Mild traumatic brain injury and anxiety sequelae: a review of the literature

There is scattered but significant psychological and neuropsychological evidence to suggest that mild traumatic brain injury (mild TBI) plays a notable role in the emergence and expression of anxiety. Conversely, there is also empirical evidence to indicate that anxiety may exert a pronounced impact on the prognosis and course of recovery of an individual who has sustained a mild TBI. Although the relationship between mild TBI and anxiety remains unclear, the present body of research attempts to elucidate a number of aspects regarding this topic. Overall, the mild TBI research is rife with inconsistencies concerning prevalence rates, the magnitude and implications of this issue and, in the case of PTSD, even whether certain diagnoses can exist at all. This review obviates the need for greater consistencies across studies, especially between varying disciplines, and calls for a shift from studies overly focused on categorical classification to those concerned with dimensional conceptualization.     

The use of herbal and over-the-counter dietary supplements for the prevention of prostate cancer

Having a high probability of experiencing prostate cancer during their lifetime, men are increasingly seeking protection against this disease with the use of over-the-counter dietary supplements containing herbs, vitamins, or plantderived biochemical agents. The use of these agents for prostate cancer prevention is driven by epidemiology supporting the idea that regional diets and consumption of specific dietary components (certain herbs, vitamins, isoflavones, and polyphenols) are associated with a lower risk for prostate cancer, in conjunction with basic research that is defining molecules within food substances that kill or suppress growth of cultured human prostate cancer cells. Moreover, there is a sense that these dietary agents lack side effects, although this assumption often is faulty. Unfortunately, at this time, there is insufficient clinical evidence to support the widespread use of these dietary supplements for chemoprevention of prostate cancer, although ongoing clinical trials of the most promising vitamins and minerals are approaching conclusion.     

Impact of dry eye syndrome on vision-related quality of life

PURPOSE: To evaluate the impact of dry eye syndrome (DES) on vision-associated quality of life. DESIGN: Cross-sectional study. METHODS: We identified 450 participants in the Women's Health Study (WHS) and 240 participants in the Physicians' Health Study (PHS) and sent a supplementary questionnaire asking how much their everyday activities were limited by symptoms of dry eye and to what degree problems with their eyes limited them in reading, driving, working at the computer, their professional activity, and watching television. By design, one-third of study subjects had clinically diagnosed DES or severe symptoms and two-thirds did not. We used logistic regression to examine relationships of DES with reported problems with everyday activities in each cohort and pooled estimates using meta-analysis methods. RESULTS: Of the participants invited, 85% completed the supplementary questionnaire, including 135 WHS and 55 PHS participants with DES, and 250 WHS and 149 PHS participants without DES. Controlling for age, diabetes, hypertension, and other factors, those with DES were more likely to report problems with reading ([odds ratio] OR = 3.64, 95% [confidence interval] CI 2.45 to 5.40, P < .0001); carrying out professional work (OR = 3.49, 95% CI 1.72 to 7.09, P= 0.001); using a computer (OR = 3.37, 95% CI 2.11 to 5.38, P < .0001); watching television (OR = 2.84, 95% CI 1.05 to 7.74, P = .04); driving during the day (OR = 2.80, 95% CI 1.58 to 4.96, P < .0001); and driving at night (OR = 2.20, 95% CI 1.48 to 3.28, P < .0001). CONCLUSIONS: DES is associated with a measurable adverse impact on several common and important tasks of daily living, further implicating this condition as an important public health problem deserving increased attention and resources.     

A novel isoform of acetylcholinesterase exacerbates photoreceptors death after photic stress

PURPOSE: To study the involvement of stress-induced acetylcholinesterase (AChE) expression in light-induced retinal damage in albino rats. METHODS: Adult albino rats were exposed for 24 hours to bright, damaging light. AChE expression was monitored by in situ hybridization, by histochemistry for AChE activity, and by immunocytochemistry. An orphan antisense agent (Monarsen; Ester Neurosciences, Ltd., Herzlia Pituach, Israel) was administered intraperitoneally to minimize light-induced AChE expression. The electroretinogram (ERG) was recorded to assess retinal function. RESULTS: Twenty-four-hour exposure to bright light caused severe reduction in the ERG responses and augmented expression of mRNA for the "read-through" variant of AChE (AChE-R) in photoreceptor inner segments (IS), bipolar cells, and ganglion cells. AChE activity increased in IS. The expressed AChE protein was a novel variant, characterized by an extended N terminus (N-AChE). Systemic administration of the orphan antisense agent, Monarsen, reduced the photic induction of mRNA for AChE-R, and of the N-AChE protein. Rats exposed to bright, damaging light and treated daily with Monarsen exhibited larger ERG responses, relatively thicker outer nuclear layer (ONL), and more ONL nuclei than did rats exposed to the same damaging light but treated daily with saline. CONCLUSIONS: The findings indicate that the photic-induced novel variant of AChE (N-AChE-R) may be causally involved with retinal light damage and suggest the use of RNA targeting for limiting such damage.     

The phenotype of early-onset retinal degeneration in persons with RDH12 mutations

PURPOSE: To describe the retinal dystrophy phenotype associated with mutations in RDH12, the gene encoding a retinoid dehydrogenase/reductase expressed in the photoreceptor cells. METHODS: Sixteen persons from 12 families with pathogenic RDH12 mutations on both alleles were studied. Retinal phenotypes were characterized by ophthalmic examination, including psychophysical and standardized electrophysiological methods and multifocal electroretinography (mfERG). RESULTS: The retinal disease in persons with RDH12 mutations in the homozygous (p.G127X, p.Q189X, p.Y226C, p.A269GfsX1, and p.L274P) or compound heterozygous state (p.R65X/p.A269GfsX1, p.H151D/p.T155I, p.H151D/p.A269GfsX1) was diagnosed initially as Leber congenital amaurosis (LCA) or early-onset retinitis pigmentosa. These individuals appeared to share a common clinical picture, independent of the type of mutation, characterized by poor, yet useful visual function in early life, followed by progressive decline due to both rod and cone degeneration. Marked pigmentary retinopathy, including bone spicules in the peripheral retina, was present in all persons older than age 6, and pronounced maculopathy was evident in persons older than 7 years. A unique view into the progressive nature of the disorder was achieved by evaluation of seven affected persons from three consanguineous families, all carrying the homozygous p.Y226C mutation. CONCLUSIONS: Ophthalmic findings in persons with RDH12 mutations suggest that RDH12 loss-of-function results in a characteristic form of early and progressive rod-cone degeneration distinct from that caused by mutations in other LCA genes. From our data, it seems likely that various clinical designations appropriately describe the diagnosis in these persons, including early-onset retinitis pigmentosa, LCA type II, and childhood retinal dystrophy.     

The Th2 cytokine,interleukin‐4, abrogates the cohesion of normal stratum corneum in mice: implications for pathogenesis of atopic dermatitis

There is mounting evidence that Th2 cytokines adversely affect skin barrier functions and contribute to the pathogenesis of atopic dermatitis (AD). AD is also characterized by abnormal cohesion in the stratum corneum (SC). However, the contribution of Th2 cytokines to this abnormality remains unknown. This study examined the effects of IL‐4, a prototypic Th2 cytokine, on the cohesion of the SC. Structural and physiological assessments revealed that repeated intradermal injections of IL‐4 compromised the cohesion of the SC of normal hairless mice. Two potential mechanisms were explored to account for the altered cohesion. First, IL‐4 decreased the amount of corneodesmosomes and down‐regulated the expression of desmoglein 1, but not of corneodesmosin (CDSN) or loricrin expression, in murine skin and in cultured human keratinocytes (KC). IL‐4 did not affect the skin surface pH, and in situ zymography revealed no net change in total serine protease activity in the IL‐4‐treated SC. Yet, IL‐4 enhanced expression of kallikrein (KLK)7, while simultaneously down‐regulating KLK5 and KLK14. Finally, IL‐4 did not alter the expression of the lympho‐epithelial Kazal‐type inhibitor (LEKTI) in KC. This study suggests that IL‐4 abrogates the cohesion of SC primarily by reducing epidermal differentiation.     

Corneal activation of prothrombin to form thrombin, independent of vascular injury

PURPOSE: Two major functions of thrombin observed in the cornea are activation of thrombin-sensitive, proteinase-activated receptors and cleavage of fibrinogen to fibrin. The purpose of this study was to determine whether the normal human cornea itself is competent to convert prothrombin to thrombin and synthesizes the mRNA for the proteins required. METHODS: Human corneas were processed for immunolocalization studies or separated into epithelial, stromal, and endothelial layers for proteins and RNA isolation. The protein extracts were used for Western blots, prothrombin time, and activated partial thromboplastin time assays and fibrinopeptide A generation tests. RNA was used for RT-PCR. Apoptosis of cultured human corneal cells was induced with sodium nitroprusside or camptothecin and activation of prothrombin tested. RESULTS: Prothrombin and its mRNA were present in all three layers of human donor cornea. It was found to be associated with the cells and the extracellular matrix at similar levels across the cornea. With corneal stromal extracts, activation of either the intrinsic or extrinsic coagulation pathways resulted in thrombin activation and fibrin formation with fibrinopeptide A release. Detection of key components of the coagulation cascades confirmed noninjured human corneas contain factors required for prothrombin activation. In addition, mRNAs for representative factors and inhibitors were detected by RT-PCR and confirmed by sequencing. Apoptotic corneal stromal cells provide a surface for prothrombin activation. CONCLUSIONS: These studies suggest that the normal avascular human cornea contains and synthesizes the components required for thrombin generation and that this process does not depend on a breech in the limbal vascular endothelium.     

Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.     

Does Maternal HIV Disclosure Self-Efficacy Enhance Parent–Child Relationships and Child Adjustment?

Nondisclosure of maternal HIV status to young children can negatively impact child functioning; however, many mothers do not disclose due to lack of self-efficacy for the disclosure process. This study examines demographic variations in disclosure self-efficacy, regardless of intention to disclose, and assesses the relationship between self-efficacy and child adjustment via the parent–child relationship among a sample of HIV+ mothers and their healthy children (N = 181 pairs). Mothers completed demographic and self-efficacy measures; children completed measures assessing the parent–child relationship and child adjustment (i.e., worry, self-concept, depression). Across demographics, few mothers reported confidence in disclosure. Results from covariance structural modeling showed mothers endorsing higher self-efficacy had children who reported better relationship quality, and, in turn, reported fewer adjustment difficulties; higher levels of disclosure self-efficacy also directly predicted fewer adjustment problems. Findings offer support for interventions aimed at providing mothers with skills to enhance confidence for disclosing their HIV status.