Cold-passaged isolates and bat-swine influenza a chimeric viruses as modified live-attenuated vaccines against influenza a viruses in pigs

Swine influenza A virus (swIAV) infections in pig populations cause considerable morbidity and economic losses. Frequent reverse zoonotic incursions of human IAV boost reassortment opportunities with authentic porcine and avian-like IAV in swine herds potentially enhancing zoonotic and even pre-pandemic potential. Vaccination using adjuvanted inactivated full virus vaccines is frequently used in attempting control of swIAV infections. Accelerated antigenic drift of swIAV in large swine holdings and interference of maternal antibodies with vaccine in piglets can compromise these efforts. Potentially more efficacious modified live-attenuated vaccines (MLVs) bear the risk of reversion of MLV to virulence. Here we evaluated new MLV candidates based on cold-passaged swIAV or on reassortment-incompetent bat-IAV-swIAV chimeric viruses. Serial cold-passaging of various swIAV subtypes did not yield unambiguously temperature-sensitive mutants although safety studies in mice and pigs suggested some degree of attenuation. Chimeric bat-swIAV expressing the hemagglutinin and neuraminidase of an avian-like H1N1, in contrast, proved to be safe in mice and pigs, and a single nasal inoculation induced protective immunity against homologous challenge in pigs. Reassortant-incompetent chimeric bat-swIAV vaccines could aid in reducing the amount of swIAV circulating in pig populations, thereby increasing animal welfare, limiting economic losses and lowering the risk of zoonotic swIAV transmission.     

Evaluation of Eye Movement Desensitization and Reprocessing in the management of tinnitus. An observational study

ObjectivesTinnitus can induce disabling psychological suffering, requiring an integrative multimodal approach, combining neuromodulation and psychotherapeutic methods. We sought to evaluate the therapeutic efficacy and acceptability of Eye Movement Desensitization and Reprocessing (EMDR) in tinnitus.Materials and methodsThis was a single-center prospective non-comparative study. Inclusion criteria comprised: adult patient, with chronic tinnitus, Tinnitus Handicap Inventory (THI) score > 17, causing psychological distress motivating active treatment after ineffective “classic” treatment (combining advice, sound therapy and first-line drug treatment), and agreement to EMDR therapy. Therapeutic efficacy was defined by a decrease in THI or Visual Analog Scale (VAS) scores. Treatment acceptability was defined by the rate of included patients who completed therapy.ResultsThirty-eight patients were included. There was a significant reduction of 53.5% in THI score in 78.9% of patients (P < 0.0001; 64.8 ± 20.8 before versus 31.8 ± 24.7 after treatment), and of 51% in VAS score in 76.3% of patients (P < 0.0001; 7.24 ± 2.12 before versus 3.58 ± 2.03 after treatment). The treatment acceptability was 86.8%.ConclusionEMDR appeared to be an effective alternative that was acceptable to the majority of patients, after failure of “classic” first-line treatment, improving quality of life in tinnitus patients and thus relieving disability.     

Association between oophorectomy and depression in patients with comorbidities: A nationwide cohort study in Taiwan

ObjectiveThis study investigated the long-term rates of depression after oophorectomy for benign gynecological conditions with or without comorbidities.Materials and methodsThis retrospective cohort study examined data from the National Health Insurance Research Database (NHIRD) involving 8199 women aged ≥20 years who underwent unilateral or bilateral oophorectomy for benign gynecological conditions (cases) between 2000 and 2013 (index date). A second cohort consisted of 32,796 women who did not undergo oophorectomy (controls) who were matched 4:1 to cases by age and index year. The follow-up time was more than 10 years. For all participants, the analysis accounted for comorbidities including hypertension, diabetes mellitus, hyperlipidemia, stroke, chronic obstructive pulmonary disease (COPD), chronic liver disease and cirrhosis, chronic kidney disease, and anxiety. Crude hazard ratios, adjusted hazard ratios, and 95% confidence intervals (CIs) were calculated according to multivariable Cox proportional hazard regression models adjusting for age, comorbidity, and the combination of oophorectomy with one comorbidity.ResultsOur results show that unilateral or bilateral oophorectomy, whether performed by laparotomy or laparoscopy, increases the overall risk of depression (aHR: 1.36, 95%CI: 1.19–1.55). Compared with controls, women aged <50 years had a significantly higher incidence of depression. Having diabetes (aHR: 1.66, 95%CI: 1.09–2.51), hypertension (aHR:1.56, 95%CI:1.14–2.14), hyperlipidemia (aHR: 1.46, 95%CI: 1.04–2.05), stroke (aHR: 1.91, 95%CI: 1.01–3.60), COPD (aHR: 2.06, 95%CI: 1.3–3.26), chronic liver cirrhosis (aHR: 1.99, 95%CI:1.52–2.61), or anxiety (aHR: 5.01, 95%CI: 3.74–6.70) increased higher risk of depression compared with not having these comorbidities after oophorectomy. The likelihood of depression was highest within the first 6 years following oophorectomy (3–5years:aHR:1.26, 95%CI:1.00–1.58).ConclusionsOopherectomy increases the overall risk of depression. We offer useful information for surgical decision-making and preoperative assessments of women undergoing oophorectomy. It is concluded that a synergistic effect exists between oophorectomy and the comorbidities. Post-surgery, physicians should carefully evaluate the risk of depression developing amongst women with comorbidities. A postoperative follow-up time of at least 6 years is recommended, as this period was associated with a significantly higher rate of depression during our over 10-year follow-up.     

Brain impedance variation of directional leads implanted in subthalamic nuclei of Parkinsonian patients

ObjectiveConventional deep brain stimulation (DBS) systems with ring-shaped leads generate spherical electrical fields. In contrast, novel directional leads use segmented electrodes. Aim of this study was to quantify the impedance variations over time in subjects with the directional Cartesia-Boston® system.MethodsImpedance records, programming settings, and clinical data of 11 consecutive Parkinsonian patients implanted with DBS directional leads in two Italian centers (Udine and Vicenza) were retrospectively evaluated. Data were collected before starting stimulation (in the operating room and at days 5 and 40) and after switching stimulation on at the successive follow-up visits (1, 6 and 12 months).ResultsDirectional leads have significantly higher impedance than ring leads. Stimulated contacts had always lower impedance compared to non-stimulated contacts. Before DBS-on, all contacts had higher impedance in the operating room, with an initial decrease five days post-surgery and a subsequent increase at day 40, more evident for directional contacts. The impedance of directional leads increased post-implantation at 1 and 6 months with a plateau at 12 months.ConclusionsThere was a significant difference between the directional and ring leads at baseline (before activation of DBS) and during follow-up (chronic DBS).SignificanceOur study reveals new information about the impedance of segmented electrodes that is useful for patient management during the initial test period, as well as during long-term DBS follow-up.     

Stress Management and Resiliency Training for public school teachers and staff: A novel intervention to enhance resilience and positively impact student interactions

BackgroundBurnout in teachers has been linked to decreased effectiveness as educators, and suboptimal interactions with students. The purpose of this pilot study was to assess the outcomes of a brief Stress Management and Resiliency Training (SMART) program for public school staff.Materials and methodsThis single-arm, prospective trial involved an investigation of the effects of a brief SMART program on participant stress, anxiety, resilience, gratitude, happiness, life satisfaction, and quality of life (QOL).ResultsSignificant improvements were noted in participant anxiety (P < 0.001), stress (P = 0.003), gratitude (P = 0.001), happiness (P < 0.001), life satisfaction (P < 0.001), and QOL (P < 0.001). Most participants reported that the skills learned positively affected interactions with students (77.2%) and coworkers (72.2%).ConclusionsThe SMART program showed promising effectiveness for improving anxiety, stress, gratitude, happiness, life satisfaction and QOL. Given the prevalence and impact of teacher burnout, larger, controlled trials and broader dissemination of the intervention are warranted.     

Anxiety and aggression in adolescents with autism spectrum disorders attending mainstream schools

This study investigated the link between anxiety and aggression in adolescents with autism spectrum disorders (ASDs) using self-report measures of anxiety and anger and teacher ratings of behaviour. Participants were 104 high school students aged 12–18: 52 students with ASDs, without intellectual disability, and their typically developing peers matched for age and gender. Students with ASDs who attend mainstream high schools reported higher levels of anxiety and reactive anger than their peers, were reported by their teachers to engage in more aggressive behaviours, and were at higher risk of being suspended from school. The results further suggested that social anxiety is a significant moderator of the relationship between autism and physical aggression. For ASD students, but not for the control students, there was a strong, positive relationship: higher levels of anxiety were associated with higher levels of physical aggression. However, ASD students with high anger control did not display physical aggression. Our results have implications for screening students for anxiety, the provision of interventions for managing anxiety and the development of anger management skills, and for the appropriateness of suspension as a mandatory response to incidents of physical aggression in schools.     

Effect of lacosamide on ethanol induced conditioned place preference and withdrawal associated behavior in mice: Possible contribution of hippocampal CRMP-2

BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal.