FKK

Music therapy for people with autism spectrum disorder

Background: The central impairments of people with autism spectrum disorder (ASD) affect social interaction and communication. Music therapy uses musical experiences and the relationships that develop through them to enable communication and expression, thus attempting to address some of the core problems of people with ASD. The present version of this review on music therapy for ASD is an update of the original Cochrane review published in 2006. Objectives: To assess the effects of music therapy for individuals with ASD. Search methods: We searched the following databases in July 2013: CENTRAL, Ovid MEDLINE, EMBASE, LILACS, PsycINFO, CINAHL, ERIC, ASSIA, Sociological Abstracts, and Dissertation Abstracts International. We also checked the reference lists of relevant studies and contacted investigators in person. Selection criteria: All randomised controlled trials (RCTs) or controlled clinical trials comparing music therapy or music therapy added to standard care to 'placebo' therapy, no treatment, or standard care for individuals with ASD were considered for inclusion. Data collection and analysis: Two authors independently selected studies, assessed risk of bias, and extracted data from all included studies. We calculated the pooled standardised mean difference (SMD) and corresponding 95% confidence interval (CI) for continuous outcomes to allow the combination data from different scales and to facilitate the interpretation of effect sizes. Heterogeneity was assessed using the I? statistic. In cases of statistical heterogeneity within outcome subgroups, we examined clients' age, intensity of therapy (number and frequency of therapy sessions), and treatment approach as possible sources of heterogeneity. Main results: We included 10 studies (165 participants) that examined the short- and medium-term effect of music therapy interventions (one week to seven months) for children with ASD. Music was superior to 'placebo' therapy or standard care with respect to the primary outcomes social interaction within the therapy context (SMD 1.06, 95% CI 0.02 to 2.10, 1 RCT, n = 10); generalised social interaction outside of the therapy context (SMD 0.71, 95% CI 0.18 to 1.25, 3 RCTs, n = 57, moderate quality evidence), non-verbal communicative skills within the therapy context (SMD 0.57, 95% CI 0.29 to 0.85, 3 RCTs, n = 30), verbal communicative skills (SMD 0.33, 95% CI 0.16 to 0.49, 6 RCTs, n = 139), initiating behaviour (SMD 0.73, 95% CI 0.36 to 1.11, 3 RCTs, n = 22, moderate quality evidence), and social-emotional reciprocity (SMD 2.28, 95% CI 0.73 to 3.83, 1 RCT, n = 10, low quality evidence). There was no statistically significant difference in non-verbal communicative skills outside of the therapy context (SMD 0.48, 95% CI -0.02 to 0.98, 3 RCTs, n = 57, low quality evidence). Music therapy was also superior to 'placebo' therapy or standard care in secondary outcome areas, including social adaptation (SMD 0.41, 95% CI 0.21 to 0.60, 4 RCTs, n = 26), joy (SMD 0.96, 95% CI 0.04 to 1.88, 1 RCT, n = 10), and quality of parent-child relationships (SMD 0.82, 95% CI 0.13 to 1.52, 2 RCTs, n = 33, moderate quality evidence). None of the included studies reported any adverse effects. The small sample sizes of the studies limit the methodological strength of these findings. Authors' conclusions: The findings of this updated review provide evidence that music therapy may help children with ASD to improve their skills in primary outcome areas that constitute the core of the condition including social interaction, verbal communication, initiating behaviour, and social-emotional reciprocity. Music therapy may also help to enhance non-verbal communication skills within the therapy context. Furthermore, in secondary outcome areas, music therapy may contribute to increasing social adaptation skills in children with ASD and to promoting the quality of parent-child relationships. In contrast to the studies included in an earlier version of this review published in 2006, the new studies included in this update enhanced the applicability of findings to clinical practice. More research using larger samples and generalised outcome measures is needed to corroborate these findings and to examine whether the effects of music therapy are enduring. When applying the results of this review to practice, it is important to note that the application of music therapy requires specialised academic and clinical training.

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry^1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis³, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach⁴, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry⁵. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth

Background: It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common.
Methods: We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group).
Results: Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose.
Conclusions: In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).

Early Convalescent Plasma for High-Risk Outpatients with Covid-19

Background: Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19.
Methods: In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause.
Results: A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups.
Conclusions: The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).

Black Phosphorus Nanosheets Passivation Using a Tripeptide

In the past several years, 2D black phosphorus (BP) has captured the research community's interest because of its unique electronic, photonic, and mechanical properties. However, the intrinsic instability of BP limits its preservation and practical application. Despite kinds of BP passivation strategies being well-documented, the use of metal ligand coordination or polymer modification may have potential long-term detrimental effects on human bodies. Here, a tailored tripeptide Fmoc-Lys-Lys-Phe (Fmoc-KKF) is synthesized for surface modification of BP nanosheets. Compared with bare BP with rapid degradation, the BP@FKK complex exhibits excellent stability, thereby significantly increasing the life span. Significantly, the BP@FKK shows favorable cell compatibility and enhanced cellular uptake compared to the bare BP.