The usefulness of Olanzapine plasma concentrations in monitoring treatment efficacy and metabolic disturbances in first-episode psychosis.

INTRODUCTION: The role of Olanzapine therapeutic drug monitoring is controversial. The present study explores the associations of Olanzapine plasma concentrations with clinical response and metabolic side effects in first episode psychosis (FEP) after 2 months of treatment. METHODS: Forty-seven patients were included. Improvement in clinical symptomatology was assessed using the PANSS. Metabolic assessment included weight, blood pressure, waist circumference, blood glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. RESULTS: The Olanzapine plasma concentrations after 2 months of treatment were positively correlated with weight gain (r = 0.49, p = 0.003), and a concentration > 23.28 ng/mL was identified as a positive predictor of weight gain (≥ 7%). The Olanzapine concentration to dose (C/D) ratio was positively correlated with the percentage of improvement in the total PANSS (r = 0.46, p = 0.004), and a C/D ratio > 2.12 was identified as a positive predictor of a good response (percentage of improvement > 30%) after 2 months of treatment. We also identified several factors that could alter Olanzapine pharmacokinetics: gender (p = 0.03), diagnosis (p = 0.05), smoking habit (p = 0.05), and co-medications such as valproic acid (p = 0.05) and anxiolytics (p = 0.01). DISCUSSION: In conclusion, our results suggest that therapeutic drug monitoring of Olanzapine could be helpful to evaluate therapeutic efficacy and metabolic dysfunction in FEP patients treated with Olanzapine.

Efficacy and safety comparison of combination of 0.04% tretinoin microspheres plus 1% clindamycin versus their monotherapy in patients with acne vulgaris: a phase 3, randomized, double-blind study.

BACKGROUND AND OBJECTIVES: There is an unmet need for topical treatments with good tolerability in management of acne vulgaris. The present study aimed to evaluate efficacy and safety of a novel tretinoin (microsphere, 0.04%) formulation in combination with clindamycin (1%) gel for treatment of acne vulgaris. MATERIALS AND METHODS: This phase 3 randomized, double-blind study included patients with moderate-to-severe acne. Patients were treated with tretinoin (microsphere, 0.04%) + clindamycin (1%) or one of the monotherapies (tretinoin, 0.025%; clindamycin, 1%). Key endpoints included percent change in lesion counts, and improvement in Investigator's Static Global Assessment (ISGA) score. RESULTS: 750 patients were randomized (combination, n = 300; tretinoin and clindamycin, each n = 150). At week 12, reductions in inflammatory (77%), non-inflammatory (71%) and total lesions (73%) were significantly greater with combination treatment versus either monotherapy (p < .03). Proportion of patients rated 'clear' or 'almost clear' with ≥2-grade ISGA improvement was higher with combination (46%) versus monotherapies (p < .02). Adverse events occurred in 20 patients, most were mild-moderate; no deaths or serious adverse events were reported. The discontinuation rates due to adverse events with combination therapy were low (≤1%). CONCLUSION: The once-daily, microsphere-based formulation was generally tolerable with a positive impact on therapeutic outcomes and patients' compliance. CLINICALTRIAL REGISTRATION NO.: CTRI/2014/08/004830.

Retrospective analysis of EMR database to assess the effectiveness of Saccharomyces boulardii CNCM I-745 in children with acute diarrhoea during routine clinical practice.

This study aimed to assess the efficacy of Saccharomyces boulardii, a yeast probiotic, in the management of acute diarrhoeal disorders in the paediatric population in outpatient settings. It was a multicentre retrospective analysis of medical records of children who were treated for acute diarrhoea by routine treatment (oral rehydration solution and zinc) with or without S. boulardii. Overall, 160 children presenting with acute diarrhoea at seven different outpatient paediatric settings were included in the study. Children were divided into two categories based on their treatment with S. boulardii (SB group) or without S. boulardii (Non-SB group). Baseline demographic, anthropometric and clinical variables were compared between the two groups. The median duration of diarrhoea post-treatment was significantly shorter in the S. boulardii group (3 days) than in the non-SB group (4 days). A significant reduction in the frequency of stools was observed post-treatment in the S. boulardii group (1.7 versus 2.5 in the non-SB group). There was a significant weight gain in the S. boulardii group post-treatment (300 g) in comparison with the non-SB group (mean loss of 400 g). This study established the positive role of S. boulardii in the management of acute diarrhoeal diseases in children. Moreover, the S. boulardii probiotic was seen to be effective in diarrhoeal diseases in children with dehydration.

Cannabis use influence on peripheral brain-derived neurotrophic factor levels in antipsychotic-naïve first-episode psychosis.

The objective of this study is to determine whether cannabis influences BDNF levels in patients with psychosis (FEP) and healthy volunteers (HV) to help understand the role of BDNF in psychosis. We assessed the association between BDNF and cannabis in a cohort of FEP antipsychotic-naïve patients and HV, whilst controlling for other potential confounding factors. 70 FEP drug-naive patients and 57 HV were recruited. A sociodemographic variable collection, structured clinical interview, weight and height measurement, substance use determination, and blood collection to determine BDNF levels by ELISA analysis were done. In FEP patients, cannabis use was associated with BDNF levels (high cannabis use was associated with lower BDNF levels). Moreover, cannabis use was statistically significantly associated with age (high use of cannabis was associated with younger age). In HV, no relationship between cannabis use and BDNF levels was observed. Otherwise, cannabis use was significantly associated with tobacco use, so that high cannabis users were also high tobacco users. This study showed a different association between cannabis use and BDNF levels in FEP patients compared with HV, particularly, with high doses of cannabis. These findings may help understand the deleterious effects of cannabis in some vulnerable individuals, as well as discrepancies in the literature.

Inverse association between negative symptoms and body mass index in chronic schizophrenia.

BACKGROUND: We investigated whether negative symptoms, such as poor motivation or anhedonia, were associated with higher body mass index (BMI) in stable patients with schizophrenia chronically treated with antipsychotic medication. METHODS: 62 olanzapine- or clozapine-treated patients with illness duration of at least four years were selected from an international multicenter study on the characterization of negative symptoms. All participants completed the Brief Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale (PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were explored, as well as multiple regression analyses. We further explored the association of two principal component factors of the BNSS and BMI. Subsidiary analyses re-modeled the above using the negative symptoms subscale of the PANSS and the EMSLEY factor for negative symptoms for convergent validity. RESULTS: Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31; p=0.015). A multiple regression analysis showed that negative symptoms (BNSS score) and age were significant predictors of BMI (p=0.037). This was mostly driven by the motivation/pleasure factor of the BNSS. Within this second factor, BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality (r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was positively associated with BNSS (r=0.873, p<0.001), but negatively associated with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach significance (r=-224, p=0.080). CONCLUSIONS: We conclude that lower negative symptoms were associated with higher BMI (assessed using both the BNSS and EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia and asociality levels.

Superior selectivity and enhanced response characteristics of palladium sensitized vanadium pentoxide nanorods for detection of nitrogen dioxide gas.

Vanadium pentoxide (V2O5) nanorods have been deposited onto the glass substrates by spraying 75ml of 30mM vanadium trichloride (VCl3) solution at optimized substrate temperature of 400°C. The XRD study confirms the formation of orthorhombic crystal structure of V2O5 nanorods. The FE-SEM micrograph shows the nanorods-like morphology of V2O5. The presence of palladium (Pd) in the Pd-sensitized V2O5 nanorods is confirmed using EDAX study. The gas sensing measurements show that the Pd-sensitized V2O5 sensing material is an outstanding candidate for nitrogen dioxide (NO2) gas detection. Obtained results demonstrate that the Pd-sensitized V2O5 nanorods show the superior selectivity for NO2 gas in comparison with other gases such as NH3, H2S, CO, CO2 and SO2 at an operating temperature of 200°C. It shows the 75% response for 100ppm NO2 gas concentration with response and recovery times of 22s and 126s, respectively. Finally, the gas sensing mechanism based on chemisorption process is proposed to illustrate how Pd nanoparticles affect the gas sensing characteristics (response and response-recovery times).

Template-free TiO2 photoanodes for dye-sensitized solar cell via modified chemical route.

Surfactant and template-free Titanium dioxide (TiO2) spheres have been deposited via ultrasonic rinsing assisted modified successive ionic layer adsorption and reaction (M-SILAR) method. The effect of M-SILAR cycle variation on the growth of TiO2 films and power conversion efficiency (PCE) of dye-sensitized solar cells (DSSCs) has been reported. Also, the significant influence of the dye adsorption time of photoelectrodes on the overall PCE of TiO2 based DSSCs has been investigated systematically. The SEM images reveal that the TiO2 microspheres are made up of densely packed and interconnected nanospheres. After dye loading maximum absorption peak around 500nm is seen with broader coverage in the visible region of the solar spectrum. The excess amount of dye for dye loading time 15h did not contribute to current and is suspected to be present either in multilayers or physisorbed on the surface of TiO2. The DSSC prepared using photoelectrode TO125 and dye loading time of 12h exhibited the highest power conversion efficiency (PCE) of 1.16% with short-circuit current density (Jsc) of 8.17mA/cm2, open circuit voltage (Voc) of 0.42V and fill factor of 0.34. The PCE is attributed to the large molecular interconnected TiO2 spheres diffusing visible light to enhance the light absorption. Also, it possesses relatively superior 3-D microsphere like structure and thus provides the effective pathway to the photogenerated electrons with low recombination rate, leading to attaining the high PCE.

Highly selective and sensitive response of 30.5 % of sprayed molybdenum trioxide (MoO3) nanobelts for nitrogen dioxide (NO2) gas detection.

The molybdenum trioxide (MoO3) thin films have been successfully deposited onto the glass substrates using chemical spray pyrolysis (CSP) deposition technique at various substrate temperatures ranging from 300°C to 450°C with an interval of 50°C. The effect of substrate temperature on the structural, morphological, optical and gas sensing properties of MoO3 thin films has been thoroughly investigated. X-ray diffraction analysis reveals that all the films have an orthorhombic crystal structure and are polycrystalline in nature. FE-SEM micrographs depict the formation of nanobelts-like morphology. AFM study reveals that the RMS surface roughness of MoO3 thin films increases from 8.6nm to 12nm with increase in substrate temperature from 300°C to 400°C and then decreases to 11.5nm for substrate temperature of 450°C. Optical results show that the band gap of MoO3 thin films decreases from 3.92eV to 3.44eV. The selectivity studies show that the gas response of various gases varies as NH3

Spanish adaptation and validation of the Brief Negative Symptoms Scale.

Negative symptoms prevalent in schizophrenia are associated with poor outcome. Developing new instruments to identify new treatments was highlighted at the NIMH-MATRICS Consensus Development Conference on Negative Symptoms. The new Brief Negative Symptoms scale (BNSS) demonstrated strong psychometric properties, but there is a need for validating it in non-English languages. A multi-center study was conducted to validate the Spanish version of the BNSS (BNSS-Sp) in 20 schizophrenia patients, following the original BNSS validation methodology. We found strong inter-rater, test-retest and internal consistency properties (for the total BNSS-Sp, intraclass correlation coefficient=0.97, Pearson's correlation coefficient r=0.95 (p<0.001), Cronbach's alpha=0.98).

Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF1α-mediated VEGF-dependent angiogenesis.

Hypoxia is a salient feature of most solid tumors, and hypoxic adaptation of cancer cells has crucial implications in propagation of malignant clonal cell population. Osteopontin (OPN) has been identified as a hypoxia-responsive gene, but the mechanistic and regulatory role of OPN under hypoxia is less characterized. The present study identifies the existence of a positive inter-regulatory loop between hypoxia and OPN. We have shown that hypoxia induces OPN expression in breast cancer cells; however, the expression was found to be HIF1α independent. OPN enabled transcriptional upregulation of HIF1α expression both under normoxia and hypoxia, whereas stability of HIF1α protein in breast cancer cells remained unaffected. Moreover, we have shown that OPN induces integrin-linked kinase (ILK)/Akt-mediated nuclear factor (NF)-κB p65 activation leading to HIF1α-dependent vascular endothelial growth factor (VEGF) expression and angiogenesis in response to hypoxia. These in vitro data are biologically important as OPN expressing cells induce greater tumor growth and angiogenesis through enhanced expressions of proangiogenic molecules as compared with control. Immunohistochemical analysis of human breast cancer specimens revealed significant correlation between OPN and HIF1α but not HIF2α. Elevated expression of HIF1α and OPN was observed in pre-neoplastic and early stage infiltrating ductal carcinoma implicating the role of these proteins in neoplastic progression of breast cancer. Together, our results substantiate the prime role of OPN in cellular adaptation through ILK and NF-κB-mediated HIF1α-dependent VEGF expression in response to hypoxia that ultimately controls breast cancer progression and angiogenesis. Our study reinforces the fact that targeting OPN and its regulated signaling network hold important therapeutic implications.

Retrospective analysis of clinicopathological factors and outcome in breast cancer in young women in a tertiary care hospital in India.

BACKGROUND: The proportion of breast cancer is rising in India. It presents at a younger age in India as compared to the western countries. AIMS: This is a retrospective study of 86 breast cancer patients less than 40 years treated in a single center from June 2006 to June 2011. The aim was to assess the factors that may influence clinical outcome. MATERIALS AND METHODS: Data were collected from medical records. Variables such as age, stage, surgery, chemotherapy, tumor size, grade, nodal status, perinodal extension, lymphovascular emboli, estrogen receptor, progesterone receptor, and HER-2 neu were analyzed in relation to outcome. RESULTS: Out of total 613 breast cancer patients, 91 (14.8%) were younger than 40 years. Five were excluded due to incomplete data; hence, 86 patients were included in this study. Median tumor size was 3 cm and lymph node positivity was 56.9%. Lymphovascular emboli were positive in 48.8% and perinodal extension was positive in 41.8%. Estrogen receptor positivity was 34.8%, progesterone receptor positivity was 45.3%, and triple negativity was 45.3%. The median follow-up period was 27 months with disease free survival being 73.2% and overall survival being 87.2%. In univariate analysis, the factors significantly associated with survival were stage at presentation, presence of lymphovascular emboli, perinodal extension and grade of the tumor. In multivariate analysis grade of tumor was the only significant factor. CONCLUSIONS: In young women with breast cancer, the factors significantly associated with survival were clinical stage at presentation, the presence of lymphovascular emboli and perinodal extension and grade of tumor.

Tuberculosis diagnosis after bleach processing for early stage tuberculosis laboratory capacity building.

The diagnosis of tuberculosis is seriously hampered in the absence of standard biosafety laboratory facilities for specimen concentration and Mycobacterium tuberculosis culture. Within a laboratory twinning arrangement, heat-fixed direct smear and sediment from 74 bleach-processed and 20 non-processed specimens from Cumura Hospital, Guinea-Bissau, were sent to Lisbon for molecular evaluation of rifampicin resistance. Sequence analysis of a 369 base-pair rpoB locus detected 3.2% (3/94) resistant specimens. To our knowledge, this represents the first report on the molecular analysis of M. tuberculosis from bleach-processed sputum, an alternative to current diagnostic practice in low-resource settings.

Chemical investigation of Iphigenia stellata blatter by GC-MS.

GC-MS analysis of Iphigenia stellata Blatter in methanol extract revealed the presence of twenty chemical compounds in corm, nine in capsule wall, seven in leaves and six in seeds. Amongst the different phytochemicals identified 2-furan-carboxaldehyde-5-(hydroxymethyl) (38% in corms), glycerine (35.4% in seeds) and n-Hexadecanoic acid (31.5% in leaves, 28% in capsule wall) were significant. Iphigenia stellata is known for the presence of colchicine. However, in the methanol extract it was not detected.

Salt stress induced alteration in growth characteristics of a grass Pennisetum alopecuroides.

Salinity is one of the major abiotic stresses that adversely affect crop productivity and quality. The present investigation was carried out to study the alterations in the growth characteristics of a grass species, Pennisetum alopecuroides under the influence of sodium chloride (NaCl) salinity. From the results it is clear that shoot length of Pennisetum alopecuroides was increased by 13.17% at 100 mM NaCl concentration while the root length was observed to be increased at 50 mM NaCI concentration by 26.93%.Maximum height of the plant was observed by 18.23% at 50 mM while shoot to root ratio was higher at 300 mM concentrations by 29.17% increase over the control. Moreover, the maximum percent increase in leaf area was recorded as 11.17% (100 mM). Fresh weight was increased by 50.92% at 100 mM while dry weight of the experimental grass was increased by 33.64% at the same concentration of salt to the rooting medium while moisture percentage was increased to a maximum by 24.61% at 50 mM. It appears that the grass species studied exhibit a moderate salinity tolerance as far as linear growth of plant is concerned.

Atypical depression is associated with suicide attempt in bipolar disorder.

OBJECTIVE: There is a dearth of research focusing on factors associated with suicide attempts. High rates of atypical depression have been reported in studies including unipolar and bipolar II patients. In this study, the association between suicide attempt and atypical depression, in addition to other major risk factors, was evaluated in 390 bipolar I and II out-patients. METHOD: Variables were defined according to DSM-IV criteria, and assessed with a Structured Interview for DSM-IV (axis I and II). History of suicide attempt was obtained through interviews with patients and relatives. Attempters and non-attempters were compared using univariate and multivariate analysis. RESULTS: Attempters showed significantly higher rates of atypical depression, family history of completed suicide, depression at index episode and cluster B personality disorder. CONCLUSION: Our results highlight the relevance of atypical depression in bipolar disorder. A more accurate identification of potential attempters may contribute to the development of effective preventive treatment strategies.

The random blood glucose level, a risk factor for mortality after acute myocardial infarction, in non-diabetic patients.

The Correlation between blood glucose level and cardio-vascular events is well established in diabetic patients. In this study, fifty three non diabetic (M:30F:23), patients after acute myocardial infarction were studied for mortality in the following two years, retrospectively. Every patient had random venous glucose estimated on admission. This glucose level was correlated with all cause mortality. At the end of 2 years, 13 patients died and 40 remained alive. There was a significant difference of blood glucose between those who died and remained alive. The difference between the mean blood glucose level is between 0.6 mmol/L and 3.8 mmol/L higher for patients who died (mean = 8.62); compared with those that were still alive (mean = 6.69). This difference was particularly observed in the group of anterior wall infarction. The subgroup analysis also revealed that the difference between the mean blood glucose levels is 9 mmol/L for female patients with heart failure compared with those who did not suffer from heart failure (mean 6.8). The study concludes that, the higher glucose level is associated with increased all cause mortality in the following 2 years of first acute myocardial infarction.

Synthesis of new pyrroles and their biological activities.

Coumarino acid hydrazides and acid hydrazide of 2-oxy 3, 5, 6-trichloropyridine were prepared in two steps. These acid hydrazides on condensation with Acetonyl acetone i.e. 2,5-hexanedione yields new pyrroles. These pyrroles showed good to moderate antimicrobial activities against Alternaria brassicicola, Aspergillus niger, E. coli and Lactobacillus.