Antipsychotics in treatment-resistant Obsessive-Compulsive Disorder: which antipsychotic, which dose and how long antipsychotic addition should be maintained

Objectives: Treatment-resistant Obsessive-Compulsive Disorder (OCD) patients are defined as those who undergo adequate trials of first-line therapies without achieving a satisfactory response. First line treatments for OCD include both serotonin reuptake inhibitors (SRIs) and cognitive behavior therapy (CBT). Because of the high number of OCD patients not responding to first-line treatments (40-60%) and considering the even greater prevalence rate of residual symptoms and significant impairment shown in patients previously described as \u201cclinical responders\u201d, the question of the proper treatment of resistant OCD is a clinically meaningful and a practical issue for psychiatrists. Antipsychotic augmentation proved to be an effective strategy for resistant OCD. However, there are unresolved questions concerning which antipsychotic is effective (or more effective) and how antipsychotics should be used in terms of doses and duration of treatment. The purpose of this study is to systematically review available studies on antipsychotic augmentation for treatment-resistant OCD, in order to guide the practical choice. Materials and methods: We searched on PubMed, Psychnet and Cochrane Libraries from inception to January 2016. Articles published in English and related to the use of antipsychotics in OCD were considered. We evaluated meta-analyses, systematic reviews and randomized controlled trials of adult patients with treatment-resistant OCD. Results: Antipsychotic augmentation is an evidence-based option for treatmentresistant OCD, with a response rate of approximately 50% within the first 4-to6 weeks. Aripiprazole (10-15\ua0mg/day) and risperidone (0.5-2\ua0mg/day) are effective, olanzapine (10\ua0mg/day) is possibly effective. Haloperidol addition is also a viable option, particularly in patients with comorbid tic disorders. Given results of studies performed to date quetiapine should be regarded as non-effective. Preliminary results from open label studies suggest that antipsychotic augmentation, once effective, should be maintained in order to maintain remission. Conclusions: Not all antipsychotics are effective as add-on treatments in resistant OCD. Characteristics of patients and side effects generally associated with each different antipsychotic may guide the practical choice. Further research is required concerning the comparative effectiveness among antipsychotics, the optimal target dose and the ideal duration of antipsychotic addition. In our opinion, antipsychotic augmentation in patients who responded to this treatment should be maintained in order to prevent relapses. However, clinicians must remember patients\u2019 exposure to the common and serious adverse effects associated with long-term antipsychotic administration, especially metabolic disturbances

Radio ejection in the evolution of X-ray binaries: the bridge between low mass X-ray binaries and millisecond pulsars

We present a scenario for the spin-up and evolution of binary millisecond pulsars. This can explain the observational properties of the recently discovered binary millisecond pulsar PSR J1740-5340, with orbital period 32.5 hrs, in the Globular Cluster NGC 6397. The optical counterpart of this system is a star as luminous as the cluster turnoff stars, but with a lower Teff (a larger radius) which we model with a star of initial mass compatible with the masses evolving in the cluster (~0.85 Msun). This star has suffered Roche lobe overflow while evolving off the main sequence, spinning up the neutron star to the present period of 3.65 ms. There are evidences that at present, Roche lobe overflow is still going on. Indeed Roche lobe deformation of the mass losing component is necessary to be compatible with the optical light curve. The presence of matter around the system is also consistent with the long lasting irregular radio eclipses seen in the system. We propose that this system is presently in a phase of `radio-ejection' mass loss. The radio-ejection phase can be initiated only if the system is subject to intermittency in the mass transfer during the spin-up phase. In fact, when the system is detached the pulsar radio emission is not quenched, and may be able to prevent further mass accretion due to the action of the pulsar pressure at the inner Lagrangian point.Comment: 6 pages, including 3 figures. To appear in the proceedings of the XXII Moriond Astrophysics Meeting "The Gamma-Ray Universe" (Les Arcs, March 9-16, 2002), eds. A. Goldwurm, D. Neumann, and J. Tran Thanh Van, The Gioi Publishers (Vietnam

Xenon Anesthesia Improves Respiratory Gas Exchanges in Morbidly Obese Patients

Background. Xenon-in-oxygen is a high density gas mixture and may improve PaO2/FiO2 ratio in morbidly obese patients uniforming distribution of ventilation during anesthesia. Methods. We compared xenon versus sevoflurane anesthesia in twenty adult morbidly obese patients (BMI > 35) candidate for roux-en-Y laparoscopic gastric bypass and assessed PaO2/FiO2 ratio at baseline, at 15 min from induction of anaesthesia and every 60 min during surgery. Differences in intraoperative and postoperative data including heart rate, systolic and diastolic pressure, oxygen saturation, plateau pressure, eyes opening and extubation time, Aldrete score on arrival to the PACU were compared by the Mann-Whitney test and were considered as secondary aims. Moreover the occurrence of side effects and postoperative analgesic demand were assessed. Results. In xenon group PaO2-FiO2 ratio was significantly higher after 60 min and 120 min from induction of anesthesia; heart rate and overall remifentanil consumption were lower; the eyes opening time and the extubation time were shorter; morphine consumption at 72 hours was lower; postoperative nausea was more common. Conclusions. Xenon anesthesia improved PaO2/FiO2 ratio and maintained its distinctive rapid recovery times and cardiovascular stability. A reduction of opioid consumption during and after surgery and an increased incidence of PONV were also observed in xenon group

Sweat Rate Monitoring During Maximal Exercise in Healthy Soccer Players: A Close Relationship with Anaerobic Threshold

Purpose: Sweating is a homeostatic phenomenon regulated by both thermal and non-thermal factors during exercise. There are no evidences whether anaerobic metabolism induced during isotonic maximal exercise can modify sweating rate. Aim of the study was to investigate the relationship between sweating and the anaerobic threshold (AT). Methods: The sweat rate in thirteen soccer players was measured by a sensor providing a continuous monitoring of sweating, whereas the anaerobic threshold was assessed with ergospirometry during maximal isotonic stress test. During stress test, cardio respiratory, metabolic and galvanic skin response (GSR) were also monitored. Results: At AT, stroke volume, heart rate and systolic blood pressure significantly increased (p<0.001), as well as GSR (p=0.04). Sweat rate abruptly increased at AT compared with rest (p<0.001). AT-to-rest changes in sweating rate were associated with concomitant changes in VO2 max (r=0.82, p<0.001), heart rate (r=0.73, p=0.04) and GSR (r=0.79, p=0.001). Conclusion: We suggest that aerobic-to-anaerobic switch is associated with a sudden increase in sweating likely induced by sympathetic activation. Considering the role of hydration in preserving the health status and optimizing the physical performance, we believe that this finding may have relevant practical implication in particular in soccer, which is characterized by an alternation of aerobic and anaerobic phases

A Small Chaperone Improves Folding and Routing of Rhodopsin Mutants Linked to Inherited Blindness

The autosomal dominant form of retinitis pigmentosa (adRP) is a blindness-causing conformational disease largely linked to mutations of rhodopsin. Molecular simulations coupled to the graph-based protein structure network (PSN) analysis and in&nbsp;vitro experiments were conducted to determine the effects of 33 adRP rhodopsin mutations on the structure and routing of the opsin protein. The integration of atomic and subcellular levels of analysis was accomplished by the linear correlation between indices of mutational impairment in structure network and in routing. The graph-based index of structural perturbation served also to divide the mutants in four clusters, consistent with their differences in subcellular localization and responses to 9-cis retinal. The stability core of opsin inferred from PSN analysis was targeted by virtual screening of over 300,000 anionic compounds leading to the discovery of a reversible orthosteric inhibitor of retinal binding more effective than retinal in improving routing of three adRP mutants

Curcumin and Andrographolide Co-Administration Safely Prevent Steatosis Induction and ROS Production in HepG2 Cell Line

Non-alcoholic fatty liver disease (NAFLD) is an emerging chronic liver disease worldwide. Curcumin and andrographolide are famous for improving hepatic functions, being able to reverse oxidative stress and release pro-inflammatory cytokines, and they are implicated in hepatic stellate cell activation and in liver fibrosis development. Thus, we tested curcumin and andrographolide separately and in combination to determine their effect on triglyceride accumulation and ROS production, identifying the differential expression of genes involved in fatty liver and oxidative stress development. In vitro steatosis was induced in HepG2 cells and the protective effect of curcumin, andrographolide, and their combination was observed evaluating cell viability, lipid and triglyceride content, ROS levels, and microarray differential gene expression. Curcumin, andrographolide, and their association were effective in reducing steatosis, triglyceride content, and ROS stress, downregulating the genes involved in lipid accumulation. Moreover, the treatments were able to protect the cytotoxic effect of steatosis, promoting the expression of survival and anti-inflammatory genes. The present study showed that the association of curcumin and andrographolide could be used as a therapeutic approach to counter high lipid content and ROS levels in steatosis liver, avoiding the possible hepatotoxic effect of curcumin. Furthermore, this study improved our understanding of the antisteatosis and hepatoprotective properties of a curcumin and andrographolide combination

Determination of volatile organic compounds in exhaled breath of heart failure patients by needle trap micro-extraction coupled with gas chromatography-tandem mass spectrometry

The analytical performances of needle trap micro-extraction (NTME) coupled with gas chromatography tandem mass spectrometry were evaluated by analyzing a mixture of twenty-two representative breath VOCs belonging to different chemical classes (i.e. hydrocarbons, ketones, aldehydes, aromatics and sulfurs). NTME is an emerging technique that guarantees detection limits in pptv range by pre-concentrating low volumes of sample, and it is particularly suitable for breath analysis. For most VOCs, detection limits between 20 and 500 pptv were obtained by pre-concentrating 25 mL of a humidified standard gas mixture at a flow rate of 15 mL/min. For all compounds, inter- and intra-day precisions were always below 15%, confirming the reliability of the method. The procedure was successfully applied to the analysis of exhaled breath samples collected from forty heart failure patients during their stay in the University Hospital of Pisa. The majority of patients (about 80%) showed a significant decrease of breath acetone levels (a factor of 3 or higher) at discharge compared to admission (acute phase) in correspondence to the improved clinical conditions during hospitalization, thus making this compound eligible as a biomarker of heart failure exacerbation