Phacoemulsification of cataract in patients receiving Coumadin therapy: ocular and hematologic risk assessment

PURPOSE: To assess the risks of intra- and postoperative bleeding tendency associated with uncomplicated cataract surgery by phacoemulsification in patients receiving Coumadin treatment. DESIGN: Prospective, nonrandomized, interventional, consecutive case series. METHODS: Sixty-three consecutive patients underwent cataract extraction with lens implantation in 75 eyes. All patients were receiving Coumadin therapy at the time of surgery, and nine patients (14.3%) were also taking antiaggregants. The operations were performed by phacoemulsification technique under topical anesthesia. All patients underwent a hemostatic work-up before intervention. Structured questionnaires were completed by the surgeon immediately after the operation. In 18 (24%) eyes, the surgery was videotaped, and the tapes were reviewed subsequently for any bleedings by an independent observer. RESULTS: Twelve patients (19%) underwent surgery in both eyes, not simultaneously. The mean prothrombin time international normalized ratio (INR) was 2.03 at the time of the surgery. No significant intraoperative bleeding occurred. Four (6.3%) patients had minor postoperative ocular bleeding. A microscopic hyphema and a dot retinal hemorrhage were each seen in one eye on the first postoperative day, and small iris hemorrhages were identified in two additional eyes at the one-week visit. All bleedings disappeared within one week without affecting the visual acuity. The mean INR of the four patients with minor bleedings was 2.1. CONCLUSIONS: Cataract surgery by phacoemulsification in uncomplicated eyes can be performed safely in patients receiving Coumadin treatment. However, a large clinical trial is required to assess the safety of continuous Coumadin treatment associated with phacoemulsification in eyes with complicated cataract.     

Molecular epidemiology of hereditary epidermolysis bullosa in a Middle Eastern population

Epidermolysis bullosa (EB) encompasses a large group of inherited blistering skin disorders caused by mutations in at least 10 genes. Numerous studies, mainly performed in European and US families with EB, have revealed a number of characteristic epidemiological and genetic features, which form the basis for current diagnostic and counseling strategies. However, little is currently known about the molecular epidemiology of EB in Middle East populations. In the present study, we assessed 55 EB families for pathogenic sequence alterations in the 10 genes known to be associated with EB. Our results show unique EB subtype distribution and patterns of inheritance in our cohort. We also failed to detect recurrent mutations frequently encountered in Europe and the US, and did not consistently observe genotype-phenotype correlations formerly established in Western populations. Thus, the molecular epidemiology of EB in the Middle East is significantly different from that previously delineated in Europe and the US. Our data raise the possibility that similar differences may also be found in other genetically heterogeneous groups of disorders, and indicate the need for population-specific diagnostic and management approaches.     

Statins,aspirin and risk of venous thromboembolic events in breast cancer patients

Venous thromboembolic events (VTE’s) are associated with decreased survival in breast cancer patients. Studies suggested that statins reduce the risk of VTE’s in the general population. Low dose Aspirin reduces risk of VTE’s in high risk populations. The Breast Cancer in Northern Israel Study is a case–control study of consecutive breast cancer cases diagnosed in northern Israel and matched controls. The present analysis was limited to cases with breast cancer enrolled in the study. Data was extracted from Clalit Health Services (CHS) database and from computerized pharmacy records. Out of 3,585 patients enrolled, 261 (7.3 %) had a VTE during median follow up of 4.2 years. The 1 and 2 year cumulative incidence was 2.64 and 3.65 %. 55.7 % of patients used statins, predominantly simvastatin (75.8 %). 44.5 % used aspirin. In multivariate analysis neither statins nor aspirin use was associated with a reduced risk for a VTE. Unadjusted HR for statin and aspirin was 1.461 (1.018–2.096) and 1.293 (0.846–1.976), respectively, and the adjusted HR were 0.86 (0.648–1.14) and 1.013 (0.737–1.392). Results were similar when only simvastatin use was assessed. Metastatic disease, chemotherapy, age, BMI and presence of comorbidities were significantly associated with risk of VTE’s. Our study is the first to look at the effect of statins and aspirin on the incidence of VTE’s in patients with breast cancer. In our cohort, statin and aspirin use did not decrease the risk for a VTE. Our results might be explained by use of low potency statins (simvastatin and pravastatin) and by alternate mechanisms for VTE formation in patients with cancer.     

Characterization of sil in Invasive Group A and G Streptococci: Antibodies against Bacterial Pheromone Peptide SilCR Result in Severe Infection

Group G beta-hemolytic streptococcus (GGS) strains cause severe invasive infections, mostly in patients with comorbidities. GGS is known to possess virulence factors similar to those of its more virulent counterpart group A streptococcus (GAS). A streptococcal invasion locus, sil, was identified in GAS. sil encodes a competence-stimulating peptide named SilCR that activates bacterial quorum sensing and has the ability to attenuate virulence in GAS infections. We found that sil is present in most GGS strains (82%) but in only 25% of GAS strains, with a similar gene arrangement. GGS strains that contained sil expressed the SilCR peptide and secreted it into the growth medium. In a modified murine model of GGS soft tissue infection, GGS grown in the presence of SilCR caused a milder disease than GGS grown in the absence of SilCR. To further study the role of the peptide in bacterial virulence attenuation, we vaccinated mice with SilCR to produce specific anti-SilCR antibodies. Vaccinated mice developed a significantly more severe illness than nonvaccinated mice. Our results indicate that the sil locus is much more prevalent among the less virulent GGS strains than among GAS strains. GGS strains express and secrete SilCR, which has a role in attenuation of virulence in a murine model. We show that the SilCR peptide can protect mice from infection caused by GGS. Furthermore, vaccinated mice that produce specific anti-SilCR antibodies develop a significantly more severe infection. To our knowledge, this is a novel report demonstrating that specific antibodies against a bacterial component cause more severe infection by those bacteria.     

Vestibulo-ocular response and balance control in children and young adults with mild-to-moderate intellectual and developmental disability: A pilot study

The vestibulo-ocular response (VOR) may not be fully developed in children with an intellectual and developmental disability (IDD). This study aimed to identify the presence of VOR deficit in children and young adults with unspecified mild-to-moderate intellectual and developmental disability and its effect on balance control. Twenty-one children and young adults with IDD ranging in age from 8 to 22 years (mean 17.5 ± 3.9 years) were included in the study. The VOR was evaluated with the Head Impulse Test and the Static and Dynamic Visual Acuity Test (S&D-VAT). Postural stability was measured in an upright standing position by the Clinical Test for Sensory Interaction in Balance (CTSIB), single leg stance (SLS) during eyes open and eyes closed, and Romberg stance under eyes open and eyes closed conditions using a force platform. Reduced vestibulo-ocular responses were found in 13 of 21 (62%) participants who were able to complete testing. In the fifth condition of the CTSIB (standing on foam with eyes closed), those without VOR deficit were able to maintain balance longer than those with VOR deficit (29 s [median 30] vs. 12 s [median 7.3], respectively; p = 0.03). The study demonstrates potential effects of VOR deficit in children and young adults with IDD and some significant differences in balance control between those with and without a VOR deficit. VOR function in children and young adults with IDD should be routinely tested to enable early detection of deficits.     

N-arachidonoyl-L-serine (AraS) possesses proneurogenic properties in vitro and in vivo after traumatic brain injury

N-arachidonoyl-L-serine (AraS) is a novel neuroprotective endocannabinoid. We aimed to test the effects of exogenous AraS on neurogenesis after traumatic brain injury (TBI). The effects of AraS on neural progenitor cells (NPC) proliferation, survival, and differentiation were examined in vitro. Next, mice underwent TBI and were treated with AraS or vehicle. Lesion volumes and clinical outcome were evaluated and the effects on neurogenesis were tested using immunohistochemistry. Treatment with AraS led to a dose-dependent increase in neurosphere size without affecting cell survival. These effects were partially reversed by CB1, CB2, or TRPV1 antagonists. AraS significantly reduced the differentiation of NPC in vitro to astrocytes or neurons and led to a 2.5-fold increase in expression of the NPC marker nestin. Similar effects were observed in vivo in mice treated with AraS 7 days after TBI. These effects were accompanied by a reduction in lesion volume and an improvement in neurobehavioral function compared with controls. AraS increases proliferation of NPCs in vitro in cannabinoid-receptor-mediated mechanisms and maintains NPC in an undifferentiated state in vitro and in vivo. Moreover, although given at 7 days post injury, these effects are associated with significant neuroprotective effects leading to an improvement in neurobehavioral functions.     

Pay-what-you-want, identity, and self-signaling in markets

We investigate the role of identity and self-image consideration under "pay-what-you-want" pricing. Results from three field experiments show that often, when granted the opportunity to name the price of a product, fewer consumers choose to buy it than when the price is fixed and low. We show that this opt-out behavior is driven largely by individuals' identity and self-image concerns; individuals feel bad when they pay less than the "appropriate" price, causing them to pass on the opportunity to purchase the product altogether.