Fear and Missing Out: Youth Anxiety and Functional Outcomes

Anxiety disorders are prevalent and associated with functional impairments. Outcome research has focused on symptom reduction, rather than positive factors such as life satisfaction and improved functioning. We review the impact of youth anxiety disorders and elevated anxiety symptoms on academic, occupational, family, social, and legal functioning. Emphasis is placed on the degree to which developmental trajectories differ for youth with and without anxiety disorders. In some areas, psychopathology generally, rather than anxiety specifically, is associated with functional impairment. Other studies support youth anxiety as a unique predictor of functional impairment. In particular, social anxiety is associated with impairments in social functioning throughout development. The short‐ and long‐term impacts of anxiety treatment in youth are discussed. Last, research directions are suggested.     

Macrophage accumulation in gut mucosa differentiates AIDS from chronic SIV infection in rhesus macaques

The relationship between recruitment of mononuclear phagocytes to lymphoid and gut tissues and disease in HIV and SIV infection remains unclear. To address this question, we conducted cross‐sectional analyses of dendritic cell (DC) subsets and CD163⁺ macrophages in lymph nodes (LNs) and ileum of rhesus macaques with acute and chronic SIV infection and AIDS. In LNs significant differences were only evident when comparing uninfected and AIDS groups, with loss of myeloid DCs and CD103⁺ DCs from peripheral and mesenteric LNs, respectively, and accumulation of plasmacytoid DCs and macrophages in mesenteric LNs. In contrast, there were fourfold more macrophages in ileum lamina propria in macaques with AIDS compared with chronic infection, and this increased to 40‐fold in Peyer's patches. Gut macrophages exceeded plasmacytoid DCs and CD103⁺ DCs by ten‐ to 17‐fold in monkeys with AIDS but were at similar low frequencies as DCs in chronic infection. Gut macrophages in macaques with AIDS expressed IFN‐α and TNF‐α consistent with cell activation. CD163⁺ macrophages also accumulated in gut mucosa in acute infection but lacked expression of IFN‐α and TNF‐α. These data reveal a relationship between inflammatory macrophage accumulation in gut mucosa and disease and suggest a role for macrophages in AIDS pathogenesis.     

High-throughput gene mapping in Caenorhabditis elegans

Positional cloning of mutations in model genetic systems is a powerful method for the identification of targets of medical and agricultural importance. To facilitate the high-throughput mapping of mutations in Caenorhabditis elegans, we have identified a further 9602 putative new single nucleotide polymorphisms (SNPs) between two C. elegans strains, Bristol N2 and the Hawaiian mapping strain CB4856, by sequencing inserts from a CB4856 genomic DNA library and using an informatics pipeline to compare sequences with the canonical N2 genomic sequence. When combined with data from other laboratories, our marker set of 17,189 SNPs provides even coverage of the complete worm genome. To date, we have confirmed >1099 evenly spaced SNPs (one every 91 +/- 56 kb) across the six chromosomes and validated the utility of our SNP marker set and new fluorescence polarization-based genotyping methods for systematic and high-throughput identification of genes in C. elegans by cloning several proprietary genes. We illustrate our approach by recombination mapping and confirmation of the mutation in the cloned gene, dpy-18.     

Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations

Although many genes have been identified for the autosomal recessive cerebellar ataxias (ARCAs), several patients are unlinked to the respective loci, suggesting further genetic heterogeneity. We combined homozygosity mapping and exome sequencing in a consanguineous Egyptian family with congenital ARCA, mental retardation and pyramidal signs. A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate with ataxia in the family. Our findings are compatible with the concept of truncating SPTBN2 mutations acting recessively, which is supported by disease expression in homozygous, but not heterozygous, knockout mice, ataxia in Beagle dogs with a homozygous frameshift mutation and, very recently, a homozygous SPTBN2 nonsense mutation underlying infantile ataxia and psychomotor delay in a human family. As there was no evidence for mutations in 23 additional consanguineous families, SPTBN2-related ARCA is probably rare.     

急性淋巴细胞白血病最新治疗策略(下)

4分子治疗分析肿瘤细胞中的分子遗传性变异及后天变异的方法正在快速成熟起来。这些方法通常涉及基因组学、转录特征性识别及蛋白质组学,有利于更深入地了解ALL的发病机理,使用于临床评估的靶向治疗全面发展。最终,这些层出不穷的新技术将营造出一个全新的个性化分子医学时代,创造出效果更好而毒性更低的治疗方案。尽管治疗方案均显示了药物介入控制细胞周期进程、基因转录、细胞运动、凋亡及细胞代谢信号通路的可行性(图1),但针对ALL的分子治疗情况(表1)仍差强人意。我们将从众多正处于临床前期或早期临床研究的分子治疗方案中,选择出那…     

Semen quality of fertile US males in relation to their mothers' beef consumption during pregnancy

BACKGROUND To look at possible long-term risks from anabolic steroids and other xenobiotics in beef, we examined men's semen quality in relation to their mother's self-reported beef consumption during pregnancy. METHODS: The study was carried out in five US cities between 1999 and 2005. We used regression analyses to examine semen parameters in 387 partners of pregnant women in relation to the amount of beef their mothers reported eating while pregnant. Mothers' beef consumption was also analysed in relation to the son's history of previous subfertility. RESULTS Sperm concentration was inversely related to mothers' beef meals per week (P = 0.041). In sons of "high beef consumers" (>7 beef meals/week), sperm concentration was 24.3% lower (P = 0.014) and the proportion of men with sperm concentration below 20 x 10(6)/ml was three times higher (17.7 versus 5.7%, P = 0.002) than in men whose mothers ate less beef. A history of previous subfertility was also more frequent among sons of "high beef consumers" (P = 0.015). Sperm concentration was not significantly related to mother's consumption of other meat or to the man's consumption of any meat. CONCLUSIONS These data suggest that maternal beef consumption, and possibly xenobiotics in beef, may alter a man's testicular development in utero and adversely affect his reproductive capacity.     

A centralised, automated dental hospital water quality and biofilm management system using neutral Ecasol™ maintains dental unit waterline output at better than potable quality: A 2-year longitudinal study

Most studies addressing biofilm formation in dental chair unit waterlines (DUWLs) have focused on a range of individual dental chair units (DCUs) and no studies on a centralised approach in a large number of DCUs have been reported to date.

Objectives

To develop a centralised, automated water quality and biofilm management system serving the distribution network providing water to Dublin Dental Hospital's 103 DCUs, capable of maintaining DUWL supply and output water at better than potable quality standards in the long-term and requiring a minimum of human intervention. The potable water standard for the European Union does not specify an upper limit of aerobic heterotrophic bacteria, whereas a maximum of 100 cfu/mL is permitted in bottled water.

Methods

Mains water of varying quality was treated by specifically selected automated filtration units to provide DCUs with water of consistent chemical composition. This water was then automatically disinfected using an electrochemically activated solution Ecasol™ (Trustwater Group, Clonmel, Ireland) (2.5 ppm) prior to distribution to DCUs. Microbiological quality of both DUWL supply and output water was monitored weekly by culture on R2A agar for 10 sentinel DCUs for a 100-week period. DUWLs were tested for the presence of biofilm by electron microscopy.

Results

Chemical composition of processed mains water consistently bettered potable water standards. DUWL supply water and output water aerobic heterotrophic bacterial counts averaged <1 and 18.1 cfu/mL, respectively, from the 10 DCUs, compared to 88 cfu/mL for unprocessed mains water. This correlated with the absence of biofilm in DUWLs. No adverse effects due to Ecasol™ treatment of supply water were observed for DUWLs or DCU instruments.

Conclusions

This centralised and automated water treatment and biofilm management system consistently maintains DUWL output water at better than potable quality simultaneously in a large number of DCUs over the long-term.