Competency-based medical education and the McNamara fallacy: Assessing the important or making the assessed important?

The McNamara fallacy refers to the tendency to focus on numbers, metrics, and quantifiable data while disregarding the meaningful qualitative aspects. The existence of such a fallacy in medical education is reviewed in this paper. Competency-based medical education (CBME) has been introduced in India with the goal of having Indian Medical Graduates competent in five different roles - Clinician, Communicator, Leader and member of the health care team, Professional, and Lifelong learner. If we only focus on numbers and structure to assess the competencies pertaining to these roles, we would be falling prey to the McNamara fallacy. To assess these roles in the real sense, we need to embrace the qualitative assessment methods and appreciate their value in competency-based education. This can be done by using various workplace-based assessments, choosing tools based on educational impact rather than psychometric properties, using narratives and descriptive evaluation, giving grades instead of marks, and improving the quality of the questions asked in various exams. There are challenges in adopting qualitative assessment starting with being able to move past the objective-subjective debate, to developing expertise in conducting and documenting such assessment, and adding the rigor of qualitative research methods to enhance its credibility. The perspective on assessment thus needs a paradigm shift - we need to assess the important rather than just making the assessed important; and this would be crucial for the success of the CBME curriculum.

Evaluation of endoscopic gastrojejunostomy revision after Roux-en-Y gastric bypass for treatment of dumping syndrome.

BACKGROUND AND AIMS: Gastrojejunostomy stomal dilation is a frequent cause of weight regain after Roux-en-Y gastric bypass and may be a contributing cause of dumping syndrome. This study aims to evaluate the long-term durability of endoscopic gastrojejunostomy revision (EGJR) to resolve dumping syndrome. METHODS: A retrospective chart review was performed of patients undergoing EGJR at a single institution from January 1, 2013 to December 1, 2018. The primary endpoint, dumping symptom resolution, was measured at 1 month and at the most recent postoperative follow-up. Continuous data are reported as mean and standard deviations and categorical data as percentages. The Fisher exact test was used to assess associations between categorical variables. RESULTS: Ninety-eight patients underwent EGJR for dumping syndrome. Mean patient age was 51 years (standard deviation [SD], 9.9), and mean body mass index (BMI) was 36.2 kg/m2 (SD, 7.1), with most patients (53%) presenting with BMIs ≥35 kg/m2. Thirty-two patients (32%) reported severe dumping (≥3 symptoms). All patients were followed-up for 1 month, and 83% had a long-term follow-up at a mean of 3.45 years (SD, 1.7) after EGJR. In addition, 88% had initial symptom resolution at 1 month, and 85% reported symptom resolution 3 years postoperatively. Patients with GERD had a statistically significant improvement in dumping syndrome at 3 years compared with those without GERD (69% vs 62%, P = .03). Long-term weight loss averaged 2.1 pounds after EGJR. CONCLUSIONS: EGJR is associated with effective and durable resolution of dumping syndrome at 3 years postoperatively, with a minimal long-term impact on weight loss. The presence of GERD preoperatively correlates with a statistically significant resolution of dumping syndrome.

Solvent Effects on the Photophysical Properties of a Donor-acceptor Based Schiff Base.

In this work, a donor-acceptor substituted aromatic system ((E)-N-((E)-3-(4 (dimethylamino)phenyl) allylidene)-4-(trifluoromethyl) benzenamine (DPATB) has been synthesized and its detailed photophysics of intramolecular charge transfer process have been explored on the basis of steady state absorption, fluorescence and time resolved spectroscopy in combination with density functional theory calculations. Large solvent dependency fluorescence spectral shift and the calculated large excited state dipole moment clearly indicate an efficient charge transfer occurring from the donor group to the acceptor moiety in the excited state. Effect on addition of acid and pH on steady state spectral properties further reveals excited state charge transfer character. Quantum chemical calculations were performed in order to study the conformation and polarity of DPATB at their ground as well as excited electronic states. The HOMO and LUMO molecular orbital pictures are obtained at DFT level using B3LYP functional and 6-311 + g(d,p) basis set which clearly support excited state intramolecular charge transfer process. The molecular electrostatic potential maps for the optimized ground state, donor twisted and acceptor twisted geometry shed insight on the electrostatic potential and charge distribution in a system which gives information about the reacting site of the probe and nature of the reaction. In this work, detailed photophysics of excited state intramolecular charge transfer process in donor-acceptor system (DPATB) was evaluated using steady state and time-resolved fluorescence spectroscopy in combination with density functional theory calculations. Large solvent dependency fluorescence spectral shift and the calculated large excited state dipole moment clearly indicate an efficient charge transfer occurring in DPATB. Molecular orbital pictures as obtained from DFT based computational analysis reveals a significant change in the distribution of electron density upon transition from HOMO to LUMO which confirms an ICT process occurring from the donor group to the acceptor moiety in the excited state.

Unravelling a novel, promising and convenient tool for differential diagnosis of delayed puberty: GnRHa-stimulated inhibin B (GnRH-iB).

BACKGROUND: Etiological diagnosis of delayed puberty is difficult. Despite availability of various basal and stimulation tests differentiation between constitutional delay in puberty and hypogonadotropic hypogonadism is still challenging. OBJECTIVE: To elucidate the role of GnRH agonist-stimulated inhibin B (GnRH-iB) for the differential diagnosis of delayed puberty. STUDY DESIGN: Participants were recruited into "exploratory cohort" (n = 39) and "validation cohort" (n = 16). "Exploratory cohort" included children with spontaneous puberty and patients with hypogonadotropic hypogonadism. "Validation cohort" constituted children who presented with delayed puberty. INTERVENTION AND OUTCOME: GnRHa (Triptorelin) stimulation test along with measurement of inhibin B level at 24 h after GnRHa injection was performed in all the study participants. Cut-offs for GnRH-iB were derived from the "exploratory cohort". These cut-offs were applied to the "validation cohort". Basal LH, basal inhibin B(INH-B), GnRHa-stimulated LH at 4 h (GnRH-LH) and GnRH-iB were evaluated for the prediction of onset of puberty on prospective follow-up. RESULTS: GnRH-iB at a cut-off value of 113.5 pg/ml in boys and 72.6 pg/ml in girls had 100% sensitivity and specificity for the documentation of puberty. In the "validation cohort" basal LH, basal INH-B, GnRH-LH, and GnRH-iB had a diagnostic accuracy of 68.75%, 81.25%, 68.75% and 93.75% respectively, for the prediction of onset of puberty. Basal LH, basal INH-B and GnRH-LH used alone or in combination were inferior to GnRH-iB used alone. CONCLUSION: GnRHa-stimulated inhibin B (GnRH-iB) is a convenient and easily employable test for the differentiation of constitutional delay in puberty from hypogonadotropic hypogonadism. CTRI REGISTRATION NO: CTRI/2019/10/021570.

Developing a competency-based undergraduate logbook for pediatrics: Process and lessons.

With the first MBBS batch admitted under the new National Medical Commission (NMC) undergraduate curriculum entering pediatric clinical posting soon, creation of a Pediatric logbook in consonance with this competency-based curriculum was felt to be a need of the hour. No such document is yet available in the public domain. The logbook template, created after enormous brainstorming amongst authors, includes 176 Shows (S), Shows How (SH) and Perform (P) level competencies. These were further segregated into certifiable (23), affective domain (25) and clinic/field visits (9) leaving 51 as documentable competencies. The institutions may use this template to build their own institute-specific logbook based on the infrastructure, faculty strength, clinical patient load, student intake and preferred assessment method(s). It would also be worthwhile to integrate this with the internship logbook (and later the postgraduate one for students opting for post-graduation in pediatrics) to provide a longitudinal record of each student's trajectory of learning.

Comparison of peak wall stress and peak wall rupture index in ruptured and asymptomatic intact abdominal aortic aneurysms.

BACKGROUND: Previous studies have suggested that finite element analysis (FEA) can estimate the rupture risk of an abdominal aortic aneurysm (AAA); however, the value of biomechanical estimates over measurement of AAA diameter alone remains unclear. This study aimed to compare peak wall stress (PWS) and peak wall rupture index (PWRI) in participants with ruptured and asymptomatic intact AAAs. METHODS: The reproducibility of semiautomated methods for estimating aortic PWS and PWRI from CT images was assessed. PWS and PWRI were estimated in people with ruptured AAAs and those with asymptomatic intact AAAs matched by orthogonal diameter on a 1 : 2 basis. Spearman's correlation coefficient was used to assess the association between PWS or PWRI and AAA diameter. Independent associations between PWS or PWRI and AAA rupture were identified by means of logistic regression analyses. RESULTS: Twenty individuals were included in the analysis of reproducibility. The main analysis included 50 patients with an intact AAA and 25 with a ruptured AAA. Median orthogonal diameter was similar in ruptured and intact AAAs (82·3 (i.q.r. 73·5-92·0) versus 81·0 (73·2-92·4) mm respectively; P = 0·906). Median PWS values were 286·8 (220·2-329·6) and 245·8 (215·2-302·3) kPa respectively (P = 0·192). There was no significant difference in PWRI between the two groups (P = 0·982). PWS and PWRI correlated positively with orthogonal diameter (both P < 0·001). Participants with high PWS, but not PWRI, were more likely to have a ruptured AAA after adjusting for potential confounders (odds ratio 5·84, 95 per cent c.i. 1·22 to 27·95; P = 0·027). This association was not maintained in all sensitivity analyses. CONCLUSION: High aortic PWS had an inconsistent association with greater odds of aneurysm rupture in patients with a large AAA.

Imaging aortic valve calcification: significance, approach and implications.

Aortic stenosis is the most prevalent valvular heart disease worldwide, and rates are increasing with the growing and more elderly population. Although the precise mechanisms that underpin aortic valve stenosis are incompletely understood, pathological valvular calcification has emerged as a key instigator in mediating the biomechanical stiffening that can lead to symptoms, the need for aortic valve replacement, and death if left untreated. Here, we review the currently understood processes leading to aortic valve calcification, summarise the contemporary imaging assessments of valve calcification, and highlight how these might improve patient care and accelerate our pathological understanding and the development of an effective medical therapy.

Frequency of resistance alleles to Cry1Ac toxin from cotton bollworm, Helicoverpa armigera (Hübner) collected from Bt-cotton growing areas of Telangana state of India.

Transgenic cotton expressing Bacillus thuringiensis (Bt) cry1Ac and cry2Ab toxin genes is widely cultivated to manage bollworm complex in India. Cotton bollworm Helicoverpa armigera (Hübner) is one of the most serious of this complex. It is likely to evolve resistance to Cry toxins in view of continual selection pressure due to extensive cultivation of Bt cotton. Monitoring susceptibility of cotton bollworm using conventional bioassays is reported to have shown its increasing tolerance to Cry1Ac over the years. We report using an F2 screen Cry1Ac resistance allele frequencies of 0.050 (95% CI 0.022-0.076) and 0.056 (95% CI 0.035-0.075) in the insect populations collected from pigeon pea grown alongside Bt cotton in the respective years of 2016 and 2017 in the Telangana state of India. Compared to our earlier studies for 2013 and 2014, resistance allele frequency to Cry1Ac in the cotton bollworm in the following two years remains unchanged. The significance of these results is discussed in the context of non-Bt host crops acting as refuge for cotton bollworm for ensuring sustainable resistance management.

Blended programmatic assessment for competency based curricula.

The uncertainty in all spheres of higher education due to the COVID-19 pandemic has had an unprecedented impact on teaching-learning and assessments in medical colleges across the globe. The conventional ways of assessment are now neither possible nor practical for certifying medical graduates. This has necessitated thoughtful considerations in making adjustments to the assessment system, with most institutions transitioning to online assessments that so far have remained underutilized. Programmatic assessment encourages the deliberate and longitudinal use of diverse assessment methods to maximize learning and assessment and at present can be utilized optimally as it ensures the collection of multiple low-stake assessment data which can be aggregated for high-stake pass/fail decisions by making use of every opportunity for formative feedback to improve performance. Though efforts have been made to introduce programmatic assessment in the competency-based undergraduate curriculum, transitioning to online assessment can be a potential opportunity if the basic tenets of programmatic assessment, choice of online assessment tools, strategies, good practices of online assessments and challenges are understood and explored explicitly for designing and implementing online assessments. This paper explores the possibility of introducing online assessment with face-to-face assessment and structuring a blended programmatic assessment in competency-based medical education.

Assessment toolbox for Indian medical graduate competencies.

The new competency-based medical education curriculum for Bachelor of Medicine and Bachelor of Surgery is being implemented in a phased manner in medical colleges across India since the year 2019. The Graduate Medical Education Regulations enlist a total of 35 global competencies for the five roles expected of an Indian medical graduate, the roles being clinician, communicator, leader, professional, and life-long learner. Along with an effective implementation of the new curriculum, both in spirit and in action, it is imperative to assess the listed competencies. The new curriculum demands a more careful and mature selection of assessment tools, based on the competency and its expected level of achievement. It is these two variables that make choosing the right assessment method not just a matter of choice, but also of expertise. An array of tools in our armamentarium can sometimes separate confuse and the teachers. So, using the right tool, in the right context, at the right juncture, supplemented by other tools, and backed by constructive feedback, can help nurture the good intent ingrained in the competency-based curriculum. Hence, an attempt was made to compile an assessment toolbox for various global competencies. A PubMed, Science Direct and Google Scholar search, with relevant keywords was carried out. To the initially extracted 90,121 articles, limitations were applied, duplicates were removed and screening for assessment of global competencies and its attributes was done to select 232 articles. Finally, 31 articles were used for designing the proposed toolbox. Prioritization for the tools for the global competencies was based on thorough literature review and extensive discussion. The evolved assessment toolbox is presented in this article, which would help teachers pick the most useful methods of assessment for global competencies.

Lack of an effective drug therapy for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) rupture is a common cause of death in adults. Current AAA treatment is by open surgical or endovascular aneurysm repair. Rodent model and human epidemiology, and genetic and observational studies over the last few decades have highlighted the potential of a number of drug therapies, including medications that lower blood pressure, correct dyslipidaemia, or inhibit thrombosis, inflammation or matrix remodelling, as approaches to managing small AAA. This review summarizes prior AAA pathogenesis data from animal and human studies aimed at identifying targets for the development of drug therapies. The review also systematically assesses past randomized placebo-controlled drug trials in patients with small AAAs. Eleven previously published randomized-controlled clinical trials testing different drug therapies aimed at slowing AAA progression were identified. Five of the trials tested antibiotics and three trials assessed medications that lower blood pressure. Meta-analyses of these trials suggested that neither of these approaches limit AAA growth. Allocation to blood pressure-lowering medication was associated with a small reduction in AAA rupture or repair, compared to placebo (relative risk 0.94, 95% confidence intervals 0.89, 1.00, P = 0.047). Three further trials assessed the effect of a mast cell inhibitor, fibrate or platelet aggregation inhibition and reported no effect on AAA growth or clinical events. Past trials were noted to have a number of design issues, particularly small sample sizes and limited follow-up. Much larger trials are needed to properly test potential therapeutic approaches if a convincingly effective medical therapy for AAA is to be identified.

Ethanolic Extract of Lagerstroemia Speciosa (L.) Pers., Induces Apoptosis and Cell Cycle Arrest in HepG2 Cells.

Lagerstroemia speciosa (L.) Pers., (Lythraceae) also called Banaba is a native plant of southeast Asia and is widely used in traditional medicinal system. Herbal tea from banaba leaves are used to reduce weight and diabetes. We investigated the cytotoxic potentials of ethanolic banaba leaves extract (EBLE) against human hepatocellular carcinoma (HepG2) cell line. Lagerstroemia speciosa leaves were extracted and obtained from M/s. Quimico Herbal Extract Manufacturer, Bengaluru, India, and it contains 20% corosolic acid. Cells were treated with 50, 100, and 150 µg/ml of EBLE for 24 h, and cytotoxicity was evaluated by MTT assay. Apoptosis-related morphology was investigated by DAPI nuclear staining. Protein and gene expressions of p-Akt, FOXO1, p53, MDM2, p21, p27, CDK4, cyclin D1, and E1 were evaluated through Western blotting and qPCR. EBLE treatments caused significant, concentration-dependent cytotoxicity. DAPI staining and flow cytometry studies showed chromatin condensation, increased apoptotic cell population and cell cycle arrest at subG0/G1 phase upon EBLE treatments respectively. Furthermore, EBLE treatments significantly increased the expressions of p53, p21, p27, FOXO1, while p-Akt, MDM2, CDK4, cyclin D1, and E1 expressions were downregulated. These findings suggested that EBLE induces G1-phase of cell cycle arrest and apoptosis in HepG2 cells. EBLE may serve as a therapeutic agent against hepatocellular carcinoma.

The power of subjectivity in competency-based assessment.

With the introduction of competency-based undergraduate curriculum in India, a paradigm shift in the assessment methods and tools will be the need of the hour. Competencies are complex combinations of various attributes, many of which being not assessable by objective methods. Assessment of affective and communication domains has always been neglected for want of objective methods. Areas like professionalism, ethics, altruism, and communication-so vital for being an Indian Medical Graduate, can be assessed longitudinally applying subjective means only. Though subjectivity has often been questioned as being biased, it has been proven time and again that a subjective assessment in expert hands gives comparable results as that of any objective assessment. By insisting on objectivity, we may compromise the validity of the assessment and deprive the students of enriched subjective feedback and judgement also. This review highlights the importance of subjective assessment in competency-based assessment and ways and means of improving the rigor of subjective assessment, with particular emphasis on the development and use of rubrics.

Studying land use dynamics using decadal satellite images and Dyna-CLUE model in the Mahanadi River basin, India.

Population growth rate indicates the proportional rate of settlement expansion and landscape modification in any river basin. The Mahanadi River basin (MRB), which is a densely populated, cropland and forest-dominated landscape, is selected as a case study area for studying the nature of built-up expansion and the corresponding land cover modifications. Satellite data-derived land use/land cover (LU/LC) maps for the years 1995, 2005, and 2015 were used for identification of landscape changes during the past three decades. One of the major LU/LC changes are observed in terms of increase in the water, which may be attributed to construction of new dams at the cost of the croplands and forest areas. Conversion of forest to cropland and expansion and densification of built-up areas in and around the existing built-up areas are also identified as a major LU/LC change. The geostatistical analysis was performed to identify the relationship between LU/LC classes with drivers, which showed that built-up areas were more in topographically flat terrain with higher soil depth, and expanded more around the existing built-up areas; cropland areas were more at lower elevation and less sloppy terrain, and forest areas were more at higher elevation. The LU/LC scenario of 2025 was projected using a spatially explicit dynamic conversion of land use and its effects (Dyna-CLUE) modeling platform with the LU/LC change trends of past 10 years (2005-2015) and 20 years (1995-2015). The major LU/LC changes observed during 2005-2015 were built-up expansion by 36.53% and deciduous forest and cropland reduction by 0.35% and 0.45%, respectively. Thus, the corresponding predicted change during 2015-2025 estimated built-up expansion by 25.70% and deciduous forest and croplands loss by 0.43% and 0.35%, respectively. On the other hand, during 1995 to 2015, the total built-up expansion and deciduous forest and cropland reduction were observed 50.79%, 0.45%, and 0.73%, respectively. Thus, the predicted changes during 2015-2025 were estimated as 18.48% built-up expansion and 0.22% and 0.21% deciduous forest and cropland loss. However, with the conditions of restricted deforestation and less landscape modification, the LU/LC projections show less built-up area expansion, reducing the cropland, fallow land, plantation, and waste land. The reduced numbers of land cover conversions types during 2005-2015 compared with 1995-2005 indicate more stabilized landscape. The input LU/LC maps and statistical analysis demonstrated the landscape modifications and causes observed in the basin. The model projected LU/LC maps are giving insights to possible changes under multiple pathways, which will help the agriculture, forest, urban, and water resource planners and managers in improved policy-making processes.

Meta-analysis of clinical trials examining the benefit of structured home exercise in patients with peripheral artery disease.

BACKGROUND: Supervised exercise is recommended for the management of peripheral artery disease (PAD); however, the uptake is limited. Structured home exercise programmes may be more feasible, but their effectiveness is unclear. This systematic review and meta-analysis examined the benefit of structured home exercise programmes for treating PAD in comparison to controls not receiving an exercise programme. METHODS: A literature search was conducted to identify RCTs comparing structured home exercise with controls not receiving an exercise programme among patients with PAD. To be included, studies had to report outcomes from treadmill or corridor walking tests, or objective assessment of physical activity. Inverse variance-weighted meta-analysis was performed to compare changes in maximum walking distance and intermittent claudication onset distance in treadmill tests, walking distance during a 6-min walking test, and physical activity measured using a pedometer or accelerometer. Summarized results are presented in terms of standard deviation differences. RESULTS: Eleven randomized trials involving 807 patients were included. Follow-up ranged from 2 to 24 months; only one trial included follow-up beyond 12 months. Meta-analyses showed that structured home exercise programmes led to significant improvements in maximum walking distance (mean difference (MD) 0·32, 95 per cent c.i. 0·15 to 0·50; P < 0·001), intermittent claudication onset distance (MD 0·45, 0·27 to 0·62; P < 0·001), walking distance in a 6-min walking test (MD 0·28, 0·09 to 0·47; P = 0·004) and physical activity (MD 0·27, 0·11 to 0·43; P = 0·001). CONCLUSION: This meta-analysis suggests that structured home exercise programmes are effective at improving walking performance and physical activity in the short term for patients with PAD.

Systematic review and meta-analysis of clinical trials examining the effect of hyperbaric oxygen therapy in people with diabetes-related lower limb ulcers.

AIM: To examine the efficacy of hyperbaric oxygen therapy in healing diabetes-related lower limb ulcers through a meta-analysis of randomized clinical trials. METHODS: A literature search was conducted to identify appropriate clinical trials. Inclusion required randomized study design and reporting of the proportion of diabetes-related lower limb ulcers that healed. A meta-analysis was performed to examine the effect of hyperbaric oxygen therapy on ulcer healing. The secondary outcomes were minor and major amputations. RESULTS: Nine randomized trials involving 585 participants were included. People allocated to hyperbaric oxygen therapy were more likely to have complete ulcer healing (relative risk 1.95, 95% CI 1.51-2.52; P<0.001), and less likely to require major (relative risk 0.54, 95% CI 0.36-0.81; P=0.003) or minor (relative risk 0.68, 95% CI 0.48-0.98; P=0.040) amputations than control groups. Sensitivity analyses suggested the findings were dependent on the inclusion of one trial. Adverse events included ear barotrauma and a seizure. Many of the trials were noted to have methodological weaknesses including absence of blinding of outcome assessors, lack of a justifiable sample size calculation and limited follow-up. CONCLUSIONS: This meta-analysis suggests hyperbaric oxygen therapy improves the healing of diabetes-related lower limb ulcers and reduces the requirement for amputation. Confidence in these results is limited by significant design weaknesses of previous trials and inconsistent findings. A more rigorous assessment of the efficacy of hyperbaric the efficacy of hyperbaric oxygen therapy is needed.

Understanding of HIV/AIDS in the international border area, Manipur: Northeast India.

Manipur, an international border region has the highest incidence of human immunodeficiency virus (HIV)-1 infection in India. Nevertheless, there have been no analytical reviews of research article published within this region. In this review, the authors aim to draw the attention of policy makers, medical practitioners and researchers in adopting new strategies to limit the expansion of HIV/acquired immunodeficiency syndrome (AIDS) not only in Manipur but also in other international border areas. A systematic search for published literature in last decade was performed based on the keywords 'Manipur' and 'HIV' using the PubMed. Twenty-six articles were selected and reviewed. There were high incidence of drug resistance (53%), emergence of recombinant virus (32%) and increased incidence of co-infection with hepatitis C virus. The prime cause of the HIV is due to the uses of 'heroin' smuggled from the 'South Asia Golden Triangle' and complex patterns of cross-border movement for trade and commerce. The drug abuse, social stigma, geographical location and resource limitation and socio-political problem of the region have contributed strongly on spreading and failure of preventively programme of HIV/AIDS. This review will provide vital knowledge for the policy makers and clinicians for sentinel surveillance of AIDS pandemic in Manipur and other international border regions.

TRPV4 activation in rat carotid artery in DOCA hypertension involves eNOS and endothelium-derived contractile factor (EDCF).

Aim: Role of TRPV4 channel in regulation of endothelial function in the carotid artery in deoxycorticosterone acetate (DOCA) model of hypertension in rat was studied. Methods: 8-10 weeks old albino Wistar rats divided into three groups namely Control, UNX and hypertensive animals. Vascular smooth muscle response was studied in isolated carotid artery of rat with acetylcholine, sodium nitroprusside, GSK1016790A (GSK) in presence and absence of L-NAME and indomethacin. Results: At the end of the 6th week, the mean systolic blood pressure was increased in DOCA-treated hypertensive rats (166 ± 8 mm Hg) compared to Control and UNX (125 ± 5 mm Hg). ACh (10-9 to 10-5 M) produced almost 100% relaxation in Control (Emax = 97.48 ± 1.06 %) and UNX animals (Emax = 93.16 ± 2.33 %) which was attenuated in DOCA-treated hypertensive animals (Emax = 70.85 ± 1.65 %). No significant changes seen in SNP (10-12 to 10-5 M) induced relaxation. GSK1016790A (10-12 to 10-7 M)-mediated relaxation was significantly attenuated in DOCA-treated hypertensive animals (Emax = 25.58 ± 13.60%) compared to the control (Emax = 80.59 ± 6.86%) and UNX (Emax = 87.32 ± 2.01%) animals. L-NAME (10-4 M) potently blocked GSK-induced relaxation, and a contractile response to GSK was observed in presence of L-NAME in all the three groups of animals which was sensitive to indomethacin (10-5 M). Conclusion: TRPV4 may regulate the vascular tone of rat carotid artery through an attenuated NO pathway and stimulation of the release of contractile prostanoids in the DOCA hypertensive rats.

Sp1 Binding Site Polymorphism at COL1A1 Gene and Its Relation to Bone Mineral Density for Osteoporosis Risk Factor Among the Sikkimese Men and Women of Northeast India.

Single nucleotide polymorphism in the first intron of Collagen type I alpha 1 (COL1A1) gene which is the binding site of specificity protein 1 (Sp1) transcription factor associated with low bone mineral density and osteoporosis. To evaluate such genetic factors among the Sikkimese population, a total of 150 cases (75 men and 75 women) with primary osteopenia and osteoporosis and 150 healthy controls (75 men and 75 women) of age range between 35 and 65 years were enrolled in this study. The COL1A1 genotypes [SS, Ss and ss] were assessed by restriction enzyme [MscI] digestion of DNA after amplification by polymerase chain reaction. There, only 2.7% women and 1.3% men cases had restriction site with heterozygous genotype (Ss) and no homozygous genotype (ss) were detected. There was no statistically significant association between low bone mass and genotypes on analysis (χ2 = 1.014, P = 0.314; RR = 1.510) that, the Sp1 binding site polymorphism at the COLIA1 gene is very rare and has no contribution in the development low bone mineral density.

Effect of interfilament hydrodynamic interaction on swimming performance of two-filament microswimmers.

The motion of two-filament artificial swimmers is modeled by assuming interfilament coupling via hydrodynamic viscous drag. The filaments are assumed to be in parallel and attached to a rigid spherical head. The boundary actuation is assumed to occur at the head-filament joint through an external oscillatory magnetic field and the filament motion is taken to be confined to the flexural plane. The hydrodynamic coupling modifies the viscous drag on one filament due to motion of the other. Assuming in-phase, small amplitude, low frequency actuation the swimmer performance metrics (propulsive thrust, propulsion speed and energy efficiency) are calculated using Lauga's formulation for the swimmer kinematics coupled with filament dynamics. The results are compared with the performance of a single-filament and an uncoupled two-filament swimmer. The hydrodynamic coupling is found to enhance the performance measures in a parametric window. Also, it is found that there occurs an optimum combination of head size and swimmer length that can maximize the microswimmer performance. The findings are in agreement with the experimental observations on multi-filament artificial microswimming.