Effectiveness of music therapy for autism spectrum disorder, dementia, depression, insomnia and schizophrenia: Update of systematic reviews

Background Music therapy (MT) aims at maintaining, restoring and furthering physical/emotional/mental health. This review assesses effectiveness of MT and its methods for autism spectrum disorder (ASD), dementia, depression, insomnia and schizophrenia. Methods A search for systematic reviews and health technology assessment reports was conducted and yielded 139 hits. Given the large amount, we focused on five frequent diagnostic groups with available Cochrane reviews. A second search was conducted in four databases. Two authors independently performed study selection, data extraction and assessed methodological quality. Only trials with moderate/low risk of bias (RoB) were selected. Results Ten randomized controlled trials (1.248 participants) met inclusion criteria. For schizophrenia, no studies with low/moderate RoB were found; therefore, updating was not possible. The Cochrane authors stated that quality of life (QoL), social functioning, global/mental state improved for schizophrenia, but not global functioning. For ASD, MT improved behaviour, social communication, brain connectivity and parent–child relationship. For depression, mood was enhanced, and for insomnia, sleep quality, stress, anxiety, total sleep time, disease severity and psychological QoL improved. MT positively affected mood, neuropsychiatric behaviour, apathy, communication and physical functions for dementia; behavioural/psychological symptoms improved only in severe, and memory and verbal fluency only in mild Alzheimer’s disease. Cognition improved for dementia in one of four studies. Both active (playing music) and receptive (listening to music) methods were used for dementia, whereas for ASD and depression, active methods were applied. For insomnia, only receptive methods were used. Conclusion These findings provide evidence that MT helps patients improving their physical/psychosocial health. More research investigating long-term effects is needed.publishedVersio

A Small-molecule Inhibitor Directed against the Chemokine Receptor CXCR4 Prevents its Use as an HIV-1 Coreceptor

The chemokine receptor CXCR4 is the major coreceptor used for cellular entry by T cell– tropic human immunodeficiency virus (HIV)-1 strains, whereas CCR5 is used by macrophage (M)-tropic strains. Here we show that a small-molecule inhibitor, ALX40-4C, inhibits HIV-1 envelope (Env)-mediated membrane fusion and viral entry directly at the level of coreceptor use. ALX40-4C inhibited HIV-1 use of the coreceptor CXCR4 by T- and dual-tropic HIV-1 strains, whereas use of CCR5 by M- and dual-tropic strains was not inhibited. Dual-tropic viruses capable of using both CXCR4 and CCR5 were inhibited by ALX40-4C only when cells expressed CXCR4 alone. ALX40-4C blocked stromal-derived factor (SDF)-1α–mediated activation of CXCR4 and binding of the monoclonal antibody 12G5 to cells expressing CXCR4. Overlap of the ALX40-4C binding site with that of 12G5 and SDF implicates direct blocking of Env interactions, rather than downregulation of receptor, as the mechanism of inhibition. Thus, ALX40-4C represents a small-molecule inhibitor of HIV-1 infection that acts directly against a chemokine receptor at the level of Env-mediated membrane fusion

Development and characterization of a new single cycle vaccine vector in the simian immunodeficiency virus model system

We have developed a new single cycle lentiviral vector, SIVsmH4i-SC27.1, as a potential SIV/HIV-1 vaccine candidate. This viral vector is capable of expressing all of the SIV gene products but is limited to one round of infection. The vector was created by mutating 27 codons dispersed among the viral , and genes to block protein function, attenuate viral replication/infectivity, and reduce the ability of the virus to manipulate the host immune system. To complement the and replication defects, SC27.1 was pseudotyped with the VSV G glycoprotein to allow particle entry. The mutation was complemented by producing particles from an APOBEC3G-negative cell line, and the Vif protein defect was validated by showing that the single cycle virus lost most of its infectivity when particles were produced in presence of APOBEC3G. To deal with the problem of an antibody response to the VSV G protein in a vaccination strategy, two additional serotypes of the VSV G protein were used to create pseudotyped virus particles, and we observed no cross-neutralization activity for two of the pseudotyped particles with a potent neutralizing antiserum to one of the VSV G proteins. We detected moderate inhibition of infectivity in normal human and macaque sera, especially to the New Jersey serotype of VSV G, but as a heat sensitive activity, presumably complement mediated. These particles can be used in a prime-boost strategy to determine if a single cycle lentiviral vaccine vector capable of expressing all of the viral gene products holds promise in inducing immunity and protection to an SIVsm challenge

Allergen Micro-Bead Array for IgE Detection: A Feasibility Study Using Allergenic Molecules Tested on a Flexible Multiplex Flow Cytometric Immunoassay

Background: Allergies represent the most prevalent non infective diseases worldwide. Approaching IgE-mediated sensitizations improved much by adopting allergenic molecules instead of extracts, and by using the micro-technology for multiplex testing. Objective and Methods: To provide a proof-of-concept that a flow cytometric bead array is a feasible mean for the detection of specific IgE reactivity to allergenic molecules in a multiplex-like way. A flow cytometry Allergenic Moleculebased micro-bead Array system (ABA) was set by coupling allergenic molecules with commercially available micro-beads. Allergen specific polyclonal and monoclonal antibodies, as well as samples from 167 allergic patients, characterized by means of the ISAC microarray system, were used as means to show the feasibility of the ABA. Three hundred and thirty-six sera were tested for 1 or more of the 16 selected allergens, for a total number of 1,519 tests on each of the two systems. Results: Successful coupling was initially verified by detecting the binding of rabbit polyclonal IgG, mouse monoclonal, and pooled human IgE toward three allergens, namely nDer s 1, nPen m 1, and nPru p 3. The ABA assay showed to detect IgE t

Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce β-chemokines

Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. We report that four human anti-phospholipid monoclonal antibodies (mAbs) (PGN632, P1, IS4, and CL1) inhibit HIV-1 CCR5-tropic (R5) primary isolate infection of peripheral blood mononuclear cells (PBMCs) with 80% inhibitory concentrations of <0.02 to ∼10 µg/ml. Anti-phospholipid mAbs inhibited PBMC HIV-1 infection in vitro by mechanisms involving binding to monocytes and triggering the release of MIP-1α and MIP-1β. The release of these β-chemokines explains both the specificity for R5 HIV-1 and the activity of these mAbs in PBMC cultures containing both primary lymphocytes and monocytes

High Viral Fitness during Acute HIV-1 Infection

Several clinical studies have shown that, relative to disease progression, HIV-1 isolates that are less fit are also less pathogenic. The aim of the present study was to investigate the relationship between viral fitness and control of viral load (VL) in acute and early HIV-1 infection. Samples were obtained from subjects participating in two clinical studies. In the PULSE study, antiretroviral therapy (ART) was initiated before, or no later than six months following seroconversion. Subjects then underwent multiple structured treatment interruptions (STIs). The PHAEDRA study enrolled and monitored a cohort of individuals with documented evidence of primary infection. The subset chosen were individuals identified no later than 12 months following seroconversion to HIV-1, who were not receiving ART. The relative fitness of primary isolates obtained from study participants was investigated ex vivo. Viral DNA production was quantified using a novel real time PCR assay. Following intermittent ART, the fitness of isolates obtained from 5 of 6 PULSE subjects decreased over time. In contrast, in the absence of ART the fitness of paired isolates obtained from 7 of 9 PHAEDRA subjects increased over time. However, viral fitness did not correlate with plasma VL. Most unexpected was the high relative fitness of isolates obtained at Baseline from PULSE subjects, before initiating ART. It is widely thought that the fitness of strains present during the acute phase is low relative to strains present during chronic HIV-1 infection, due to the bottleneck imposed upon transmission. The results of this study provide evidence that the relative fitness of strains present during acute HIV-1 infection may be higher than previously thought. Furthermore, that viral fitness may represent an important clinical parameter to be considered when deciding whether to initiate ART during early HIV-1 infection

Natural Products as Anti-HIV Agents and Role in HIV-Associated Neurocognitive Disorders (HAND): A Brief Overview

As the threat of Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) persists to rise, effective drug treatments are required to treat the infected people. Even though combination antiretroviral therapy (cART) provides stable viral suppression, it is not devoid of undesirable side effects, especially in persons undergoing long-term treatment. The present therapy finds its limitations in the emergence of multidrug resistance and accordingly finding new drugs and novel targets is the need of the hour to treat the infected persons and further to attack HIV reservoirs in the body like brain, lymph nodes to achieve the ultimate goal of complete eradication of HIV and AIDS. Natural products such as plant-originated compounds and plant extracts have enormous potential to become drug leads with anti-HIV and neuroprotective activity. Accordingly, many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action and for HIV-associated neurocognitive disorders (HAND). The basic challenge that still persists is to develop viral replication-targeted therapy using novel anti-HIV compounds with new mode of action, accepted toxicity and less resistance profile. Against this backdrop, the World Health Organization (WHO) suggested the need to evaluate ethno-medicines for the management of HIV/AIDS. Consequently, there is need to evaluate traditional medicine, particularly medicinal plants and other natural products that may yield effective and affordable therapeutic agents. Although there are a good number of reports on traditional uses of plants to treat various diseases, knowledge of herbal remedies used to manage HIV/AIDS and HAND are scanty, vague and not well documented. In this review, plant substances showing a promising action that is anti-HIV and HAND will be explored along with what they interact. Since some plant substances are also known to modulate several cellular factors which are also involved in the replication of HIV and hence their role as potential candidates will be discussed. HIV/AIDS being an exceptional epidemic, demands an exceptional approach and that forms very much focus for the current review