Diffusion MRI correlation with p16 status and prediction for tumor progression in locally advanced head and neck cancer.

Purpose: To investigate p16 effects on diffusion image metrics and associations with tumor progression in patients with locally advanced head and neck cancers. Methods: Diffusion images pretreatment and after 20 Gy (2wk) of RT were analyzed in patients with cT4/N3 p16+ oropharynx cancer (OPSCC) (N=51) and locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) (N=28), enrolled onto a prospective adaptive RT trial. Mean ADC values, subvolumes with ADC <1.2 um2/ms (TVLADC), and peak values of low (µL) and high (µH) components of ADC histograms in primary and total nodal gross tumor volumes were analyzed for prediction of freedom from local, distant, or any progression (FFLP, FFDP or FFLRDP) using multivariate Cox proportional-hazards model with clinical factors. P value with false discovery control <0.05 was considered as significant. Results: With a mean follow up of 36 months, 18 of LAHNSCC patients and 16 of p16+ OPSCC patients had progression. After adjusting for p16, small µL and ADC values, and large TVLADC of primary tumors pre-RT were significantly associated with superior FFLRDP, FFLP and FFDP in the LAHNSCC (p<0.05), but no diffusion metrics were significant in p16+ oropharynx cancers. Post ad hoc analysis of the p16+ OPSCC only showed that large TVLADC of the total nodal burden pre-RT was significantly associated with inferior FFDP (p=0.05). Conclusion: ADC metrics were associated with different progression patterns in the LAHNSCC and p16+ OPSCC, possibly explained by differences in cancer biology and morphology. A deep understanding of ADC metrics is warranted to establish imaging biomarkers for adaptive RT in HNSCC.

Effectiveness of teachers' training in assessment techniques: participants' perception.

BACKGROUND: Medical education has experienced a rapidly changing scenario especially during the past three decades. Teachers training programs have emerged in recent years as a more in depth and comprehensive mechanisms for strengthening instructional skills and formulating assessment techniques among faculty members. OBJECTIVE: The present study was carried out with the aim of assessing effectiveness of teacher training workshop on assessment techniques at B.P. Koirala Institute of Health sciences (BPKIHS), Dharan, Nepal. Methods: In this prospective questionnaire based study, the 26 entry level teachers were enrolled. They were requested to fill the questionnaire before and after the workshop on the assessment techniques at BPKIHS, Dharan. METHODS: Twenty six teachers majority of whom were entry level teachers comprising of medical, dental, nursing and allied sciences participated in pre- and post test analysis on the various components of written and oral examinations. A two and half days long training was conducted having 9 hours of teaching interactive sessions, 6 hours of group exercises, daily evaluation and 3 hours of presentation by participants. There was high degree of agreement with most topics of the assessment training. RESULTS: There was a significant gain in knowledge (p < 0.001) by the participants. All the participants (100%) agreed upon the training being informative and learned new things about assessment. More practice session with longer duration with invited resource persons were also suggested for an effective session. CONCLUSION: Thereis an immense opportunity for a better and comprehensive training in evaluation techniques in medical education..

Evaluation of lipid peroxidation and antioxidants' status in metabolic syndrome.

BACKGROUND: Metabolic syndrome is a constellation of physical conditions and metabolic abnormalities, commonly occurring together, that increases an individual's risk for development of type 2 diabetes mellitus and cardiovascular diseases. Oxidative stress is associated with diabetes, hypertension and other cardiovascular diseases while the role of oxidative stress in pathogenesis of MS is not clearly defined. OBJECTIVES: The study aims to find out the prevalence of metabolic syndrome in faculty and staff members at BP Koirala Institute of Health Sciences, Dharan, Nepal and to evaluate oxidative stress levels in subjects with metabolic syndrome. METHODS: 118 healthy participants working at B. P. Koirala Institute of Health Sciences, Dharan, Nepal were selected at random for this cross-sectional study and blood samples were collected for the estimation of the following biochemical analytes; fasting glucose; triglycerides; total cholesterol; high density lipoprotein cholesterol; Albumin; uric acid; Bilirubin; Malondialdehyde; Catalase; Glutathione peroxidase; Superoxide Dismutase; Glutathione; vitamin C; and lastly vitamin E. Results In this cross-sectional study, 39% subjects were diagnosed with metabolic syndrome , particularly in sedentary subjects. There was no difference in oxidative stress except significant rises in serum uric acid levels and catalase activity in subjects diagnosed with metabolic syndrome . CONCLUSION: The prevalence of metabolic syndrome is higher without oxidative stress in this study, which suggests that oxidative stress does not contribute to the pathogenesis of MS in otherwise healthy subjects.

Preparing tutors for problem-based learning: an experience from B. P. Koirala Institute of Health Sciences, Nepal.

BACKGROUND: Problem based learning (PBL) has made major impact on curricular designing and practice in medical education for the last forty years. Incorporation of PBL approach in medical education has been a challenge and opportunity for both educationists on how to impart change and medical teachers on how to internalise the change. OBJECTIVES: This paper aimed to investigate experiences, achievement and responses of medical teachers at B. P. Koirala Institute of Health Sciences (BPKIHS), Nepal. MATERIALS AND METHODS: There were 25 heterogeneous groups of teachers, majority of them were entry level. Pre- and Post-test question were taken from various topics relevant to PBL such as learning strategy and principles of adult learning, PBL practice at BPKIHS, tutorial session and role of a tutor, making resource session interactive, designing PBL problems, planning educational objectives in PBL, formulation of problem for PBL. In addition to it participants' perception on development and dissemination of PBL manual and effectiveness of workshop were also included in the questionnaire. RESULTS: There was significant gain in knowledge following the workshop (p<0.001). The perception of the teacher found quite relevant and useful for adopting new role as tutor. The respondent teachers noted that skills they learned during the training will be applicable to their job situation. They stressed for an additional training for reinforcement and update with new trends and tools in PBL. CONCLUSION: Therefore, such trainings for faculty development would be highly beneficial to inculcate new competencies in PBL.

Evaluation of non-HDL-c and total cholesterol: HDL-c ratio as cumulative marker of cardiovascular risk in diabetes mellitus.

BACKGROUND: Cardiovascular disease (CVD), is the primary cause of morbidity and mortality in patients with diabetes and have approximately--two to four times higher CVD rate than adult without diabetes. Low density lipoprotein cholesterol (LDL-C) is primarily used as the marker of cardiovascular risk in diabetes despite its several limitations. Although several newer markers of CVD are emerging, no marker has been established in Nepal. OBJECTIVES: The study was designed to evaluate the non-high-density-lipoprotein- cholesterol(Non-HDL-C) and Total Cholesterol to High density lipoprotein cholesterol (TC:HDL-C ratio) as CVD risk marker in diabetes mellitus. METHODS: The study was conducted in the Department of Biochemistry, Kathmandu University School of Medical Sciences. The study comprised of 76 diabetic subjects and 60 non-diabetic subjects. The anthropometric and biochemical parameters were measured. The Non-HDL-C and TC:HDL-C ratio were also calculated employing their respective formula. RESULTS: Body mass index (BMI), waist circumference (WC), blood pressure and lipid parameters were significantly different between diabetic subjects and non-diabetic subjects. There was increased non-HDL-C and TC:HDL-C ratio in subjects with diabetes mellitus. Furthermore, statistically significant correlations of non-HDL-C and TC:HDL-C ratio were obtained with BMI, WC, total cholesterol, HDL-C and LDL-C in diabetic subjects. CONCLUSIONS: The present study observation revealed that the Non-HDL-C and TC: HDL-C strongly correlate with established independent risk factors such as obesity(WC), elevated blood pressure, HDL-C and LDL-C in diabetes. Thus, the evaluation of Non-HDL-C and TC: HDL-C ratio can be used as the simple, cost-effective and cumulative marker of cardiovascular risk in diabetes mellitus.

Assessment of iodine nutrition status among school age children of Nepal by urinary iodine assay.

The present study was undertaken to evaluate the iodine status of Nepalese school age children by measuring urinary iodine excretion (UIE). A population based cross-sectional study was conducted during November-December 2006 among 1,094 school age children. Spot urine samples were collected from all children and UIE was measured during February to March 2007 by an ammonium persulfate digestion microplate (APDM) method. The median UIE at the national level was 193.10 microg/l, indicating adequate iodine intake in Nepalese schoolchildren. The proportion of the population having UIE below 50 microg/l and below 100 microg/l were 4.5% and 22.0%, respectively. Determination of precision of the method was done following calculation of the inter- and intra-assay coefficient of variation (CV). At low, medium and high concentrations of urinary iodine the intra-assay CVs were 6.3, 1.8 and 1.9%, respectively. The inter-assay CVs for low, medium and high concentrations of urinary iodine were 11.9, 4.9 and 6.2%, respectively. Therefore, current iodine nutrition status is at satisfactory levels in Nepal. An effective monitoring program must be continued to ensure optimal iodine status and prevent the population from developing iodine deficiency disorder (IDD).

Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters.

Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness and relatively broad drug spatial distribution. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body with high spatial and temporal precision. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle meet these needs, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs, beyond a few niche applications. Here, we develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted delivery of hydrophobic drugs with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that are scalable and yield sterile, stable, and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, we exhibit a new potential application of these nanoemulsions for local control of vascular tone. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for efficacious, noninvasive, and localized ultrasonic drug uncaging for myriad targets in the brain and body.

Multisite Concordance of DSC-MRI Analysis for Brain Tumors: Results of a National Cancer Institute Quantitative Imaging Network Collaborative Project.

BACKGROUND AND PURPOSE: Standard assessment criteria for brain tumors that only include anatomic imaging continue to be insufficient. While numerous studies have demonstrated the value of DSC-MR imaging perfusion metrics for this purpose, they have not been incorporated due to a lack of confidence in the consistency of DSC-MR imaging metrics across sites and platforms. This study addresses this limitation with a comparison of multisite/multiplatform analyses of shared DSC-MR imaging datasets of patients with brain tumors. MATERIALS AND METHODS: DSC-MR imaging data were collected after a preload and during a bolus injection of gadolinium contrast agent using a gradient recalled-echo-EPI sequence (TE/TR = 30/1200 ms; flip angle = 72°). Forty-nine low-grade (n = 13) and high-grade (n = 36) glioma datasets were uploaded to The Cancer Imaging Archive. Datasets included a predetermined arterial input function, enhancing tumor ROIs, and ROIs necessary to create normalized relative CBV and CBF maps. Seven sites computed 20 different perfusion metrics. Pair-wise agreement among sites was assessed with the Lin concordance correlation coefficient. Distinction of low- from high-grade tumors was evaluated with the Wilcoxon rank sum test followed by receiver operating characteristic analysis to identify the optimal thresholds based on sensitivity and specificity. RESULTS: For normalized relative CBV and normalized CBF, 93% and 94% of entries showed good or excellent cross-site agreement (0.8 ≤ Lin concordance correlation coefficient ≤ 1.0). All metrics could distinguish low- from high-grade tumors. Optimum thresholds were determined for pooled data (normalized relative CBV = 1.4, sensitivity/specificity = 90%:77%; normalized CBF = 1.58, sensitivity/specificity = 86%:77%). CONCLUSIONS: By means of DSC-MR imaging data obtained after a preload of contrast agent, substantial consistency resulted across sites for brain tumor perfusion metrics with a common threshold discoverable for distinguishing low- from high-grade tumors.

Interventions to increase physician efficiency and comfort with an electronic health record system.

OBJECTIVE: To determine comfort when using the Electronic Health Record (EHR) and increase in documentation efficiency after an educational intervention for physicians to improve their transition to a new EHR. METHODS: This study was a single-center randomized, parallel, non-blinded controlled trial of real-time, focused educational interventions by physician peers in addition to usual training in the intervention arm compared with usual training in the control arm. Participants were 44 internal medicine physicians and residents stratified to groups using a survey of comfort with electronic media during rollout of a system-wide EHR and order entry system. Outcomes were median time to complete a progress note, notes completed after shift, and comfort with EHR at 20 and 40 shifts. RESULTS: In the intervention group, 73 education sessions averaging 14.4 (SD: 7.7) minutes were completed with intervention group participants, who received an average of 3.47 (SD: 2.1) interventions. Intervention group participants decreased their time to complete a progress note more quickly than controls over 30 shifts (p < 0.001) and recorded significantly fewer progress notes after scheduled duty hours (77 versus 292, p < 0.001). Comfort with EHRs increased significantly in both groups from baseline but did not differ significantly by group. Intervention group participants felt that the intervention was more helpful than their standard training (3.47 versus 1.95 on 4-point scale). CONCLUSION: Physicians teaching physicians during clinical work improved physician efficiency but not comfort with EHRs. More study is needed to determine best methods to assist those most challenged with new EHR rollouts.

Public perception about drinking jar water and its bacteriological analysis.

The consumption of jar water has been increasing consistently in these days. To improve such water quality and supply, information is needed to assess water contamination in a variety of community, including those that rely primarily on unimproved distributed sources of drinking water. This study was done to assess the public perception on drinking jar water and assessment of drinking jar water distributed in Kathmandu Valley which was conducted in the Department of Microbiology, Amrit Science Campus, Thamel, Kathmandu during the period of Aug 2009 to Dec 2009. A total 57 water samples of different drinking jar water having different brand names were proceed using standard protocols and analyzed for the presence of total coliforms and fecal coliforms. All identified fecal coliforms isolates from different water samples were subjected to in-vitro antimicrobial susceptibility test by Kirby-Bauer disc diffusion method. In order to know the perception of people in drinking jar water, semi structured questionnaires were made and purposively selected for the study in 525 populations who were using jar water for drinking purpose. Most population rated their drinking jar water good but found to be highly concerned with the quality. Among total water samples, 91.2% (n=52) were found contaminated with total coliforms and 59.6% were with fecal coliforms. During the study, 117 isolates of enteric bacteria were isolated, of which 33.3% (n=39) were Escherichia coli followed by other gram negative bacteria. Similarly, out of 58 fecal coliforms isolates, 43.1%, 39.6%, 12.2% were E. coli, Klebsiella spp, and Enterobacter aerogens. Of those fecal coliforms, all were sensitive to antibiotic ciprofloxacin and resistant to ampicilin. The finding indicates that jar water is not safe for drinking purpose without treatment.

Oxidative stress in benign prostate hyperplasia.

Benign Prostate Hyperplasia (BPH) is the common health problem in ageing male. Free radicals and reactive oxygen species (ROS) are produced more with advancement of age leads to oxidative stress. This study aims to assess Malondialdehyde (MDA), the marker of lipid peroxidation and vitaminic antioxidants e.g. alpha-Tocopherol (Toc) and Ascorbate (Asc) status in plasma of BPH patients. This is a case control study conducted in Department of Biochemistry in collaboration with Dept of Surgery, BPKIHS. Forty eight (n = 48) confirmed patients of BPH and forty six (n = 46) healthy age matched controls were enrolled. Plasma MDA, Asc and alpha-Toc were estimated. Plasma MDA level showed 4.81 +/- 1.87 nmol/ml in BPH patients compared to 3.69 +/- 1.56 nmol/ml in healthy controls (p < 0.001). There were significant decrease in plasma alpha-Toc and Asc level which were 0.85 +/- 0.12 mg/dl and 0.93 +/- 0.13 mg/dl in BPH patients compared to 1.37 +/- 0.31 mg/dl and 1.44 +/- 0.38 mg/dl in healthy controls respectively. Inverse correlation of plasma MDA with a- Toc (r = -0.09) and Asc (r = -0.51) was found in BPH patients. There was mild elevation of PSA in BPH patients compared with control but was not statistically significant. Thus, our study showed the evidence of association of oxidative stress in BPH patients.

Oxidative stress in patients with benign prostate hyperplasia.

Benign Prostate Hyperplasia (BPH) is a common health problem in aging male. Free radicals and Reactive Oxygen Species (ROS) are produced in overwhelming quantity with advancement of age. When in oxidative stress, these reactive species cause extensive damage to various organ in the body, may be associated with pathogenesis of BPH also. This study aimed at assessing Malondialdehyde (MDA), the marker of lipid peroxidation and anti-oxidants e.g. alpha-Tocopherol and Ascorbate status in plasma in BPH patients. Forty eight (n=48) cases of BPH and forty six (n = 46) healthy age matched controls were enrolled. Plasma MDA level showed 4.81+/-1.87 nmol/ml in cases compared to 3.69+/-1.56 nmol/ml in healthy controls (p<0.001). There were significant decrease in plasma alpha-Tocopherol and ascorbate level which were 0.85+/-0.12 mg/dl and 0.93 +/- 0.13 mg/dl in cases compared to 1.37+/-0.31 mg/dl and 1.44+/-0.38 mg/dl in healthy controls respectively. Inverse correlation of plasma MDA with alpha-Tocopherol (r = -0.09, p>0.05) and Ascorbate (r =-0.51, p=0.008) was found in BPH patients. There was mild elevation of PSA in BPH patients compared with control but was not statistically significant. Thus, our study showed the evidence of association of oxidative stress in BPH patients.

Oxidative stress in patients with benign prostate hyperplasia.

Benign Prostate Hyperplasia (BPH) is a common health problem in aging male. Free radicals and Reactive Oxygen Species (ROS) are produced in overwhelming quantity with advancement of age. When in oxidative stress, these reactive species cause extensive damage to various organ in the body, may be associated with pathogenesis of BPH also. This study aimed at assessing Malondialdehyde (MDA), the marker of lipid peroxidation and anti-oxidants e.g. alpha-Tocopherol and Ascorbate status in plasma in BPH patients. Forty eight (n=48) cases of BPH and forty six (n = 46) healthy age matched controls were enrolled. Plasma MDA level showed 4.81+/-1.87 nmol/ml in cases compared to 3.69+/-1.56 nmol/ml in healthy controls (p<0.001). There were significant decrease in plasma alpha-Tocopherol and ascorbate level which were 0.85+/-0.12 mg/dl and 0.93 +/- 0.13 mg/dl in cases compared to 1.37+/-0.31 mg/dl and 1.44+/-0.38 mg/dl in healthy controls respectively. Inverse correlation of plasma MDA with alpha-Tocopherol (r = -0.09, p>0.05) and Ascorbate (r =-0.51, p=0.008) was found in BPH patients. There was mild elevation of PSA in BPH patients compared with control but was not statistically significant. Thus, our study showed the evidence of association of oxidative stress in BPH patients.

Oxidative stress in benign prostate hyperplasia.

Benign Prostate Hyperplasia (BPH) is the common health problem in ageing male. Free radicals and reactive oxygen species (ROS) are produced more with advancement of age leads to oxidative stress. This study aims to assess Malondialdehyde (MDA), the marker of lipid peroxidation and vitaminic antioxidants e.g. alpha-Tocopherol (Toc) and Ascorbate (Asc) status in plasma of BPH patients. This is a case control study conducted in Department of Biochemistry in collaboration with Dept of Surgery, BPKIHS. Forty eight (n = 48) confirmed patients of BPH and forty six (n = 46) healthy age matched controls were enrolled. Plasma MDA, Asc and alpha-Toc were estimated. Plasma MDA level showed 4.81 +/- 1.87 nmol/ml in BPH patients compared to 3.69 +/- 1.56 nmol/ml in healthy controls (p < 0.001). There were significant decrease in plasma alpha-Toc and Asc level which were 0.85 +/- 0.12 mg/dl and 0.93 +/- 0.13 mg/dl in BPH patients compared to 1.37 +/- 0.31 mg/dl and 1.44 +/- 0.38 mg/dl in healthy controls respectively. Inverse correlation of plasma MDA with a- Toc (r = -0.09) and Asc (r = -0.51) was found in BPH patients. There was mild elevation of PSA in BPH patients compared with control but was not statistically significant. Thus, our study showed the evidence of association of oxidative stress in BPH patients.