Database analysis of children and adolescents with Bipolar Disorder consuming a micronutrient formula

<p>Abstract</p> <p>Background</p> <p>Eleven previous reports have shown potential benefit of a 36-ingredient micronutrient formula (known as EMPowerplus) for the treatment of psychiatric symptoms. The current study asked whether children (7-18 years) with pediatric bipolar disorder (PBD) benefited from this same micronutrient formula; the impact of Attention-Deficit/Hyperactivity Disorder (ADHD) on their response was also evaluated.</p> <p>Methods</p> <p>Data were available from an existing database for 120 children whose parents reported a diagnosis of PBD; 79% were taking psychiatric medications that are used to treat mood disorders; 24% were also reported as ADHD. Using Last Observation Carried Forward (LOCF), data were analyzed from 3 to 6 months of micronutrient use.</p> <p>Results</p> <p>At LOCF, mean symptom severity of bipolar symptoms was 46% lower than baseline (effect size (ES) = 0.78) (<it>p </it>< 0.001). In terms of responder status, 46% experienced >50% improvement at LOCF, with 38% still taking psychiatric medication (52% drop from baseline) but at much lower levels (74% reduction in number of medications being used from baseline). The results were similar for those with both ADHD and PBD: a 43% decline in PBD symptoms (ES = 0.72) and 40% in ADHD symptoms (ES = 0.62). An alternative sample of children with just ADHD symptoms (n = 41) showed a 47% reduction in symptoms from baseline to LOCF (ES = 1.04). The duration of reductions in symptom severity suggests that benefits were not attributable to placebo/expectancy effects. Similar findings were found for younger and older children and for both sexes.</p> <p>Conclusions</p> <p>The data are limited by the open label nature of the study, the lack of a control group, and the inherent self-selection bias. While these data cannot establish efficacy, the results are consistent with a growing body of research suggesting that micronutrients appear to have therapeutic benefit for children with PBD with or without ADHD in the absence of significant side effects and may allow for a reduction in psychiatric medications while improving symptoms. The consistent reporting of positive changes across multiple sites and countries are substantial enough to warrant a call for randomized clinical trials using micronutrients.</p

Impact of periodic health examination on surgical treatment for uterine fibroids in Beijing: a case-control study

<p>Abstract</p> <p>Background</p> <p>During the past 2 decades, there has been a rapid proliferation of "health examination center (HEC)" across China. The effects of their services on public's health have not been systemically investigated. This study aimed to assess the impact of periodic health examination (PHE) at HEC on surgical treatment for uterine fibroids in Beijing residents.</p> <p>Methods</p> <p>We identified 224 patients with a primary diagnosis of uterine fibroids who had surgical treatment at four Level-1 general hospitals in Beijing, from June 1, 2009 to October 20, 2009. Controls were women who did not have surgery for uterine fibroids, matched (1:1 ratio) for age (within 2 years). A standard questionnaire was used to inquire about whether participants had PHE at HEC during the previous 2 years.</p> <p>Results</p> <p>PHE at HEC within 2 years were associated with surgical treatment for uterine fibroids. Odds ratios was 4.05 (95% CI, 2.61-6.29 P < 0.001), after adjustment for marital status, whether have children, annual family income, health insurance, education level and self-rated uterine fibroids-related symptom severity.</p> <p>Conclusions</p> <p>Our study showed PHE currently provided at HEC in China were associated with significantly increased use of surgical treatment for uterine fibroids in women. Further studies are needed to assess the effects of PHE on clinical as well as on broad societal outcomes in Chinese in contemporary medical settings.</p

The -786T>C promoter polymorphism of the NOS3 gene is associated with prostate cancer progression

<p>Abstract</p> <p>Background</p> <p>There is no biological or epidemiological data on the association between <it>NOS3 </it>promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of <it>NOS3 </it>gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage.</p> <p>Methods</p> <p>This study aimed evaluating the <it>NOS3 </it>promoter polymorphisms by PCR-SSCP and sequencing, associating genotypes and haplotypes with <it>NOS3 </it>expression levels through semi-quantitative RT-PCR, and with <it>PCA</it>3 mRNA detection, a specific tumor biomarker, in the peripheral blood of pre-surgical samples from 177 patients; 83 PCa and 94 BPH.</p> <p>Results</p> <p>Three novel SNPs were identified -764A>G, -714G>T and -649G>A in the <it>NOS3 </it>gene promoter region, which together with the -786T>C generated four haplotypes (N, T, C, A). <it>NOS3 </it>gene expression levels were affected by the -786T>C polymorphism, and there was a 2-fold increase in <it>NOS3 </it>levels favored by the incorporation of each C allele. <it>NOS3 </it>levels higher than 80% of the constitutive gene expression level (<it>B2M</it>) presented a 4-fold increase in PCa occurrence.</p> <p>Conclusion</p> <p>The -786T>C polymorphism was the most important promoter alteration of the <it>NOS3 </it>gene that may affect the PCa progression, but not its occurrence, and the incorporation of the C allele is associated with increased levels of <it>NOS3 </it>transcripts. The <it>NOS3 </it>transcript levels presented a bimodal behavior in tumor development and may be used as a biomarker together with the <it>PCA3 </it>marker for molecular staging of the prostate cancer.</p

Aerosolized Delivery of Antifungal Agents

Pulmonary infections caused by Aspergillus species are associated with significant morbidity and mortality in immunocompromised patients. Although the treatment of pulmonary fungal infections requires the use of systemic agents, aerosolized delivery is an attractive option in prevention because the drug can concentrate locally at the site of infection with minimal systemic exposure. Current clinical evidence for the use of aerosolized delivery in preventing fungal infections is limited to amphotericin B products, although itraconazole, voriconazole, and caspofungin are under investigation. Based on conflicting results from clinical trials that evaluated various amphotericin B formulations, the routine use of aerosolized delivery cannot be recommended. Further research with well-designed clinical trials is necessary to elucidate the therapeutic role and risks associated with aerosolized delivery of antifungal agents. This article provides an overview of aerosolized delivery systems, the intrapulmonary pharmacokinetic properties of aerosolized antifungal agents, and key findings from clinical studies

Meta-analysis on the effect of the N363S polymorphism of the glucocorticoid receptor gene (GRL) on human obesity

BACKGROUND: Since both excess glucocorticoid secretion and central obesity are clinical features of some obese patients, it is worthwhile to study a possible association of glucocorticoid receptor gene (GRL) variants with obesity. Previous studies have linked the N363S variant of the GRL gene to increased glucocorticoid effects such as higher body fat, a lower lean-body mass and a larger insulin response to dexamethasone. However, contradictory findings have been also reported about the association between this variant and obesity phenotypes. Individual studies may lack statistical power which may result in disparate results. This limitation can be overcome using meta-analytic techniques. METHODS: We conducted a meta-analysis to assess the association between the N363S polymorphism of the GRL gene and obesity risk. In addition to published research, we included also our own unpublished data -three novel case-control studies- in the meta-analysis The new case-control studies were conducted in German and Spanish children, adolescents and adults (total number of subjects: 1,117). Genotype was assessed by PCR-RFLP (Tsp509I). The final formal meta-analysis included a total number of 5,909 individuals. RESULTS: The meta-analysis revealed a higher body mass index (BMI) with an overall estimation of +0.18 kg/m(2 )(95% CI: +0.004 to +0.35) for homo-/heterozygous carriers of the 363S allele of the GRL gene in comparison to non-carriers. Moreover, differences in pooled BMI were statistically significant and positive when considering one-group studies from the literature in which participants had a BMI below 27 kg/m(2 )(+ 0.41 kg/m(2 )[95% CI +0.17 to +0.66]), but the differences in BMI were negative when only our novel data from younger (aged under 45) and normal weight subjects were pooled together (-0.50 kg/m(2 )[95% CI -0.84 to -0.17]). The overall risk for obesity for homo-/heterozygous carriers of the 363S allele was not statistically significant in the meta-analysis (pooled OR = 1.02; 95% CI: 0.56–1.87). CONCLUSION: Although certain genotypic effects could be population-specific, we conclude that there is no compelling evidence that the N363S polymorphism of the GRL gene is associated with either average BMI or obesity risk

Design and methods for a cluster randomized trial of the Sunless Study: A skin cancer prevention intervention promoting sunless tanning among beach visitors

<p>Abstract</p> <p>Background</p> <p>Skin cancer is the most prevalent yet most preventable cancer in the US. While protecting oneself from ultraviolet radiation (UVR) can largely reduce risk, rates of unprotected sun exposure remain high. Because the desire to be tan often outweighs health concerns among sunbathers, very few interventions have been successful at reducing sunbathing behavior. Sunless tanning (self-tanners and spray tans), a method of achieving the suntanned look without UVR exposure, might be an effective supplement to prevention interventions.</p> <p>Methods and Design</p> <p>This cluster randomized trial will examine whether a beach-based intervention that promotes sunless tanning as a substitute for sunbathing and includes sun damage imaging and sun safety recommendations is superior to a questionnaire only control group in reducing sunbathing frequency. Female beach visitors (N = 250) will be recruited from 2 public beaches in eastern Massachusetts. Beach site will be the unit of randomization. Follow-up assessment will occur at the end of the summer (1-month following intervention) and 1 year later. The primary outcome is average sunbathing time per week. The study was designed to provide 90% power for detecting a difference of .70 hours between conditions (standard deviation of 2.0) at 1-year with an intra-cluster correlation coefficient of 0.01 and assuming a 25% rate of loss to follow-up. Secondary outcomes include frequency of sunburns, use of sunless tanning products, and sun protection behavior.</p> <p>Discussion</p> <p>Interventions might be improved by promoting behavioral substitutes for sun exposure, such as sunless tanners, that create a tanned look without exposure to UVR.</p> <p>Trial registration</p> <p>NCT00403377</p

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II

PURPOSE: The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS: GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS: From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL (P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION: Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL

Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder

Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder

Patterns and rates of exonic de novo mutations in autism spectrum disorders

Autism spectrum disorders (ASD) are believed to have genetic and environmental origins, yet in only a modest fraction of individuals can specific causes be identified1,2. To identify further genetic risk factors, we assess the role of de novo mutations in ASD by sequencing the exomes of ASD cases and their parents (n= 175 trios). Fewer than half of the cases (46.3%) carry a missense or nonsense de novo variant and the overall rate of mutation is only modestly higher than the expected rate. In contrast, there is significantly enriched connectivity among the proteins encoded by genes harboring de novo missense or nonsense mutations, and excess connectivity to prior ASD genes of major effect, suggesting a subset of observed events are relevant to ASD risk. The small increase in rate of de novo events, when taken together with the connections among the proteins themselves and to ASD, are consistent with an important but limited role for de novo point mutations, similar to that documented for de novo copy number variants. Genetic models incorporating these data suggest that the majority of observed de novo events are unconnected to ASD, those that do confer risk are distributed across many genes and are incompletely penetrant (i.e., not necessarily causal). Our results support polygenic models in which spontaneous coding mutations in any of a large number of genes increases risk by 5 to 20-fold. Despite the challenge posed by such models, results from de novo events and a large parallel case-control study provide strong evidence in favor of CHD8 and KATNAL2 as genuine autism risk factors