Aggressive versus Low Dose Inhibition of the Renin-Angiotensin System for the Treatment of Microalbuminuria in Type 2 Diabetic Patients: A Pilot Study

Objective. This study compares low dose versus aggressive inhibition of the renin angiotensin system (RAS) to treat microalbuminuria (MA). Methods. Patients with MA after a run-in period to control BP to <130/80 mm Hg with 10 mg benazepril plus other drugs and HbA1c levels to <8.0% were randomized to either continue 10 mg benazepril (N = 12) or to take maximal doses of benazepril plus losartan in monthly stepwise increases to achieve normoalbuminuria (N = 11). Because MA is associated with CVD and inflammation, carotid intima medial thickness (CIMT) and endothelial function by peripheral arterial tonometry (PAT) as surrogate indices of atherosclerosis and highly sensitive C-reactive protein (hs-CRP) to assess inflammation were measured every six months. Results. BP, HbA1c levels, albumin : creatinine ratios, CIMT, PAT, and hs-CRP did not differ over a mean of 12 months between the two groups. Conclusions. Aggressive inhibition of the RAS is unnecessary to treat MA

Lessons Learned: Case Studies in Sustainable Use, Conclusion

The conclusion of Lessons Learned: Case Studies in Sustainable Use summarizes the overarching lessons learned from the case studies provided in the volume. 1. Sustainability of uses of renewable natural resources is dependent on the existence of a 'sustainable society'at the local, national and global levels. 2. Successful biological conservation is a function of equity and democracy. 3. To achieve greater sustainability of uses of natural resources will likely require modification of the roles of organizations and government agencies in authority. 4. The current conservation paradigm of Protected Areas (including as applied to the 'biodiversity hotspots'concept) may not be economically viable in many developing countries, simply because the opportunitycosts often exceed the value local people receive from their existence. National and international agencies and organizations realize most of the value from designation of protected areas and 'hotspots'. 5. It is not possible to transpose directly the combination of factors that influence one case to another site, and expect the same impact or result.6. Donor agencies and/or central government policies need to consider management requirements beyond project cycles in order to promote long-term sustainability of resource uses.7. External factors such as war and natural disasters can have an over-riding influence on the sustainability of resource use. 8. Interventions on key resources by external institutions often pressure transformation of local governance systems. The impact of these changes is often overlooked. More specific observations of common features. Furthermore, the conclusion provides lessons related to policy, social processes, institutions, and information

Prevalence of and factors associated with anxiety and depression among women in a lower middle class semi-urban community of Karachi, Pakistan

Objective: To study the prevalence of, and factors associated with anxiety and depression among women.Design: A cross sectional survey.SETTING: A lower middle class semi-urban community of Karachi, Pakistan.PARTICIPANTS: A total of 1218 women between the ages of 18-50 years.METHODOLOGY: Systematically every third household was identified from which a woman was randomly selected. The Aga Khan University Anxiety and Depression Scale and a socio-demographic questionnaire were administered verbally by trained interviewers for assessing the prevalence of, and associated factors for anxiety and depression.Results: A prevalence of 30% was found. Increasing age, lack of education and verbal abuse were the associated factors found to have an independent relationship.CONCLUSION: Providing education and reducing domestic abuse could lead to decrease in the prevalence of anxiety and depression in women

Evaluation of some biological activities of Abelia triflora R Br (Caprifoliaceae) constituents

Purpose: To investigate the antioxidant, anti-inflammatory, antidiabetic,  cardiovascular and cytotoxic activities of the leaf extract and major compounds isolated from Abelia triflora R. Br. (Caprifoliaceae)Methods: The chloroform soluble fraction of A. triflora leaves was subjected to several column chromatographic separations to isolate its constituents.  Anti-inflammatory and antioxidant activities were determined in terms of the ability to inhibit NF-kB, iNOS activity and lipoxygenase enzyme, and to decrease oxidative stress in HepG2 cells. Antidiabetic and cardiovascular activities were determined by screening for peroxisome proliferator-activated receptor alpha (PPARα) and PPARɣ agonistic activities. In vitro cytotoxic activity was determined against a set of four human cancer cell lines (SK-MEL, KB, BT-549, SK-OV-3) and two  non-cancerous kidney cell lines (LLC-PK1 and VERO). Cell viability was measured by neutral red assay.Results: Three triterpene acids were isolated from the chloroform fraction namely; ursolic acid (4), 2, 3-dihydroxy ursolic acid (5) and 2, 3, 21-trihydroxy ursolic acid (6). The results showed that ursolic acid exhibited potent inhibition of lipoxygenase enzyme and iNOS (inducible nitric oxide synthase) activity with IC50 (half-maximal inhibitory concentration) value of 13.0 μg/mL, compared to parthenolide positive standard (IC50, 0.3μg/mL); furthermore, it inhibited NF-kB (nuclear factor-kappa B) with IC50 of 25.0 μg/mL, compared to parthenolide (positive standard, (IC50, 0.5 μg/mL). Also, ursolic acid possessed the highest cytotoxic effect against the three cell lines, SK-MEL (IC50, 14.5 μg/mL), BT-549 (IC50, 16.0 μg/mL) and SK-OV-3 (IC50, 12.5 μg/mL). Only 2,3-dihydroxy ursolic acid activated PPARɣ (1.5-fold at 25 μM), compared to rosiglitazone (positive standard, 3.7 fold at 10 μM)Conclusion: Among the investigated compounds, ursolic acid exhibited the highest anti-inflammatory and cytotoxic activities, while 2,3-dihydroxy ursolic acid demonstrated antidiabetic activity via activation of PPARɣ.Keywords: Abelia triflora, Anti-inflammatory, Antidiabetic, Cardiovascular activity, Antioxidant, Cytotoxi

MAVE-NN: learning genotype-phenotype maps from multiplex assays of variant effect

Multiplex assays of variant effect (MAVEs) are a family of methods that includes deep mutational scanning experiments on proteins and massively parallel reporter assays on gene regulatory sequences. Despite their increasing popularity, a general strategy for inferring quantitative models of genotype-phenotype maps from MAVE data is lacking. Here we introduce MAVE-NN, a neural-network-based Python package that implements a broadly applicable information-theoretic framework for learning genotype-phenotype maps-including biophysically interpretable models-from MAVE datasets. We demonstrate MAVE-NN in multiple biological contexts, and highlight the ability of our approach to deconvolve mutational effects from otherwise confounding experimental nonlinearities and noise

Suitability of PSA-detected localised prostate cancers for focal therapy: Experience from the ProtecT study

This article is available through a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. Copyright @ 2011 Cancer Research UK.Background: Contemporary screening for prostate cancer frequently identifies small volume, low-grade lesions. Some clinicians have advocated focal prostatic ablation as an alternative to more aggressive interventions to manage these lesions. To identify which patients might benefit from focal ablative techniques, we analysed the surgical specimens of a large sample of population-detected men undergoing radical prostatectomy as part of a randomised clinical trial. Methods: Surgical specimens from 525 men who underwent prostatectomy within the ProtecT study were analysed to determine tumour volume, location and grade. These findings were compared with information available in the biopsy specimen to examine whether focal therapy could be provided appropriately. Results: Solitary cancers were found in prostatectomy specimens from 19% (100 out of 525) of men. In addition, 73 out of 425 (17%) men had multiple cancers with a solitary significant tumour focus. Thus, 173 out of 525 (33%) men had tumours potentially suitable for focal therapy. The majority of these were small, well-differentiated lesions that appeared to be pathologically insignificant (38–66%). Criteria used to select patients for focal prostatic ablation underestimated the cancer's significance in 26% (34 out of 130) of men and resulted in overtreatment in more than half. Only 18% (24 out of 130) of men presumed eligible for focal therapy, actually had significant solitary lesions. Conclusion: Focal therapy appears inappropriate for the majority of men presenting with prostate-specific antigen-detected localised prostate cancer. Unifocal prostate cancers suitable for focal ablation are difficult to identify pre-operatively using biopsy alone. Most lesions meeting criteria for focal ablation were either more aggressive than expected or posed little threat of progression.National Institute for Health Researc

The prospective non-conventional alternate and renewable energy sources in Pakistan - A focus on biomass energy for power generation, transportation, and industrial fuel

Pakistan is experiencing an undersupply of electricity, causing load shedding several hours per day due to the adherence to conventional energy resources having quantitative and environmental limitations. Fossil fuels generate more than half of the country's total electricity, but they will ultimately run out due to their limited supply. Their combustion emits greenhouse gases, posing environmental threats. Since the world is tending toward efficient and sustainable alternative methods for harvesting energy from nature, Pakistan has also been investigating an elevated deployment of renewable energy projects. This paper presents a critical analysis of the present energy sector of Pakistan along with global scenarios. Pakistan relies on mainly thermal, hydro, and nuclear energy for power generation. National solar, wind, geothermal, and biomass resources have not been extensively explored and implemented. This paper provides an insight into the potential of these resources in Pakistan to generate electricity for the national grid on a large scale. It focuses on biomass energy, which can be harnessed from bagasse, poultry waste, and municipal waste for power production, and biomass-based fuel for industries and transportation. It concludes that biomass is the most sustainable, available, implementable, and environment-friendly resource that can be utilized to lessen the energy demand and supply gap in Pakistan.University of Malay

Association of various reproductive rights, domestic violence and marital rape with depression among Pakistani women

<p>Abstract</p> <p>Background</p> <p>Depression among women is common in developing countries. Gender inequality can contribute to women's risk for depression. Lack of reproductive and sexual rights is an important marker of gender inequality and women do not have the freedom to express their reproductive and sexual needs in many parts of the world. Therefore we designed this study to determine the association of depression with lack of various reproductive rights and domestic violence among married women in Karachi, Pakistan.</p> <p>Methods</p> <p>A case-control study with 152 cases and 152 controls, which included women 15-48 years, recruited from two teaching hospitals from 1^stJune 2007 through 31^stAugust 2007. The SRQ was administered to all subjects. A cut off score of 8 was used to confirm cases of depression diagnosed by physicians, and to exclude cases of depression from the controls. Self-administered questionnaire was used to assess the risk factors.</p> <p>Results</p> <p>61% of the cases and 43% of the controls were ever abused by spouse and the frequency of marital rape was 33% in cases and 13% in controls. After adjusting for the effects of other variables in the model, less than 18 years of age at marriage (OR 2.00; 95% CI = 1.07, 3.7), decision for marriage by parents (OR 3.51; 95% CI = 1.67, 7.37), abuse by in laws (OR 4.91; 95% CI = 2.66, 9.06), ≤ 3 hours per day spent with husband (OR 2.33; 95% CI = 1.34, 4.08), frequency of intercourse ≤ 2 times per week (OR 1.85; 95% CI = 1.06, 3.22) and marital rape (OR 3.03; 95% CI = 1.50, 6.11) were associated with depression among women.</p> <p>Conclusion</p> <p>In our study depression in married women was associated with younger age at marriage, lack of autonomy in marriage decisions, marital rape and domestic abuse by in-laws. Efforts should be directed towards creating awareness about the reproductive and sexual rights of women in Pakistan. Physicians should be trained to screen and identify women who may be at risk for psychological distress as a result of denial of reproductive rights so that they can support positive mental health outcomes through individual, family or marital counseling.</p