Frequency-Dependent Squeezed Vacuum Source for the Advanced Virgo Gravitational-Wave Detector.

In this Letter, we present the design and performance of the frequency-dependent squeezed vacuum source that will be used for the broadband quantum noise reduction of the Advanced Virgo Plus gravitational-wave detector in the upcoming observation run. The frequency-dependent squeezed field is generated by a phase rotation of a frequency-independent squeezed state through a 285 m long, high-finesse, near-detuned optical resonator. With about 8.5 dB of generated squeezing, up to 5.6 dB of quantum noise suppression has been measured at high frequency while close to the filter cavity resonance frequency, the intracavity losses limit this value to about 2 dB. Frequency-dependent squeezing is produced with a rotation frequency stability of about 6 Hz rms, which is maintained over the long term. The achieved results fulfill the frequency dependent squeezed vacuum source requirements for Advanced Virgo Plus. With the current squeezing source, considering also the estimated squeezing degradation induced by the interferometer, we expect a reduction of the quantum shot noise and radiation pressure noise of up to 4.5 dB and 2 dB, respectively.

PAX1 Methylation Status in Cervical Scrapes as Novel Diagnostic Biomarker in CIN 2/3 and Invasive Squamous Cell Carcinoma.

Objectives: DNA methylation of paired box-1 (PAX-1) gene has been shown to be a potential biomarker for the detection of high-grade cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer. The objective of this pilot study was to quantify and compare methylation percentage of PAX1 gene in benign cervical lesion, pre-invasive and invasive cervical cancer. Methods: A total of 200 screen positive women (VIA, VILI and Pap test) underwent colposcopy. Cervical scrapes taken were taken and stored for DNA analysis and PAX 1 methylation status. Women with Swede score of 5 or more (n = 98) were biopsied. Cervical scrapes and biopsy were taken from women with obvious cervical growth (n = 14), without prior colposcopy. Sixty women were recruited to the study and allocated into three groups on the basis of histopathology, i.e., benign cervix (Group 1; n = 20), CIN 2/3 (Group 2; n = 20) and invasive cervical carcinoma (Group; n = 20). PAX 1 methylation percentage was calculated from the DNA extracted from the cervical scrapes of the women recruited. Results: The mean PAX1 methylation percentage in benign lesions, CIN 2/3 and invasive cancer was 9.58% (SD ± 2.37%), 18.21% (SD ± 2.67%) and 24.34% (SD ± 4.09%), respectively, with p-value of < 0.001. Conclusions: PAX 1 gene methylation has a promising role in identifying high-grade lesions and invasive cancer.

Prevalence and predictors of adverse outcomes in neonatal seizures.

OBJECTIVES: Neonatal seizures are significant cause of neonatal mortality and morbidity. Current study was planned to study prevalence of adverse outcomes in neonatal seizures and identify its predictors. METHODS: This observational descriptive study was carried out on 220 neonates with seizures. Neonates who succumbed to illness/ death before investigations, or whose maternal records were incomplete were excluded. Blood sugar, serum calcium, serum electrolytes, and USG skull were done in all patients. CT scan, MRI and inborn errors of metabolism profile were done as and when indicated. Adverse outcomes were defined as death, phenobarbitone non responders, or abnormal examination at discharge. Antenatal, perinatal and neonatal predictors of adverse outcomes in neonatal seizures were evaluated. RESULTS: Out of 220 neonates with seizures 76(34.5%) had adverse outcomes. Very low birth weight babies (≤1500 gm) [OR 1.27(CI 0.57-2.84)], microcephaly [OR 5.93 (CI 0.55-64.41)], Apgar score≤3 at 5 minutes [OR 11.28(CI 14.18-30.45)], seizure onset within 24 hours [OR 5.99(CI 12.43-14.78)], meningitis [OR 2.63(CI 0.08-6.39)], septicemia [OR1.22(CI 0.45-3.31)] and abnormal cranial USG [OR 7.95(CI 12.61-24.22)] were significant predictors of adverse outcomes in neonates with seizures. CONCLUSION: Prematurity, very low birth weight, birth asphyxia, meningitis, septicemia and abnormal USG could predict adverse outcomes in neonatal seizures. Improved antenatal and neonatal clinical practices may help reduce adverse outcomes in these patients.

Adipose tissue expression of UCP1 and PRDM16 genes and their association with postprandial triglyceride metabolism and glucose intolerance.

AIMS: UCP1 and PRDM16 genes, primarily involved in browning of adipose tissue that can affect lipid metabolism are also associated with diabetes risk. Therefore, we planned to study the adipose tissue expression of UCP1 and PRDM 16 genes in subjects with glucose intolerance to find out its association with postprandial triglyceride (PPTg) measures and T2DM. METHODS: A total of 30 subjects were recruited in three groups i.e., NGT, prediabetes and T2DM (NDDM + known T2DM) who were matched for age, sex and BMI. An 8-hour standardized fat challenge test was performed to study lipemic responses. UCP1 and PRDM16 genes quantification in adipose tissue was performed by real-time PCR followed by SDS PAGE. RESULTS: UCP1 gene expression in SAT was significantly lower in T2DM and prediabetes as compared to NGT group while PRDM16 gene expression was significantly lower in T2DM group as compared to NGT group. UCP1 gene expression correlated with PPTg measures as well as with glycaemic measures while PRDM16 gene expression correlated with glycaemic measures only. CONCLUSION: This study found downregulation of PRDM16 and UCP1 gene expression in SAT in subjects with glucose intolerance. The association of UCP1 gene expression with PPTg dysmetabolism may contribute to greater predisposition to T2DM.

Effect of postprandial triglycerides on DDT/ppDDE levels in subjects with varying degree of glucose intolerance.

BACKGROUND: Organochlorine pesticides such as DDT as well as postprandial hypertriglyceridemia have been linked with insulin resistance and diabetes mellitus. The cardiometabolic risk of PPhTg could also be due to its potential to increase the serum levels of this highly lipophilic pesticide. We studied the effect of postprandial triglyceride responses to a standard oral fat challenge on the levels of DDT and its metabolites in subjects with varying degree of glucose intolerance METHODS: A standard fat challenge was performed in 60 subjects who were categorized as NGT, prediabetes, and NDDM based on an earlier OGTT. Fasting and postprandial levels of serum triglycerides, plasma DDT and its metabolites were estimated and compared in the 3 groups and their association with each other, and measures of glycemia and insulin resistance were also determined. RESULTS: Peak Tg and TgAUC levels were significantly higher in NDDM group as compared to NGT and PD groups. TgAUC showed positive correlation with fasting plasma glucose (r=0.33, p=0.01), postprandial plasma glucose (r=0.39, p=0.002) and HOMA IR(r=0.63, p=0.001). ppDDE levels were found to be significantly higher in NDDM subjects compared with NGT group. ppDDE-AUC was significantly higher in the NDDM group compared with the other two study groups. Mean ppDDE levels also showed strong positive correlation with peak Tg (r=0.295 p=0.022), TgAUC (r=0.303 p=0.018), iPPTgAUC(r=0.57 p≤0.001) and iPPpeakTg(r=0.51 p≤0.001) as well as with FPG (r=0.269 p=0.038) PPPG (r=0.424 p=0.001) and HbA1c (r=0.321 p=0.012). CONCLUSION: The findings of this study support the concept that the cardiometabolic risk associated with PPhTg may at least in part be related to the associated increase in serum levels of lipophilic OCPs like DDT.

Bounds on Lorentz Invariance Violation from MAGIC Observation of GRB 190114C.

On January 14, 2019, the Major Atmospheric Gamma Imaging Cherenkov telescopes detected GRB 190114C above 0.2 TeV, recording the most energetic photons ever observed from a gamma-ray burst. We use this unique observation to probe an energy dependence of the speed of light in vacuo for photons as predicted by several quantum gravity models. Based on a set of assumptions on the possible intrinsic spectral and temporal evolution, we obtain competitive lower limits on the quadratic leading order of speed of light modification.

Attenuation of oxidative stress and neurotoxicity involved in the antidepressant-like effect of the MK-801(dizocilpine) in Bacillus Calmette-Guerin-induced depression in mice.

Background The emerging line of research suggests that neuro-inflammation and oxidative stress are linked to the development of depression-like behavior. The tryptophan metabolizing enzyme, indolamine 2,3-dioxygenase (IDO), serves as an important interface between chronic inflammation and depression. IDO is induced by pro-inflammatory cytokines and diverts tryptophan towards the kynurenine pathway, decreasing serotonin synthesis. Further, the metabolites of kynurenine pathway increase brain oxidative stress and also cause N-methyl-D-aspartate (NMDA) receptor-mediated exitotoxicity. The resulting oxidative damage and dysfunction in glutamatergic neurotransmission alters the network connectivity of the brain, which may be the further mechanism for emergence of depression-like symptoms. Methods A depression-like illness was induced in mice by injecting Bacillus Calmette-Guerin (BCG) suspended in isotonic saline at a dose of 107 CFU I.P. The mice were then divided into different groups and were administered MK-801 or normal saline for the next 21 days, after which a battery of behavior and biochemical tests were conducted to assess them. Results The BCG group had significantly reduced sucrose preference index and an increase in immobility time in forced swim test (FST) and Tail Suspension Test (TST) as compared to the saline group. There was also a significant increase in the brain MDA levels and a decline in the brain GSH levels. The hippocampal tissue from the BCG group had significantly more comet cells than the saline group. The NMDA receptor antagonist, MK-801, was able to reverse the BCG-induced depression-like behaviour. MK-801 also showed significant decrease in brain oxidative stress but failed to show significant protection against BCG-induced neurotoxicity observed in comet assay. Conclusions The NMDA receptor antagonist, MK-801, mitigated BCG-induced, depressive-like behavior in mice by improving the sucrose preference and decreasing the duration of immobility time in TST and FST. The overall improvement in depression-like behavior was accompanied by a reduction in brain oxidative stress and comet cells, thus suggesting the antioxidant and neuroprotective action of MK-801.

Association of PPARγ gene expression with postprandial hypertriglyceridaemia and risk of type 2 diabetes mellitus.

PURPOSE: Peroxisome proliferator-activated receptor γ (PPARγ) gene is strongly associated with type 2 diabetes mellitus, as well as postprandial lipemia, and plays an important role in Wnt dependent adipogenesis in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). We aimed to study the expression of PPARγ gene in SAT and VAT to find out its correlation with postprandial hypertriglyceredemia and glucose intolerance. METHODS: Thirty subjects who were scheduled to undergo abdominal surgery were recruited in three groups (n = 10 in NGT, n = 10 in prediabetes, and n = 10 in T2DM). A standardized oral fat challenge was performed. Anthropometry, plasma glucose, HbA1c, and fasting serum insulin were also measured. SAT and VATs were collected during surgery for PPARγ gene expression studies by real-time PCR. RESULTS: PPARγ gene expression was 5.5-fold lower in T2DM and 1.7-fold lower in prediabetes as compared with NGT subjects in VAT. There was a significant negative correlation of expression of PPARγ gene in VAT {Tgauc (r = -0.57, p < 0.007), Peak Tg (r = -0.51, p < 0.01)} as well as in subcutaneous adipose tissue {Tgauc (r = -0.45, p < 0.02)} with PPTg responses measures. CONCLUSION: Reduced adipocyte expression of PPARγ gene and the resultant postprandial hypertriglyceredemia is associated with greater risk of diabetes and prediabetes.

High Resolution Based Quantitative Determination of Methylation Status of CDH1 and VIM Gene in Epithelial Ovarian Cancer.

BACKGROUND: DNA promoter methylation is widely explored epigenetic phenomena, known to effect gene expression and further perturbation in cellular homeostasis. Myriad of studies have leveraged promoter methylation and its potential as biomarker for various types of cancer. Aim of present study is to investigate promoter methylation of CDH1 and VIM gene and etiology of epithelial ovarian cancer (EOC). METHODS: Most of previous studies were qualitative; we have quantitatively assessed methylation levels in 50 EOC cases and control each through high recognition melt (HRM) technique. RESULTS: At 10 % cutoff for CDH1 94% of EOC cases were found to be methylated with mean methylation of 45±13.8, whereas for control mean methylation was found to be 7.3±3.7 amongst 16 % methylation positive control samples. For VIM methylation was detected in 96% of cases with mean of 50.44±11.7 in EOC and in 12% methylation positive samples for control mean methylation was 6.24±4.3. CONCLUSION: In short HRM based DNA methylation can serve as a robust and sensitive diagnostic method for promoter methylation detection and as a biomarker for early epithelial ovarian cancer detection.

Heptachlor-induced epithelial to mesenchymal transition in HK-2 cells mediated via TGF-ß1/Smad signalling.

This study investigated the effect of heptachlor-induced oxidative stress (OS) on transforming growth factor (TGF)-ß1-mediated epithelial to mesenchymal transition (EMT) in human renal proximal tubular epithelial (HK-2) cells. Following treatment of HK-2 cells with an increasing concentration of heptachlor (0.01-10 µM) for 24 h, the intracellular reactive oxygen species and malondialdehyde level increased, whereas the glutathione-s-hydroxylase (GSH) level declined significantly in a dose-dependent manner. Pretreatment with N-acetyl cysteine attenuates the heptachlor-induced OS. In this study, we have shown that heptachlor-induced OS regulates the mRNA expression of TGF-ß1-mediated Smad signalling genes accompanied by increased nuclear localization of phosphorylated Smad-2 and phosphorylated Smad-3. Furthermore, the m-RNA and protein level of epithelial marker, that is, E-cadherin decreased while the mesenchymal marker, that is, α-smooth muscle actin increased in heptachlor exposed HK-2 cells. In conclusion, heptachlor-induced OS might be responsible for the activation of TGF-ß1/Smad signalling which ultimately leads to renal damage by means of EMT.

Risk Factors Associated With Musculoskeletal Injury: A Prospective Study of British Infantry Recruits.

BACKGROUND: Musculoskeletal Injury (MSKI), a common problem in both military and physically active civilian populations, has been suggested to result from both extrinsic and intrinsic factors. OBJECTIVE: To investigate prospectively whether gait biomechanics, aerobic fitness levels and smoking status as well as entry military selection test variables can be used to predict MSKI development during recruit training. METHODS: British infantry male recruits (n = 562) were selected for the study. Plantar pressure variables, smoking habit, aerobic fitness as measured by a 1.5 mile run time and initial military selection test (combination of fitness, Trainability score) were collected prior to commencement of infantry recruit training. Injury data were collected during the 26 week training period. RESULTS: Incidence rate of MSKI over a 26 week training period was 41.28% (95 % CI: 37.28 - 45.40%). The injured group had a higher medial plantar pressure (p < 0.03), shorter time to peak heel rotation (p < 0.02), current smoking status (p < 0.001) and a slower 1.5 mile run time (p < 0.03). In contrast, there were no significant differences (p > 0.23) in lateral heel pressure, age, weight, height, BMI and military selection test. A logistic regression model predicted MSKI significantly (p= 0.03) with an accuracy of 34.50% of all MSK injury and 76.70% of the non-injured group with an overall accuracy of 69.50%. CONCLUSION: The logistic regression model combining the three risk factors was capable of predicting 34.5% of all MSKI. A specific biomechanical profile, slow 1.5 mile run time and current smoking status were identified as predictors of subsequent MSKI development. The proposed model could include evaluation of other potential risk factors and if validated then further enhance the specificity, sensitivity and applicability.

Propoxur-induced oxidative DNA damage in human peripheral blood mononuclear cells: protective effects of curcumin and α-tocopherol.

The present study enumerates the attenuating effects of curcumin and α-tocopherol against propoxur induced oxidative DNA damage in human peripheral blood mononuclear cells (PBMC). Cultured cells were isolated from peripheral blood of healthy volunteers, and were exposed to varying concentrations of propoxur (0-21 µg/ml) for 6, 12, and 24 h, and in combination with curcumin (9.2 µg/ml) or α-tocopherol (4.3 µg/ml) or both. Cytotoxic effect of propoxur was examined by MTT assay. The role of oxidative stress beneath the cytotoxicity of propoxur was evaluated by the measurement of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels in cell lysate. A concentration-dependent cell death, depletion of GSH, an increase in the level of both MDA and 8-OH-dG were observed. Co-treatment with curcumin or α-tocopherol significantly attenuates depleted GSH, decrease in MDA and 8-OH-dG levels in propoxur exposed cells (p < 0.05). The results of the present study provide experimental evidence of involvement of oxidative stress in propoxur-mediated genotoxicity in human PBMC and highlight the antioxidant role of curcumin and α-tocopherol following propoxur exposure.

CYP1A1 expression and organochlorine pesticides level in the etiology of bladder cancer in North Indian population.

Urinary bladder cancer (UBC) is one of the most common malignancies worldwide. The etiology of UBC is multifactorial and includes both exogenous and endogenous factors. Exogenous risk factors include exposure to heavy metals, aromatic amines, and environmental pollutants including pesticides such as organochlorine pesticides (OCPs). Environmental factors alone are incapable of directly producing DNA damage and may require activation by phase I metabolizing enzymes like cytochrome P450 in order to become active carcinogen. The present study is designed to study CYP1A1 gene expression, OCP level in cases of UBC, as well as to explore the plausible role of gene-environment interaction in the etiology of UBC among North Indian population. A total of 60 cases with equal number of controls were enrolled under this study, the OCP levels were estimated using gas chromatography, CYP1A1 mRNA expression was quantified by real-time quantitative polymerase chain reaction, and fold change was calculated using the ΔΔCt method. In the present study, the levels of OCP were found to be significantly higher with the upregulation of CYP1A1 mRNA expression among UBC cases as compared to controls. While putting multiple linear regression, it has been observed that there is a significant interaction between the levels of OCPs and ΔCt value of CYP1A1 gene taken into account hematuria episodes as dependent variable. The study concludes that when there is predisposition of OCPs and upregulation of CYP1A1 gene, then the result will be an increment in hematuria episodes which indicates that gene-environment interaction plays a significant role in the causation of UBC among North Indian population.

Assessment of urinary cotinine levels in women with gynecological complaints at a tertiary care hospital: A pilot study.

Gynecological effects due to smokeless tobacco exposure are not well studied. This cross-sectional study was undertaken with the objective to evaluate the urinary cotinine levels in women of reproductive age with gynecological complaints. The study was conducted in 2015 at the outpatient clinic of the Department of Obstetrics and Gynecology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi. A total of 192 consecutive women presenting with gynecological complaints (pelvic inflammatory disease (PID), infertility, and menstrual abnormality) were recruited. Their demographic details and tobacco exposure were recorded. All of them denied exposure to any form of tobacco. Urinary cotinine level of each participant was measured. The mean urinary cotinine level was 23.60 ± 12.00 ng/ml. PID was the most common gynecological complaint. Women with PID had significantly higher urinary cotinine levels compared to those with menstrual complaints and infertility: 24.9548 (±12.259) ng/ml versus 20.2042 (±10.9248) ng/ml. This study highlights the importance of addressing the issue of secondhand smoke exposure and reproductive morbidities in women.

Relationship of levels of Vitamin D with flow-mediated dilatation of brachial artery in patients of myocardial infarction and healthy control: A case-control study.

BACKGROUND: Cardiovascular diseases (CVD) remain the leading cause of death worldwide. Vitamin D deficiency has been linked to increased risk of adverse CV events. Vitamin D deficiency may be responsible for endothelial dysfunction which in turn affects the onset and progression of coronary artery disease and its risk factors, directly or indirectly through various mechanisms. MATERIALS AND METHODS: It was case-control study. A total of 50 cases of acute myocardial infarction (AMI) (aged 40-60 years), admitted to medicine emergency/CCU, were taken as per ACC/AHA 2007 guidelines. An equal number of age- and sex-matched controls were also taken. Risk factors of AMI, flow-mediated dilatation (FMD), and 25(OH)D levels were studied in all cases and controls. Correlation was also studied between FMD and 25(OH)D. RESULTS: The mean values of FMD were 18.86 ± 5.39% and 10.35 ± 4.90% in controls and cases, respectively (P < 0.05). The endothelial dilatation after glyceryl trinitrate (GTN) was also studied and was found to be 26.175 ± 4.25% and 18.80 ± 5.72% in controls and cases, respectively (P < 0.05). The mean levels of 25(OH)D in controls and cases were 25.45 ± 12.17 and 14.53 ± 8.28 ng/ml, respectively. In this study, 56% of subjects were Vitamin D deficient, 25% were Vitamin D insufficient, and only 19% had Vitamin D in normal range. A positive correlation coefficient was found between FMD and 25(OH) Vitamin D levels (r = 0.841, P < 0.01). In this study, a positive correlation coefficient was also found between endothelial dilatation after GTN and 25(OH)D levels (r = 0.743, P < 0.01). CONCLUSION: In this study, it was found that FMD was markedly impaired in patients of AMI when compared to controls. It was also found that majority of the study population was Vitamin D deficient; however, the deficiency was more severe in patients of AMI. We also found out that FMD was positively correlated (r = 0.841) to the deficiency state of Vitamin D in all the study subjects.

Association of organochlorine pesticides with the mRNA expression of tumour necrosis factor-alpha (TNF-α) & cyclooxygenase-2 (COX-2) genes in idiopathic preterm birth.

BACKGROUND & OBJECTIVES: Preterm birth (PTB) is an important cause of prenatal death, neonatal morbidity and mortality and adult illness. Increased inflammation occurs in normal parturition, and inflammatory cytokines and oxidative stress are found to be higher in PTB cases. The present study was planned to investigate the association of organochlorine pesticides (OCPs) with mRNA expression of inflammatory pathway genes such as tumour necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in preterm delivery (PTD) cases. METHODS: Maternal blood samples of PTD (n=30) cases and equal number of term delivery (n=30) were collected at the time of labour. Women occupationally exposed to OCPs and other high risk factors such as anaemia, hypertension, bacterial vaginosis, renal and heart disease, diabetes, etc. were excluded. The OCP levels were estimated by gas chromatography, and mRNA expressions of TNF-α and COX-2 genes were analysed using real-time PCR (qPCR). RESULTS: Significantly higher levels of ß-HCH (beta-hexachlorocyclohexane, 95% CI=2.08-4.633, p0 =0.001), p'p'-DDE (para, para-dichlorodiphenyldichloroethylene, 95% CI=0.546-2.551, p0 =0.003), and o'p'-DDD (ortho, para-dichlorodiphenyldichloroethane, 95% CI=0.004-0.690, P=0.047) were observed in maternal blood of PTB cases as compared to term delivery. The mRNA expressions of COX-2 and TNF-α genes were 3.13 and 2.31 folds higher in PTB cases in comparison to term delivery. l0 inear positive correlations were observed between period of gestation (POG) and ΔCt of COX-2 and TNF-α genes. INTERPRETATION & CONCLUSIONS: Environmental factors such as OCPs may be associated with inflammatory events showing gene-environment interaction in PTB cases. Evaluating the molecular control of inflammation along with gene environment interaction may be used as a model to explore the aetiology of idiopathic PTB cases and may be considered for the prognosis of adverse reproductive outcomes.

To Evaluate the Efficacy of Combination Antioxidant Therapy on Oxidative Stress Parameters in Seminal Plasma in the Male Infertility.

INTRODUCTION: Infertility is defined as inability to conceive after 1 year of unprotected intercourse and it affects 7% of male population and 8-10% of couples. According to estimates WHO, 13-19 million couples in India are infertile. Oxidative stress is the causative factor in 25% of infertile males. AIM: To study the efficacy of antioxidant therapy on oxidative stress parameters in seminal plasma of infertile male. MATERIALS AND METHODS: Forty patients of male infertility were enrolled in study after two abnormal semen analyses reports at 2-3 weeks interval, of oligozoospermia and/or asthenozoospermia, as per WHO guide line 1999. First semen sample was collected at a time of enrollment of study and second semen sample was collected three months after combined antioxidant therapy. Semen samples from the infertile male (the second confirmatory sample of oligoasthenozoospermia) were taken and after liquefaction semen sample were utilized for various analyses, 0.5 ml of sample for standard semen analysis, 1.2 ml sample for separation of seminal plasma to evaluate Oxidative stress (OS) parameters like Malondialdehyde (MDA), Protein Carbonyl (PC) and antioxidant capacity by Glutathione (GSH). We followed the patient for three months after completion of the treatment. RESULTS: Semen parameters - Out of 40 patients recruited in the study group 7 patients had only oligospermia (1 to 20 million/ml) and 31 patients had oligoasthenozoospermia (motility range 0-50%) and 2 patients had oligoasthenoteratozoospermia. There was no patient with asthenospermia alone as abnormal semen parameters. After the three months treatment with combined antioxidants the semen parameters like count (mean SD = -1.70±1.44) and motility (mean +SD= -9.56±9.05) were significantly increased (p-value=0.000). Oxidative Stress Assessment - The level of MDA which is a marker of oxidative stress was significantly lower after the three months therapy of antioxidants (p-value=0.002) whereas another marker which is denoted by PC was also lower after the treatment but not statistically significant (p-value=0.584). The level of antioxidants GSH also significantly increased after the treatment (p-value=0.000). After the treatment out of 40, five patients conceived (16.7%). CONCLUSION: As we have seen through this study antioxidant dramatically reduced the oxidative stress markers and enhancing the antioxidant enzymes. They should be used on routine basis in case of male infertility.

Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice.

BACKGROUND: The inflammatory response system has been implicated in the pathophysiology of major depression. The pro-inflammatory cytokines like interferon-γ induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the availability of tryptophan for serotonin synthesis. Furthermore, the metabolites of kynurenine pathway have neurotoxic property, which along with decreased serotonin may account for depression-like illness. METHODS: The aim of this study was to compare the effects of treatment with fluoxetine and 1-methyl-L-tryptophan (1-MT) on Bacillus Calmette-Guerin (BCG)-induced inflammatory model of depression in mice. Behavioral tests included locomotor activity, forced swim test (FST) and tail suspension test (TST). Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in homogenized whole brain samples. Comet assays were performed to assess neurotoxicity. RESULTS: The results of this study demonstrate that BCG treatment resulted in an increase in duration of immobility in FST and TST as compared to the saline group. Further, it produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. The hippocampal tissue from BCG group had significantly more comet cells than the saline group. 1-MT and fluoxetine were able to reverse the BCG-induced depression-like behavior and the derangement in oxidative stress parameters. Fluoxetine and 1-MT also reversed the BCG-induced neurotoxicity in such mice. CONCLUSIONS: 1-Methyl-L-tryptophan exhibits antidepressant-like effect comparable to that of fluoxetine in treating BCG-induced depression-like behavior in mice.

Prolonged esophageal acid exposures induce synaptic downscaling of cortical membrane AMPA receptor subunits in rats.

BACKGROUND: We recently reported the involvement of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunit upregulation and phosphorylation in the rostral cingulate cortex (rCC) as the underlying mechanism of acute esophageal acid-induced cortical sensitization. Based on these findings, we proposed to investigate whether prolonged esophageal acid exposures in rats exhibit homeostatic synaptic scaling through downregulation of AMPA receptor expression in rCC neurons. We intended to study further whether this compensatory mechanism is impaired when rats are pre-exposed to repeated esophageal acid exposures neonatally during neuronal development. METHODS: Two different esophageal acid exposure protocols in rats were used. Since AMPA receptor trafficking and channel conductance depend on CaMKIIα-mediated phosphorylation of AMPA receptor subunits, we examined the effect of esophageal acid on CaMKIIα activation and AMPA receptor expression in synaptoneurosomes and membrane preparations from rCCs. KEY RESULTS: In cortical membrane preparations, GluA1 and pGluA1Ser(831) expression were significantly downregulated following prolonged acid exposures in adult rats; this was accompanied by the significant downregulation of cortical membrane pCaMKIIα expression. No change in GluA1 and pGluA1Ser(831) expression was observed in rCC membrane preparations in rats pre-exposed to acid neonatally followed by adult rechallenge. CONCLUSIONS & INFERENCES: This study along with our previous findings suggests that synaptic AMPA receptor subunits expression and phosphorylation may be involved bidirectionally in both esophageal acid-induced neuronal sensitization and acid-dependent homeostatic plasticity in cortical neurons. The impairment of homeostatic compensatory mechanism as observed following early-in-life acid exposure could be the underlying mechanism of heightening cortical sensitization and esophageal hypersensitivity in patients with gastroesophageal reflux disease.

High genetic diversity and distribution of Bubu-DQA alleles in swamp buffaloes (Bubalus bubalis carabanesis): identification of new Bubu-DQA loci and haplotypes.

In this study, genetic diversity analysis of MHC class II-DQA locus helped in identification of 25 new Bubu-DQA nucleotide sequences in swamp buffaloes (Bubalus bubalis carabanesis, Bubu). Phylogenetic analysis revealed the distribution of the buffalo DQA sequences in two major clusters of DQA1 and DQA2 genes, sharing common lineages with corresponding cattle alleles, possibly due to trans-species evolution. However, a highly divergent sequence, Bubu-DQA*2501, homologous to cattle (BoLA) DQA3 allele, was identified, indicating the existence of an additional locus; putative DQA3 in buffalo. PCR-RFLP analysis revealed extensive duplication of DQA locus in swamp buffaloes, sharing DQA1, DQA2, and DQA3 alleles in different combinations in duplicated haplotypes. Higher dN than dS values and Wu-Kabat variability at peptide-binding regions in Bubu-DQA indicated high polymorphism with balancing selection. Levels of genetic diversity within DQA sequences and duplication in a small population of swamp buffalo indicate the genetic richness of the species, important for fitness.