Ankyrin-G regulates forebrain connectivity and network synchronization via interaction with GABARAP.

GABAergic circuits are critical for the synchronization and higher order function of brain networks. Defects in this circuitry are linked to neuropsychiatric diseases, including bipolar disorder, schizophrenia, and autism. Work in cultured neurons has shown that ankyrin-G plays a key role in the regulation of GABAergic synapses on the axon initial segment and somatodendritic domain of pyramidal neurons, where it interacts directly with the GABAA receptor-associated protein (GABARAP) to stabilize cell surface GABAA receptors. Here, we generated a knock-in mouse model expressing a mutation that abolishes the ankyrin-G/GABARAP interaction (Ank3 W1989R) to understand how ankyrin-G and GABARAP regulate GABAergic circuitry in vivo. We found that Ank3 W1989R mice exhibit a striking reduction in forebrain GABAergic synapses resulting in pyramidal cell hyperexcitability and disruptions in network synchronization. In addition, we identified changes in pyramidal cell dendritic spines and axon initial segments consistent with compensation for hyperexcitability. Finally, we identified the ANK3 W1989R variant in a family with bipolar disorder, suggesting a potential role of this variant in disease. Our results highlight the importance of ankyrin-G in regulating forebrain circuitry and provide novel insights into how ANK3 loss-of-function variants may contribute to human disease.

Effectiveness of a programme to reduce the burden of catheter-related bloodstream infections in a tertiary hospital.

The objective of this study was to assess the effectiveness of a catheter-related bloodstream infection (CR BSI) reduction programme and healthcare workers' compliance with recommendations. A 3-year surveillance programme of CR BSIs in all hospital settings was implemented. As part of the programme, there was a direct observation of insertion and maintenance of central venous catheters (CVCs) to determine performance. A total of 38 education courses were held over the study period and feedback reports with the results of surveillance and recommendations were delivered to healthcare workers every 6 months. A total of 6722 short-term CVCs were inserted in 4982 patients for 58 763 catheter-days. Improvements of compliance with hand hygiene was verified at the insertion (87·1-100%, P < 0·001) and maintenance (51·1-72·1%, P = 0·029) of CVCs; and the use of chlorhexidine for skin disinfection was implemented at insertion (35·7-65·4%, P < 0·001) and maintenance (33·3-45·9%, P < 0·197) of CVCs. There were 266 CR BSI incidents recorded with an annual incidence density of 5·75/1000 catheter-days in the first year, 4·38 in the second year [rate ratio (RR) 0·76, 95% confidence interval (CI) 0·57-1·01] and 3·46 in the third year (RR 0·60, 95% CI 0·44-0·81). The education programme clearly improved compliance with recommendations for CVC handling, and was effective in reducing the burden of CR BSIs.

Seasonal influenza in octogenarians and nonagenarians admitted to a general hospital: epidemiology, clinical presentation and prognostic factors.

OBJECTIVE: Seasonal influenza is responsible for high annual morbidity and mortality worldwide, especially in elderly patients. The aim of the study was to analyse the epidemiological, clinical and prognostic features of influenza in octogenarians and nonagenarians admitted to a general hospital, as well as risk factors associated with mortality. METHODS: Retrospective, cross-sectional, descriptive study in patients admitted and diagnosed with influenza by molecular biology in the General University Hospital of Alicante from 1 January to 31 April 2015. RESULTS: A total of 219 patients were diagnosed with influenza in the study period: 55 (25.1%) were ≤64 years-old; 77 (35.2%) were aged 65-79; 67 (30.6%) were aged 80-89 years; and 20 (9.1%) were aged ≥90 years. Most flu episodes were caused by influenza A (n=181, 82.6%). Patients aged 80 years or older had lower glomerular filtration rate (mean: 49.7 mL/min vs. 62.2 mL/min; p=0.006), a greater need for non-invasive mechanical ventilation (22% vs 9.3%; p=0.02), greater co-morbidity due to cardiac insufficiency (40.5% vs. 16.4%; p<0.001) and chronic renal disease (32.9 vs. 20%, p=0.03), and greater mortality (19% vs. 2.9%; p<0.001). In a multivariate analysis, mortality was higher in those aged 80 or over (adjusted odds ratio [ORa] 9.2, 95% confidence interval [CI] 1.65-51.1), those who had acquired the flu in a long-term care facility (ORa 11.9, 95% CI 1.06-134), and those with hyperlactataemia (ORa 1.89, 95% CI 1.20-3.00). CONCLUSIONS: Seasonal influenza is a serious problem leading to elevated mortality in octogenarian and nonagenarian patients admitted to a general hospital.

In vitro activity of new fluoroquinolones and linezolid against non-tuberculous mycobacteria.

The objective of the study was to determine the activity of new fluoroquinolones and linezolid against 108 clinical isolates of different species of non-tuberculous mycobacteria isolated in Spain. Gatifloxacin and moxifloxacin were found to be more effective than levofloxacin. Mycobacterium kansasii was more susceptible to the fluoroquinolones tested than M. avium complex and M. fortuitum was more susceptible than M. chelonae. Linezolid was more active against M. kansasii than against M. avium complex. A better understanding of the relationship between the in vitro activity of these compounds and their usefulness in the treatment of these infections is needed. The new fluoroquinolones exhibit good activity against M. kansasii and M. fortuitum and linezolid is active against M. kansasii.

[Etiology of community-acquired pneumonia in ambulatory patients. Usefulness of a diagnostic investigation protocol using detection of Streptococcus pneumoniae and Legionella pneumophila antigens in urine samples]. / Etiología de la neumonía adquirida en la comunidad tratada ambulatoriamente. Utilidad de un protocolo diagnóstico con pruebas microbiológicas convencionales y detección de antígenos de Streptococcus pneumoniae y Legionella pneumophila en orina.

BACKGROUND: To determine the etiology of community-acquired pneumonia (CAP) in ambulatory patients and to assess the efficiency of a diagnostic protocol by using tests to detect bacterial antigens in urine samples. PATIENTS AND METHOD: One-year prospective study that included blood and sputum cultures, serologic studies, and detection of Legionella pneumophila and Streptococcus pneumoniae urinary antigens. RESULTS: 49 patients were recruited and an etiological diagnosis was attained in 34 (69%). Microorganisms most frequently isolated were S. pneumoniae (12 cases), Mycoplasma pneumoniae (7), Haemophilus influenzae (4), respiratory viruses (4) and Coxiella burnetii (3 cases). CONCLUSIONS: By means of a non-invasive protocol with urinary antigen tests, a microbial etiology can be established in two thirds of patients with mild CAP. S. pneumoniae is the main cause of mild CAP.

[Automatic analysis of the alternate movements of the arms in patients with type 2 spino cellular ataxia]. / Análisis automático de los movimientos alternativos de miembros superiores en pacientes con ataxia espinocerebelosa tipo 2.

INTRODUCTION: A patient with type 2 spino cerebellar ataxia has difficulty in carrying out alternate movements such as pronation and supination. OBJECTIVES. To evaluate the function of an automatized system for measuring disorders of alternate movements. PATIENTS AND METHODS: We studied the measurement of diadochokinesia in two groups of healthy patients, a first group (64 persons) to determine the normal intervals and a second group to validate the test (52 persons). We also studied 100 patients for validation of the system. A further 53 patients were evaluated before and after rehabilitation. RESULTS: Analysis of the basic measurements for diagnosis of duodochokinesia showed that the higher the cut off point, the greater the sensitivity of the test, whereas the opposite occurred with the specificity. Thus, regarding a higher cut off, there is a five times greater probability of a positive results in the patients than in healthy persons. However, the probability of a normal result is six times higher in healthy than in affected persons. The results of variant analysis done on patients before and after rehabilitation suggest that the presence of quantitative changes in the second study was due to the positive effect of neuro rehabilitation. CONCLUSION: The technique used is effective for differentiation of affected from healthy persons and its use is justified in the evaluation of co ordination ability after rehabilitation

[Comparative activity of several antibiotics against Toxoplasma gondii in a mouse model]. / Actividad comparada de varios antibióticos frente a Toxoplasma gondii en un modelo murino.

BACKGROUND: Infections with Toxoplasma gondii poses a great hazard to immunocompromised patients and to pregnant women. Currently, the recommended therapy for toxoplasmosis is the synergistic combination of pyrimethamine and sulfadiazine (P/S). However, this therapeutic regimen may be toxic or only partially effective. Because pyrimethamine is potentially teratogenic, its use during the early months of pregnancy is not recommended. There is a critical need for newer and safer compounds for the treatment of toxoplasmosis. These considerations led us to evaluate other potential therapeutic agents--minocycline, clindamycin, roxithromycin, azithromycin, clarithromycin and miocamycin--as well as comparison of P/S and spiramycin efficacy against T. gondii. METHODS: The activity of antibiotics was tested in a murine model of acute toxoplasmosis. NMRI mice were infected intraperitoneally with 200 tachyzoites of the highly virulent RH strain of T. gondii, and treated, every 12 h or 24 h, for ten consecutive days. RESULTS: P/S (a dose of 4/250 mg/kg of body weight per day), minocycline (200 mg/kg) and azithromycin (200 mg/kg) were the most active compounds (100% of mice survival). Clindamycin, roxithromycin, spiramycin and clarithromycin were less effective. Miocamycin was not effective in this model. CONCLUSIONS: Our findings support the view that minocycline and azithromycin could be useful in many cases of toxoplasmosis. Clinical studies are needed to determinate the relative efficacy and safety of these antibiotics for the treatment of toxoplasmosis in humans.