Gender differential and implications in the epidemiology of stress fractures among cadets of Indian Armed Forces.

BACKGROUND: Most studies on stress fractures in India have been carried out among recruits as against officer trainees and limited to males. With the continuous induction of women in the Armed Forces, it was decided to carry out a study among officer trainees of the three services and compare the epidemiology among genders. METHODS: A prospective study was carried out in 2011-2012 at Training Institutes of the three services where male and female cadets train together. Baseline data was collected for all trainees who joined the academy during the study period. All cadets were followed up for development of stress fractures for which details were taken. Additional information was taken from the Training Institute. RESULTS: A total of 3220 cadets (2612 male and 608 female cadets) were included in the study. Overall 276 cadets were observed to have stress fractures during training - making an incidence of 6.9% for male cadets and 15.8% for female cadets. Females were found to have a significantly higher incidence of stress fractures. Further the distribution and onset of stress fractures in females was observed to be distinct from males. CONCLUSION: The significant gender differential observed in the study indicates differential role of intrinsic and extrinsic risk factors in the causation of stress fractures among male and female. Special consideration needs to be given to these while planning and implementing measures for prevention. Further studies may be carried out on subject and on the effect of interventions in stress fracture prevention.

Conformational Sub-states and Populations in Enzyme Catalysis.

Enzyme function involves substrate and cofactor binding, precise positioning of reactants in the active site, chemical turnover, and release of products. In addition to formation of crucial structural interactions between enzyme and substrate(s), coordinated motions within the enzyme-substrate complex allow reaction to proceed at a much faster rate, compared to the reaction in solution and in the absence of enzyme. An increasing number of enzyme systems show the presence of conserved protein motions that are important for function. A wide variety of motions are naturally sampled (over femtosecond to millisecond time-scales) as the enzyme complex moves along the energetic landscape, driven by temperature and dynamical events from the surrounding environment. Areas of low energy along the landscape form conformational sub-states, which show higher conformational populations than surrounding areas. A small number of these protein conformational sub-states contain functionally important structural and dynamical features, which assist the enzyme mechanism along the catalytic cycle. Identification and characterization of these higher-energy (also called excited) sub-states and the associated populations are challenging, as these sub-states are very short-lived and therefore rarely populated. Specialized techniques based on computer simulations, theoretical modeling, and nuclear magnetic resonance have been developed for quantitative characterization of these sub-states and populations. This chapter discusses these techniques and provides examples of their applications to enzyme systems.

A Case Presenting with Splenic Infarct Diagnosed as Primary Bone Marrow CD5 Positive DLBCL: A Clinicopathological Correlation.

De novo CD5+ Diffuse large B cell lymphoma (DLBCL) is a rare and aggressive subtype of DLBCL. It is a distinct clinicopathologic entity with complex molecular profile and poor prognosis. A 59 year old female presented with pyrexia of unknown origin since 1 month. On examination, there was severe pallor, hepatosplenomegaly and no palpable lymphadenopathy. Complete blood count revealed bicytopenia with normal total leucocyte count. Liver and renal function tests were normal. Ultrasonography abdomen revealed splenic enlargement with two focal lesions attributed to either splenic abscess or infarcts. Patient was being managed as splenic infarct but continued to have bicytopenia. Further investigation showed elevated serum ferritin, triglycerides and LDH. With a clinical suspicion of infection and haemophagocytic lymphohistiocytosis bone marrow aspiration (BMA) and biopsy (BMBx) was done. BMA showed extensive haemophagocytosis and ~7.4 % large lymphoma-like cells. On this basis PET-CT was suggested which showed enlarged spleen with diffuse uptake. BMBx showed nodular and intrasinusoidal collection of abnormal lymphoid cells. On immunohistochemistry, these cells were positive for CD20, CD5, MUM1, BCL-2, BCL-6 and negative for CD3, CD10 and CD23. CD34 highlighted focal intrasinusoidal pattern. The complete clinicopathological profile suggested the diagnosis of de novo CD5+ DLBCL, with primary hepatosplenic pattern of involvement. CD5+ DLBCL presenting as splenic infarct is very rare. This case was unusual as the diagnosis of a primary aggressive lymphoma with haemophagocytosis was established in a patient who presented with fever and splenic infarct without lymphadenopathy. This indicates the importance of good morphological assessment of a bone marrow aspirate and biopsy to make a correct diagnosis.

Gastric Mucormycosis with Hemolytic Uremic Syndrome.

Mucormycosis, is an emerging fungal infection in immunocompromised and diabetic individuals, usually affects rhino-orbito-cerebral, cutaneous and pulmonary regions. But mucormycosis in immunocompetent environment is rare and occurrence of gastric mucormycosis is unusual. We report a case of 19 year old female, with no pre-existing co-morbidities, presented with fever, dysentery, vomiting, and melena for 4 days. On evaluation she was found to have pancytopenia, acute kidney injury, hemolytic anemia, coagulopathy and hepatic derangement and treated with hemodialysis, plasmapheresis along with antibiotics and packed cell RBC transfusion. Upper gastrointestinal endoscopy revealed presence of extensive esophageal and gastric ulcer. In view of persistent bleeding despite endoscopic sclerotherapy, repetition of upper gastrointestinal endoscopy and CT abdomen with oral contrast was done, which revealed perforated gastric ulcer. Exploratory laparotomy and excision of ulcer was done. The biopsy of gastric ulcer had shown the presence of granulomatous necrotic areas positive for mucormycosis. Then she was managed with amphotericin-B, posoconazole with which she improved.

A multicentre, multinational, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of gemigliptin (LC15-0444) in patients with type 2 diabetes.

AIM: This study was designed to assess the efficacy and safety of the dipeptidyl peptidase IV inhibitor gemigliptin (LC15-0444) 50 mg versus placebo in patients with type 2 diabetes. METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled phase III trial in 182 patients (74 from Korea and 108 from India) with type 2 diabetes. After an initial 2 weeks of a diet and exercise programme followed by 2 weeks of a single-blind placebo run-in period, eligible patients were randomized to gemigliptin 50 mg or placebo, receiving the assigned treatment for 24 weeks. HbA1c and fasting plasma glucose (FPG) were measured periodically, and oral glucose tolerance test was performed at baseline and weeks 12 and 24. RESULTS: At week 24, gemigliptin treatment led to significant reductions in HbA1c measurements compared to placebo (adjust mean after subtracting the placebo effect size: -0.71%, 95% confidence interval: -1.04 to -0.37%). A significantly greater proportion of patients achieved an HbA1c <7% with gemigliptin than with placebo. The placebo-subtracted FPG change from baseline at week 24 was -19.80 mg/dl. The overall incidence rates for adverse events were similar in the gemigliptin and placebo groups. CONCLUSIONS: This study showed the efficacy and safety of gemigliptin 50 mg administered once daily as a monotherapy for type 2 diabetes patients.

Liver metastases, a rare cause of portal hypertension and stoma bleeding. Brief review of literature.

INTRODUCTION: Portal hypertension is an unusual complication of liver metastases, which is frequently occurring in malignant disease. Portal hypertension may cause oesophageal varices and also stoma varices (colostomy and ileostomy). Oesophageal varices and bleeding from these varices have been frequently reported in literature. Stomal varices have also been reported in literature mostly associated with liver cirrhosis. These stomal varices lead to the massive bleeding causing morbidity and mortality. Portal hypertension is a pathological increase in portal pressure gradient (the difference between pressure in the portal and inferior vena cava veins). It is either due to an increase in portal blood flow or an increase in vascular resistance or combination of both. In liver cirrhosis, the primary factor leading to portal hypertension is increase in portal blood flow resistance and later on development of increased portal blood flow. It has been postulated that in liver metastasis the increase in portal flow resistance occurs at any site within portal venous system as a consequence of mechanical architectural disturbance. PRESENTATION OF CASE: We report a case of a 64 year old gentleman who developed portal hypertension due to secondary metastases from colorectal cancer. He subsequently developed bleeding varices in his end colostomy. DISCUSSION: We believe that the combination of extensive metastases and chemotherapy induced portal hypertension in our patient. CONCLUSION: Our case and other literature review highlight that the recurrent bleeding stoma associated with colorectal cancer should be investigated for portal hypertension.

Former smoking is a risk factor for chronic kidney disease after lung transplantation.

Chronic kidney disease (CKD) is a common complication after lung transplantation (LTx). Smoking is a risk factor for many diseases, including CKD. Smoking cessation for >6 months is required for LTx enlistment. However, the impact of smoking history on CKD development after LTx remains unclear. We investigated the effect of former smoking on CKD and mortality after LTx. CKD was based on glomerular filtration rate (GFR) ((125) I-iothalamate measurements). GFR was measured before and repeatedly after LTx. One hundred thirty-four patients never smoked and 192 patients previously smoked for a median of 17.5 pack years. At 5 years after LTx, overall cumulative incidences of CKD-III, CKD-IV and death were 68.5%, 16.3% and 34.6%, respectively. Compared to never smokers, former smokers had a higher risk for CKD-III (hazard ratio [HR] 95% confidence interval [95%CI]= 1.69 [1.27-2.24]) and IV (HR = 1.90 [1.11-3.27]), but not for mortality (HR = 0.99 [0.71-1.38]). Adjustment for potential confounders did not change results. Thus, despite cessation, smoking history remained a risk factor for CKD in LTx recipients. Considering the increasing acceptance for LTx of older recipients with lower baseline renal function and an extensive smoking history, our data suggest that the problem of post-LTx CKD may increase in the future.

Is there an effect of perioperative blood pressure on intraoperative complications during phacoemulsification surgery under local anaesthesia?

PURPOSE: The practice of deferring phacoemulsification procedure on recording raised blood pressure (BP) in the immediate perioperative period is based on the perception of increased intraoperative risk. The significance of perioperative BP recordings on the surgical complications during phacoemulsification procedure was evaluated. SETTING: Hairmyres Hospitals, Lanarkshire Acute Hospitals NHS Trust. PATIENTS AND METHODS: Patients were classified as hypertensive on the basis of the British Hypertension Society Guidelines. BP recordings during preoperative assessment, admission, and 1-hour postoperatively were recorded in 734 hypertensives and 740 normotensives undergoing phacoemulsification procedure. In addition, BP recordings in the holding area before giving local anaesthesia were noted in the 734 hypertensives. Patient's peri- and intraoperative complications during the procedure were noted. RESULTS: The mean age was 72+/-10.5 years and 74+/-11.6 years among the hypertensives and normotensives. There was a significant increase in the number of hypertensives who developed isolated systolic hypertension in the holding area (95% confidence interval=2.82, P<0.001) where the mean BP was 171.38/78.31 mm Hg (+/-30.55/16.29). A total of 21 hypertensives and 18 normotensives developed intraoperative complications during the phacoemulsification procedure. There was no significant difference (P=0.41) in the intraoperative complications between the hypertensives and normotensives. CONCLUSION: Perioperative increase in BP noted in the holding area among hypertensives did not increase the risk of surgical complications during phacoemulsification procedure when compared with normotensives. We recommend that BP should not be routinely measured in the holding area before phacoemulsification surgery under local anaesthesia.

The effect of socio-economic deprivation on severity of glaucoma at presentation.

OBJECTIVE: To evaluate the influence of socio-economic factors on severity of glaucoma at presentation METHODS: All newly diagnosed glaucoma patients at the University Hospitals-NHS, Aberdeen and South Glasgow University Hospitals-NHS, in 2006, were included. Glaucoma was severe at presentation if there was a repeatable visual-field loss with a mean deviation index greater than 12 dB in the Humphreys visual fields test or an absolute paracentral scotoma within the central 5 degrees of the visual fields. Home address was used to determine the Scottish Index of Multiple Deprivation (SIMD) rank. The SIMD rank, demographics and severity of glaucoma at presentation were investigated using general linear modelling. RESULTS: There were 48 patients with severe glaucoma and 74 patients with non-severe glaucoma. In four, the severity could not be determined. Severity of glaucoma at presentation was significantly associated with SIMD rank, being most severe in patients from areas with the lowest ranks (p = 0.026). Age was a significant factor (p = 0.024), with severe glaucoma being more common in elderly patients. CONCLUSIONS: Age and socio-economic deprivation were associated with severity of glaucoma at presentation, with patients from areas of higher socio-economic deprivation presenting with more advanced glaucoma.

Ulcer healing properties of ethanolic extract of Eugenia jambolana seed in diabetic rats: study on gastric mucosal defensive factors.

Diabetes has been reported to cause an increase in offensive and decrease in defensive gastric mucosal factors, the imbalance of which can cause ulceration and delay the ulcer healing. Eugenia jambolana has been documented to have both antidiabetic and antiulcer activities. The present study evaluates the effects of ethanolic extract of E. jambolana on gastric ulcer healing and on rat gastric mucosal defensive factors in gastric ulcer with co-occurring diabetes. E. jambolana extract was administered orally in the dose of 200 mg/kg once daily for 10 days. E. jambolana extract increased mucin secretion, mucosal glycoprotein and glutathione levels and decreased the lipid peroxidation in gastric mucosa of diabetic rats. Its treatment also reversed the decrease in life span of gastric mucosal cells as indicated by decreased cell shedding in the gastric juice but found to have no effect on cell proliferation, indicating enhanced defensive status. E. jambolana extract was effective in reversing the delayed healing of gastric ulcer in diabetic rats near to the normal level. E. jambolana showed better ulcer healing effect than glibenclamide, because of its both antihyperglycemic and mucosal defensive actions. It could thus, be a better choice for treating gastric ulcers co-occurring with diabetes.

Effect of methanolic extract of Pongamia pinnata Linn seed on gastro-duodenal ulceration and mucosal offensive and defensive factors in rats.

Pongamia pinnata has been advocated in Ayurveda for the treatment of various inflammatory conditions and dyspepsia. The present work includes initial phytochemical screening and study of ulcer protective and healing effects of methanolic extract of seeds of P. pinnata (PPSM) in rats. Phytochemical tests indicated the presence of flavonoids in PPSM. PPSM when administered orally (po) showed dose-dependent (12.5-50 mg/kg for 5 days) ulcer protective effects against gastric ulcer induced by 2 h cold restraint stress. Optimal effective dose of PPSM (25 mg/kg) showed antiulcerogenic activity against acute gastric ulcers (GU) induced by pylorus ligation and aspirin and duodenal ulcer induced by cysteamine but not against ethanol-induced GU. It healed chronic gastric ulcer induced by acetic acid when given for 5 and 10 days. Further, its effects were studied on various parameters of gastric offensive acid-pepsin secretion, lipid peroxidation (LPO) and nitric oxide (NO) and defensive mucosal factors like mucin secretion and mucosal cell shedding, glycoproteins, proliferation and antioxidants; catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) levels. PPSM tended to decrease acid output and increased mucin secretion and mucosal glycoproteins, while it decreased gastric mucosal cell shedding without any effect on cell proliferation. PPSM significantly reversed the increase in gastric mucosal LPO, NO and SOD levels caused by CRS near to the normal level while it tended to increase CAT and GSH level decreased by CRS and ethanol respectively. Thus, the ulcer protective effects of PPSM may be attributed to the presence of flavonoids and the actions may be due to its effects both on mucosal offensive and defensive factors.

Penetration of topical and subconjunctival corticosteroids into human aqueous humour and its therapeutic significance.

Topical and subconjunctival corticosteroids are some of the most effective and compelling treatment options in ocular inflammatory diseases. A systematic review of literature indexed by Ovid MEDLINE & EMBASE was performed up to December 2008. There are few studies on their aqueous penetration in human subjects. This review article discusses the penetration of different ocular corticosteroids into human aqueous humour along with the therapeutic implications on management of ocular surface diseases, immune-related corneal diseases, anterior uveitis and postoperative anti-inflammatory use. In the context of the paucity of well-constructed, prospective clinical trials comparing the efficacy of different corticosteroids, it provides guiding principles for the use of topical corticosteroids. Dexamethasone alcohol 0.1% and prednisolone acetate 1% are potent corticosteroids, but the latter achieves the highest aqueous concentration within 2 h and maintains higher levels for 24 h. Subconjunctival corticosteroids provide very high concentrations in the aqueous which maintain higher concentrations for longer periods.

Evaluation of wound healing activity of extracts of plantain banana (Musa sapientum var. paradisiaca) in rats.

Plantain banana (M. sapientum var. paradisiaca, MS) has been shown to possess ulcer healing activity. The present work with plantain banana was undertaken with the premise that the drug promoting ulcer healing could have effect on wound healing also. Wound healing activity of MS was studied in terms of (i) percent wound contraction, epithelization period and scar area; (ii) wound breaking strength and (iii) on granulation tissue antioxidant status [estimation of superoxide dismutase (SOD) and reduced glutathione (GSH), free radical (lipid peroxidation, an indicator of tissue damage) and connective tissue formation and maturation (hexuronic acid, hydroxyproline and hexosamine levels)] in excision, incision and dead space wound models respectively. The rats were given graded doses (50-200 mg/kg/day) of aqueous (MSW) and methanolic (MSE) extracts of MS orally for a period of 10-21 days depending upon the type of study. Both extracts (100 mg/kg) when studied for incision and dead space wounds parameters, increased wound breaking strength and levels of hydroxyproline, hexuronic acid, hexosamine, superoxide dismutase, reduced glutathione in the granulation tissue and decreased percentage of wound area, scar area and lipid peroxidation when compared with the control group. Both the extracts showed good safety profile. Plantain banana thus, favoured wound healing which could be due to its antioxidant effect and on various wound healing biochemical parameters.

Antidiabetic and antiulcer effects of extract of Eugenia jambolana seed in mild diabetic rats: study on gastric mucosal offensive acid-pepsin secretion.

Diabetes has been reported to increase propensity to peptic ulceration through its effect both on offensive and defensive mucosal factors. Seeds of Eugenia jambolana (EJ) have been reported to have both antidiabetic as well as ulcer protective effects. The present study evaluates the antidiabetic effects of ethanolic extract of dried seed kernel of Eugenia jambolana (EJE) and its comparative effect on gastric ulceration and acid-pepsin secretion with standard antisecretory FL-blocker. Ranitidine and antidiabetic glibenclamide with a premise that Eugenia jambolana may show better ulcer healing effects by promoting defensive or reducing offensive mucosal factors in mild diabetes (MD) rats. MD was produced in adult rats by administration of streptozotocin (45 mg/kg, ip). EJE was given orally in the doses of 100-400 mg/kg for 10 days and in the dose of 200 mg/kg for 30 days respectively to study its dose- and time-dependent effects on various diabetic parameters like blood glucose, serum cholesterol and triglycerides, insulin level and glycosylated hemoglobin. For ulcer protective and gastric secretion studies, EJE (200 mg/kg) was given orally for 10 days against 2 h cold restraint stress (CRS)-, 4 h pylorus ligation (PL), aspirin (ASP, 200 mg/kg, 4 h)--and 95% ethanol (EtOH, 1 ml/200 g, 1 h)-induced gastric ulcers and offensive acid-pepsin secretion after 4 h PL with co-occurring MD in rats. EJE showed dose-dependent decrease in blood glucose level in MD rats. Blood glucose level remained stable in mild diabetic rats from 3rd day onwards after streptozotocin administration (taken as 1st day for treatment) and EJE (200 mg/kg) showed anti-hyperglycemic effect on 10th day of its administration. Further, EJE in the above dose also decreased cholesterol level with little or no effect on triglycerides level and reversed the decrease and increase in insulin and glycosylated hemoglobin level near to the normal level as observed alter 30 days treatment in MD rats. MD rats exhibited an increased propensity to gastric ulceration induced by CRS, ASP, EtOH and PL and caused increase in acid-pepsin secretion. EJE was not only effective in reversing the increased propensity to ulceration in diabetic rats but also decreased the acid-pepsin output better than glibenclamide. The ulcer protective effect of Eugenia jambolana seems to be due to its antidiabetic and gastric antisecretory effects.

Metabolic syndrome.

The Metabolic syndrome is a widely prevalent and multi-factorial disorder. The syndrome has been given several names, including- the metabolic syndrome, the insulin resistance syndrome, the plurimetabolic syndrome, and the deadly quartet. With the formulation of NCEP/ATP III guidelines, some uniformity and standardization has occurred in the definition of metabolic syndrome and has been very useful for epidemiological purposes. The mechanisms underlying the metabolic syndrome are not fully known; however resistance to insulin stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors. The clinical relevance of the metabolic syndrome is related to its role in the development of cardiovascular disease. Management of the metabolic syndrome involves patient-education and intervention at various levels. Weight reduction is one of the main stays of treatment. In this article we comprehensively discuss this syndrome- the epidemiology, pathogenesis, clinical relevance and management. The need to do a comprehensive review of this particular syndrome has arisen in view of the ever increasing incidence of this entity. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population. Hardly any issue of any primary care medical journal can be opened without encountering an article on type 2 diabetes, dyslipidemia or hypertension. It is rare to see type 2 diabetes, dyslipidemia, obesity or hypertension in isolation. Insulin resistance and resulting hyperinsulinemia have been implicated in the development of glucose intolerance (and progression to type 2 diabetes), hypertriglyceridemia, hypertension, polycystic ovary syndrome, hypercoagulability and vascular inflammation, as well as the eventual development of atherosclerotic cardiovascular disease manifested as myocardial infarction, stroke and myriad end organ diseases. Conversely, treatment and consequent improvement of insulin resistance have been shown to result in better outcomes in virtually all of these conditions.

Coarse and reliable geometric alignment for protein docking.

We present an efficient algorithm for generating a small set of coarse alignments between interacting proteins using meaningful features on their surfaces. The proteins are treated as rigid bodies, but the results are more generally useful as the produced configurations can serve as input to local improvement algorithms that allow for protein flexibility. We apply our algorithm to a diverse set of protein complexes from the Protein Data Bank, demonstrating the effectivity of our algorithm, both for bound and for unbound protein docking problems.

Myelomatous pleural effusion.

Pleural effusions in multiple myeloma are relatively infrequent and more so myelomatous ones. We report a 66-year-old man who presented with multiple myeloma and a myelomatous right-sided pleural effusion. The diagnosis was made by repeated cytopathological pleural fluid examinations. The patient received one cycle of cyclophosphamide and methylprednisolone but despite therapy patient showed a downhill course. We reviewed the clinical features of this case and literature concerning multiple myeloma presenting as pleural effusion.