Genetic risk factors in patients with deep venous thrombosis, a retrospective case control study on Iranian population

Background: Venous thromboembolism (VTE) could be manifested as deep venous thrombosis (DVT) or pulmonary embolism (PE). DVT is usually the more common manifestation and is usually formation of a thrombus in the deep veins of lower extremities. DVT could occur without known underlying cause (idiopathic thrombosis) which could be a consequence of an inherited underlying risk factor or could be a consequence of provoking events, such as trauma, surgery or acute illness (provoked thrombosis). Our aim in this study was to assess the impact of some previously reported genetic risk factors including, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, plasminogen activator inhibitor-1(PAI-1) 4G/5G, prothrombin 20210 and FV Leiden on occurrence of DVT in a population of Iranian patients. Methods: This long-term study was conducted on 182 patients with DVT and also 250 age and sex matched healthy subjects as control group. The diagnosis of DVT was based on patient's history, clinical findings, D-dimer test, and confirmed by Doppler ultrasonography. After confirmation of DVT, both groups were assessed for the five mentioned mutations. The relationship between mutations and predisposition to DVT was calculated by using logistic regression and expressed as an OR with a 95 confidence interval (CI). Results: Our results revealed that FV Leiden (OR 6.7; 95 CI = 2.2 to 20.3; P = 0.001), MTHFR C677T (OR 6.0; 95 CI = 2.2 to 16.4; P < 0.001), MTHFR A1298C (OR 8.3; 95 CI = 4.4 to 15.8; P < 0.001), and PAI-1 4G/5G (OR 3.8; 95 CI = 2.1 to 7.2; P < 0.001) mutations were all significantly associated with an increased risk of DVT. Prothrombin 20210 was found in none of the patients and controls. Conclusion: Our findings suggest that genetic risk factors have a contributory role on occurrence of DVT. © 2015 Hosseini et al

Tactile Learning Within the Early Phase of Experimental Autoimmune Encephalomyelitis in Mice

The purpose of this study was to assess tactile learning in the early phase of experimental autoimmune encephalomyelitis (EAE), which was induced in C57BL/6 mice by subcutaneous injections on flank of myelin oligodendrocyte glycoprotein, MOG35-55 (250 µg per mouse). Tactile learning was assessed one week after EAE induction using the novel object recognition test (NORT) in a dark room. The procedure consisted of two phases. During the training phase (T1), the animals explored two similar objects; within the test phase (T2, occurring 4 h later) the mice explored one novel and one familiar object. On average, mice developed significant behavioral disabilities related to EAE 13.2 ± 1.9 days following immunization. In the EAE group, the locomotor activity level (assessed by measuring the distance travelled) in the T1 and T2 phases did not differ significantly, as compared to the related phases in the control group (P > 0.05). Within phase T1, no reliable differences were found for the frequency (number) of visits to the sample objects and for total exploration time between experimental groups. For phase T2, no difference was also found in the discrimination ratio when comparing the control group with the EAE group. Our study demonstrates that tactile learning in male mice may not be affected 7 days after immunization with MOG35-55 (i.e., within the early EAE phase).Розвиток експериментального аутоімунного енцефаломієліту (ЕАЕ) викликали у мишей за допомогою ін’єкцій мієлінового олігодендроцитарного глікопротеїну (MOG35- 55, 250 мкг на мишу). Здатність до тактильного навчання оцінювали через один тиждень після індукції ЕАЕ, використовуючи тест впізнавання нового об’єкта (NORT) у темному приміщенні. Процедура тестування складалася з двох фаз; протягом першої з них (T1) тварини обстежували два однакових об’єкта, а в перебігу другої фази (T2) миші обстежували один новий і один раніше обстежений об’єкти. Істотні поведінкові розлади, зумовлені ЕАЕ, розвивались у мишей в середньому через 13.2 ± 1.9 доби після імунізації. У групі ЕAЕ рівень локомоторної активності (оцінюваний за відстанню, котру тварини проходили в період обстеження) в межах фаз T1 та T2 не відрізнявся істотно від такого в контрольній групі (P > 0.05). У фазі T1 не спостерігалося істотних міжгрупових різниць частоти (кількості) відвідань тест-об’єктів та загального часу, який було витрачено на ознайомлення з ними. У межах фази T2 не виявлялося також достовірних різниць величин коефіцієнта дискримінації в контрольній та ЕAЕ-групах. Отже, наші тести показали, що, видимо, тактильне навчання мишей-самцівне піддається істотним змінам через сім діб після імунізації MOG35-55 (тобто в межах ранньої фази ЕAЕ)

Bilateral maxillary, sphenoid sinuses and lumbosacral spinal cord extramedullary relapse of CML following allogeneic stem cell transplant

Isolated extramedullary relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant is rare. There is a case report of a child who developed a granulocytic sarcoma of the maxillary and sphenoid sinuses and lumbosacral spinal cord mass 18 months after allogeneic bone marrow transplant for CML. He was presented with per orbital edema and neurological deficit of lower extremities and a mass lesion was found on spinal cord imaging. No evidence of hematologic relapse was identified at that time by bone marrow histology or cytogenetic. The patient died 1 month later with a picture of pneumonia, left ventricular dysfunction and a cardiopulmonary arrest on a presumed underlying sepsis with infectious etiology. Granulocytic sarcoma should be considered in the differential diagnosis of mass lesions presenting after allogeneic bone marrow transplantation for CML, even if there is no evidence of bone marrow involvement. © 2016, Tehran University of Medical Sciences (TUMS). All Rights Reserved

Expression of TRPV1 receptors increased in hippocampus following pentylenetetrazole-induced kindling in male rats

Background: The exact pathogenesis of epilepsy is not clear well. Recent studies showed the possible involvement of transient receptor potential vanilloid type 1 (TRPV1) receptors in this disease. Objectives: The aim of this study was to measure the expression of TRPV1 receptors in hippocampus following pentylenetetrazole (PTZ)-induced kindling in male rats. Materials and Methods: In this experimental study, 14 male Wistar rats were allocated into two groups of experimental and control (seven rats in each group). The kindling group received a subconvulsive dose of PTZ (35 mg/kg, intraperitoneally) every 48 hours for 15 sessions, while the control rats were injected with an equal dose of saline. At the end of the injections, rats were decapitated, and their brains were removed. TRPV1 receptor expression in hippocampus region was assessed by real-time polymerase chain reaction method. Results: The results of the current study showed that expressions of TRPV1 receptors were increased in hippocampus following PTZ-induced kindling in male rats. Conclusions: Since the expression of TRPV1 receptors increased in hippocampus of epileptic rats, the TRPV1 receptors may be good candidates for epilepsy treatment. � 2016, Tehran University of Medical Sciences

Effects of electrical stimulation of dorsal raphe nucleus on neuronal response properties of barrel cortex layer IV neurons following long-term sensory deprivation

Abstract: Objective To evaluate the effect of electrical stimulation of dorsal raphe nucleus (DRN) on response properties of layer IV barrel cortex neurons following long-term sensory deprivation. Methods: Male Wistar rats were divided into sensory-deprived (SD) and control (unplucked) groups. In SD group, all vibrissae except the D2 vibrissa were plucked on postnatal day one, and kept plucked for a period of 60 d. After that, whisker regrowth was allowed for 8-10 d. The D2 principal whisker (PW) and the D1 adjacent whisker (AW) were either deflected singly or both deflected in a serial order that the AW was deflected 20 ms before PW deflection for assessing lateral inhibition, and neuronal responses were recorded from layer IV of the D2 barrel cortex. DRN was electrically stimulated at inter-stimulus intervals (ISIs) ranging from 0 to 800 ms before whisker deflection. Results: PW-evoked responses increased in the SD group with DRN electrical stimulation at ISIs of 50 ms and 100 ms, whereas AW-evoked responses increased at ISI of 800 ms in both groups. Whisker plucking before DRN stimulation could enhance the responsiveness of barrel cortex neurons to PW deflection and decrease the responsiveness to AW deflection. DRN electrical stimulation significantly reduced this difference only in PW-evoked responses between groups. Besides, no DRN stimulation-related changes in response latency were observed following PW or AW deflection in either group. Moreover, condition test (CT) ratio increased in SD rats, while DRN stimulation did not affect the CT ratio in either group. There was no obvious change in 5-HT2A receptor protein density in barrel cortex between SD and control groups. Conclusion: These results suggest that DRN electrical stimulation can modulate information processing in the SD barrel cortex

Antifungal susceptibility testing of <i>Candida </i>species isolated from the immunocompromised patients admitted to ten university hospitals in Iran

Abstract Background Antifungal susceptibility testing is a subject of interest in the field of medical mycology. The aim of the present study were the distributions and antifungal susceptibility patterns of various Candida species isolated from colonized and infected immunocompromised patients admitted to ten university hospitals in Iran. Methods In totally, 846 Candida species were isolated from more than 4000 clinical samples and identified by the API 20 C AUX system. Antifungal susceptibility testing was performed by broth microdilution method according to CLSI. Results The most frequent Candida species isolated from all patients was Candida albicans (510/846). The epidemiological cutoff value and percentage of wild-type species for amphotericin B and fluconazole in Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei were 0.5 μg/ml (95%) and 4 μg/ml (96%); 1 μg/ml (95%) and 8 μg/ml (95%); 0.5 μg/ml (99%) and 19 μg/ml (98%); and 4 μg/ml (95%) and 64 μg/ml (95%), respectively. The MIC90 and epidemiological cutoff values to posaconazole in Candida krusei were 0.5 μg/ml. There were significant differences between infecting and colonizing isolates of Candida tropicalis in MIC 90 values of amphotericin B, and isolates of Candida glabrata in values of amphotericin B, caspofungin, and voriconazole (P < 0.05). Conclusions Our findings suggest that the susceptibility patterns of Candida species (colonizing and infecting isolates) in immunocompromised patients are not the same and acquired resistance was seen in some species

Laboratory Diagnosis of Factor XIII Deficiency in Developing Countries: An Iranian Experience

Factor XIII (FXIII) deficiency is an extremely rare bleeding disorder with an approximately 12-times higher than the rest of the world. The International Society for Thrombosis and Hemostasis (ISTH) suggested a standard algorithm for precise diagnosis and classification of FXIII deficiency (FXIIID). However, due to lack of investment in proper equipment and procedures in Iran, almost no part of this algorithm can be used to diagnose Iranian patients. Thus, this study proposes a guideline for accurate molecular and laboratory diagnosis of FXIIID based on the available tools. Because this study suggests a simple and reliable algorithm for early diagnosis, it can therefore, reduce the rates of morbidity and mortality of FXIIID patients with this condition. © 2016 American Society for Clinical Pathology, 2016. All rights reserved

Long term follow up study on a large group of patients with congenital factor XIII deficiency treated prophylactically with fibrogammin P®

Factor XIII deficiency (FXIIID) is an extremely rare hemorrhagic disorder with a prevalence of 1/3-5 million. Management of disease is performed by fresh frozen plasma (FFP), Cryoprecipitate (CP) or FXIII concentrate (Fibrogammin P®). Our objective was to assess safety and effectiveness of Fibrogammin P® in patients with FXIIID. For this purpose we designed this long-term follow up study on a large group of patients with FXIIID. This prospective study was conducted on 213 patients with FXIIID since 2009 to 2013. Administrated dose for Fibrogammin P® according to clinical situations of patients ranged from 10 to 26 IU/kg every 4-6 weeks. All patients in 6-month intervals were checked for human immunodeficiency virus (HIV), hepatitis A, B and C viruses (HAV, HBV, HCV). Twelve percent of participants had at least one ICH episode until 2008 but after administration of Fibrogammin P® did not have any major bleeding or episode of ICH, except in one patient. We also had 7 females with recurrent miscarriage that were managed successfully with a dose of 10 to 26 IU/kg every 4-6 weeks. This dose also was quite successful in management of major and minor surgery. None of the participants showed allergic reaction during treatment. A total of 7155450 IU of Fibrogammin P® were infused but nobody was positive for HIV, HAV, HBV, and HCV. We found that Fibrogammin P® is a safe and effective therapeutic choice in management of FXIIID. © 2016 by School of Pharmacy

The global burden of tuberculosis: results from the Global Burden of Disease Study 2015

Background: An understanding of the trends in tuberculosis incidence, prevalence, and mortality is crucial to tracking of the success of tuberculosis control programmes and identification of remaining challenges. We assessed trends in the fatal and non-fatal burden of tuberculosis over the past 25 years for 195 countries and territories. Methods: We analysed 10 691 site-years of vital registration data, 768 site-years of verbal autopsy data, and 361 site-years of mortality surveillance data using the Cause of Death Ensemble model to estimate tuberculosis mortality rates. We analysed all available age-specific and sex-specific data sources, including annual case notifications, prevalence surveys, and estimated cause-specific mortality, to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how observed tuberculosis incidence, prevalence, and mortality differed from expected trends as predicted by the Socio-demographic Index (SDI), a composite indicator based on income per capita, average years of schooling, and total fertility rate. We also estimated tuberculosis mortality and disability-adjusted life-years attributable to the independent effects of risk factors including smoking, alcohol use, and diabetes. Findings: Globally, in 2015, the number of tuberculosis incident cases (including new and relapse cases) was 10·2 million (95% uncertainty interval 9·2 million to 11·5 million), the number of prevalent cases was 10·1 million (9·2 million to 11·1 million), and the number of deaths was 1·3 million (1·1 million to 1·6 million). Among individuals who were HIV negative, the number of incident cases was 8·8 million (8·0 million to 9·9 million), the number of prevalent cases was 8·9 million (8·1 million to 9·7 million), and the number of deaths was 1·1 million (0·9 million to 1·4 million). Annualised rates of change from 2005 to 2015 showed a faster decline in mortality (–4·1% [–5·0 to –3·4]) than in incidence (–1·6% [–1·9 to –1·2]) and prevalence (–0·7% [–1·0 to –0·5]) among HIV-negative individuals. The SDI was inversely associated with HIV-negative mortality rates but did not show a clear gradient for incidence and prevalence. Most of Asia, eastern Europe, and sub-Saharan Africa had higher rates of HIV-negative tuberculosis burden than expected given their SDI. Alcohol use accounted for 11·4% (9·3–13·0) of global tuberculosis deaths among HIV-negative individuals in 2015, diabetes accounted for 10·6% (6·8–14·8), and smoking accounted for 7·8% (3·8–12·0). Interpretation: Despite a concerted global effort to reduce the burden of tuberculosis, it still causes a large disease burden globally. Strengthening of health systems for early detection of tuberculosis and improvement of the quality of tuberculosis care, including prompt and accurate diagnosis, early initiation of treatment, and regular follow-up, are priorities. Countries with higher than expected tuberculosis rates for their level of sociodemographic development should investigate the reasons for lagging behind and take remedial action. Efforts to prevent smoking, alcohol use, and diabetes could also substantially reduce the burden of tuberculosis

Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0.71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50.2% exceed this threshold for suitability in at least one 5×5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify