Protection from angiotensin II-mediated vasculotoxic and hypertensive response in mice lacking PI3Kgamma

Hypertension affects nearly 20% of the population in Western countries and strongly increases the risk for cardiovascular diseases. In the pathogenesis of hypertension, the vasoactive peptide of the renin-angiotensin system, angiotensin II and its G protein-coupled receptors (GPCRs), play a crucial role by eliciting reactive oxygen species (ROS) and mediating vessel contractility. Here we show that mice lacking the GPCR-activated phosphoinositide 3-kinase (PI3K)gamma are protected from hypertension that is induced by administration of angiotensin II in vivo. PI3Kgamma was found to play a role in angiotensin II-evoked smooth muscle contraction in two crucial, distinct signaling pathways. In response to angiotensin II, PI3Kgamma was required for the activation of Rac and the subsequent triggering of ROS production. Conversely, PI3Kgamma was necessary to activate protein kinase B/Akt, which, in turn, enhanced L-type Ca(2+) channel-mediated extracellular Ca(2+) entry. These data indicate that PI3Kgamma is a key transducer of the intracellular signals that are evoked by angiotensin II and suggest that blocking PI3Kgamma function might be exploited to improve therapeutic intervention on hypertension.     

Studies in Emergency Department Data Collection: Shared versus Split Responsibility for Patient Enrollment

OBJECTIVES: To compare patient enrollment in six clinical studies using shared coverage (24 emergency department [ED] rooms-two students share enrollment responsibility) with enrollment using split coverage (12 rooms each per student). The academic associate (AA) program uses undergraduate students to collect data for clinical studies in the ED by providing double coverage 16 hours/day, seven days/week. Prior studies have shown that this system captures >85% of eligible patients. Methods to obtain closer to 100% enrollment are desired. METHODS: During consecutive 15-day periods with the same 24 AAs, the daily ED census, hours of AA coverage, and enrollment in each of six studies were evaluated prospectively in the ED. Data are presented as means with 95% confidence intervals (CIs). RESULTS: There was no difference between the shared and split enrollment periods with respect to hours of AA coverage (30.3 vs. 30.7 hours/day; p = 0.7) or average daily ED census (133.7 vs. 141.8; p = 0.15). Overall, the percentages of ED patients recruited for study participation were not different depending on whether the split versus shared recruitment strategy was used (907 patients recruited out of 2005 ED patients (45.2%; 95% CI = 43.0 to 47.4) vs. 937 of 2127 (44.0%; 95% CI = 41.9 to 46.1). The 95% CI for the 1.2% difference was -1.8% to 4.2%. Patient enrollments in six individual studies were similar regardless of recruitment strategy. Following the 30-day trial, AAs were surveyed: 17 of 24 (71%) found the split strategy to be "more helpful in enrolling subjects," and 20 of 24 (83%) found split strategy helped them "keep better track" of patients. CONCLUSIONS: Study subject enrollment was not affected by the use of either the shared or split responsibility strategy for recruitment. Students generally preferred the split strategy because it was more helpful and easier to monitor. Therefore, this may be the best option for similar student-oriented data collection programs.     

Mechanical Analysis of the Uterosacral Ligament: Swine vs. Human

The uterosacral ligament (USL) is a major suspensory structure of the female pelvic floor, providing support to the cervix and/or upper vagina. It plays a pivotal role in surgical procedures for pelvic organ prolapse (POP) aimed at restoring apical support. Despite its important mechanical function, little is known about the mechanical properties of the USL due to the constraints associated with in vivo testing of human USL and the lack of validated large animal models that enable such investigations. In this study, we provide the first comparison of the mechanical properties of swine and human USLs. Preconditioning and pre-creep data up to a 2 N load and creep data under a 2 N load over 1200 s were obtained on swine (n = 9) and human (n = 9) USL specimens by performing planar equi-biaxial tensile tests and using the digital image correlation method. No differences in the peak strain during preconditioning tests, secant modulus of the pre-creep response, and strain at the end of creep tests were detected in the USLs from the two species along both axial loading directions (the main in vivo loading direction and the direction that is perpendicular to it). These findings suggest that the swine holds promise as large animal model for studying the mechanical role of the USL in apical vaginal support and treatment of POP.     

Can consumer choice replace trust in the National Health Service in England? Towards developing an affective psychosocial conception of trust in health care

Trust has long been regarded as a vitally important aspect of the relationship between health service providers and patients. Recently, consumer choice has been increasingly advocated as a means of improving the quality and effectiveness of health service provision. However, it is uncertain how the increase of information necessary to allow users of health services to exercise choice, and the simultaneous introduction of markets in public health systems, will affect various dimensions of trust, and how changing relations of trust will impact upon patients and services. This article employs a theory‐driven approach to investigate conceptual and material links between choice, trust and markets in health care in the context of the National Health Service in England. It also examines the implications of patient choice on systemic, organisational and interpersonal trust. The article is divided into two parts. The first argues that the shift to marketisation in public health services might lead to an over‐reliance on rational‐calculative aspects of trust at the expense of embodied, relational and social attributes. The second develops an alternative psychosocial conception of trust: it focuses on the central role of affect and accounts for the material and symbolic links between choice, trust and markets in health care.     

Sexual Function in Normal Elders,MCI and Patients with Mild Dementia

Sexuality is part of human nature throughout life and a large amount among elders considers sexual function as an integral part in their life. The sample of our research consists of 265 participants, 60–85 years old. Data were collected by Sexual Satisfaction and Experience Questionnaire, demographics, medical history and individual interviews. According to ANOVA test, changes in the general sexual function during the last month were observed in dementia group compared to control group for both men and women (p = 0.01). Furthermore, lower sexual activity between men among control and MCI participants has also been highlighted the previous month (p = 0.038). Hence the ANOVA test showed statistical significant changes between controls and patients with mild dementia (p = 0.021) and between MCI participants and patients with mild dementia (p = 0.045) during the last year. These findings indicate that sexual activity is decreased in parallel with cognitive impairment. The importance given to sexual function during earlier years played an important role in the observed changes (p = 0.01) and overall sexual action (p = 0.01) during aging for both men and women in MCI and healthy participants. Those who reported that their sexual function have been changed negatively because of specific factors, highlighted disease status, medication and the partner, as the main factors for this change according to Related two samples test. According to results, elders’ sexual activity is strongly depended on aging, gender and medical status. During the progress of cognitive decline, sexual activity is being reduced, especially among men who notice this deterioration at a great level compared to women.     

Sublingual immunization with a subunit influenza vaccine elicits comparable systemic immune response as intramuscular immunization,but also induces local IgA and TH17 responses

Influenza is a vaccine-preventable disease that remains a major health problem world-wide. Needle and syringe are still the primary delivery devices, and injection of liquid vaccine into the muscle is still the primary route of immunization. Vaccines could be more convenient and effective if they were delivered by the mucosal route. Elicitation of systemic and mucosal innate and adaptive immune responses, such as pathogen neutralizing antibodies (including mucosal IgA at the site of pathogen entry) and CD4⁺ T-helper cells (especially the Th17 subset), have a critical role in vaccine-mediated protection. In the current study, a sublingual subunit influenza vaccine formulated with or without mucosal adjuvant was evaluated for systemic and mucosal immunogenicity and compared to intranasal and intramuscular vaccination. Sublingual administration of adjuvanted influenza vaccine elicited comparable antibody titers to those elicited by intramuscular immunization with conventional influenza vaccine. Furthermore, influenza-specific Th17 cells or neutralizing mucosal IgA were detected exclusively after mucosal immunization.     

Is Internet addiction a psychopathological condition distinct from pathological gambling?

Aims

The behavioural-addiction perspective suggests that Internet addiction (IA) and pathological gambling (PG) could share similar characteristics with substance dependence. Despite the similarities between IA and PG, it is not clear whether these disorders share different or similar psychopathological conditions. The aim of the present study was to test whether IA patients presented different psychological symptoms, temperamental traits, coping strategies and relational patterns compared with PG patients. The hypothesis was that IA patients will show greater interpersonal disengagement than PG patients.

Methods

Two clinical groups (31 IA patients and 11 PG patients) and a control group (38 healthy subjects) matched with the clinical groups for gender and age were enrolled. The clinical groups were gathered in a psychiatric service for IA and PG in a hospital. Anxiety, depression, coping strategies, attachment, temperament, and global assessment of functioning were measured. MANOVAs, ANOVAs and post-hoc comparisons were carried out in order to test the hypothesis.

Results

Despite IA and PG showing similar differences with the control group on the levels of depression, anxiety and global functioning, the two clinical groups showed different temperamental, coping and social patterns. Specifically IA patients compared with the PG patients showed a greater mental and behavioural disengagement associated with an important interpersonal impairment. The two clinical groups shared an impulsive coping strategy and socio-emotional impairments.

Conclusions

Despite IA and PG patients presenting similar clinical symptoms, IA condition was characterised by a more relevant mental, behavioural, and social disengagement compared to PG condition.     

Dopamine transporter availability in motor subtypes of de novo drug-naïve Parkinson’s disease

Tremor dominant (TD) and akinetic-rigid type (ART) are two motor subtypes of Parkinson’s disease associated with different disease progression and neurochemical/neuropathological features. The role of presynaptic nigrostriatal dopaminergic damage is still controversial, poorly explored, and only assessed in medicated patients. In this study, we investigated with FP-CIT SPECT the striatal dopamine transporter (DAT) availability in drug-naïve PD patients with ART and TD phenotypes. Fifty-one de novo, drug-naïve patients with PD underwent FP-CIT SPECT studies. Patients were evaluated with Unified Parkinson’s Disease Rating Scale (UPDRS) part III and Hoehn and Yahr scale (H&Y) and divided into ART (24/51) and TD (27/51) according to UPDRS part III. ART and TD patients were not different with regard to age, gender, and disease duration. However, compared to TD, ART patients presented higher UPDRS part III (p = 0.01) and H&Y (p = 0.02) and lower DAT availability in affected and unaffected putamen (p = 0.008 and p = 0.007, respectively), whereas no differences were found in caudate. Moreover, in the whole group of patients, rigidity and bradykinesia, but not tremor scores of UPDRS part III were significantly related to FP-CIT binding in the putamen. These results suggest that in newly diagnosed drug-naïve PD patients DAT availability might be different between ART and TD in relation to different disease severity.     

Mutations in CYP2U1, DDHD2 and GBA2 genes are rare causes of complicated forms of hereditary spastic paraparesis

Complicated hereditary spastic paraplegias (HSP) are a heterogeneous group of HSP characterized by spasticity associated with a variable combination of neurologic and extra-neurologic signs and symptoms. Among them, HSP with thin corpus callosum and intellectual disability is a frequent subtype, often inherited as a recessive trait (ARHSP-TCC). Within this heterogeneous subgroup, SPG11 and SPG15 represent the most frequent subtypes. We analyzed the mutation frequency of three genes associated with early-onset forms of ARHSP with and without TCC, CYP2U1/SPG56, DDHD2/SPG54 and GBA2/SPG46, in a large population of selected complicated HSP patients by using a combined approach of traditional-based and amplicon-based high-throughput pooled-sequencing. Three families with mutations were identified, one for each of the genes analyzed. Novel homozygous mutations were identified in CYP2U1 (c.1A>C/p.Met1?) and in GBA2 (c.2048G>C/p.Gly683Arg), while the homozygous mutation found in DDHD2 (c.1978G>C/p.Asp660His) had been previously reported in a compound heterozygous state. The phenotypes associated with the CYP2U1 and DDHD2 mutations overlap the SPG56 and the SPG54 subtypes, respectively, with few differences. By contrast, the GBA2 mutated patients show phenotypes combining typical features of both the SPG46 subtype and the recessive ataxia form, with marked intrafamilial variability thereby expanding the spectrum of clinical entities associated with GBA2 mutations. Overall, each of three genes analyzed shows a low mutation frequency in a general population of complicated HSP (<1 % for either CYP2U1 or DDHD2 and approximately 2 % for GBA2). These findings underline once again the genetic heterogeneity of ARHSP-TCC and the clinical overlap between complicated HSP and the recessive ataxia syndromes.