Astrocytes propel neurovascular dysfunction during cerebral cavernous malformation lesion formation.

Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in 1 of 3 genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2- and KLF4-dependent elevation of eNOS in CCM endothelium. The increased brain endothelial production of NO stabilized HIF-1α in astrocytes, resulting in increased VEGF production and expression of a "hypoxic" program under normoxic conditions. We showed that the upregulation of cyclooxygenase-2 (COX-2), a direct HIF-1α target gene and a known component of the hypoxic program, contributed to the development of CCM lesions because the administration of a COX-2 inhibitor significantly prevented the progression of CCM lesions. Thus, non-cell-autonomous crosstalk between CCM endothelium and astrocytes propels vascular lesion development, and components of the hypoxic program represent potential therapeutic targets for CCMs.

Isolation and Purification of Mouse Brain Endothelial Cells to Study Cerebral Cavernous Malformation Disease.

We describe a method to purify primary brain microvascular endothelial cells (BMEC) from mice bearing floxed alleles of Krit1 (Krit1fl/fl) or Pdcd10 (Pdcd10fl/fl) and an endothelial-specific tamoxifen-regulated Cre recombinase (Pdgfb-iCreERT2), and used these to delete Krit1 or Pdcd10 genes in a time-controlled manner. These BMEC culture models contain a high degree of purity and have been used to identify the major molecular processes involved in loss of Krit1/Pdcd10-induced altered brain endothelial phenotype and function. In addition, these in vitro models of cerebral cavernous malformations (CCMs) enable molecular, biochemical, and pharmacological studies that have contributed significantly to understand the pathogenesis of CCMs. The findings using this in vitro CCMs model have been validated in mouse CCM models and observed in human CCMs. In this chapter, we summarize procedures for isolation and purification of BMEC from transgenic mice, as well as our experience to genetically inactivate CCM genes in the brain endothelium.

Clinical outcomes are associated with changes in ultrasonographic structural appearance after platelet-rich plasma treatment for knee osteoarthritis.

BACKGROUND: Hyaluronic acid (HA) and platelet-rich plasma (PRP) are two treatment options used for knee osteoarthritis (KOA) but studies comparing the efficacy of the two yield conflicting results. In addition, the association of clinical outcomes of PRP intra-articular injections with changes in the ultrasonography structural appearance of the knee has not been investigated. AIM: To compare the efficacy of PRP and HA intra-articular injections as mono-therapeutic options for primary KOA, and to determine whether the clinical outcomes are associated with changes in the ultrasonography structural appearance. SUBJECTS AND METHODS: A randomized clinical trial was conducted on 89 patients with KOA. The patients were given either PRP (n = 45) or HA (n = 44) intra-articular injections. The patients received three injections in the knee, which was more symptomatic at baseline evaluation, with a 2-week interval between injections. The outcome measures included visual analog score - pain, International Knee Documentation Committee Score, and assessment of synovial hypertrophy, synovial vascularity and knee effusion using ultrasonography. Outcome measures were assessed at baseline and at 3 and 6 months post-injection. RESULTS: While both PRP and HA injections resulted in the improvement of all outcome measures at 3 and 6 months follow up, they were significantly better in the PRP group than in the HA group. CONCLUSION: Intra-articular injection of PRP is an effective treatment that reduced pain and improved functional status in patients with KOA. The clinical outcomes of the intra-articular injections of PRP are associated with improved synovial hypertrophy and vascularity scores, and less effusion.

Seroprevalence of antibodies against varicella zoster virus and rubella virus among newly recruited expatriate healthcare workers: a cross-sectional study.

OBJECTIVES: To assess the state of immunity to varicella zoster virus (VZV) and rubella virus (RV) among newly recruited healthcare workers (HCWs) in Kuwait before they begin work, and to determine whether there are differences in the prevalence of seronegativity according to nationality, gender, age group and occupation group. SETTING: This cross-sectional study involved analysis of blood samples from workers newly recruited to the Kuwaiti healthcare system. PARTICIPANTS: All new non- national HCWs recruited during the study period (n=1540). INTERVENTION: Enzyme-linked immunoassays for VZV-specific and RV-specific IgG were performed. RESULTS: Among HCWs, 81.9% and 93.5% were immune to VZV and RV, respectively. Male seronegativity was higher than that of females for both viruses. Regarding VZV, the majority of seronegative individuals were Indians (23.5%), followed by Somalis (12.5), Filipinos (6.5) and Egyptians (5.4%); the between-group differences were significant for all groups. The age groups 20-30 and 30-40 years were most likely to be seronegative, with prevalences of 18.2% and 18.9%, respectively. VZV seronegativity was most common among nurses (21.1%) and least common among physicians (9.2%), and the difference was significant. In addition, RV seronegativity was most frequent among Somalis (12.5%) and lowest among Indians (5.3%); other nationalities (Egyptian, Filipino and others) ranged between 9.1% and 9.6%. Seronegative individuals were most frequently in the younger age group (<20 years old) (17.5%), followed by the >40 years old group (10.4%). RV seronegativity was highest among nurses (6.9%) and lowest among physicians (5.2%). CONCLUSION: The prevalence of seronegativity is highest among Indians for VZV and Somalis for RV, and HCWs aged 20-40 years for VZV and <20 years for RV. For both viruses, the seronegativity rate was highest for male HCWs, and for nurses compared with other HCWs, with physicians having the lowest prevalence of both viruses.

Determinants of Adherence with Malaria Chemoprophylactic Drugs Used in a Traveler's Health Clinic.

Background. The WHO recommends mefloquine, atovaquone/proguanil, and doxycycline for malaria chemoprophylaxis. Adherence to a drug is determined by many factors. Objective. To detect the determinants of travelers' adherence to malaria chemoprophylaxis. Methods. A prospective comparative study was conducted from January 2012 to July 2013 that included travelers (928 travelers) to malaria endemic countries who visited the THC. They were classified into 3 groups: the 1st is the mefloquine group (396 travelers), the 2nd is the doxycycline group (370 travelers), and finally those who did not receive any drugs (162 travelers). The participants from the 1st and 2nd groups enrolled in the study. Results. Univariate and multivariate analyses were performed. The predictors for adherence in the mefloquine group were travel to an African destination [OR = 51 (6.8-2385)], higher than a secondary school education [OR = 21 (4.1-144.2)], organized travel [OR = 4 (2.1-6.5)], traveling for leisure [OR = 2.1 (1.1-0.4)], and nationality [OR = 2 (1.11-4.00)]. In the doxycycline group, the predictors included higher than a secondary education [OR = 20.1 (4.5-125.1)], organized travel [OR = 11.4 (5.5-20.9)], travel for leisure [OR = 7 (2.3-22.9)], travel to an African destination [OR = 6.1 (0.41-417)], and nationality [OR = 4.5 (2.3-9.5)]. Conclusion. Adherence with malaria chemoprophylaxis could be affected by many factors such as nationality, education, and organized travel.

Travel risk behaviors as a determinants of receiving pre-travel health consultation and prevention.

BACKGROUND: An estimated 30-60 % of travelers experience an illness while traveling. The incidence of travel-related illness can be reduced by preventive measures such as those provided by the Traveler Health Clinic (THC) in Kuwait. METHODS: The present study is an analytical comparative study between groups of travelers visiting the THC during the study period (May 2009 - December 2010) and an age- and gender-matched control group of non-visitors (800 people). Both groups completed a modified pre-departure questionnaire. RESULTS: Bivariate analysis revealed that Kuwaitis (68.2 %), those traveling for work (25.3 %) or leisure (59.5 %), those living in camps (20.4 %) or hotels (64.0 %), and those with knowledge of the THC from the media (28.1 %) or other sources (57.3 %), were more likely to be associated with a high frequency of visits to the THC (p < 0.001). Additionally, travelers heading to Africa (47 %) and South America (10 %) visited the THC more than did others (P < 0.05). Multivariate analysis revealed that nationality, followed by purpose of travel, duration of stay, and choice of travel destination are independent predictors of receiving pre-travel consultation from the THC. CONCLUSION: Nationality, purpose of travel, length of stay, and travel destination are predictors for receiving a pre-travel consultation from the THC.

Prevalence of obesity among adolescents (10 to 14 years) in Kuwait.

The purpose of this cross-sectional study was to find out the prevalence of obesity and overweight among intermediate school adolescents aged 10 to 14 years. The study comprised a multistage stratified random sample that included 5402 children (2657 males and 2745 females). They represent 12.7% of the total number of children between 10 and 14 years during the educational year 2005-2006. The weights and heights of adolescents were measured, from which the body mass index (BMI) was calculated, which is the weight in kilograms divided by the height in meters squared (kg/m(2)). BMI values higher than 95 percentile were accepted as being obese and those in between 85 and 94 percentile were accepted as overweight. Dietary intake was assessed by the investigators using food exchange lists designed by American Diabetic Association and physical fitness was measured by modified Harvard step test. Data regarding monthly income of the chosen sample were collected from parents of those children. The overall prevalence of overweight and obesity in adolescent Kuwaiti children aged 10 to 14 years was 30.7% and 14.6%, respectively. The overall prevalence of overweight and obesity among males was 29.3% and 14.9%, respectively (P < .001) and the prevalence of overweight and obesity among females was 32.1% and 14.2%, respectively (P < .001). High daily caloric intake by the obese and overweight children and physical inactivity was reported among the majority of them. Health education programs should be conducted to control this syndrome in order to prevent future risk of obesity-related disease, and physical activity programs should be incorporated in the schools. Any management plan for overweight and obese children should include 3 major components: diets, exercise, and family-based behavior and they should not be placed on restrictive diets because adequate calories are needed for proper growth.