Multiplex real-time PCR for detection of anaplasma phagocytophilum and Borrelia burgdorferi

A multiplex real-time PCR assay was developed for the simultaneous detection of Anaplasma phagocytophilum and Borrelia burgdorferi. The assay was tested on various Anaplasma, Borrelia, Erhlichia, and Rickettsia species, as well as on Bartonella henselae and Escherichia coli, and the assay was found to be highly specific for A. phagocytophilum and the Borrelia species tested (B. burgdorferi, B. parkeri, B. andersonii, and B. bissettii). The analytical sensitivity of the assay is comparable to that of previously described nested PCR assays (A. phagocytophilum, 16S rRNA; B. burgdorferi, fla gene), amplifying the equivalent of one-eighth of an A. phagocytophilum-infected cell and 50 borrelia spirochetes. The dynamic range of the assay for both A. phagocytophilum and B. burgdorferi was >/=4 logs of magnitude. Purified DNA from A. phagocytophilum and B. burgdorferi was spiked into DNA extracted from uninfected ticks and from negative control mouse and human bloods, and these background DNAs were shown to have no significant effect on sensitivity or specificity of the assay. The assay was tested on field-collected Ixodes scapularis ticks and shown to have 100% concordance compared to previously described non-probe-based PCR assays. To our knowledge, this is the first report of a real-time multiplex PCR assay that can be used for the simultaneous and rapid screening of samples for A. phagocytophilum and Borrelia species, two of the most common tick-borne infectious agents in the United States.     

Replication and meta-analyses nominate numerous eosinophilic esophagitis risk genes

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Familial Mediterranean fever: the segregation of four different mutations in 13 individuals from one inbred family: genotype-phenotype correlation and intrafamilial variability

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring attacks of fever and serositis. Six sequence alterations (M694V, V726A, K695R, M680I, M694I, and E148Q), in the MEFV gene, account for the majority of FMF chromosomes. Differences in the clinical expression have been mainly attributed to MEFV allelic heterogeneity. Homozygotes for the M694V mutation have a more severe form of the disease and more frequently demonstrate articular and renal complications. The clinical manifestations associated with mutation M680I are considered less severe. Mutations E148Q, K695R and V726A have reduced penetrance, and many individual homozygotes or compound heterozygotes for these mutations remain asymptomatic. Here we report on one inbred family with 13 individuals (one grandparent, three parents, and nine grandchildren), either homozygotes or compound heterozygotes, for one or two of four mutations (V726A, M694V, M680I, and K695R). Three parents and one grandparent who each carried two mutated alleles remained asymptomatic. Of nine grandchildren who were compound heterozygotes for two mutations in the MEFV gene, only those with either the M694V/V726A or the M694V/M680I genotypes manifested the disease, bearing further evidence to the severity of mutation M694V in individuals sharing a similar genetic and environmental background. Nevertheless, one father and one grandmother who carried the M694V/V726A compound heterozygous genotype were symptom-free, while the four grandchildren with the same genotype manifested the disease from early age, providing further evidence for the role of additional environmental and genetic modifiers. The occurrence of four different mutations in two sets of consanguineous parents merits consideration per se.     

Patient-based utilities for bipolar disorder-related health states

BACKGROUND: Bipolar disorder is a psychiatric disorder which impacts patient functioning and well-being. With increasing interest in cost-effectiveness of treatments, it is necessary to provide estimates of patient's perspectives on treatment outcomes. This study estimated health state utilities for hypothetical bipolar-related health states and patient's current health from bipolar I patients. METHODS: Clinicians completed Young Mania Rating Scale, Montgomery-Asberg Depression Rating Scale, and Global Assessment Score. Patients completed structured standard gamble (SG) utility assessment interviews, and the other patient-based measures. Interviews obtained utilities for hypothetical bipolar-related health states describing symptom severity, functioning and well-being, and treatment-related side effects. RESULTS: Ninety-six patients were recruited from psychiatry outpatient practices. Mean utilities for inpatient states ranged from 0.12 to 0.33; outpatient mania states ranged from 0.29 to 0.64; outpatient stable states ranged from 0.53 to 0.85. Mean utility for current health was 0.80 (S.D.=0.22). Patients preferred monotherapy compared with combination therapy health states. Ordinary least squares regression indicated weight gain was associated with a 0.066 decrease in health state utilities (P=0.013). LIMITATIONS: Study sample consisted of selected stable and educated patients and small sample sizes may limit generalizability for some utilities. CONCLUSIONS: Bipolar disorder patients are capable of participating in utility assessment and providing ratings for hypothetical health states associated with different mood stabilizer treatments.     

Dietary Supplement Use and Interactions with Tamoxifen and Aromatase Inhibitors in Breast Cancer Survivors Enrolled in Lifestyle Interventions

The use of dietary supplements is common in the general population and even more prevalent among cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research specifies that dietary supplements should not be used for cancer prevention. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. This analysis examined the prevalence of self-reported dietary supplement use and the potential interactions with tamoxifen and aromatase inhibitors (AIs) among breast cancer survivors enrolled in three randomized controlled trials of lifestyle interventions conducted between 2010 and 2017. The potential interactions with tamoxifen and AIs were identified using the Natural Medicine Database. Among 475 breast cancer survivors (2.9 (mean) or 2.5 (standard deviation) years from diagnosis), 393 (83%) reported using dietary supplements. A total of 108 different types of dietary supplements were reported and 36 potential adverse interactions with tamoxifen or AIs were identified. Among the 353 women taking tamoxifen or AIs, 38% were taking dietary supplements with a potential risk of interactions. We observed a high prevalence of dietary supplement use among breast cancer survivors and the potential for adverse interactions between the prescribed endocrine therapy and dietary supplements was common.     

Organizing for power: A comparative case study

The purpose of this paper is to present a case study of two conceptually similar community organizing efforts that highlights commonalities and important differences. This study first presents a qualitative analysis of two approaches to community organizing for power. Our analysis was made possible by participation and collaboration with members of community organizations which opened the way for access to documents, events, interviews, and settings that formed the basis of our case study. We also present some quantitative data concerning participant perceptions of organizing experiences and outcomes. These data highlight important differences in community organizing approaches, differences we believe can be useful to our field as we struggle with the important concepts of empowerment and power.