Correlation of Peroxisome Proliferator-Activated Receptor (PPAR-γ) mRNA Expression with Pro12Ala Polymorphism in Obesity

Our study aimed to analyze whether the expression of PPARγ mRNA in subcutaneous adipocyte tissue correlates with Pro12Ala PPARγ2 polymorphism in the obesity context. We found that mRNA expression of PPARγ in subcutaneous adipose tissue was greater in obese subjects (P < 0.05) than in the nonobese control group. Concurrently, genotyping of the Pro12Ala polymorphism showed that obese subjects possess a significantly higher frequency of the Pro/Pro genotype than nonobese controls (90.5 vs 79.5%; P = 0.03), suggesting that this genotype is involved in an increased risk of obesity in the Tunisian population. Taken together, our results demonstrate that the Pro12 allele is accompanied by an overexpression of PPARγ mRNA in subcutaneous adipocyte tissue, suggesting that the PPARγ Pro12Ala variant may contribute to the observed variability in PPARγ mRNA expression and consequently in body mass index and insulin sensitivity in the general population.     

Fungal silver nanoparticles: synthesis,application and challenges

Purpose: This paper aims to summarize recent developments regarding the synthesis, application and challenges of fungal AgNPs. Possible methods to overcome the challenge of synthesis and reduce the toxicity of AgNPs have been discussed.

Materials and methods: This review consults and summary a large number of papers.

Results: Silver nanoparticles (AgNPs) have great potential in many areas, as they possess multiple novel characteristics. Conventional methods for AgNPs biosynthesis involve chemical agents, causing environmental toxicity and high energy consumption. Fungal bioconversion is a simple, low-cost and energy-efficient biological method, which could successfully be used for AgNPs synthesis. Fungi can produce enzymes that act as both reducing and capping agents, to form stable and shape-controlled AgNPs.

Conclusions: AgNPs have great potential in the medical and food industries, due to their antimicrobial, anticancer, anti-HIV, and catalytic activities. However, the observed in vitro and in vivo toxicity poses considerable challenges in the synthesis and application of AgNPs.     

Towards National Surgical Surveillance in the UK – A Pilot Study

Objective

The Bristol heart inquiry in the United Kingdom (UK) highlighted the lack of standards for evaluating surgical performance and quality. In 2009, the World Health Organisation (WHO) proposed six standardised metrics for surgical surveillance. This is the first study to collect and analyse such metrics from a cohort of National Health Service (NHS) Trusts in England, helping to determine their feasibility and utility in measuring surgical performance, its impact on public health and mortality, and for tracking surgical trends over time.

Methods

Freedom of Information Act 2000 (FOI) requests for WHO standardised surgical metrics were made to 36 NHS Trusts in England during July to November 2010. Additional data on Hospital Standardised Mortality Ratio (HSMR), Patient Safety Score and Abdominal Aortic Aneurysm (AAA) volume and mortality was obtained from Dr Foster Health and The Guardian Newspaper. Analysis was performed using mixed-effect logistic regression.

Results

30/36 trusts responded (83%). During 2005–9, 5.4 million operations were performed with a 24.2% increase in annual number of operations. This rising volume within hospitals was associated with lower mortality ratios. A 10% increase in operative volume was associated with a lower day of surgery death rate (DDR OR = 0.94, p = 0.056) and post-operative inpatient 30-day mortality (PDR30 OR = 0.93, p = 0.001). For every 10,000 more operations that an NHS Trust does, a 4% drop in PDR30 mortality was achieved. A 10% increase in the volume of elective AAAs was associated with lower elective AAA (OR = 0.96, p = 0.032) and emergency AAA (OR = 0.95, p = 0.009) PDR30 mortality. Lower DDR mortality was noted for emergency AAA mortality (OR = 0.95, p = 0.025) but not elective AAAs (OR = 0.97, p = 0.116).

Conclusion

Standarised surgical metrics can provide policy makers and commissioners with valuable summary data on surgical performance allowing for statistical process control of a complex intervention. This study has shown their collection is feasible albeit using FOI and the first to show a statistically significant volume-outcome relationship for surgery as a whole within hospitals. It adds weight to the argument that patients are safer in larger hospitals or those that become larger by growing their patient base. Together with other measures, such metrics can help build a picture of surgical surveillance in the UK and potentially lead us to safer surgery.     

Impact of Intensive Handwashing Promotion on Secondary Household Influenza-Like Illness in Rural Bangladesh: Findings from a Randomized Controlled Trial

Rationale

There is little evidence for the efficacy of handwashing for prevention of influenza transmission in resource-poor settings. We tested the impact of intensive handwashing promotion on household transmission of influenza-like illness and influenza in rural Bangladesh.

Methods

In 2009–10, we identified index case-patients with influenza-like illness (fever with cough or sore throat) who were the only symptomatic person in their household. Household compounds of index case-patients were randomized to control or intervention (soap and daily handwashing promotion). We conducted daily surveillance and collected oropharyngeal specimens. Secondary attack ratios (SAR) were calculated for influenza and ILI in each arm. Among controls, we investigated individual risk factors for ILI among household contacts of index case-patients.

Results

Among 377 index case-patients, the mean number of days between fever onset and study enrollment was 2.1 (SD 1.7) among the 184 controls and 2.6 (SD 2.9) among 193 intervention case-patients. Influenza infection was confirmed in 20% of controls and 12% of intervention index case-patients. The SAR for influenza-like illness among household contacts was 9.5% among intervention (158/1661) and 7.7% among control households (115/1498) (SAR ratio 1.24, 95% CI 0.92–1.65). The SAR ratio for influenza was 2.40 (95% CI 0.68–8.47). In the control arm, susceptible contacts <2 years old (RR_adj 5.51, 95% CI 3.43–8.85), those living with an index case-patient enrolled ≤24 hours after symptom onset (RR_adj 1.91, 95% CI 1.18–3.10), and those who reported multiple daily interactions with the index case-patient (RR_adj 1.94, 95% CI 1.71–3.26) were at increased risk of influenza-like illness.

Discussion

Handwashing promotion initiated after illness onset in a household member did not protect against influenza-like illness or influenza. Behavior may not have changed rapidly enough to curb transmission between household members. A reactive approach to reduce household influenza transmission through handwashing promotion may be ineffective in the context of rural Bangladesh.

Trial Registration

ClinicalTrials.gov NCT00880659     

Prostate cancer is known by the companionship with ATM and miRNA it keeps: craftsmen of translation have dual behaviour with tailors of life thread

Research on prostate cancer progression has focused extensively on the concept of miRNA, which can operate either as promoters or as suppressors of carcinogenesis. Moreover, recent genetic studies and emerging functional work show that strikingly similar and overlapping pathways are involved in prostate carcinogenesis. Unswervingly, these elements constitute a recently explored ‘network of networks’ that dynamically reorganizes during DNA damage and is responsible for positively or negatively regulating genome organization and integrity. We consider these facets of convergence and discuss how insights from diametrically opposed interactions of ataxia–telangiectasia mutated and mitrons can inform us about, and possibly help us to get a step closer to personalized medicine. Copyright © 2012 John Wiley & Sons, Ltd.     

Relationship between vitamin B12, folate and homocysteine levels and H. pylori infection in patients with functional dyspepsia: A cross-section study

ABSTRACT: BACKGROUND: H. pylori infection has been associated with many micronutrient deficiencies. There is a dearth of data from communities with nutritional deficiencies and high prevalence of H. pylori infection. The aim of this study was to determine the impact of H. pylori infection on serum levels of vitamin B12, folate and homocysteine in patients with functional dyspepsia (FD). METHODS: One hundred and thirty-two patients with FD undergoing gastroscopy were enrolled. The serum was analyzed for B12, folate and homocysteine levels before gastroscopy. H. pylori infection was diagnosed by histopathological examination of gastric biopsies and urea breath test. An independent sample t-test and the Mann-Whitney test were used to compare mean serum concentrations of biomarkers between H. pylori-positive and H. pylori-negative groups of patients. A Chi-square test was performed to assess the differences among proportions, while Spearman's rho was used for correlation analysis between levels of B12 and homocysteine. RESULTS: The mean age of the group was 40.3 +/- 11.5 (19-72) years. Folate deficiency was seen in 43 (34.6%), B12 deficiency in 30 (23.1%) and hyperhomocysteinemia in 60 (46.2%) patients. H. pylori was present in 80 (61.5%) patients with FD while it was absent in 50 (38.5%). Mean serum levels of B12, folate and homocysteine in the H. pylori-positive group of patients were not significantly different from the levels in the H. pylori-negative group (357 +/- 170 vs. 313 +/- 136 pg/mL; p = 0.13), (4.35 +/- 1.89 vs. 4.42 +/- 1.93 ng/mL; p = 0.84); (15.88 +/- 8.97 vs. 16.62 +/- 7.82 mumol/L; p = 0.24); respectively. B12 deficiency ([less than or equal to]200 pg/mL) was 23.8% in the H. pylori-positive patients versus 22.0% in the H. pylori-negative patients. Folate deficiency ([less than or equal to]3.5 ng/mL) was 33.8% in the H. pylori-positive group versus 36% in the H. pylori-negative group. Hyperhomocysteinemia (>15 mumol/L) was present in 46.2% of H. pylori-positive patients compared to 44% in the H. pylori-negative group. Correlation analysis indicated that serum B12 levels were inversely associated with serum levels of homocysteine in patients with FD (rho = 0.192; p = 0.028). CONCLUSIONS: This study demonstrated an inverse relationship between serum levels of B12 and homocysteine in patients with FD. Moreover, no impact of the presence of H. pylori was found on B12, folate and homocysteine levels in such patients.     

Alcohol and PRAS40 knockdown decrease mTOR activity and protein synthesis via AMPK signaling and changes in mTORC1 interaction

The mTORC1 protein kinase complex consists of mTOR, raptor, mLST8/GβL and PRAS40. Previously, we reported that mTOR plays an important role in regulating protein synthesis in response to alcohol (EtOH). However, the mechanisms by which EtOH regulates mTORC1 activity have not been established. Here, we investigated the effect of EtOH on the phosphorylation and interaction of components of mTORC1 in C2C12 myocytes. We also examined the specific role that PRAS40 plays in this process. Incubation of myocytes with EtOH (100 mM, 24 h) increased raptor and PRAS40 phosphorylation. Likewise, there were increased levels of the PRAS40 upstream regulators Akt and IRS‐1. EtOH also caused changes in mTORC1 protein–protein interactions. EtOH enhanced the binding of raptor and PRAS40 with mTOR. These alterations occurred in concert with increased binding of 14‐3‐3 to raptor, while the PRAS40 and 14‐3‐3 interaction was not affected. The shRNA knockdown (KD) of PRAS40 decreased protein synthesis similarly to EtOH. PRAS40 KD increased raptor phosphorylation and its association with 14‐3‐3, whereas decreased GβL–mTOR binding. The effects of EtOH and PRAS40 KD were mediated by AMPK. Both factors increased in vitro AMPK activity towards the substrate raptor. In addition, KD enhanced the activity of AMPK towards TSC2. Collectively, our results indicate that EtOH stabilizes the association of raptor, PRAS40, and GβL with mTOR, while likewise increasing the interaction of raptor with 14‐3‐3. These data suggest a possible mechanism for the inhibitory effects of EtOH on mTOR kinase activity and protein synthesis in myocytes. J. Cell. Biochem. 109: 1172–1184, 2010. © 2010 Wiley‐Liss, Inc.     

Anticholinesterse and antioxidant investigations of crude extracts,subsequent fractions,saponins and flavonoids of atriplex laciniata L.: potential effectiveness in Alzheimer’s and other neurological disorders

Background

Atriplex laciniata L. was investigated for phenolic, flavonoid contents, antioxidant, anticholinesterase activities, in an attempt to explore its effectiveness in Alzheimer’s and other neurological disorders. Plant crude methanolic extract (Al.MeF), subsequent fractions; n-hexane (Al.HxF), chloroform (Al.CfF), ethyl acetate (Al.EaF), aqueous (Al.WtF), Saponins (Al.SPF) and Flavonoids (Al.FLVF) were investigated for DPPH, ABTS and H₂O₂ free radical scavenging activities. Further these extracts were subjected to acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities using Ellman’s assay. Phenolic and Flavonoid contents were determined and expressed in mg Gallic acid GAE/g and Rutin RTE/g of samples respectively.

Results

In DPPH free radicals scavenging assay, Al.FLVF, Al.SPF and Al.MeF showed highest activity causing 89.41 ± 0.55, 83.37 ± 0.34 and 83.37 ± 0.34% inhibition of free radicals respectively at 1 mg/mL concentration. IC₅₀ for these fractions were 33, 83 and 82 μg/mL respectively. Similarly, plant extracts showed high ABTS scavenging potential, i.e. Al.FLVF (90.34 ± 0.55), Al.CfF (83.42 ± 0.57), Al.MeF (81.49 ± 0.60) with IC₅₀ of 30, 190 and 70 μg/ml respectively. further, H₂O₂ percent scavenging was highly appraised in Al.FLVF (91.29 ± 0.53, IC₅₀ 75), Al.SPF (85.35 ± 0.61, IC₅₀ 70) and Al.EaF (83.48 ± 0.67, IC₅₀ 270 μg/mL). All fractions exhibited concentration dependent AChE inhibitory activity as; Al.FLVF, 88.31 ± 0.57 (IC₅₀ 70 μg/mL), Al.SPF, 84.36 ± 0.64 (IC₅₀ 90 μg/mL), Al.MeF, 78.65 ± 0.70 (IC₅₀ 280 μg/mL), Al.EaF, 77.45 ± 0.46 (IC₅₀ 270 μg/mL) and Al.WtF 72.44 ± 0.58 (IC₅₀ 263 μg/mL) at 1 mg/mL. Likewise the percent BChE inhibitory activity was most obvious in Al.FLVF 85.46 ± 0.62 (IC₅₀ 100 μg/mL), Al.CfF 83.49 ± 0.46 (IC₅₀ 160 μg/mL), Al.MeF 82.68 ± 0.60 (IC₅₀ 220 μg/mL) and Al.SPF 80.37 ± 0.54 (IC₅₀ 120 μg/mL).

Conclusions

These results stipulate that A. laciniata is enriched with phenolic and flavonoid contents that possess significant antioxidant and anticholinestrase effects. This provide pharmacological basis for the presence of compounds that may be effective in Alzheimer’s and other neurological disorders.