oxidized versus native omega-3 fatty acids on the endothelial expression of chemokines MCP-1 and IL-8, and, if effective in inhibiting chemokine expression, to determine the mechanism for the inhibition of chemokine expression. Methods and Results— Using enzyme-linked immunosorbent assays, we show that oxidized EPA and DHA but not unoxidized EPA or DHA inhibit cytokine-induced endothelial expression of monocyte chemoattractant protein (MCP)-1 and, to a lesser extent, IL-8. In electrophoretic mobility shift assays, oxidized EPA but not unoxidized EPA potently inhibited cytokine-induced activation of endothelial nuclear factor-κB (NF-κB). Using Western blot analyses, we show that the inhibition of NF-κB activation was not caused by prevention of phosphorylation of IκBα because oxidized EPA did not inhibit cytokine-induced phosphorylation and ubiquination of IκBα. Furthermore, oxidized EPA inhibited NF-κB activation in endothelial cells derived from wild-type mice but had no inhibitory effects on NF-κB activation in endothelial cells derived from peroxisome proliferator-activated receptor α (PPARα)-deficient mice, indicating that oxidized EPA requires PPARα for its inhibitory effects on NF-κB. Conclusions— These studies show that the antiinflammatory effects of fish oil may result from the inhibitory effects of oxidized omega-3 fatty acids on NF-κB activation via a PPARα-dependent pathway.

Background Various cardiac electrophysiologic effects have been attributed to erythromycin. During the course of treating a pneumonia patient with IV erythromycin, the conversion of atrial fibrillation to a sinus rhythm, and its subsequent reversal, appeared to be causally related to the introduction and cessation of this antibiotic. Objective This observation suggested the need for studying the changes in the ECG following the use of IV erythromycin in a typical clinical setting. Design A prospective comparative drug study. Setting A university-affiliated teaching hospital. Patients Nineteen patients being treated for uncomplicated community-acquired pneumonia. Intervention IV erythromycin, 500 mg, and/or IV cefuroxime, 750 mg, infused in 250 mL of saline over 20 min. In the 11 patients who were receiving both of the antibiotics, cefuroxime was administered immediately before erythromycin was infused. Measurements The 12-lead ECG measurements were obtained before infusion, at 5-min intervals during each infusion, and at 5 and 10 min after the infusions had been completed. All of the ECG complexes and intervals were measured using a software program (Interpretive Cardiograph; Hewlett Packard; Palo Alto, CA). Results The administration of IV erythromycin increased heart rate and prolonged the corrected QT (QTc) interval. These changes were significant at 15 min of the infusion, and were no longer evident 5 min after the infusion had been stopped. The administration of IV cefuroxime did not produce any ECG changes. Conclusions A single, standard dose of IV erythromycin prolongs the QTc interval; therefore, the drug should always be administered as a slow infusion. ECG monitoring should accompany erythromycin therapy in critically ill patients, in patients with electrolyte disorders, or in patients taking other drugs with similar cardiac effects.

Introduction: Currently, surgical repair for vesicovaginal fistula (VVF) provides excellent results, but the recurrent VVF is difficult to treat as compared to primary. Patients and Methods: Sixty-eight patients (44 primipara and 24 multipara) with recurrent VVF repair from January 2002 to December 2007 were included in present study. The mean size of fistula was 2.8 cm (1.0–6.5). The previous surgical repair was through the abdominal route in 50 patients (73.53%) and through the vaginal route in the remaining 18 patients (26.47%). Results: The procedure was successful in 62 of 68 patients (91.17%). The mean duration of surgery was 146.6 min (100–210). Mean blood loss was 160 ml (110–400) and mean hospital stay was 5.6 days (4–10). Eight patients developed complications. Conclusion: Recurrent VVF is difficult to treat, but excellent results can still be achieved by strictly sticking to the principals of surgical repair for VVF.

Background Maternal death reviews have been utilized in several countries as a means of identifying social and health care quality issues affecting maternal survival. From 2005 to 2009, a standardized community-based maternal death inquiry and response initiative was implemented in eight Indian states with the aim of addressing critical maternal health policy objectives. However, state-specific contextual factors strongly influenced the effort's success. This paper examines the impact and implications of the contextual factors. Methods We identified community, public health systems and governance related contextual factors thought to affect the implementation, utilization and up-scaling of the death inquiry process. Then, according to selected indicators, we documented the contextual factors' presence and their impact on the process' success in helping meet critical maternal health policy objectives in four districts of Rajasthan, Madhya Pradesh and West Bengal. Based on this assessment, we propose an optimal model for conducting community-based maternal death inquiries in India and similar settings. Results The death inquiry process led to increases in maternal death notification and investigation whether civil society or government took charge of these tasks, stimulated sharing of the findings in multiple settings and contributed to the development of numerous evidence-based local, district and statewide maternal health interventions. NGO inputs were essential where communities, public health systems and governance were weak and boosted effectiveness in stronger settings. Public health systems participation was enabled by responsive and accountable governance. Communities participated most successfully through India's established local governance Panchayat Raj Institutions. In one instance this led to the development of a multi-faceted intervention well-integrated at multiple levels. Conclusions The impact of several contextual factors on the death inquiry process could be discerned, and suggested an optimal implementation model. District and state government must mandate and support the process, while the district health office should provide overall coordination, manage the death inquiry data as part of its routine surveillance programme, and organize a highly participatory means, preferably within an existing structure, of sharing the findings with the community and developing evidence-based maternal health interventions. NGO assistance and the support of a development partner may be needed, particularly in locales with weaker communities, public health systems or governance.

Increased heart rate during graded exercise is related to increased sympathetic activity and withdrawal of vagal tone. Return of heart rate towards baseline immediately after exercise is usually due to resurgence of vagal tone. As it is an established fact that cardiovascular morbidity and mortality in part has direct relation with parasympathetic dysfunction, it is natural that reduced heart rate recovery (HRR) after exercise, a parameter of parasympathetic dysfunction, could be a predictor of morbidity and mortality. Accordingly 390 TMT positive patients were analysed for HRR as per standard guidelines and followed up for 5 years. While 244(62.6%) showed a normal HRR, 146(37.4%) showed an abnormal HRR. Abnormal HRR was more common in the elderly, in patients with higher resting heart rate, hypertension, diabetes mellitus, current smoking and prior established coronary artery disease (CAD). There were a total of 36 deaths (9.23%) during the 5 year follow-up period. There was mortality advantage in patients who were subjected to revascularization procedure in general (7.5% deaths in revascularised arm vs 10.4% in conservative arm). Analysis reveals persistence of such benefit in patients having normal HRR (2.85% deaths in revascularised arm vs 7.25% in conservative arm). However, mortality benefit was not observed among both groups of patients with abnormal HRR(16.6% deaths in revascularised vs 15.2% in conservatively managed7rpar;. Secondary end points like recurrent angina, arrhythmia, acute myocardial infarction, hospitalization for cardiovascular cause and heart failure were observed in significantly more number of cases with abnormal HRR in comparison to normal. We therefore conclude the abnormal HRR after TMT is an adverse prognostic indicator in patients with symptomatic CAD on long term follow-up.

M-mode echocardiography has been accepted as gold standard for measuring left atrial (LA) size. Electrocardiography (ECG) offers a simple, non-invasive, cost-effective and reproducible method to assess LA size and it is mostly in agreement with echocardiography though discrepancies exist. ECGs and echocardiograms were obtained in 100 consecutive patients suspected of having left atrial enlargement due to different underlying heart diseases. The diagnostic accuracy of six ECG criteria of LA enlargement were evaluated comparing with LA size in M-mode echo study. Various criteria were found to be poor to mildly sensitive (8% to 78%) but highly specific (85% to 100%) for left atrial enlargement. Morris Index (PTFV1) was found to be the best criterion having 76% sensitivity and 92% specificity. Combination of criteria enhances the sensitivity at the cost of specificity. Overall predictive index of electrocardiogram for left atrial enlargement is not encouraging.

Background Several studies investigated the association of anemia with health related quality of life (HRQL) in patients with chronic disease. However, there is little evidence regarding the association of anemia with HRQL in patients with chronic obstructive pulmonary disease (COPD). Methods This is a post-hoc analysis of a study which enrolled a population of adults aged 35–79 randomly selected from residents of Erie and Niagara Counties, NY, between 1996 and 2000. In addition to demographic information and physical measurements, we obtained spirometry data and hemoglobin levels. We used modified Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria to define COPD, and World Health Organization (WHO) criteria to define anemia. To assess HRQL we used the Short Form-36 (SF-36) to assess physical functioning (PF), physical component summary (PCS) measures and mental component summary (MCS) measures. Results In the entire study population (n = 2704), respondents with anemia had lower scores on the physical functioning domain [45.4 (SD10.9) vs. 49.2 (SD 9.1); p < 0.0001]. Among patients with COPD (n = 495) the PF scores (39.9 vs. 45.4) and the PCS (41.9 vs. 45.9) were significantly lower in individuals with anemia compared to those without. In multiple regression analysis, the association between hemoglobin and PCS was positive (regression coefficient 0.02, p = 0.003). There was no significant association of hemoglobin with PF scores or the mental component summary measure after adjusting for covariates in patients with COPD. Conclusion In patients with moderate to very severe COPD anemia may be associated with worse HRQL. However, co-morbidities may explain part or all of this association in these patients.

OBJECTIVE: To report a case of nontraumatic rhabdomyolysis complicated by oliguric, acute renal failure following an intentional overdose of ethanol and diphenhydramine. CASE SUMMARY: A 21-year-old white man was admitted through the emergency department following an intentional overdose of ethanol and diphenhydramine. The patient subsequently developed acute renal failure, and a diagnosis of nontraumatic rhabdomyolysis was made. With the absence of other common causes in this case, the rhabdomyolysis was believed to be due to the combined ethanol and diphenhydramine overdose. DISCUSSION: Rhabdomyolysis is a severe and life-threatening syndrome caused by various insults to skeletal muscle, including drug-induced injury. Early detection and institution of effective treatments are essential to minimizing the complications of this syndrome. A delay in establishing the diagnosis in this case likely contributed to the severity of the renal failure. CONCLUSIONS: Nontraumatic rhabdomyolysis is an uncommon adverse outcome of drug and toxin ingestion. Due to the potential severity of the complications of this syndrome and the importance of early recognition and treatment to prevent renal failure, clinicians should have a high index of suspicion for rhabdomyolysis following overdoses that involve alcohol or antihistamines.

Background Cysticercosis cellulosae rarely involves the oral region in humans. Methods Six cases of oral cysticercosis were diagnosed, three each in lips and buccal mucosa. Diagnosis was made by characteristic gross and histopathologic appearances. Results Of 146 cases of cysticercosis, 6 (4.1%) were of the oral cavity. All 6 cases were initially seen with painless swellings. Clinical differential diagnosis ranged from retention cyst, lipoma, fibroma, neurofibroma, and angular stomatitis. Histopathologic examination revealed cysticercus larvae. Conclusions The oral cavity is a rare site of involvement by cysticercosis, even in an endemic area. Histopathologic findings of the excised cyst are diagnostic of the lesion. © 2001 John Wiley & Sons, Inc. Head Neck 23: 497–499, 2001.

The source and nature of zona lytic factors during zona escape of hamster blastocyts were investigated. When cultured in hamster embryo culture medium (HECM)-2h, all 8-cell embryos (n = 135) developed to zona escaped-blastocysts with complete zona lysis. In addition, 2-cell embryos, when co-cultured with zona escaping-blastocysts (at a ratio of 1:10), exhibited zona lysis. Various other embryos at the 1-8-cell stages also showed zona lysis when cultured with zona-escaping blastocysts. However, zonae from mice, rats, sheep and humans were resistant to lysis under these conditions. Pronase treatment resulted in rapid zona lysis in hamsters (7 +/- 1 s), whereas in other species zona lysis was much slower: mouse (662 +/- 27 s), rat (532 +/- 16 s), sheep (120 +/- 12 s) and human (104 +/- 8 s). When cysteine protease inhibitors (antipain, leupeptin, E-64 and p-hydromercuricbenzoate) were tested, they completely inhibited zona escape, while trypsin inhibitors (TLCK and SBTI) did not. Uterine zona lysin contribution in zona escape was discounted since: (i) uterine luminal flushing and endometrial extract from day 4 (the time of zona escape in vivo) pregnant females failed to lyse zonae and (ii) endogenous oocytes and transferred 2-cell embryos (to day 3 pseudopregnant recipients) were all zona-intact, while 71% of transferred blastocysts exhibited zona escape, following their recovery after 24 h. These observations suggest that a species-specific, embryonic proteolytic factor, with a cysteine protease-like activity, is involved in the zona escape of blastocysts in hamsters.

Sleep-related hallucinations (hypnagogic and hypnopompic) are transient and occur in normal individuals. Rarely, they are prominent and distressing and are associated with diverse conditions including narcolepsy. We report a case of prominent hypnopompic auditory hallucinations — which gradually became continuous and distressing with characteristics of schizophrenia-like hallucinations — that responded to a low dose of olanzapine.