Interleukin 6 −174G>C polymorphism and cancer risk: Meta-analysis reveals a site dependent differential influence in Ancestral North Indians

In our earlier studies, single nucleotide polymorphisms (SNPs) associated with anti-inflammatory cytokines were found to influence risk for breast cancer in western Indian women. Analysis of Interleukin 6 (IL-6) −174G>C polymorphism in this cohort (patients = 182; controls = 236) suggested a protective role for IL-6 −174C allele associated with the lower expression of the cytokine (OR = 0.54; 95% CI 0.32–0.89, dominant model). Together these observations suggested that in comparison to Caucasians, inflammation associated-cytokine gene polymorphisms may have higher influence on risk for cancer in this population. To examine this possibility we analyzed data assessing influence of Interleukin 6 (IL-6) −174G>C polymorphism on risk for various cancers. Overall, there was a marginally higher risk for rare allele homozygotes compared to wild type homozygotes (OR = 1.07; 95% CI 1.00–1.15). Increased risks for genitourinary cancers and for skin cancer were also indicated. The ethnicity based analysis indicated a protective effect of the minor allele in Ancestral North Indians (OR = 0.73; 95% CI 0.55–0.97). Site by ethnicity analysis once again revealed a significant protection against breast cancer (OR = 0.51; 95% CI = 0.37–0.70; dominant model) but an opposite influence on the risk of genitourinary malignancies (OR = 2.51; 95% CI 1.59–3.96; recessive model) in this population alone. The observations imply that contribution of IL-6 to inflammation or effector immunity may depend on the site of malignancy. Assessment of available data in relation to prognosis in breast cancer patients also revealed trends that are compatible with the observations of the meta-analysis. Thus, IL-6 −174G>C polymorphism clearly represents a potential modulator of risk for malignant disorders with ethnicity and site dependent trends. The results also support the possibility of higher influence of inflammation related cytokine gene polymorphisms on the risk for cancers in Ancestral North Indians.     

Comparison of Q-switched Nd:YAG laser alone versus its combination with ultrapulse CO2 laser for the treatment of black tattoo

Background: Q-switched lasers are conventionally used for the treatment of black tattoo. However, they require multiple sittings, and the response may be slow due to competing epidermal pigment in dark skin. Objective: To compare the efficacy of Q-switched Nd:YAG laser alone with its combination with ultrapulse CO₂ for the removal of black tattoo. Materials and methods: Sixty patients with black tattoo were randomized into two groups viz., group A and group B. Group A was treated with QS Nd:YAG laser (1064 nm) alone, and group B received combination of ablative ultrapulse CO₂ followed by fixed-dose QS Nd:YAG laser (1064 nm), at 6-week interval for a maximum of 6 sittings. After each sitting, 3 independent physicians noted percentage of improvement that was evaluated using visual analogue scale (VAS) and grading system for tattoo ink lightening (TIL). Results: Combination laser (group B) showed statistically significant improvement in mean VAS score in the last 2 noted visits as compared to 1st session (p < 0.007, p < 0.001) and TIL mean score in last three noted visits as compared to 1st session (p < 0.008, p < 0.020, and p < 0.004). There was no statistically significant difference in the side effect profile of both the groups. Conclusion: For refractory professional tattoos, combination of ultrapulse CO₂ laser and QS Nd:YAG laser is superior to QS Nd:YAG laser alone.     

NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and in human sporadic ALS patients

Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of motoneurons in the cerebral cortex, brainstem and spinal cord. Neuroinflammation plays an important role in the pathogenesis of ALS and involves the activation of microglia and astrocytes. Intracellular inflammasome complexes are part of the innate immunity as they sense and execute host inflammatory responses. The best characterized component is the NLRP3 inflammasome comprised of the NLR protein NLRP3, the adaptor ASC and pro‐caspase 1. The NLRP3 inflammasome is critical for the activation of caspase 1 and the processing and release of IL1β and IL18. In this study, we investigated the expression, activation and co‐localization of the NLRP3 inflammasome in the spinal cord of male SOD1(G93A) mice carrying a mutant human superoxide dismutase 1 (SOD1) variant and regarded as an animal model for ALS as well as in post‐mortem tissue of ALS patients. NLRP3 and its molecular components as well as IL1β were already detectable in SOD1 mice at a pre‐symptomatic stage after 9 weeks and further increased in 14 week old animals. Spinal cord astrocytes were identified as the major cell type expressing NLRP3 components. In human ALS tissue, we also found increased NLRP3, ASC, IL18 and active caspase 1 levels compared to control patients. Our findings suggest that astroglial NLRP3 inflammasome complexes are critically involved in neuroinflammation in ALS. GLIA 2015;63:2260–2273     

Molecular dynamics-based simulation of trace amine membrane permeability

Trace amines are endogenous compounds, typified by 2-phenylethylamine (PE) and p-tyramine (TA), found in the vertebrate central nervous system. Although synthesized in pre-synaptic terminals, trace amines do not appear to act as neurotransmitters, but rather modulate responsivity to co-existing neurotransmitters. Trace amines are neither actively accumulated in synaptic vesicles, nor released in an activity-dependent manner. Further, Trace Amine-Associated Receptor 1 (TAAR1), which is selectively activated by PE and TA, is intracellular. As such, PE and TA need to cross cell membranes in order to exert their effects. This has been assumed to occur by simple diffusion, but has not previously been systematically examined. Experimental data were obtained using Fluorosome^® technology. A permeability coefficient of 25.3 ± 3.8 Å/s (n = 6) was obtained for TA which was not significantly different from that obtained for the monoamine neurotransmitter noradrenaline (20.3 ± 3.8 Å/s, n = 8). PE was unsuitable for use with this system. We have also used molecular dynamics computer simulation techniques to determine the potential of mean force (PMF) associated with trace amine passage across lipid bilayers. A PMF peak barrier of 25 ± 6 kcal/mol (protonated) and 13 ± 1 kcal/mol (deprotonated) was obtained for PE. Protonated TA peak energy barriers were even greater at 31 ± 1 kcal/mol. Application of a homogeneous solubility-diffusion model combining the measured permeability coefficients and simulated PMF allows fitting of the diffusion coefficient for trace amines in the hydrophobic region of the lipid bilayer. The diffusion coefficients in other regions of the membrane were found to make negligible contributions to the permeability coefficient for the calculated PMF. The fit obtained a value for the diffusion coefficient of (163 ± 25) × 10^?10 m²/s for TA⁺ in the hydrophobic core region. The diffusion coefficient for TA⁺ in the aqueous compartment was also calculated directly by simulation yielding a value of (0.62 ± 0.26) × 10^?10 m²/s. The adopted simulation methods failed to yield diffusion coefficients in the core region indicating that further work will be required to accurately predict permeability coefficients for trace amines passing through membranes.     

Defining Obesity Using a Biological End Point in Sri Lankan Children

Objective

To identify the percentage of body fat mass (FM) that would define obesity among Sri Lankan children.

Methods

A cross-sectional study was conducted among 5–15 y old children in the district of Colombo. FM was assessed using Bio Impedance Assay (BIA). After a 12 h overnight fast, blood was drawn for fasting blood glucose (FBS) and lipid profile. Oral-glucose-tolerance test (OGTT) was done along with 2 h random blood sugar (RBS). Metabolic syndrome (MetS) was diagnosed by a high waist circumference (WC) with ≥2 metabolic derangements [FBS/RBS, high density lipoprotein-cholesterol (HDL-C), triglyceride, and systolic and diastolic blood pressure (SBP/DBP)]. Receiver-Operator Characteristics (ROCs) were drawn to determine the best %FM that predicted MetS.

Results

Nine hundred twenty children were studied (547 boys). Fifteen (1.6 %) had MetS. Ninety five (10.3 %) had two and 16(1.7 %) had ≥3 metabolic derangements. MetS in boys was associated with %FM of 28.6 (sensitivity 1.000; specificity 0.870) and in girls 33.7 (sensitivity 0.875; specificity 0.808).

Conclusions

FM associated with adverse health outcomes in this population is comparable to other available data. A %FM of 28.6 % for boys and 33.7 % for girls would be acceptable cutoff limits.

     

Health-related quality of life and its predictors among the type 2 diabetes population of Bangladesh: A nation-wide cross-sectional study

Aims/IntroductionWe aimed to assess the health‐related quality of life (HRQoL) and identify its predictors among type 2 diabetes patients of Bangladesh.Materials and MethodsThis nationwide cross‐sectional study assessed HRQoL among 1,806 type 2 diabetes patients using the EuroQol‐5 Dimensions Questionnaire (EQ‐5D‐5L), and the responses were further translated into a single summary crosswalk index score using the UK time trade‐off value set. The predictors were determined using multinomial logistic regression analysis.ResultsThe mean EQ‐5D‐5L index score was 0.62 (standard deviation 0.25), and men scored better than women. More than half of the study participants (53.4%) were ranked as “average” HRQoL. Overall, 64% of respondents had a “problem” at least in one of the dimensions of the EQ‐5D‐5L, and the burden of reported “problems” was higher among women (70%). Among the five dimensions, the highest reported “problem” was 79.8% for anxiety/depression, 77.7% for pain/discomfort and 60.1% for mobility. However, younger participants (aged <30 years) showed a higher burden of anxiety/depression (95%) compared with the rest of the population. The specific predictors of average/good HRQoL (odds ratio >1) were being men, living in a rural area, married, literate, a monthly income >19,488 BDT, absence of comorbidity and had a duration of diabetes ≤5 years.ConclusionsThe majority of Bangladesh’s type 2 diabetes patients had an “average” HRQoL based on the EQ‐5D‐5L index score. In broad terms, the identified predictors were sex, place of residence, marital status, literacy, monthly income, comorbidity and duration of diabetes.     

Negative affect moderates the link between body image dissatisfaction and disordered eating among psychiatric outpatients in a multi-ethnic Asian setting

INTRODUCTIONFew studies have investigated the factors that affect the relationship between body image dissatisfaction and disordered eating locally. Our study aimed to investigate the moderating effects of depression and anxiety levels on the body dissatisfaction-disordered eating link in Singapore.METHODSA total of 329 participants completed a set of questionnaires that included various scales pertaining to eating behaviours, body image, psychological distress and quality of life.RESULTSParticipants were diagnosed with schizophrenia (47.4%), depression (46.8%) and substance use disorders (5.8%). Moderation analyses revealed that depression (F [9, 251] = 18.50, p < 0.001, R² change = 0.021) and anxiety levels (F [9, 268] = 19.54, p < 0.001, R² change = 0.014) were significant moderators of the relationship between body dissatisfaction and disordered eating scores. Subsequent multivariate linear logistic regression analyses showed that high disordered eating scores were significantly associated with lower physical (F [8, 273] = 9.59, R² = 0.22, p < 0.001, β = −0.27, p < 0.001), psychological (F [8, 273] = 10.51, R² = 0.49, p < 0.001, β = −0.27, p < 0.001), social (F [8, 256] = 6.78, R² = 0.18, p < 0.001, β = −0.18, p = 0.004) and environment (F [8, 273] = 5.29, R² = 0.13, p < 0.001, β = −0.19, p = 0.001) quality of life scores after controlling for sociodemographic covariates.CONCLUSIONGreater effort should be dedicated to the screening of disordered eating behaviours in psychiatric outpatients presenting with greater psychological distress.     

Anxiety and depression,personality traits relevant to tinnitus: A scoping review

Objective: Scoping reviews of existing literature were conducted to identify key personality traits relevant to tinnitus, and examine the relationship between affective disorders and tinnitus. Design: The methodological framework of Arksey and O’Malley was followed. Study sample: Sixty studies were chosen for charting the data, 14 studies examined personality traits exclusively, 31 studies examined affective disorders exclusively, and 15 studies investigated both. Results: The presence of one or more specific personality traits of high neuroticism, low extraversion, high stress reaction, higher alienation, lower social closeness, lower well-being, lower self control, lower psychological acceptance, presence of a type D personality, and externalized locus of control were associated with tinnitus distress. Anxiety and depression were more prevalent among the tinnitus clinical population and at elevated levels. Conclusions: Personality traits have a consistent association with the distress experienced by adult tinnitus help-seekers, and help-seekers are also more likely to experience affective symptoms and/or disorders.     

Anti-allergic and Anti-hyperglycemic Potentials of Lumnitzera racemose Leaves: In vivo and In silico Studies

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Lumnitzera racemosa a mangrove plant locally used to treat asthma, diabetes, herpes and hypertension. Present...