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1.  IL-6-mediated induction of MMP-9 is modulated by JAK-dependent IL-10 expression in macrophages1 
Journal of immunology (Baltimore, Md. : 1950)  2013;192(1):10.4049/jimmunol.1301906.
The mechanisms by which IL-6 contributes to the pathogenesis of chronic inflammatory diseases and cancer are not fully understood. We previously reported that cyclooxygenase-2 (Cox-2)-dependent PGE2 synthesis regulates macrophage matrix metalloproteinase (MMP)-9 expression, an endopeptidase that participates in diverse pathologic processes. In these studies, we determined whether IL-6 regulates the Cox-2→PGE2→MMP-9 pathway in murine macrophages. IL-6 co-induced Cox-2 and microsomal prostaglandin E synthase-1 (mPGES-1), and inhibited the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), leading to increased levels of PGE2. In addition, IL-6 induced MMP-9 expression, suggesting that the observed proteinase expression was regulated by the synthesis of PGE2. However, inhibition of PGE2 synthesis partially suppressed IL-6–mediated induction of MMP-9. In the canonical model of IL-6-induced signaling, JAK activation triggers STAT and MAPKerk1/2-signaling pathways. Therefore, the ability of structural diverse JAK inhibitors to block IL-6-induced MMP-9 expression was examined. Inhibition of JAK blocked IL-6 induced phosphorylation of STAT3, but failed to block the phosphorylation of MAPKerk1/2, and unexpectedly enhanced MMP-9 expression. In contrast, MEK-1 inhibition blocked IL-6 induced phosphorylation of MAPKerk1/2 and MMP-9 expression without affecting the phosphorylation of STAT3. Thus, IL-6-induced MMP-9 expression is dependent on the activation of MAPKerk1/2 and restrained by a JAK-dependent gene product. Utilizing pharmacologic and genetic approaches, JAK-dependent induction of IL-10 was identified as a potent feedback mechanism controlling IL-6 induced MMP-9 expression. Together, these data reveal that IL-6 induces MMP-9 expression in macrophages via Cox-2-dependent and -independent mechanisms, and identifies a potential mechanism linking IL-6 to the pathogenesis of chronic inflammatory diseases and cancer.
PMCID: PMC3872272  PMID: 24285838
2.  Cost-effectiveness of sentinel lymph node biopsy vs inguinofemoral lymphadenectomy in women with vulval cancer 
British Journal of Cancer  2013;109(10):2533-2547.
This study examines the cost-effectiveness of sentinel lymph node biopsy, a potentially less morbid procedure, compared with inguinofemoral lymphadenectomy (IFL) among women with stage I and stage II vulval squamous cell carcinoma.
A model-based economic evaluation was undertaken based on clinical evidence from a systematic review of published sources. A decision tree model was developed with the structure being informed by clinical input, taking the perspective of the health-care provider.
For overall survival for 2 years, IFL was found to be the most cost-effective option and dominated all other strategies, being the least costly and most effective. For morbidity-free related outcomes for 2 years, sentinel lymph node (SLN) biopsy with 99mTc and blue dye and haematoxylin & eosin (H&E) histopathology, with ultrastaging and immunohistochemistry reserved for those that test negative following H&E is likely to be the most effective approach.
SLN biopsy using 99mTc and blue dye with ultrastaging may be considered the most cost-effective strategy based on the outcome of survival free of morbidity for 2 years. The findings here also indicate that using blue dye and H&E for the identification of the SLN and the identification of metastasis, respectively, are not sensitive enough to be used on their own.
PMCID: PMC3833218  PMID: 24129233
vulvar cancer; cost-effectiveness; sentinel lymph node biopsy; inguinofemoral lymphadenectomy
3.  Behavior of a Competitive System of Second-Order Difference Equations 
The Scientific World Journal  2014;2014:283982.
We study the boundedness and persistence, existence, and uniqueness of positive equilibrium, local and global behavior of positive equilibrium point, and rate of convergence of positive solutions of the following system of rational difference equations: xn+1 = (α1 + β1xn−1)/(a1 + b1yn), yn+1 = (α2 + β2yn−1)/(a2 + b2xn), where the parameters αi, βi, ai, and bi for i ∈ {1,2} and initial conditions x0, x−1, y0, and y−1 are positive real numbers. Some numerical examples are given to verify our theoretical results.
PMCID: PMC4052555  PMID: 24959605
4.  Surgical outcomes for older patients with glioblastoma multiforme: preoperative factors associated with decreased survival 
Journal of neurosurgery  2010;114(3):587-594.
As the population ages, the incidence of glioblastoma multiforme (GBM) among older patients (age > 65 years) will increase. Older patients, unlike their younger counterparts, are not often offered aggressive surgery because of their age, comorbidities, and potential inability to tolerate surgery. The goal of this study was to identify preoperative factors associated with decreased survival for older patients who underwent resection of a GBM. The identification of these factors may provide insight into which patients would benefit most from aggressive surgery.
All patients older than 65 years who underwent nonbiopsy resection of an intracranial GBM at a single institution between 1997 and 2007 were retrospectively reviewed. Factors associated with overall survival were assessed using multivariate proportional hazards regression analysis after controlling for peri- and postoperative factors known to be associated with outcome (extent of resection, carmustine wafer implantation, temozolomide chemotherapy, and radiation therapy). Variables with p < 0.05 were considered statistically significant.
A total of 129 patients with an average age of 73 ± 5 years met the inclusion/exclusion criteria. At last follow-up, all 129 patients had died, with a median survival of 7.9 months. The preoperative factors that were independently associated with decreased survival were Karnofsky Performance Scale (KPS) score less than 80 (p = 0.001), chronic obstructive pulmonary disease (p = 0.01), motor deficit (p = 0.01), language deficit (p = 0.005), cognitive deficit (p = 0.02), and tumor size larger than 4 cm (p = 0.002). Patients with 0–1 (Group 1), 2–3 (Group 2), and 4–6 (Group 3) of these factors had statistically different survival times, where the median survival was 9.2, 5.5, and 4.4 months, respectively. In log-rank analysis, the median survival for Group 1 was significantly longer than that for Group 2 (p = 0.004) and Group 3 (p < 0.0001), while Group 2 had longer survival than Group 3 (p = 0.02).
Older patients with an increasing number of these factors may not benefit as much from aggressive surgery as patients with fewer factors. This may provide insight into identifying which patients older than 65 years of age may benefit from aggressive surgery.
PMCID: PMC4020429  PMID: 20887095
elderly patient; function; glioblastoma multiforme; glioblastoma; survival
5.  Blockade of BFA-mediated apoptosis in macrophages by the HIV-1 Nef protein 
Cell Death & Disease  2014;5(2):e1080-.
HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of Nef and of the translation elongation factor eEF1A in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway suggested that cytoplasmic relocalization of eEF1A, mediated by Exp-t occurs in Nef-treated monocyte-derived macrophages (MDMs). We observed the presence of tRNA in the Nef/eEF1A complexes. Nucleocytoplasmic relocalization of the Nef/eEF1A complexes prevented stress-induced apoptosis of MDMs treated with brefeldin A. Blockade of stress-induced apoptosis of MDMs treated with HIV-1 Nef resulted from enhanced nucleocytoplasmic transport of eEF1A with decreased release of mitochondrial cytochrome c, and from increased tRNA binding to cytochrome c, ultimately leading to an inhibition of caspase activation. Our results indicate that HIV-1 Nef, through the nucleocytoplasmic relocalization of eEF1A and tRNAs, enhances resistance to stress-induced apoptosis in primary human macrophages.
PMCID: PMC3944234  PMID: 24556695
Nef; eEF1A; tRNA; cytochrome c; apoptosis; macrophage
6.  Antibiotic Resistance and Usage—A Survey on the Knowledge, Attitude, Perceptions and Practices among the Medical Students of a Southern Indian Teaching Hospital 
Background: Examining the knowledge, attitude, perceptions and practices (KAP) of the medical students regarding antibiotic resistance (ABR) and use can help us in devising suitable educational interventions for them, tailored according to their earlier held knowledge, beliefs, capabilities and experience.
Methods: A cross sectional, questionnaire based survey was conducted among the second year medical students of a teaching hospital, whereby their KAP regarding antibiotic use and resistance was assessed by using a five point Likert scale, whose responses ranged from ‘strongly agree’ to ‘strongly disagree,’ ‘always’ to ‘never and ‘very important’ to ‘unimportant’. The data was analyzed by using simple descriptive statistics. Wherever it was relevant, the Chi-square test was used to determine any significant difference.
Results: The response rate was 100 per cent. The number of respondents who agreed that ABR was an important and a serious public health issue in our teaching hospital (n= 66, 68 per cent), was significantly less (p < 0.001) as compared to the number of respondents who agreed that ABR was an important and a serious issue which the country (n = 86, 88.65 per cent) and the world (n = 88, 90.7 per cent) were facing. Only 77.3 per cent (n= 75) of the respondents were aware that bacteria were not responsible for causing colds and flu, while the remaining 22.7 per cent (n = 22) were not knowledgeable about this fact. More than 80 per cent rated the adverse effect profile of the antibiotic and the risk of a superinfection as the important factors which deserved consideration. Cost of the antibiotic was considered to be an important factor deserving consideration by only 56.7 percent (n=55) of the participants.
Conclusions: Our survey revealed that most of the students were aware of the antimicrobial resistance and its consequences. The only concern was their casual attitude regarding the antibiotic use. Further educational interventions are necessary to improve their understanding and perceptions on antibiotic resistance, as well as their attitude towards antibiotic use.
PMCID: PMC3782911  PMID: 24086854
Education; Undergraduates; Knowledge; Antibiotics; Antimicrobial chemotherapy
7.  Accelerometry analysis of physical activity and sedentary behavior in older adults: a systematic review and data analysis 
Accelerometers objectively monitor physical activity and sedentary patterns and are increasingly used in the research setting. It is important to maintain consistency in data analysis and reporting, therefore, we: (1) systematically identified studies using accelerometry (ActiGraph, Pensacola, FL, USA) to measure moderate-to-vigorous physical activity (MVPA) and sedentary time in older adults, and (2) based on the review findings, we used different cut-points obtained to analyze accelerometry data from a sample of community-dwelling older women. We identified 59 articles with cut-points ranging between 574 and 3,250 counts/min for MVPA and 50 and 500 counts/min for sedentary time. Using these cut-points and data from women (mean age, 70 years), the median MVPA minutes per day ranged between 4 and 80 min while percentage of sedentary time per day ranged between 62 % and 86 %. These data highlight (1) the importance of reporting detailed information on the analysis assumptions and (2) that results can differ greatly depending on analysis parameters.
PMCID: PMC3990855  PMID: 24765212
Accelerometer; Measurement; Analysis assumptions; Physical activity; Sedentary behavior
8.  A Study on the Usage Pattern of Antimicrobial Agents for the Prevention of Surgical Site Infections (SSIs) in a Tertiary Care Teaching Hospital 
Context: Inappropriate antimicrobial use increases the incidence of drug resistance, drug toxicity and superinfections, thereby increasing the healthcare costs. Various approaches for rationalizing the antimicrobial therapy, have been suggested. Collection of baseline data on the pattern of the antimicrobial use is usually suggested as the first step in this direction, which will help in identifying the problem areas, which demand our attention.
Aims: To study the usage pattern of prophylactic antimicrobials in surgical patients, in order to detect any inappropriateness concerning the selection, timing, redosing and the duration of antimicrobial administration.
Settings and Design: A retrospective review of the randomly selected medical records of general surgical cases over an 8 month period in a tertiary care teaching hospital.
Methods and Material: The medical records of 258 patients who had undergone surgical procedures were verified for the appropriateness of the antimicrobial prophylaxis, with respect to the choice of the antimicrobial agent, the time of its administration, the intraoperative dosing, and the duration of the postoperative use. The obtained data was analyzed and conclusions were drawn with the help of descriptive statistics.
Results: Third generation cephalosporins were used preoperatively in all the 258(100%) patients through the intravenous route. In addition, 77(30%) patients received metronidazole or amikacin. The antimicrobials were administered half an hour to one hour before the surgery. No intraoperative redosing was given. The duration of the postoperative prophylaxis was extended to 36 hours or more in 248(96%) of the cases.
Conclusions: The timing of administration of the preoperative dose was appropriate and well delegated to the operating room nurse. The intra operative dose was appropriately omitted. The main concern was the increasing use of the third generation cephalosporins and the unnecessary prolonged duration of the postoperative prophylaxis, which needed to be addressed.
PMCID: PMC3644441  PMID: 23730643
Antimicrobial; Usage pattern; Surgical site infection
9.  Matrix metalloproteinase (MMP)-1 and MMP-3 induce macrophage MMP-9: Evidence for the role of TNF-α and cyclooxygenase-2 
MMP-9 (gelatinase B) participates in a variety of diverse physiologic and pathologic processes. We recently characterized a cyclooxygenase-2 (Cox-2)→PGE2→EP4 receptor axis that regulates macrophage MMP-9 expression. In the current studies, we determined whether MMPs, commonly found in inflamed and neoplastic tissues, regulate this prostanoid-EP receptor axis leading to enhanced MMP-9 expression. Results demonstrate that exposure of murine peritoneal macrophages and RAW264.7 macrophages to MMP-1 (collagenase-1) or MMP-3 (stromelysin-1) lead to a marked increase in Cox-2 expression, PGE2 secretion and subsequent induction of MMP-9 expression. Proteinase-induced MMP-9 expression was blocked in macrophages pre-incubated with the selective the Cox-2 inhibitor celecoxib or transfected with Cox-2 siRNA. Likewise, proteinase-induced MMP-9 was blocked in macrophages pre-incubated with the EP4 antagonist ONO-AE3-208 or transfected with EP4 siRNA. Exposure of macrophages to MMP-1 and MMP-3 triggered the rapid release of TNF-α, which was blocked by MMP-inhibitors. Furthermore, both Cox-2 and MMP-9 expression were inhibited in macrophages pre-incubated with anti-TNF-α IgG or transfected with TNF-α siRNA. Thus, proteinase-induced MMP-9 expression by macrophages is dependent on the release of TNF-α, induction of Cox-2 expression and PGE2 engagement of EP4. The ability of MMP-1 and -3 to regulate macrophage secretion of PGE2 and expression of MMP-9 defines a nexus between MMPs and prostanoids that is likely to play a role in the pathogenesis of chronic inflammatory diseases and cancer. These data also suggest that this nexus is targetable utilizing anti-TNF-α therapies and/or selective EP4 antagonists.
PMCID: PMC3621723  PMID: 19923455
10.  Matrix metalloproteinase (MMP)-dependent microsomal prostaglandin E synthase (mPGES)-1 expression in macrophages: Role of TNF-α and the EP4 prostanoid receptor1 
MMP-9 contributes to the pathogenesis of chronic inflammatory diseases and cancer. Thus, identifying targetable components of signaling pathways that regulate MMP-9 expression may have broad therapeutic implications. Our previous studies revealed a nexus between metalloproteinases and prostanoids whereby MMP-1 and MMP-3, commonly found in inflammatory and neoplastic foci, stimulate macrophage MMP-9 expression via the release of TNF-α and subsequent induction of cyclooxygenase-2 (Cox-2), and PGE2 engagement of EP4 receptor. In the present studies, we determined whether MMP-induced Cox-2 expression was coupled to the expression of PGE synthase family members. We found that MMP-1 and MMP-3-dependent release of TNF-α induced rapid and transient expression of Egr-1 in macrophages followed by sustained elevation in mPGES-1 expression. Metalloproteinase-induced PGE2 levels and MMP-9 expression were markedly attenuated in macrophages in which mPGES-1 was silenced, thereby identifying mPGES-1 as a therapeutic target in the regulation of MMP-9 expression. Finally, the induction of mPGES-1 was regulated, in part, through a positive feedback loop dependent on PGE2 binding to EP4. Thus, in addition to inhibiting macrophage MMP-9 expression, EP4 antagonists emerge as potential therapy to reduce mPGES-1 expression and PGE2 levels in inflammatory and neoplastic settings.
PMCID: PMC3273587  PMID: 22227567
11.  Why we get a blue stain 
Eye  2011;26(2):335-336.
PMCID: PMC3272196  PMID: 22079963
12.  Potential damage to a potential space 
Eye  2011;26(2):339-340.
PMCID: PMC3272207  PMID: 22116458
13.  Increasing Prevalence of Type 2 Diabetes in a Rural Bangladeshi Population: A Population Based Study for 10 Years 
Diabetes & Metabolism Journal  2013;37(1):46-53.
To observe changes in the prevalence of type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG) and its associated risk factors in a rural Bangladeshi population over a 10-year period.
Three cross-sectional studies were undertaken in a rural community (aged ≥20 years) in 1999, 2004, and 2009. Structured questionnaires including sociodemographic parameters, anthropometric measurements, blood pressure, and blood glucose values were recorded. DM and IFG were diagnosed using 1999 World Health Organization criteria.
Age standardized prevalence of DM increased significantly (P<0.001) from 1999 to 2009 (2.3%, 6.8%, and 7.9% in 1999, 2004, and 2009, respectively). The prevalence of IFG increased significantly (P=0.011) from 4.6% to 5.8% between 1999 and 2004 but then decreased from 5.8% to 5.3% during 2004 to 2009. Significant linear trends were shown in both sexes for general and central obesity as indicated by body mass index, waist circumference, and waist hip ratio (WHR). Increasing age and systolic blood pressure were significant risk factors for DM in all three studies. WHR for males was also significantly associated with the risk of DM in all three studies. WHR for females was only significantly associated with DM in 2009.
A significant rise in the prevalence of DM was observed in this population over 10 years. This increase was seen in both sexes, and in all age groups. A significant increase in the prevalence of the associated risk factors of general and central obesity was observed in both sexes.
PMCID: PMC3579152  PMID: 23439676
Bangladesh; Diabetes mellitus; Impaired fasting glucose; Population based study; Prevalence
14.  Diabetes awareness through religious leaders 
PMCID: PMC3659894  PMID: 23776880
15.  Prevalence of Type 2 Diabetes and Impaired Glucose Regulation with Associated Cardiometabolic Risk Factors and Depression in an Urbanizing Rural Community in Bangladesh: A Population-Based Cross-Sectional Study 
Diabetes & Metabolism Journal  2012;36(6):422-432.
To determine the prevalence of type 2 diabetes (T2DM) and impaired glucose regulation (impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]) in an urbanizing rural population of Bangladesh and associated cardiometabolic risk indicators and depression.
A total of 2,293 subjects aged ≥20 years in an urbanizing rural Bangladeshi community were investigated. Socio-demographic and anthropometric details, blood pressure, fasting plasma glucose (FPG), 2 hours after 75 g plasma glucose (2hPG), glycosylated hemoglobin, fasting serum insulin and lipid profiles were studied. Presence of depressive symptoms using Montogomery-Asberg Depression Rating Scale was also assessed.
The prevalence of IFG, IGT, IFG+IGT, and T2DM were 3.4%, 4.0%, 1.2%, and 7.9%, respectively. The prevalence of T2DM and impaired glucose regulation differed between males and females, but, both increased with age in both sexes. FPG and 2hPG had positive correlation. Employing logistic regression, it was found that increased age, waist to hip ratio, systolic blood pressure, total cholesterol, triglycerides, and depression were independent risk indicators for diabetes. Both insulin resistance and β-cell deficiency were significantly related for causation of diabetes. Among the study population, 26.2% had general obesity, 39.8% central obesity, 15.5% hypertension, 28.7% dyslipidemia, 17.6% family history of diabetes, and 15.3% had depression. Physical inactivity and smoking habits were significantly higher in male.
Rising prevalence of diabetes and impaired glucose regulation in this urbanizing rural population exist as a significant but hidden public health problem. Depression and other cardiometabolic risk indicators including obesity, hypertension, and dyslipdemia were also prevalent in this population.
PMCID: PMC3530713  PMID: 23275936
Bangladesh; Diabetes mellitus; Impaired glucose regulation; Prevalence
16.  Hip protectors: recommendations for biomechanical testing—an international consensus statement (part I) 
Hip protectors represent a promising strategy for preventing fall-related hip fractures. However, clinical trials have yielded conflicting results due, in part, to lack of agreement on techniques for measuring and optimizing the biomechanical performance of hip protectors as a prerequisite to clinical trials.
In November 2007, the International Hip Protector Research Group met in Copenhagen to address barriers to the clinical effectiveness of hip protectors. This paper represents an evidence-based consensus statement from the group on recommended methods for evaluating the biomechanical performance of hip protectors.
Results and conclusions
The primary outcome of testing should be the percent reduction (compared with the unpadded condition) in peak value of the axial compressive force applied to the femoral neck during a simulated fall on the greater trochanter. To provide reasonable results, the test system should accurately simulate the pelvic anatomy, and the impact velocity (3.4 m/s), pelvic stiffness (acceptable range: 39–55 kN/m), and effective mass of the body (acceptable range: 22–33 kg) during impact. Given the current lack of clear evidence regarding the clinical efficacy of specific hip protectors, the primary value of biomechanical testing at present is to compare the protective value of different products, as opposed to rejecting or accepting specific devices for market use.
PMCID: PMC3471980  PMID: 19806286 CAMSID: cams2425
Aged; Biomechanics; Hip Fractures; Materials testing; Prevention; Standards
17.  The de Morton Mobility Index: Normative Data for a Clinically Useful Mobility Instrument 
Journal of Aging Research  2012;2012:353252.
Determining mobility status is an important component of any health assessment for older adults. In order for a mobility measure to be relevant and meaningful, normative data are required for comparison to a healthy reference population. The DEMMI is the first mobility instrument to measure mobility across the spectrum from bed bound to functional levels of independent mobility. In this cross-sectional observational study, normative data were obtained for the DEMMI from a population of 183 healthy, community-dwelling adults age 60+ who resided in Vancouver, Canada and Melbourne, Australia. Older age categories had significantly lower DEMMI mobility mean scores (P < 0.05), as did individuals who walked with a mobility aid or lived in semi-independent living (assisted living or retirement village), whereas DEMMI scores did not differ by sex (P = 0.49) or reported falls history (P = 0.21). Normative data for the DEMMI mobility instrument provides vital reference scores to facilitate its use across the mobility spectrum in clinical, research, and policymaking settings.
PMCID: PMC3440954  PMID: 22988509
18.  Social Ecological Analysis of an Outbreak of Pufferfish Egg Poisoning in a Coastal Area of Bangladesh 
Recurrent outbreaks of marine pufferfish poisoning in Bangladesh highlight the need to understand the context in which the outbreaks occurred. In a recent outbreak investigation, a multidisciplinary team conducted a mixed-method study to identify the demography and clinical manifestation of the victims and to explore different uses of pufferfish, and local buying, selling, and processing practices. The outbreak primarily affected a low income household where an elderly woman collected and cooked pufferfish egg curry. Nine persons consumed the curry, and symptoms developed in 6 (67%) of these persons. Symptoms included vomiting, diarrhea, paresis, and tingling sensation; 2 (22%) persons died. The unstable income of the affected family, food crisis, and the public disposal of unsafe pufferfish byproducts all contributed to the outbreak. A multi-level intervention should be developed and disseminated with the participation of target communities to discourage unsafe discarding of pufferfish scraps and to improve the community knowledge about the risk of consuming pufferfish.
PMCID: PMC3163873  PMID: 21896811
19.  Malaria burden in human population of Quetta, Pakistan 
Malaria is a serious global health challenge, which is responsible for more than one million deaths a year. Malarial infection is more prevalent in developing countries including Pakistan. Significant efforts have been made to control malaria; however, due to socio-environmental factors, it remains a frequent problem in Quetta. The present study was undertaken to determine the malarial incidence, species prevalence, and its demographic evaluation in human population of Quetta, Pakistan. A total of 1831 subjects, comprising 1072 male and 759 female presenting symptoms of malaria, were included in this study. Blood samples from clinically suspected individuals were subjected to the standard immunochromatographic and malaria parasite smear analysis for malaria diagnosis. Out of 1831 subjects, 338 (18.45%) patients were positive for malarial parasite while the species prevalence was found as 276 (81.66%) and 62 (18.34%) for Plasmodium vivax, and Plasmodium falciparum, respectively. Furthermore, seasonal variations gradual increase in the prevalence rate. The age group of 21–30 years (30.47%) was found more prone to malaria. The suspected malaria cases were found more frequent in rural (72.1%) as compared to urban (27.9%). In addition, the malaria burden was high in urban area (22.89%) population as compared to the rural area (16.74%) population. It was observed that the highest disease occurrence was caused by P. vivax, which reflects a serious threat for public health. The current findings will be helpful to plan effective strategies to prevent and control malaria in this area.
PMCID: PMC3962755  PMID: 24688766
malaria; prevalence rate; Quetta
22.  Does frequency of resistance training affect tibial cortical bone density in older women? A randomized controlled trial 
Osteoporosis International  2012;24(2):623-632.
This randomized controlled trial evaluated the effect of resistance training frequency (0, 1, and 2 times/week) on cortical volumetric bone mineral density (vBMD) at the tibia in older women. There was no mean difference in change in tibial cortical vBMD in older women who engaged in resistance training (RT) one or two times/week compared with the control group over 12 months after adjusting for baseline values.
National guidelines recommend RT two to three times/week to optimize bone health. Our objective was to determine the effect of a 12-month intervention of three different RT frequencies on tibial volumetric cortical density (CovBMD) in healthy older women.
We randomized participants to the following groups: (1) 2×/week balance and tone group (i.e., no resistance beyond body weight, BT), (2) 1×/week RT (RT1), and (3) 2×/week RT (RT2). Treatment allocation was concealed, and measurement team and the bone data analyst were blinded to group allocation. We used peripheral quantitative computed tomography to acquire one 2.3-mm scan at the 50 % tibia, and the primary outcome was CovBMD. Data were collected at baseline, 6 and 12 months, and we used linear mixed modeling to assess the effect at 12 months.
We assessed 147 participants; 100 women provided data at all three points. Baseline unadjusted mean (SD) tibial CovBMD (in milligrams per cubic centimeter) at the 50 % site was 1,077.4 (43.0) (BT), 1,087.8 (42.0) (RT1), and 1,058.7 (60.4) (RT2). At 12 months, there were no statistically significant differences (−0.45 to −0.17 %) between BT and RT groups for mean difference in change in tibial CovBMD for exercise interventions (BT, RT1, RT2) after adjusting for baseline tibial CovBMD.
We note no mean difference in change in tibial CovBMD in older women who engaged in RT one or two times/week compared with the control group over 12 months. It is unknown if RT of 3× or 4×/week would be enough to promote a statistically significant difference in change of bone density.
PMCID: PMC3557371  PMID: 22581292
Aging; Bone density; Bone strength; Resistance training; pQCT
23.  Second generation endometrial ablation techniques for heavy menstrual bleeding: network meta-analysis 
Objective To determine the relative effectiveness of second generation ablation techniques in the treatment of heavy menstrual bleeding.
Design Network meta-analysis on the primary outcome measures of amenorrhoea, heavy bleeding, and patients’ dissatisfaction with treatment.
Data sources Nineteen randomised controlled trials (involving 3287 women) were identified through electronic searches of the Cochrane Library, Medline, Embase and PsycINFO databases from inception to April 2011. The reference lists of known relevant articles were searched for further articles. Two reviewers independently selected articles without language restrictions.
Eligibility criteria for selecting studies Randomised controlled trials involving second generation endometrial destruction techniques for women with heavy menstrual bleeding unresponsive to medical treatment.
Results Of the three most commonly used techniques, network meta-analysis showed that bipolar radiofrequency and microwave ablation resulted in higher rates of amenorrhoea than thermal balloon ablation at around 12 months (odds ratio 2.51, 95% confidence interval 1.53 to 4.12, P<0.001; and 1.66, 1.01 to 2.71, P=0.05, respectively), but there was no evidence of a convincing difference between the three techniques in the number of women dissatisfied with treatment or still experiencing heavy bleeding. Compared with bipolar radio frequency and microwave devices, an increased number of women still experienced heavy bleeding after free fluid ablation (2.19, 1.07 to 4.50, P=0.03; and 2.91, 1.23 to 6.88, P=0.02, respectively). Compared with radio frequency ablation, free fluid ablation was associated with reduced rates of amenorrhoea (0.36, 0.19 to 0.67, P=0.004) and increased rates of dissatisfaction (4.79, 1.07 to 21.5, P=0.04). Of the less commonly used devices, endometrial laser intrauterine thermotherapy was associated with increased rates of amenorrhoea compared with all the other devices, while cryoablation led to a reduced rate compared with bipolar radio frequency and microwave.
Conclusions Bipolar radio frequency and microwave ablative devices are more effective than thermal balloon and free fluid ablation in the treatment of heavy menstrual bleeding with second generation endometrial ablation devices.
PMCID: PMC3339574  PMID: 22529302
24.  A possible genetic answer to a recently reported novel phenotype 
Eye  2011;25(4):529.
PMCID: PMC3171235  PMID: 21242988
25.  Inhibition of ER stress-mediated apoptosis in macrophages by nuclear-cytoplasmic relocalization of eEF1A by the HIV-1 Nef protein 
Cell Death & Disease  2012;3(4):e292-.
HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of the Nef/eEF1A (eukaryotic translation elongation factor 1-alpha) complex in nucleocytoplasmic shuttling in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway suggested that cytoplasmic relocalization of eEF1A, mediated by Exp-t, occurs in Nef-treated monocyte-derived macrophages (MDMs). We observed the presence of tRNA in the Nef/eEF1A complexes. Nucleocytoplasmic relocalization of the Nef/eEF1A complexes prevented stress-induced apoptosis of MDMs treated with brefeldin-A. Blockade of stress-induced apoptosis of MDMs treated with HIV-1 Nef resulted from enhanced nucleocytoplasmic transport of eEF1A with decreased release of mitochondrial cytochrome c, and from increased tRNA binding to cytochrome c, ultimately leading to an inhibition of caspase activation. Our results indicate that HIV-1 Nef, through the nucleocytoplasmic relocalization of eEF1A and tRNAs, enhances resistance to stress-induced apoptosis in primary human macrophages.
PMCID: PMC3358010  PMID: 22476100
Nef; eEF1A; tRNA; cytochrome; apoptosis; macrophage

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