Comparative study of non-contrast silent and time-of-flight magnetic resonance angiographic sequences in the evaluation of intracranial dural arteriovenous fistula.

AIM: To compare the performance of two non-contrast magnetic resonance angiography (MRA) sequences, silent MRA and time of flight (TOF) MRA, in the evaluation of intracranial dural arteriovenous fistula (DAVF). MATERIALS AND METHODS: Forty consecutive patients with DAVF were enrolled and evaluated prospectively using silent MRA, TOF MRA, and digital subtraction angiography (DSA). The location, Cognard classification, arterial feeders, and venous drainage were evaluated. The therapeutic strategy and possible route were predicted on both silent and TOF MRA and these were compared with DSA during subsequent endovascular treatment. RESULTS: Sensitivity and accuracy of silent and TOF MRA for localisation (96.4% versus 96% and 96% versus 95%, respectively) and classification (96% versus 94% and 96% versus 93.5%, respectively) were high. Silent MRA showed higher sensitivity than TOF MRA for arterial feeders and draining veins (87% versus 79% and 81.6% versus 67%). This improved to a sensitivity of 96.4% and 89% when prominent feeders were considered. The sensitivity and accuracy were 92.6% and 85.8% for immediate draining veins. Both silent and TOF MRA were accurate for therapeutic planning (96% versus 85%), although silent MRA was more accurate. CONCLUSION: Silent MRA can more reliably evaluate the various angioarchtectural components of DAVF compared to TOF MRA.

Cutaneous Metastasis in Breast Cancer: A Case Series.

The most frequent reason for cutaneous metastases is breast cancer in females. Breast cancer patients can present with cutaneous manifestations of breast disease at the time of their initial diagnosis; however, cutaneous metastases more often present well after the initial diagnosis and treatment of the breast disease. We described three cases of carcinoma of breast metastasis to the skin of the breast and the chest wall, each with a unique dermatological presentation. A 52-year-old woman presented with a cutaneous erythematous papule for the past month. She underwent a modified radical mastectomy one year before. On presentation, she was diagnosed to have erythematous papule near the operative scar and surrounding chest wall and referred to the dermatology outdoor department, where a skin biopsy was done, which confirmed erysipeloides carcinoma. The second case includes a 38-year-old premenopausal lady who was diagnosed with carcinoma of the right breast with a locally advanced stage. She was treated with neoadjuvant chemotherapy (NACT) followed by modified radical mastectomy and subsequently presented with biopsy-proven multiple skin nodules on the chest wall at the same side. She was discussed in a multidisciplinary tumor board and planned for palliative chemotherapy followed by hormonal therapy. In the third case, a 42-year-old perimenopausal woman diagnosed with locally advanced left breast carcinoma presented in the surgical oncology outdoor patient department (OPD) with multiple skin erythema over the left breast. Biopsy was done from the skin erythema site showing metastasis to the skin. She was discussed in a multidisciplinary tumor board and planned for systemic chemotherapy followed by assessment for surgery. Skin erythema and erythematous papules are rare manifestations of cutaneous metastasis in patients with carcinoma of the breast; typically, patients present with a chest wall nodule. Careful examination and early detection of these uncommon skin lesions can lower morbidity and slow the progression of diseases in these patients.

Utility of silent magnetic resonance angiography in the evaluation and characterisation of intracranial dural arteriovenous fistula.

AIM: To evaluate the utility of silent magnetic resonance angiography (MRA) in the diagnosis, characterisation, and therapeutic planning of intracranial dural arteriovenous fistula (DAVF). MATERIALS AND METHODS: Twenty consecutive patients with DAVF were enrolled prospectively and were evaluated using silent MRA and digital subtraction angiography (DSA) as a part of routine work-up. The diagnosis and location of fistula, Borden and Cognard classification, entire arterial feeders, and venous drainage were analysed. A therapeutic strategy was formulated, and the accessible route and vessel were predicted, which was confirmed on endovascular treatment. RESULTS: Silent MRA was 100% sensitive and accurate for location and classification of fistulas. Silent MRA showed a sensitivity of 82% and 76.5% for entire arterial feeders and draining veins, which improved to a sensitivity of 90% and 94% when prominent feeders and immediate venous drainage was considered. Among the missed veins, thrombosed sinus, slow sinus flow, small calibre, reduced image quality were the causes. The therapeutic decision matched with DSA in all cases and silent MRA accurately identified the potential accessible feeder in 94% cases. CONCLUSION: Silent MRA is a promising MR technique that can provide both diagnostic and therapeutic information similar to that obtained from DSA.

Clinicopathological profile and its association with peritoneal disease among gastric cancer patients.

BACKGROUND: There are no clinicopathological criteria or test to predict peritoneal metastasis either in primary or recurrent gastric cancer. The early prediction will help in altering or adding other adjuvant potential therapy modalities like HIPEC and maintenance chemotherapy. METHODS: Paraffin based blocks of 110 gastric tumor specimens were subjected to IHC staining to assess VEGF, Her 2 neu, E cadherin, bcl 2 and p 53 expression and its association with peritoneal disease evaluated. RESULTS: Her 2 neu uptake was present in 17.3%, bcl-2 expression in 19.1%, P53 expression in 40.9%, VEGF in 41.8% and E cadherin expression in 49.1% patients. On univariate analysis, a younger age(p = .029), female sex(p = .026), positive VEGF expression (p = .001) and p53 expression(p = .015) were significantly associated with peritoneal disease. A binomial logistic regression was performed to ascertain the effects of independent variables evaluated on univariate analysis. Of the 10 predictors variables, only three were statistically significant: tumor type, P53, and VEGF. Positive VEGF expression had 48.7, E cadherin 2.6 and Her2neu 1.5 times higher odds of exhibiting peritoneal disease. CONCLUSION: A younger age, female sex, distal 2/3rd, diffuse variant, VEGF staining in >10% cells and decrease p53 expression were associated with peritoneal disease.

Combinatorial effects of trans-cinnamaldehyde with fluoride and chlorhexidine on Streptococcus mutans.

AIMS: The aim of this study was to investigate the effects of trans-cinnamaldehyde (TC) and its synergistic activity with chlorhexidine (CHX) and fluoride against Streptococcus mutans. METHODS AND RESULTS: Streptococcus mutans UA159 was treated with TC alone and in combination with CHX or sodium fluoride. The synergy profile was analysed using the Zero Interaction Potency model. TC showed strong synergism (synergy score of 21·697) with CHX, but additive effect (synergy score of 5·298) with fluoride. TC and the combinations were tested for acid production (glycolytic pH drop) and biofilm formation by S. mutans, and nitric oxide production in macrophages. TC significantly inhibited sucrose-dependent biofilm formation and acid production by S. mutans. Mechanistic studies were carried out by qRT-PCR-based transcriptomic studies which showed that TC acts by impairing genes related to metabolism, quorum sensing, bacteriocin expression, stress tolerance and biofilm formation. CONCLUSIONS: trans-Cinnamaldehyde potentiates CHX and sodium fluoride in inhibiting S. mutans biofilms and virulence through multiple mechanisms. This study sheds significant new light on the potential to develop TC as an anti-caries treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Oral diseases were classified as a 'silent epidemic' in the US Surgeon General's Report on Oral Health. Two decades later, >4 billion people are still affected worldwide by caries, having significant effects on the quality of life. There is an urgent need to develop novel compounds and strategies to combat dental caries. Here, we prove that TC downregulates multiple pathways and potentiates the CHX and fluoride to prevent S. mutans biofilms and virulence. This study sheds significant new light on the potential to develop TC in combination with CHX or fluoride as novel treatments to arrest dental caries.

Do pediatricians routinely perform genitourinary examinations during well-child visits? A review from a large tertiary pediatric hospital.

BACKGROUND: The male genital examination is a common source of discomfort for the patient and medical provider. Performance of male genital examination is imperative; however, as many treatable diagnoses can be made. Undescended testicles (UDTs), hernias, testicular tumors, and urethral abnormalities are all potentially concerning findings which can be discovered on routine examination. OBJECTIVE: The objectives of this study are to determine the rate at which general pediatricians perform routine genitourinary (GU) examinations in the pediatric population and to determine the rate at which UDT are diagnosed or documented in the patient's history. The authors hypothesize the rate of pediatric GU examination during routine well-child visits to be in line with the previously reported rates in the adult literature. STUDY DESIGN: Nine hundred ninety-six consecutive male well-child visits conducted by general pediatricians at the study institution were reviewed. These visits were evaluated for documentation of a detailed GU examination as well as the presence of UDT from these examinations. In addition, past medical and surgical histories were reviewed to determine if a diagnosis of UDT was noted. RESULTS: Pediatricians at the study institution documented GU examinations 99.1% of the time during male well-child visits. Only 1.1% of the cohort had a documentation of UDT at any time point. Of the 11 patients with UDT, 6 boys (54.5%) had spontaneous descent with no referral to urology, whereas 5 (45.5%) required orchidopexy. DISCUSSION: Prior reports suggest 70-75% of routine office visits include a genital examination. None of these reports reviewed the pediatric population, thus making this review novel in this respect. In addition, the results are vastly different from these prior studies as the authors demonstrated over 99% of male well-child examinations included documentation of a thorough genital examination. A limitation of the study is its retrospective nature, which creates a lack of standardization across the data set. In addition, without being physically present in the examination room, one cannot discern whether an examination is simply being documented without actual performance because of the template format of the electronic medical record (EMR). Furthermore, the study was not designed to best evaluate the true rate of UDTs; therefore, the reported rate of 1.1% cannot be accurately associated with a particular age at diagnosis. CONCLUSIONS: Pediatricians do, in fact, document GU examinations on a routine basis. This finding cannot be taken with complete certainty as verification of actual examination performance is impractical. While the data demonstrated a lower than expected rate of UDT, depending upon age at diagnosis, this could indicate that although examinations are being documented, their accuracy may be diminished because of various factors at play in the healthcare system as a whole, including improper exam performance and EMR templates. Follow-up studies are required to verify these potentially changing rates of UDT and to determine if there is discordance between documentation and performance of GU examinations.

Risk of subsequent fracture after prior fracture among older women.

Among 377,561 female Medicare beneficiaries who sustained a fracture, 10% had another fracture within 1 year, 18% within 2 years, and 31% within 5 years. Timely management to reduce risk of subsequent fracture is warranted following all nontraumatic fractures, including nonhip nonvertebral fractures, in older women. INTRODUCTION: Prior fracture is a strong predictor of subsequent fracture; however, postfracture treatment rates are low. Quantifying imminent (12-24 month) risk of subsequent fracture in older women may clarify the need for early postfracture management. METHODS: This retrospective cohort study used Medicare administrative claims data. Women ≥ 65 years who sustained a clinical fracture (clinical vertebral and nonvertebral fracture; index date) and were continuously enrolled for 1-year pre-index and ≥ 1-year (≥  2 or ≥ 5 years for outcomes at those time points) post-index were included. Cumulative incidence of subsequent fracture was calculated from 30 days post-index to 1, 2, and 5 years post-index. For appendicular fractures, only those requiring hospitalization or surgical repair were counted. Death was considered a competing risk. RESULTS: Among 377,561 women (210,621 and 10,969 for 2- and 5-year outcomes), cumulative risk of subsequent fracture was 10%, 18%, and 31% at 1, 2, and 5 years post-index, respectively. Among women age 65-74 years with initial clinical vertebral, hip, pelvis, femur, or clavicle fractures and all women ≥ 75 years regardless of initial fracture site (except ankle and tibia/fibula), 7-14% fractured again within 1 year depending on initial fracture site; risk rose to 15-26% within 2 years and 28-42% within 5 years. Risk of subsequent hip fracture exceeded 3% within 5 years in all women studied, except those < 75 years with an initial tibia/fibula or ankle fracture. CONCLUSIONS: We observed a high and early risk of subsequent fracture following a broad array of initial fractures. Timely management with consideration of pharmacotherapy is warranted in older women following all fracture types evaluated.

Persistence at 24 months with denosumab among postmenopausal women with osteoporosis: results of a prospective cohort study.

Persistence with prescribed medications for chronic diseases is important; however, persistence with osteoporosis treatments is historically poor. In this prospective cohort study of postmenopausal women treated for osteoporosis in real-world clinical practice settings in the USA and Canada, 24-month persistence with denosumab was 58%. PURPOSE: Patients who persist with their prescribed osteoporosis treatment have increased bone mineral density (BMD) and reduced risk of fracture. Twelve-month persistence with denosumab in routine clinical practice is as high as 95%, but there are limited data on longer-term persistence with denosumab in this setting. METHODS: This single-arm, prospective, cohort study evaluated 24-month persistence with denosumab administered every 6 months in postmenopausal women receiving treatment for osteoporosis in real-world clinical practice in the USA and Canada. Endpoints and analyses included the percentage of patients who persist with denosumab at 24 months (greater than or equal to four injections with a gap between injections of no more than 6 months plus 8 weeks), the total number of injections received by each patient, changes in BMD in persistent patients, and the incidence of serious adverse events (SAEs) and fractures. RESULTS: Among 935 enrolled patients, 24-month persistence was 58% (50% in US patients and 75% in Canadian patients). A majority of patients received at least four injections over the observation period (62% of US patients and 81% of Canadian patients). Among patients who were persistent at 24 months and who had a baseline, 12-month, and 24-month DXA scan, mean BMD increased from baseline to 24 months by 7.8% at the lumbar spine and 2.1% at the femoral neck. SAEs and fractures were reported for 122 (13.0%) patients and 54 (5.8%) patients, respectively. CONCLUSIONS: Persistence with denosumab for 24 months yields improvement in BMD among postmenopausal women with osteoporosis treated in routine clinical practice in the USA and Canada.

An evaluation of mini-laparotomy cholecystectomy in the laparoscopic era: a rural experience.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the gold standard for the management of symptomatic cholelithiasis and complications of gallstone disease. Mini laparotomy cholecystectomy (MOC) may be a more appropriate option in the resource constrained rural setting due to its widespread applicability and comparable outcome with LC. The study aimed to provide an epidemiological analysis of gallstone disease in the rural population and to evaluate the outcome of MOC in a rural hospital. METHOD: A retrospective chart analysis of 248 patients undergoing cholecystectomy in a rural regional referral hospital in KwaZulu-Natal from January 2009 to December 2013 was undertaken. RESULTS: Of the 248 patients, the majority were females (n = 211, [85%]). The most frequent indications for cholecystectomy included: biliary colic (n = 115, [46.3%]); acute cholecystitis (n = 80, [32.3%]); gallstone pancreatitis (n = 27, [10.8%]). Forty cases (16.1%) were converted to open cholecystectomy (OC). The median operative time was 40 minutes (range18-57). Twenty-three morbidities (9.3%) occurred including: bile leaks (n = 6, [2.4%]); bleeding from drain site (n = 1, [0.4%]), incisional hernia (n = 8 [3.2%]) and wound sepsis (n = 8 [3.2%]). The median length of hospital stay in patients who underwent MOC was 48 hours (range: 24-72 hours) and the median time to return to work was 10 days (range: 4-14 days). There was one mortality in the entire cohort. CONCLUSION: MOC is a safe and feasible operation for symptomatic cholelithiasis when cholecystectomy is indicated. The low operative morbidity and mortality in the context of a high risk patient profile and complicated gallstone disease makes this procedure an alternative to LC where LC is inaccessible.

An evaluation of mini-laparotomy cholecystectomy in the laparoscopic era: a rural experience

Background: Laparoscopic cholecystectomy (LC) is the gold standard for the management of symptomatic cholelithiasis and complications of gallstone disease. Mini laparotomy cholecystectomy (MOC) may be a more appropriate option in the resource constrained rural setting due to its widespread applicability and comparable outcome with LC. The study aimed toprovide an epidemiological analysis of gallstone disease in the rural population and to evaluate the outcome of MOC in a rural hospital.Methods: A retrospective chart analysis of 248 patients undergoing cholecystectomy in a rural regional referral hospital in KwaZulu-Natal from January 2009 to December 2013 was undertaken.Results: Of the 248 patients, the majority were females (n = 211, [85%]). The most frequent indications for cholecystectomy included: biliary colic (n = 115, [46.3%]); acute cholecystitis (n = 80, [32.3%]); gallstone pancreatitis (n = 27, [10.8%]). Forty cases (16.1%) were converted to open cholecystectomy (OC). The median operative time was 40 minutes (range18­57). Twenty-three morbidities (9.3%) occurred including: bile leaks (n = 6, [2.4%]); bleeding from drain site (n = 1, [0.4%]), incisional hernia (n = 8 [3.2%]) and wound sepsis (n = 8 [3.2%]). The median length of hospital stay in patients who underwent MOC was 48 hours (range: 24­72 hours) and the median time to return to work was 10 days (range: 4­14 days). There was one mortality in the entire cohort.Conclusion: MOC is a safe and feasible operation for symptomatic cholelithiasis when cholecystectomy is indicated. The low operative morbidity and mortality in the context of a high risk patient profile and complicated gallstone disease makes this procedure an alternative to LC where LC is inaccessible

Illuminating gravitational waves: A concordant picture of photons from a neutron star merger.

Merging neutron stars offer an excellent laboratory for simultaneously studying strong-field gravity and matter in extreme environments. We establish the physical association of an electromagnetic counterpart (EM170817) with gravitational waves (GW170817) detected from merging neutron stars. By synthesizing a panchromatic data set, we demonstrate that merging neutron stars are a long-sought production site forging heavy elements by r-process nucleosynthesis. The weak gamma rays seen in EM170817 are dissimilar to classical short gamma-ray bursts with ultrarelativistic jets. Instead, we suggest that breakout of a wide-angle, mildly relativistic cocoon engulfing the jet explains the low-luminosity gamma rays, the high-luminosity ultraviolet-optical-infrared, and the delayed radio and x-ray emission. We posit that all neutron star mergers may lead to a wide-angle cocoon breakout, sometimes accompanied by a successful jet and sometimes by a choked jet.

Predictive modeling of respiratory tumor motion for real-time prediction of baseline shifts.

Baseline shifts in respiratory patterns can result in significant spatiotemporal changes in patient anatomy (compared to that captured during simulation), in turn, causing geometric and dosimetric errors in the administration of thoracic and abdominal radiotherapy. We propose predictive modeling of the tumor motion trajectories for predicting a baseline shift ahead of its occurrence. The key idea is to use the features of the tumor motion trajectory over a 1 min window, and predict the occurrence of a baseline shift in the 5 s that immediately follow (lookahead window). In this study, we explored a preliminary trend-based analysis with multi-class annotations as well as a more focused binary classification analysis. In both analyses, a number of different inter-fraction and intra-fraction training strategies were studied, both offline as well as online, along with data sufficiency and skew compensation for class imbalances. The performance of different training strategies were compared across multiple machine learning classification algorithms, including nearest neighbor, Naïve Bayes, linear discriminant and ensemble Adaboost. The prediction performance is evaluated using metrics such as accuracy, precision, recall and the area under the curve (AUC) for repeater operating characteristics curve. The key results of the trend-based analysis indicate that (i) intra-fraction training strategies achieve highest prediction accuracies (90.5-91.4%); (ii) the predictive modeling yields lowest accuracies (50-60%) when the training data does not include any information from the test patient; (iii) the prediction latencies are as low as a few hundred milliseconds, and thus conducive for real-time prediction. The binary classification performance is promising, indicated by high AUCs (0.96-0.98). It also confirms the utility of prior data from previous patients, and also the necessity of training the classifier on some initial data from the new patient for reasonable prediction performance. The ability to predict a baseline shift with a sufficient look-ahead window will enable clinical systems or even human users to hold the treatment beam in such situations, thereby reducing the probability of serious geometric and dosimetric errors.

Glucocorticoid exposure and fracture risk in patients with new-onset rheumatoid arthritis.

Retrospective claims analysis indicated that high levels of daily and cumulative doses of systemic glucocorticoids were associated with elevated fracture risk in a large cohort of new RA patients under age 65. Heightened risk began to decline within months of discontinuation. Findings were similar among patients age <50 years. INTRODUCTION: We evaluated the impact of systemic glucocorticoid exposure on fracture risk among relatively young patients with new-onset rheumatoid arthritis (RA). METHODS: Using administrative data, we identified 42,127 RA patients diagnosed January 1, 2005-December 31, 2012, age 18-64 years, with benefits coverage for ≥12 months before RA diagnosis. Follow-up extended to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IR) were stratified by glucocorticoid exposure expressed as prednisone equivalent doses. Cox's proportional hazards models estimated fracture risk adjusted for demographics and baseline clinical characteristics to assess dose-response relationships with current (daily) and prior (cumulative) dose, and by time since discontinuation. RESULTS: Most patients (85 %) had glucocorticoid exposure. Exposed and unexposed patients were demographically similar (74 % female; mean age 49.7 and 48.8 years); 1 % had prior fracture. Fracture IRs (95 % confidence intervals) were 5 to 9 per 1000 person-years at doses <15 mg/day, 16.0 (11.0, 22.6) at doses ≥15 mg/day, and 13.4 (10.7, 16.7) at cumulative doses ≥5400 mg. Adjusted fracture risk was approximately 2-fold higher at highest dose levels compared with 0 mg/day current daily dose and <675 mg cumulative dose, respectively. Fracture risk was 29 % lower at 60-182 days post-discontinuation compared with ongoing use and was similar to unexposed patients by 12 months. Findings were similar among patients age <50 years. CONCLUSIONS: Among younger, new-onset RA patients, fracture risk was significantly elevated at high levels of daily and cumulative dose, and was similar to unexposed patients by 12 months post-discontinuation.

Interplay Between Inflammation and Hemostasis in Patients with Coronary Artery Disease.

Coronary artery disease (CAD) is a global epidemic currently. This study was planned to evaluate markers of inflammation and hemostasis and their possible association, if any, in patients with CAD. The study was carried out in 60 patients with acute myocardial infarction (AMI) and 60 age and gender matched controls. The following parameters were assayed in all study subjects-inflammatory-interleukin (IL)-10, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, fibrinogen; hemostatic-fibrinogen, fibrin D-dimer and a novel risk factor-homocysteine. Inflammatory markers (hs-CRP, TNF-α and IL-10), fibrinogen, fibrin D-dimer and homocysteine levels were significantly higher in the patients with AMI, as compared with controls. A positive correlation was observed between D-dimer and the inflammatory markers-hs-CRP and TNF-α. Upon multivariate analysis, TNF-α emerged as the best determinant of CAD in our study. Our results indicate that there is a possible interplay of inflammation and hemostasis in CAD, underlining their synergistic role in the pathogenesis of CAD.

Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study.

UNLABELLED: To determine persistence with subcutaneous denosumab every 6 months in women being treated for osteoporosis, we conducted a single-arm prospective, observational study in the United States and Canada. Among 935 patients enrolled, 12-month persistence was 82%, with 66 patients (7%) reporting serious adverse events and 19 patients (2%) reporting fractures. INTRODUCTION: Increased persistence with osteoporosis therapy is associated with reduced fracture risk. Denosumab reduced fracture risk in clinical trials; persistence in community settings is undetermined. This study evaluates persistence with denosumab in community practice in the United States (US) and Canada. METHODS: In a 24-month multicenter, prospective, single-arm, observational study, women being treated for osteoporosis were enrolled ≤4 weeks after the first subcutaneous injection of denosumab. For this 12-month prespecified interim analysis, endpoints include persistence (one injection at study entry and another within 6 months + 8 weeks), attributes associated with persistence (univariate analysis), and serious adverse events (SAEs). RESULTS: Among 935 patients (mean age 71 years), mean baseline T-scores were -2.18 (femoral neck) and -2.00 (lumbar spine); 50% of patients had experienced osteoporotic fracture(s). At 12 months, 82 % of patients were persistent with denosumab. Baseline factors significantly (p < 0.05) associated with higher persistence included use of osteoporosis medications >5 years previously, lumbar spine T-score > -2.5, and treatment by female physicians (US). Lower persistence was associated (p < 0.05) with psychiatric diagnoses including depression, southern US residence, being divorced, separated, or widowed (US), and prior hip fracture (Canada). SAEs were reported in 66 patients (7%); no SAEs of osteonecrosis of the jaw, atypical femoral fracture, fracture healing complications, hypocalcemia, eczema, or hypersensitivity were reported. Nineteen patients (2%) reported osteoporotic fractures. CONCLUSIONS: The 12-month persistence observed in this single-arm open-label study of US and Canadian community practice extends the evidence regarding denosumab's potential role in reducing fracture risk in postmenopausal women with osteoporosis.

Risk factors for fracture among current, persistent users of bisphosphonates.

SUMMARY: Bisphosphonate therapy reduces fracture risk but does not eliminate fracture occurrence. We determined the fracture incidence and risk factors for fractures among 14,674 bisphosphonate users in a community setting. Bisphosphonate users remained at risk of fracture, and additional measures to prevent fractures in these patients would be beneficial. INTRODUCTION: Bisphosphonate therapy reduces but does not eliminate fracture occurrence. The incidence of fracture and risk factors for fractures among persistent, current users of bisphosphonates in a community setting have not been well studied. METHODS: We conducted a retrospective cohort study of 14,674 bisphosphonate users in a health maintenance organization. Patients were followed until a 3-month gap in therapy, creating a pool of highly compliant [mean medication possession ratio (MPR) of 94%] current users. We used Cox proportional hazards models to identify risk factors for fractures among these persistent, current users. RESULTS: There were 867 fractures over the period of observation or 3.7 fractures per 100 users per year. Older patients who take multiple medications, have lower bone mineral density, have a history of prior fracture, and suffer from particular comorbidities (i.e., dementia, chronic kidney disease, and rheumatoid arthritis) are at higher risk of fracture while taking bisphosphonates. CONCLUSION: Persistent, current bisphosphonate users remain at risk of fracture, and additional measures to prevent fractures in these patients would be of benefit.

Antioxidative activity of different parts of the plant Lepidium sativum Linn.

Lepidium sativum Linn. has been used in traditional and folklore medicine for the treatment of bronchial asthma, diabetes, local and rheumatic pain. An ethanolic extract of cress (L. sativum L.) shoot, leaf, stem and seed has been studied for antioxidative active against 1,1-diphenyl-2-picrylhydrazyl (DPPH), total glutathione S-transferase assay, reduced glutathione activity, reducing power (Fe3+-Fe2+ Transformation Ability), and ascorbic acid is also estimated. The percentage yields of free radical scavenging activity (DPPH) obtained for different ethanolic extracts of L. sativum. Supreme scavenging activity was detected in shoot (12.19 ± 02%) and least in stem (2.69 ± 05%). The activity of total glutathione S-transferase enzyme was found to be more in seed (9600 ± 56.3 µg/ml) than other plant parts. The reduced glutathione content of the ethanolic extracts of L. sativum was found to be more in leaf (9 ± 0.2 µg/ml). In the reducing power assay, ethanolic extracts gives the optical density in increasing concentration in all plant parts it shows that it has the reducing ability of Fe3+-Fe2+. Presence of vitamin C was tested. It was found that the shoot extract has highest amount of vitamin C. The results of present data were shown that the ethanolic extract of L. sativum L. plant parts have contributed high potential in vitro antioxidant activity.

Role of TRPC1 and TRPC3 channels in contraction and relaxation of mouse thoracic aorta.

BACKGROUND/AIMS: Canonical transient receptor potential (TRPC) channels modulate membrane potential and intracellular Ca(2+). We examined the role of TRPC1 and TRPC3 channels in vasocontraction and relaxation in mouse aorta. METHODS: Vasocontraction and relaxation of aorta from wild-type (WT), TRPC1 KO and TRPC3 knockout (KO) mice were measured for phenylephrine (Phe) and carbachol (CCh). Intracellular Ca(2+) was measured in primary aorta endothelial cells (EC) and whole cell K(+) current in freshly isolated smooth muscle cells (SMC). RESULTS AND CONCLUSION: TRPC1 KO aorta showed increased vasocontraction to Phe compared to WT and TRPC3 KO aorta due to diminished role of BK(Ca) channels. BK(Ca) mRNA (aorta) and whole cell current (SMC) were reduced versus WT. Contraction in WT aorta was increased to TRPC1 KO level by BK(Ca) channel inhibition. Relaxation to CCh was reduced in TRPC1 KO and TRPC3 KO aortas with concomitant reduction in EC Ca(2+) response. Pyr3 (TRPC3 blocker) reduced the Ca(2+) response to CCh in EC from WT, but not TRPC3 KO mice. In summary, TRPC1 attenuates receptor-mediated contraction through activation and/or expression of SMC BK(Ca) channels while TRPC3 does not contribute to receptor-mediated constriction. Both TRPC1 and TRPC3 participate in EC Ca(2+) influx and vasorelaxation of aorta.

Formulation of multiple choice questions as a revision exercise at the end of a teaching module in biochemistry.

The graduate medical students often get less opportunity for clarifying their doubts and to reinforce their concepts after lecture classes. Assessment of the effect of MCQ preparation by graduate medical students as a revision exercise on the topic "Mineral metabolism." At the end of regular teaching module on the topic "Mineral metabolism," graduate medical students were asked to prepare the stems of 15 MCQs based on the four discriminators given for each. They were told that one of the discriminators could be the answer for the MCQ and the remaining three could be the distracters. They were further guided in their task by providing few key word(s) in the stem of the expected MCQ. In the first phase of the exercise, the students attempted the MCQ preparation individually without peer consultation. In the second phase, the students participated in small group discussion to formulate the best MCQs of the group. The effects on low, medium, and high achievers were evaluated by pre and post-tests with the same set of MCQs. Both the individual endeavor in Phase 1 and small group discussion in Phase 2 for the formulation of MCQs significantly contributed to the gain from the exercise. The gains from the individual task and from small group discussion were equal among the different categories of students. Both phases of the exercise were equally beneficial for the low, medium, and high achievers. The high and medium achievers retained the gain from the exercise even after 1 week of the exercise whereas the low achievers could not retain the gain completely. Formulation of MCQs is an effective and useful unconventional revision exercise in Biochemistry for graduate medical students.