Lack of viral control and development of combination antiretroviral therapy escape mutations in macaques after bone marrow transplantation

We have previously demonstrated robust control of simian/human immunodeficiency virus (SHIV1157-ipd3N4) viremia following administration of combination antiretroviral therapy (cART) in pigtailed macaques. Here, we sought to determine the safety of hematopoietic stem cell transplantation (HSCT) in cART-suppressed and unsuppressed animals

Complete sequence of the 22q11.2 allele in 1,053 subjects with 22q11.2 deletion syndrome reveals modifiers of conotruncal heart defects

The 22q11.2 deletion syndrome (22q11.2DS) results from non-allelic homologous recombination between low-copy repeats termed LCR22. About 60%-70% of individuals with the typical 3 megabase (Mb) deletion from LCR22A-D have congenital heart disease, mostly of the conotruncal type (CTD), whereas others have normal cardiac anatomy. In this study, we tested whether variants in the hemizygous LCR22A-D region are associated with risk for CTDs on the basis of the sequence of the 22q11.2 region from 1,053 22q11.2DS individuals. We found a significant association (FDR p < 0.05) of the CTD subset with 62 common variants in a single linkage disequilibrium (LD) block in a 350 kb interval harboring CRKL. A total of 45 of the 62 variants were associated with increased risk for CTDs (odds ratio [OR) ranges: 1.64-4.75). Associations of four variants were replicated in a meta-analysis of three genome-wide association studies of CTDs in affected individuals without 22q11.2DS. One of the replicated variants, rs178252, is located in an open chromatin region and resides in the double-elite enhancer, GH22J020947, that is predicted to regulate CRKL (CRK-like proto-oncogene, cytoplasmic adaptor) expression. Approximately 23% of patients with nested LCR22C-D deletions have CTDs, and inactivation of Crkl in mice causes CTDs, thus implicating this gene as a modifier. Rs178252 and rs6004160 are expression quantitative trait loci (eQTLs) of CRKL. Furthermore, set-based tests identified an enhancer that is predicted to target CRKL and is significantly associated with CTD risk (GH22J020946, sequence kernal association test (SKAT) p = 7.21 × 10-5) in the 22q11.2DS cohort. These findings suggest that variance in CTD penetrance in the 22q11.2DS population can be explained in part by variants affecting CRKL expression

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian Consensus Conference on Pain in Neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present

Parental practices and pedestrian risk behaviors in Chilean adolescents Prácticas parentales y conductas de riesgo del peatón en una muestra de adolescentes chilenos

© 2014, Sociedad Medica de Santiago. All rights reserved.Background: Traffic accidents are the second leading cause of death among adolescents and young adults in Chile. However, few studies have examined this behavior among this age group. Parental practices have a great influence on risk behaviors in adolescents, such as substance use, sexuality and violence, among others. Specifically, we propose that these practices will influence pedestrian risk behaviors among adolescents. Aim: To study the role of parental practices such as mother and father support, and behavioral control (monitoring and presence of rules) in pedestrian risk behaviors of teenagers. Material and Methods: A sample of 470 adolescents attending schools in the Metropolitan Region of Santiago, Chile were studied. They answered a self-administered questionnaire in which they were asked about parental practices and pedestrian risk behaviors. Analyses were performed using descriptive and inferential statistics, using m

Virtual reality and mobile phones in the treatment of generalized anxiety disorders: a phase-2 clinical trial

Several studies have demonstrated that exposure therapy-in which the patient is exposed to specific feared situations or objects that trigger anxiety-is an effective way to treat anxiety disorders. However, to overcome a number of limitations inherent in this approach-lack of full control of the situation, costs and time required, etc.-some therapists have started to add virtual reality (VR) to the in vivo exposure-based therapy, providing in-office, controlled exposure therapy. Compared to the in vivo exposure, VR Exposure Therapy (VRET) is completely controlled: the quality, the intensity and the frequency of the exposure are decided by the therapist, and the therapy can be stopped at any time if the patient does not tolerate it. Moreover, the flexibility of a virtual experience allows the patient to experience situations that are often much worse and more exaggerated than those that are likely to be encountered in real life. However, a critical issue underlying the use of VRET in the treatment of anxiety-related disorders is the lack of a virtual reality system in the patient's real-life context. In this paper, we present a clinical protocol for the treatment of Generalized Anxiety Disorders (GAD) based on the ubiquitous use of a biofeedback-enhanced VR system. The protocol includes the use of a mobile exposure system allowing patients to perform the virtual experience in an outpatient setting. A between-subjects study, involving 25 GAD patients, was carried out to verify the efficacy of the proposed approach. The clinical data in this pilot study seemed to support the efficacy of the ubiquitous approach

Presence-Inducing Media for Mental Health Applications

Presence inducing media have recently emerged as a potentially effective way to provide general and specialty mental health services, and they appear poised to enter mainstream clinical delivery. However, to ensure appropriate development and use of these technologies, clinicians must have a clear understanding of the opportunities and challenges they will provide to professional practice. This chapter attempts to outline the current state of clinical research related to the use of presence-inducing technologies, virtual reality in particular. Through presence, virtual reality helps the patient both to confront his/her problems in a meaningful yet controlled and safe setting. Further, it opens the possibility of experiencing his/her life in another, more satisfactory, way. In fact, virtual reality therapists are using presence to provide meaningful experiences which are capable of inducing deep and permanent changes in their patients. Finally, the chapter discusses the possible evolution of presence-inducing media from virtual reality to augmented reality, to interreality