RhoA/Rho-kinase as a therapeutic target for the male urogenital tract

IntroductionRho‐kinase (ROCK) is a serine/threonine kinase and is one of the major downstream effectors of the small guanosine triphosphatase Rho. In the past few years, evidence has been accumulating to suggest that the RhoA/ROCK system may play an important role in the pathogenesis of a number of cardiovascular and urogenital disorders.AimThe aim of this study is to review the literature pertaining to the role of the RhoA/ROCK system in male urogenital function.MethodsComprehensive literature review was performed using PubMed.Main Outcome MeasuresInhibitors of ROCK may have potential therapeutic applications, as derived from preclinical and a few clinical studies.ResultsPublished reports suggest that elevated RhoA/Rho‐kinase signaling plays a role in the development of benign prostatic hyperplasia, erectile dysfunction, kidney failure, ejaculation disorders, prostate and bladder cancer initiation, and eventual metastasis.ConclusionsThis review focuses on our current understanding of the role of the RhoA/Rho‐kinase pathway in the regulation of the male urogenital system. Rho‐kinase inhibitors may evolve into an important pharmacologic option in the future treatment of urogenital system disorders. Gur S, Kadowitz PJ, and Hellstrom WJG. RhoA/Rho‐kinase as a therapeutic target for the male urogenital tract.     

Ventrolateral prefrontal cortex and the effects of task demand context on facial affect appraisal in schizophrenia

Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.     

Biological reconstruction of bone defects: the role of the free fibula flap

This review describes the kinds of skeletal bone defects in bones which develop through enchondral ossification. It focuses on the biological reconstruction of those defects according to the two main subtypes, intercalary and osteoarticular. We list the causes of bone defects and outline the different types and configurations that result from them. We then review the currently available reconstructive options according to the patient’s age and describe the theoretical options as well. Finally, the history, surgical anatomy and clinical use of the free fibula flap will be reviewed. From our own clinical experience and review of the literature, we conclude that biological reconstruction is, in many ways, superior to alloplastic materials, especially in children, adolescents and young adults.     

Surgical ablation and free flap reconstruction in children with malignant head and neck tumors

We assessed the feasibility and safety of free flap reconstruction in children undergoing extensive surgical excision of malignant head and neck tumors. We performed a retrospective review in a tertiary referral center of all patients aged 18 years or younger who underwent free flap reconstruction following resection of malignant head and neck tumors at our institution. Main outcome measures included complications at the primary and donor sites, functional and esthetic outcome, and tumor control. Eight of the 237 (3.4%) free flap reconstructions were performed on children. All tumors were malignant sarcomas. Ablative surgery was via a transfacial (n = 4) or a combined approach (n = 4). Transferred free flaps were the rectus abdominis (n = 3), gracilis (n = 3), fibula (n = 1), and anterolateral thigh (n = 1). The mean follow-up was 25.5 months. The overall early and late complication rates were 50% and 25%, respectively. There were no flap losses and no donor site complications. Functional outcome, including mastication, deglutition, and speech, was satisfactory. Local tumor control rate at last follow-up was 87.5%. Free flap reconstruction is an efficient and relatively safe technique for reconstructing surgical defects of the head and neck in children undergoing extensive surgery for malignant disease.     

Group and site differences on the California Verbal Learning Test in persons with schizophrenia and their first-degree relatives: findings from the Consortium on the Genetics of Schizophrenia (COGS)

Genetic studies of schizophrenia focus increasingly on putative endophenotypes because their genetic etiology may be simpler than clinical diagnosis. The Consortium on the Genetics of Schizophrenia (COGS), a multisite family study, aims to identify the genetic basis of several endophenotypes including verbal declarative memory (VDM), a neurocognitive function that shows robust impairment in schizophrenia. We present data on one type of measure of VDM, the California Verbal Learning Test, Second Edition (CVLT-II), in schizophrenia probands (n=305), their full biological siblings (n=449) and parents (n=232), and in community comparison subjects (CCS; n=509) across seven sites. Probands performed more poorly on each of five CVLT-II measures compared to related sibling and parent groups and CCS. Siblings and parents performed significantly worse than CCS on one measure (Discriminability), but with smaller effect sizes and less impairment than observed previously. The results raise questions about the homogeneity of VDM as an endophenotype, about methodological issues related to sampling, and about psychometric issues that impact the utility of the CVLT for detecting VDM deficits in nonpsychotic relatives of persons with schizophrenia.     

Amygdala abnormalities in first-degree relatives of individuals with schizophrenia unmasked by benzodiazepine challenge

Rationale  

Impaired emotion processing in schizophrenia predicts broader social dysfunction and has been related to negative symptom severity and amygdala dysfunction. Pharmacological modulation of emotion-processing deficits and related neural abnormalities may provide useful phenotypes for pathophysiological investigation.     

Baby massage – what's not to like?

Procianoy RS, Mendes EW, Silverira RC. Massage therapy improves neurodevelopment outcome at two years corrected for very low birth weight infants. Early Hum Dev 2010; 86: 7–11.