Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy.

BACKGROUND: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. MATERIALS AND METHODS: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. RESULTS: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an 'immune-desert' group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TMEHigh patients receiving neoadjuvant anti-PD-1 had significantly increased overall survival (P = 0.04). Moreover, TMEHigh patients treated with adjuvant anti-PD-1 or oncolytic virus (PVSRIPO) showed a trend towards improved survival. CONCLUSIONS: We have established a novel TME-based classification system for application in intracranial malignancies. TME subtypes represent canonical 'termini a quo' (starting points) to support an improved precision immunotherapy treatment approach.

Role of C and B4C barrier layers in controlling diffusion propagation across the interface of Cr/Sc multilayers.

The optical performance of low-bilayer-thickness metallic multilayers (ML) can be improved significantly by limiting the intermixing of consecutive layers at the interfaces. Barrier layers are supposed to exhibit a decisive role in controlling diffusion across the interfaces. The element-specific grazing incidence extended X-ray absorption fine structure technique using synchrotron radiation has been used in conjunction with grazing incidence X-ray reflectivity and diffuse X-ray scattering measurements to study the impact of the two most common barrier layers, viz., C and B4C, at the interfaces of Cr/Sc MLs. The diffusion propagation is reduced by both the barrier layers; however, it is found that the improvement is more significant with the B4C barrier layer. It is seen that C forms an intermixed layer with Sc and leads to carbide formation at the interface, which then acts as shielding and prevents further interdiffusion, while B4C hardly penetrates into Sc and stops the overlap between Sc and Cr directly by wetting the corresponding interface. Thus, the above measurements reveal crucial and precise information regarding the elemental diffusion kinetics at the interfaces of Cr/Sc MLs in a non-destructive way, which is very important for technological applications of these MLs as X-ray optical devices.

Interface modification of Cr/Ti multilayers with C barrier layer for enhanced reflectivity in the water window regime.

The influence of a carbon barrier layer to improve the reflectivity of Cr/Ti multilayers, intended to be used in the water window wavelength regime, is investigated. Specular grazing-incidence X-ray reflectivity results of Cr/Ti multilayers with 10 bilayers show that interface widths are reduced to ∼0.24 nm upon introduction of a ∼0.3 nm C barrier layer at each Cr-on-Ti interface. As the number of bilayers increases to 75, a multilayer with C barrier layers maintains almost the same interface widths with no cumulative increase in interface imperfections. Using such interface-engineered Cr/C/Ti multilayers, a remarkably high soft X-ray reflectivity of ∼31.6% is achieved at a wavelength of 2.77 nm and at a grazing angle of incidence of 16.2°, which is the highest reflectivity reported so far in the literature in this wavelength regime. Further investigation of the multilayers by diffused grazing-incidence X-ray reflectivity and grazing-incidence extended X-ray absorption fine-structure measurements using synchrotron radiation suggests that the improvement in interface microstructure can be attributed to significant suppression of inter-diffusion at Cr/Ti interfaces by the introduction of C barrier layers and also due to the smoothing effect of the C layer promoting two-dimensional growth of the multilayer.

Oregano Oil and Its Principal Component, Carvacrol, Inhibit HIV-1 Fusion into Target Cells.

Oregano essential oil has long been known for its health-promoting benefits. Here, we report its activity against viral replication. Oregano oil was found to specifically inhibit lentiviruses, such as human and simian immunodeficiency viruses (HIV and SIV), irrespective of virus tropism, but not hepatitis C virus, adenovirus 5 (ADV5), Zika virus, and influenza (H1N1) virus. Oregano oil's most abundant components, carvacrol and its isomer, thymol, were shown to block virus-target cell fusion while not perturbing other stages of the virus life cycle. We detected changes in virus particle density, suggesting that cholesterol depletion from the HIV-1 envelope membrane reduces virus entry. Furthermore, infection was rescued by adding exogenous cholesterol. The evolution of viral resistance to carvacrol supported this mechanism of action with the identification of mutations in the viral gp41 fusion protein that counteracted cholesterol depletion. In addition, resistance to carvacrol emerged later than typically observed for other clinically used drugs, strengthening its antiviral potential. Structure-activity relationship studies revealed key motifs of carvacrol and thymol required for HIV neutralization and identified previously unknown active analogs. Carvacrol was also shown to additively cooperate with antiretroviral therapy. In sum, oregano oil and improved carvacrol and thymol analogs could be considered to supplement current HIV therapeutics.IMPORTANCE Oregano essential oil has multiple benefits in traditional medicine, cosmetics, and food industries. Carvacrol and its analog, thymol, are well-described components of oregano oil. Here, we show that these compounds inhibit HIV-target cell fusion independently of viral tropism. Our results suggest that carvacrol and thymol alter the cholesterol content of the viral membrane, blocking HIV-1 entry into the target cell. Resistance to carvacrol has selected for viruses with mutations in the viral envelope glycoprotein, gp41. This protein is known for its interaction with cholesterol present in membrane lipid rafts. Together, these results demonstrate the potential of therapies targeting the viral envelope membrane, and oregano oil is a safe supplement to antiretrovirals, potentially delaying disease progression and resistance development.

Distortion energy-electronic energy compensation determines the nature of solute interactions with irradiation induced vacancies in ferritic steel.

Fundamental knowledge of vacancy-solute atom (in particular, Cu and Ni) interactions at the electronic level is of utmost importance to understand experimentally observed Cu-precipitation in reactor pressure vessel (RPV) steel. In the present investigation, using first-principles electronic structure calculations within the framework of density functional theory (DFT), we unravel the nature of such interactions between a vacancy (V) or di-vacancy and solute atoms (mainly Cu and Ni) in the bcc-Fe lattice. One of the very novel features of the present investigation is that we demonstrate the importance of distortion energy-electronic energy compensation in stabilizing the formation of vacancy-Cu and vacancy-Ni clusters in ferritic steel. Further decomposition of the electronic energy contribution into different bonding contributions in conjugation with differential charge density analyses clearly reveals the origin of stability as a consequence of mutual compensation of different energy modes. For both Cu-Cu and Ni-Ni interactions, the presence of a vacancy leads to a more attractive interaction, implying that such vacancies generated due to irradiation make solute aggregation easier compared with the case of model steel with no defects. We have also demonstrated that the formation of CumNin clusters (m, n = 1, 5) is energetically favorable in addition to demonstrating that the stability increases with an increasing number of Cu or Ni atoms. The rate of increase of stability with the addition of solute atoms is higher in the case of the addition of Cu atoms into a Ni cluster than it is for adding Ni atoms into a Cu cluster. The present investigation thus provides a deeper electronic level understanding of solute-point defect interaction and cluster formation probability for Cu and Ni atoms in the ferritic steel.

Catheter-related blood stream infections: prevalence, risk factors and antimicrobial resistance pattern.

BACKGROUND: Intravascular devices have significant potential for producing iatrogenic diseases resulting in catheter-related blood stream infections (CRBSIs). A study was undertaken to find the prevalence of CRBSI among patients in acute wards and to analyze the associated risk factors, causative pathogens with their antibiotic susceptibility (ABST) patterns. METHODS: Randomly ten days per month were chosen, for a period of two years. All the acute wards patients who were on indwelling blood catheters were identified. Those fulfilling the CRBSI criteria were further worked up for confirmation of diagnosis by differential time to positivity. The catheter tip was cultured by Maki's semiquantitative method. ABST of the isolates obtained was performed by Kirby-Bauer disk diffusion method. RESULTS: The prevalence of CRBSI was found to be 39.25% with the most common organism isolate being Serratia marcescens (23.81%). The immunocompromised status of the patients and catheterisation time were significant risk factors. Methicillin resistance was found to be 33.33% in coagulase-negative staphylococci. The resistance to vancomycin among the Entercoccus faecium isolates was found to be 33.33%. Among the gram negatives, resistance to aminoglycosides, fluoroquinolones and third-generation cephalosporins was high. CONCLUSION: The study highlights the importance of regular surveillance programs, an efficient infection control program, strict adherence to antiseptic measures and use of a rational antibiotic policy for the early diagnosis and better management of CRBSI.

Spin-Reorientation-Induced Band Gap in Fe_{3}Sn_{2}: Optical Signatures of Weyl Nodes.

Temperature- and frequency-dependent infrared spectroscopy identifies two contributions to the electronic properties of the magnetic kagome metal Fe_{3}Sn_{2}: two-dimensional Dirac fermions and strongly correlated flat bands. The interband transitions within the linearly dispersing Dirac bands appear as a two-step feature along with a very narrow Drude component due to intraband contribution. Low-lying absorption features indicate flat bands with multiple van Hove singularities. Localized charge carriers are seen as a Drude peak shifted to finite frequencies. The spectral weight is redistributed when the spins are reoriented at low temperatures; a sharp mode appears suggesting the opening of a gap due to the spin reorientation as the sign of additional Weyl nodes in the system.

Myocarditis in admitted patients with dengue fever.

PURPOSE: Cardiac involvement in dengue fever is underdiagnosed due to low index of clinical suspicion and its contribution to hemodynamic instability in severe dengue is not well known. METHODS: A prospective observational study was conducted among admitted patients ≥ 14 years of age having confirmed dengue fever. Patients on medications affecting heart rhythm/rate, pre-existing heart disease and electrolyte abnormalities were excluded. A baseline electrocardiography (ECG), Trop-I and NT-proBNP were done for all patients. The biomarkers were measured using enzyme-linked fluorescent assay and recommended cut-off were used. Patients with elevated biomarkers underwent 2-dimensional echocardiography. Diagnosis of myocarditis was as per European Society of Cardiology (ESC) 2013 criteria. RESULTS: A total of 182 patients were recruited with mean age of 30 ± 12.6 years and 31% were females. Dengue with warning signs was present in 85 (47%) and severe dengue in 60 (33%) patients. ECG abnormalities were observed in 44 (24%) patients, biomarkers were elevated in 27 (15%) patients and 11 (6%) patients had echocardiographic abnormalities. According to ESC 2013 criteria, dengue fever with myocarditis was diagnosed in 13 [7.1% (95% CI 3.4-10.9)] patients. The patients with myocarditis were more likely to have shortness of breath, bleeding manifestations and higher respiratory rate at baseline. Clinical features of fluid overload were more common (69% vs. 1.7%, p < 0.01) and the duration of hospital stay longer in myocarditis group (7 ± 4.3 vs. 4.8 ± 1.9 days, p < 0.01). CONCLUSION: Myocarditis among admitted dengue patients is not uncommon and may lead to increased morbidity.

In silico and in vitro evaluation of the impact of mutations in non-severe haemophilia A patients on assay discrepancies.

Haemophilia A (HA) is caused by a lack or reduced amount of factor VIII protein (FVIII). About one-third of patients with non-severe HA carrying specific missense mutations show discrepant results between FVIII activity (FVIII:C), measured by one-stage or chromogenic two-stage assays. The aim of this study was to elucidate the mechanism underlying the assay discrepancy in vitro and in silico. Thirteen missense mutations in the Factor 8-gene associated with discrepant results in patients were transiently expressed. FVIII:C of the mutations was determined using two one-stage assays (FVIII:C1st, FVIII:CBonn) and a two-stage chromogenic assay (FVIII:Cchr). Furthermore, thrombin generation test (TGT) and in silico analysis were performed to investigate the haemostatic potential as well as the structural impact of the variants, respectively. For the majority (9/13) of the analysed mutations, the discrepancy was confirmed. Moreover, we established a modified TGT protocol for in vitro characterization of FVIII. Hence, TGT parameters were significantly impaired in the group of variants associated with higher chromogenic values. Additionally, in silico analysis revealed the impact of the mutations on FVIII protein structure leading to assay discrepancy. Moreover, the data shows that also among one-stage clotting assays, assay discrepancy is observed. Our results show that for the majority of mutations, application of a global assay like TGT method could help to improve diagnosis or correct assessment of the severity of HA.

Guidelines for the safe practice of total intravenous anaesthesia (TIVA): Joint Guidelines from the Association of Anaesthetists and the Society for Intravenous Anaesthesia.

Guidelines are presented for safe practice in the use of intravenous drug infusions for general anaesthesia. When maintenance of general anaesthesia is by intravenous infusion, this is referred to as total intravenous anaesthesia. Although total intravenous anaesthesia has advantages for some patients, the commonest technique used for maintenance of anaesthesia in the UK and Ireland remains the administration of an inhaled volatile anaesthetic. However, the use of an inhalational technique is sometimes not possible, and in some situations, inhalational anaesthesia is contraindicated. Therefore, all anaesthetists should be able to deliver total intravenous anaesthesia competently and safely. For the purposes of simplicity, these guidelines will use the term total intravenous anaesthesia but also encompass techniques involving a combination of intravenous infusion and inhalational anaesthesia. This document is intended as a guideline for safe practice when total intravenous anaesthesia is being used, and not as a review of the pros and cons of total intravenous anaesthesia vs. inhalational anaesthesia in situations where both techniques are possible.

Potent suppression of HIV-1 cell attachment by Kudzu root extract.

There is a constant need to improve antiretrovirals against HIV since therapy is limited by cost, side effects and the emergence of drug resistance. Kudzu is a climbing vine from which the root extract (Pueraria lobata), rich in isoflavones and saponins, has long been used in traditional Chinese medicine for a variety of purposes, from weight loss to alcoholism prevention. Here we show that Kudzu root extract significantly inhibits HIV-1 entry into cell lines, primary human CD4+T lymphocytes and macrophages, without cell-associated toxicity. Specifically, Kudzu inhibits the initial attachment of the viral particle to the cell surface, a mechanism that depends on the envelope glycoprotein gp120 but is independent from the HIV-1 cell receptor CD4 and co-receptors CXCR4/CCR5. This activity seems selective to lentiviruses since Kudzu inhibits HIV-2 and simian immunodeficiency virus, but does not interfere with Hepatitis C, Influenza, Zika Brazil and adenovirus infection. Importantly, depending on the dose, Kudzu can act synergistically or additively with the current antiretroviral cocktails against HIV-1 and can block   viruses resistant to the fusion inhibitor Enfuvirtide. Together our results highlight Kudzu's root extract value as a supplement to current antiretroviral therapy against HIV.

Type-3 von Willebrand disease in India-Clinical spectrum and molecular profile.

INTRODUCTION: Type 3 von Willebrand disease (VWD) is the rare and most severe form of VWD which results from a near-complete deficiency of the von Willebrand factor (VWF). This study evaluates in detail the molecular pathology of type-3 VWD in India. One hundred and two patients from 90 families were evaluated. PATIENTS AND METHODS: Phenotypic data, including bleeding scores (BS), were documented using structured questionnaires. Diagnosis of type 3 VWD was based on undetectable VWF antigen levels in the plasma. Genomic DNA from these patients was screened for mutations in VWF gene. Structural modeling and expression studies were carried out for missense mutations. RESULTS: Out of 102 patients, mutations could be identified in 91% (n = 93). Fifty-five different gene variants were identified. Thirty-four (61.8%) were novel. Mutations could be identified in both the alleles in 90 patients, while no causative mutation could be identified in 9 patients; twenty-four (23.5%) patients had mutations clustered in the propeptide region of VWF. Interestingly, five mutations accounted for the defects in 37/93 (39.8%) patients. Structural analysis and in vitro studies on missense mutations imply impaired processes associated with secretion of VWF. CONCLUSION: This study is one of the largest series to define the molecular basis of type-3 VWD.

Diagnostic accuracy of haptoglobin within ovarian cyst fluid as a potential point-of-care test for epithelial ovarian cancer: an observational study.

OBJECTIVE: To investigate haptoglobin within ovarian cyst fluid (OCF) as a diagnostic biomarker for epithelial ovarian cancer (EOC) and develop an in vitro diagnostic point-of-care device test (IVDPCT) for use in the operating theatre. DESIGN: Retrospective and prospective cohort study. SETTING: South-East Asia. POPULATION: Women with suspicious ovarian cysts. METHODS: Proteomic, immunohistochemical and ELISA methods measured haptoglobin in OCF to differentiate benign and EOCs. Diagnostic performance of haptoglobin was compared with CA125, risk malignancy indices (RMI) and frozen section. Blinded validation of the IVDPCT was performed. MAIN OUTCOME MEASURES: Prediction of malignancy. RESULTS: Haptoglobin concentration measured by ELISA was 0.70 ± 0.09 mg/ml in patients with benign cysts (n = 87), 6.22 ± 0.53 mg/ml in early stage-EOC (n = 17), and 6.57 ± 0.65 mg/ml in late stage-EOC (n = 20). Haptoglobin in EOCs was significantly higher than in benign cysts (P < 0.0001). Haptoglobin using rapid colorimetric assay (RCA) on a training set had a sensitivity of 97.3% and a specificity 92.0%, comparable to ELISA and frozen sections. The haptoglobin AUROC curve was 0.999 (95% CI 0.997-1.000) compared with 0.895 (95% CI 0.814-0.977, P < 0.05) for CA125. Haptoglobin performed significantly better than all the RMIs (P < 0.01). Blinded validation studies showed a minor drop in average diagnostic performance (sensitivity 85.2% and specificity 90.5%) compared with the training set. However, when compared with frozen section, haptoglobin was no worse in diagnostic accuracy for malignancy. CONCLUSION: Haptoglobin was identified as a biomarker for the detection of EOC with potential as a point-of-care diagnostic tool. TWEETABLE ABSTRACT: Haptoglobin within ovarian cyst fluid: a biomarker for epithelial ovarian cancer and point-of-care diagnostics.

Interaction of α-crystallin with some small molecules and its effect on its structure and function.

BACKGROUND: α-Crystallin acts like a molecular chaperone by interacting with its substrate proteins and thus prevents their aggregation. It also interacts with various kinds of small molecules that affect its structure and function. SCOPE OF REVIEW: In this article we will present a review of work done with respect to the interaction of ATP, peptide generated from lens crystallin and other proteins and some bivalent metal ions with α-crystallin and discuss the role of these interactions on its structure and function and cataract formation. We will also discuss the interaction of some hydrophobic fluorescence probes and surface active agents with α-crystallin. MAJOR CONCLUSIONS: Small molecule interaction controls the structure and function of α-crystallin. ATP and Zn+2 stabilize its structure and enhance chaperone function. Therefore the depletion of these small molecules can be detrimental to maintenance of lens transparency. However, the accumulation of small peptides due to protease activity in the lens can also be harmful as the interaction of these peptides with α-crystallin and other crystallin proteins in the lens promotes aggregation and loss of lens transparency. The use of hydrophobic probe has led to a wealth of information regarding the location of substrate binding site and nature of chaperone-substrate interaction. Interaction of surface active agents with α-crystallin has helped us to understand the structural stability and oligomeric dissociation in α-crystallin. GENERAL SIGNIFICANCE: These interactions are very helpful in understanding the mechanistic details of the structural changes and chaperone function of α-crystallin. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.

Comparison of F13A1 gene mutations in 73 patients treated with recombinant FXIII-A2.

INTRODUCTION: Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder usually caused by mutations in the F13A1 gene that produce a severe quantitative (type I) deficiency of the FXIII-A subunit. AIM: To determine the genotypes of patients with severe FXIII-A deficiency treated with recombinant FXIII-A subunit (rFXIII-A2 ) participating in three international efficacy and safety trials. METHODS: We determined the genotypes of 73 patients in total; 32 had already undergone genotype analysis and were known to carry F13A1 mutations that have been previously reported in the literature. Mutation screening was performed in 41 patients with unknown genetic status using direct sequencing. RESULTS: In total, 51 distinct mutations in 73 patients were identified. Two patients showed a phenotype of severe FXIII-A deficiency, despite having heterozygous missense mutations. Two siblings carried a missense mutation in the F13A1 gene (p.Ser296Arg) in combination with a novel, probably polymorphic variant of the F13B gene (p.Ser654Phe). Molecular modelling of five F13A1 novel missense mutations (p.Leu171Phe, p.Glu204Lys, p.Leu276Phe, p.Asp405His and p.Gly411Cys) predicted a damaging effect of these mutations on protein structure. Although five patients treated with rFXIII-A2 had transient, low-titre, non-neutralizing anti-rFXIII antibodies, no patients developed FXIII-neutralizing antibodies (inhibitors). CONCLUSION: The identified mutations are causally implicated in severe FXIII deficiency; however, they do not appear to increase the risk of neutralizing antibody development against rFXIII-A2 .

Preterm prelabour rupture of membranes: a retrospective cohort study of association with adverse outcome in subsequent pregnancy.

OBJECTIVE: To assess the association of first pregnancy preterm prelabour rupture of membranes (PPROM) with adverse maternal and perinatal outcomes in the next pregnancy. DESIGN: Retrospective cohort study. SETTING: Grampian, Scotland, UK. POPULATION: Women with first deliveries recorded in the Aberdeen Maternity Neonatal Databank, 1986-2005. METHODS: Women identified from the AMND database (n = 37 776) were classified into exposed (PPROM in first pregnancy; n = 1979) and unexposed (no PPROM in first pregnancy; n = 35 797) cohorts. Each cohort (exposed n = 1174; unexposed n = 20 860) was followed up until December 2012 for next singleton pregnancy. MAIN OUTCOME MEASURES: Second pregnancy, miscarriage, pregnancy-induced hypertension (PIH), pre-eclampsia (PE), antepartum haemorrhage (APH) and postpartum haemorrhage, repeat PPROM, type of labour, mode of delivery, preterm delivery, low birth weight (LBW), admission to neonatal unit, neonatal infections and death. RESULTS: PPROM in the first singleton pregnancy was associated with an equal likelihood of second pregnancy but with a significantly increased risk of adverse outcomes in the next singleton pregnancy: PPROM [odds ratio (OR) (95% confidence interval (CI)): 6.6 (5.4-7.9)], PE [2.4 (1.7-3.5)], instrumental [2.2 (1.7-2.8)] and caesarean delivery [1.8 (1.5-2.3)], PIH [1.5 (1.2-1.9)] and APH [1.3 (1.1-1.6)] in the mother, and neonatal infection [5.4 (1.4-20.3)], death [2.6 (1.0-6.7)], admission to neonatal unit [2.4 (2.0-2.9)], preterm delivery [2.3 (1.8-2.9)] and LBW [1.44 (1.1-1.9)]. Even in women without a recurrent PPROM, there was still a significant increase in PIH [1.4 (1.1-1.8)], PE [2.3 (1.6-3.5)], instrumental [2.2 (1.7-2.9)] and caesarean delivery [1.9 (1.5-2.4)], and neonatal unit admission [1.6 (1.3-2.0)]. CONCLUSIONS: PPROM in the first pregnancy is associated with significant adverse maternal and perinatal outcomes in the next pregnancy, but not reduced likelihood of second pregnancy. TWEETABLE ABSTRACT: PPROM in the first singleton pregnancy increases risk of adverse maternal and perinatal outcomes in the next singleton pregnancy.

Physical comorbidity in schizophrenia & its correlates.

The presence of common physical comorbidities, their demographic and clinical correlates and impact on functioning was assessed in 100 patients with schizophrenia. The patients had a mean age of 35.12±10.7 yr with mean duration of illness of 8.3±0.58 years. Seventy per cent were detected to have a comorbid physical condition. Common conditions included hypertension (21%), diabetes mellitus (15%) and anaemia (12%). Increasing age, being female, being married, longer duration of illness and longer duration of treatment were associated with higher risk of having a comorbid physical illness. Further studies need to be done with a large sample to confirm these findings.

Semen characteristics and biochemical composition of cloacal foam of male Japanese quails (Coturnix coturnix Japonica) fed diet incorporated with selenium.

An attempt was made to investigate the effect of dietary selenium (Se) on physical and cloacal gland size, foam production, biochemical composition of foam and semen biochemical characteristics of male Japanese quail (Coturnix coturnix Japonica). Two hundred twenty-five (225)-day-old male Japanese quail were randomly distributed to three dietary treatment groups for a period of 20 weeks. Each treatment comprised of three replicates, each containing 25 chicks. Three experimental diets were supplemented with 0, 0.5 and 1.0 mg Se/kg (T1 , T2 and T3, respectively), and diet T1 was considered as control. Sodium selenite was used as the source of selenium. All the birds were provided with feed and water ad libitum. Cloacal foam characteristics, that is cloacal gland index and foam weight, were significantly higher in T2 group. However, body weight, frequency of foam discharge and testes weight (left and right) did not differ significantly (p > 0.05). Physical characteristics of semen, that is semen volume and sperm concentration, did not differ (p > 0.05) among the Se-treated groups. The sperm motility, live-dead count and abnormality improved significantly (p < 0.05) in 0.5 mg/Se-supplemented group compared to 0 or 1.0 mg/Se-supplemented groups. Similarly, fertility and hatchability percentages were higher (p < 0.05) in 0.5 mg/Se-supplemented group than in control or 1.0 mg/Se-supplemented counterparts. The biochemical characteristics of foam in terms of total protein, acid phosphatase (ACP) and nitric oxide did not differ (p > 0.05), while the concentration of glucose was higher (p < 0.05) in 0.5 mg/Se-supplemented diet. On the other hand, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were lower (p < 0.05) in 0.5 mg/Se-supplemented group compared to control or 1.0 mg/Se-supplemented groups. From this study, it was concluded that supplementation of 0.5 mg Se/kg diet was beneficial for foam variables, biochemical composition of foam, semen characteristics and fertility in male Japanese quail.

Impact of feeding chromium supplemented flaxseed based diet on fatty acid profile, oxidative stability and other functional properties of broiler chicken meat.

A total of 240 broiler chicken of same hatch with uniform weight were used in a biological experiment with completely randomized design to investigate the effects of incorporating organic chromium (Cr) in flaxseed meal based diet on the fatty acid profile, oxidative stability and functional properties of broiler chicken meat. Five diets were formulated as per the recommendations of BIS (Nutrient requirements for poultry 13: 9863, Bureau of Indian Standards, New Delhi, 1992) in which flaxseed meal was used to replace 10% of soyabean in basal diet and four levels of Cr (0.0, 0.5, 1.0 and 1.5 mg/kg diet) as Cr-picolinate were used. The results revealed that flaxseed feeding significantly increased the percentage of unsaturated fatty acids, including MUFA, PUFA, ω-3, ω-6 fatty acids and ω-3:ω-6 and PUFA:SFA ratios, whereas, significant decline was seen in saturated fatty acids and no effect of Cr was observed on the fatty acid profile of broiler chicken. Flaxseed feeding significantly reduced the cholesterol and fat percentage of meat, whereas, significant progressive reduction was observed with increasing Cr levels. The combination of 10% flaxseed with 1.0 mg Cr/kg diet increased the final pH of broiler meat. The addition of flaxseed significantly reduced water holding capacity, extract release volume and antioxidant potential of broiler meat, whereas, increasing Cr supplementation progressively increased them. Flaxseed feeding significantly increased the drip loss and lipid peroxidation of broiler meat, whereas, Cr supplementation decreased them. It was concluded that inclusion of 10% flaxseed and 1.5 mg Cr/kg diet results in desirable fatty acid profile, oxidative stability and functional properties of broiler chicken meat.