Assessment of Patient Preference in Allocation and Observation of Anti-Tuberculosis Medication in three Districts in Tanzania.

The new tuberculosis (TB) treatment in Tanzania contains rifampicin for six months. Direct observation of drug intake at the health facility for this period is not feasible. Patients and health staff in three districts were interviewed to assess the burden of the current treatment strategy, and opinions on a proposed new strategy where patients are able to choose the place of treatment and the treatment supervisor, and receive treatment as a daily combination tablet. The study included 343 patients in 42 facilities. Daily collection of drugs was perceived as burdensome irrespective of distance needed to travel. Eighty percent of patients viewed medication taken at home or at a closer health facility as an improvement in TB-services. The proposed new treatment strategy was rated favorably by 85% of patients and 75% of health staff. Fifty-three percent of patients would opt for home-based treatment, and 75% would choose a family member or the spouse as treatment supporter. Home-based supervision of TB treatment with fewer drugs is an expressed preference of TB patients in Tanzania. Such a strategy is now being assessed in a pilot study. If effective and feasible, the strategy will contribute to an improved TB control strategy

A simple approach for detecting HLA-A02 alleles in archival formalin-fixed paraffin-embedded tissue samples and an application example for studying cancer immunoediting

The HLA system represents a central component of the antigen presentation machinery. As every patient possesses a defined set of HLA molecules, only certain antigens can be presented on the cell surface. Thus, studying HLA type-dependent antigen presentation can improve the understanding of variation in susceptibility to various diseases, including infectious diseases and cancer. In archival formalin-fixed paraffin-embedded (FFPE) tissue, the HLA type is difficult to analyze because of fragmentation of DNA, hindering the application of commonly used assays that rely on long DNA stretches. Addressing these difficulties, we present a refined approach for characterizing presence or absence of HLA-A*02, the most common HLA-A allele in the Caucasian population, in archival samples. We validated our genotyping strategy in a cohort of 90 samples with HLA status obtained by an NGS-based method. 90% (n = 81) of the samples could be analyzed with the approach. For all of them, the presence or absence of HLA-A*02 alleles was correctly determined with the method, demonstrating 100% sensitivity and specificity (95% CI: 91.40%-100% and 91.19%-100%). Furthermore, we provide an example of application in an independent cohort of 73 FFPE microsatellite-unstable (MSI) colorectal cancer samples. As MSI cancer cells encompass a high number of mutations in coding microsatellites, leading to the generation of highly immunogenic frameshift peptide antigens, they are ideally suited for studying relations between the mutational landscape of tumor cells and interindividual differences in the immune system, including the HLA genotype. Overall, our method can help to promote studying HLA type-dependency during the pathogenesis of a wide range of diseases, making archival and historic tissue samples accessible for identifying HLA-A*02 alleles.Peer reviewe

Blueberry anthocyanin intake attenuates the postprandial cardiometabolic effect of an energy-dense food challenge: results from a double blind, randomized controlled trial in metabolic syndrome participants

Background & aims: Whilst the cardioprotective effects of blueberry intake have been shown in prospective studies and short-term randomized controlled trials (RCTs), it is unknown whether anthocyanin-rich blueberries can attenuate the postprandial, cardiometabolic dysfunction which follows energy-dense food intakes; especially in at-risk populations. We therefore examined whether adding blueberries to a high-fat/high-sugar meal affected the postprandial cardiometabolic response over 24 h. Methods: A parallel, double-blind RCT (n = 45; age 63.4 ± 7.4 years; 64% male; BMI 31.4 ± 3.1 kg/m 2) was conducted in participants with metabolic syndrome. After baseline assessments, an energy-dense drink (969 Kcals, 64.5 g fat, 84.5 g carbohydrate, 17.9 g protein) was consumed with either 26 g (freeze-dried) blueberries (equivalent to 1 cup/150 g fresh blueberries) or 26 g isocaloric matched placebo. Repeat blood samples (30, 60, 90, 120, 180, 360 min and 24 h), a 24 h urine collection and vascular measures (at 3, 6, and 24 h) were performed. Insulin and glucose, lipoprotein levels, endothelial function (flow mediated dilatation (FMD)), aortic and systemic arterial stiffness (pulse wave velocity (PWV), Augmentation Index (AIx) respectively), blood pressure (BP), and anthocyanin metabolism (serum and 24 h urine) were assessed. Results: Blueberries favorably affected postprandial (0–24 h) concentrations of glucose (p < 0.001), insulin (p < 0.01), total cholesterol (p = 0.04), HDL-C, large HDL particles (L-HDL-P) (both p < 0.01), extra-large HDL particles (XL-HDL-P; p = 0.04) and Apo-A1 (p = 0.01), but not LDL-C, TG, or Apo-B. After a transient higher peak glucose concentration at 1 h after blueberry intake ([8.2 mmol/L, 95%CI: 7.7, 8.8] vs placebo [6.9 mmol/L, 95%CI: 6.4, 7.4]; p = 0.001), blueberries significantly attenuated 3 h glucose ([4.3 mmol/L, 95%CI: 3.8, 4.8] vs placebo [5.1 mmol/L, 95%CI: 4.6, 5.6]; p = 0.03) and insulin concentrations (blueberry: [23.4 pmol/L, 95%CI: 15.4, 31.3] vs placebo [52.9 pmol/L, 95%CI: 41.0, 64.8]; p = 0.0001). Blueberries also improved HDL-C ([1.12 mmol/L, 95%CI: 1.06, 1.19] vs placebo [1.08 mmol/L, 95%CI: 1.02, 1.14]; p = 0.04) at 90 min and XL-HDLP levels ([0.38 × 10-6, 95%CI: 0.35, 0.42] vs placebo [0.35 × 10-6, 95%CI: 0.32, 0.39]; p = 0.02) at 3 h. Likewise, significant improvements were observed 6 h after blueberries for HDL-C ([1.17 mmol/L, 95%CI: 1.11, 1.24] vs placebo [1.10 mmol/L, 95%CI: 1.03, 1.16]; p < 0.001), Apo-A1 ([1.37 mmol/L, 95%CI: 1.32, 1.41] vs placebo [1.31 mmol/L, 95%CI: 1.27, 1.35]; p = 0.003), L-HDLP ([0.70 × 10-6, 95%CI: 0.60, 0.81] vs placebo [0.59 × 10-6, 95%CI: 0.50, 0.68]; p = 0.003) and XL-HDLP ([0.44 × 10-6, 95%CI: 0.40, 0.48] vs placebo [0.40 × 10-6, 95%CI: 0.36, 0.44]; p < 0.001). Similarly, total cholesterol levels were significantly lower 24 h after blueberries ([4.9 mmol/L, 95%CI: 4.6, 5.1] vs placebo [5.0 mmol/L, 95%CI: 4.8, 5.3]; p = 0.04). Conversely, no effects were observed for FMD, PWV, AIx and BP. As anticipated, total anthocyanin-derived phenolic acid metabolite concentrations significantly increased in the 24 h after blueberry intake; especially hippuric acid (6-7-fold serum increase, 10-fold urinary increase). In exploratory analysis, a range of serum/urine metabolites were associated with favorable changes in total cholesterol, HDL-C, XL-HDLP and Apo-A1 (R = 0.43 to 0.50). Conclusions: For the first time, in an at-risk population, we show that single-exposure to the equivalent of 1 cup blueberries (provided as freeze-dried powder) attenuates the deleterious postprandial effects of consuming an energy-dense high-fat/high-sugar meal over 24 h; reducing insulinaemia and glucose levels, lowering cholesterol, and improving HDL-C, fractions of HDL-P and Apo-A1. Consequently, intake of anthocyanin-rich blueberries may reduce the acute cardiometabolic burden of energy-dense meals. Clinical trial registry: NCT02035592 at www.clinicaltrials.gov

Patient-centred tuberculosis treatment delivery under programmatic conditions in Tanzania: a cohort study

<p>Abstract</p> <p>Background</p> <p>Directly observed therapy (DOT) remains the cornerstone of the global tuberculosis (TB) control strategy. Tanzania, one of the 22 high-burden countries regarding TB, changed the first-line treatment regimen to contain rifampicin-containing fixed-dose combination for the full 6 months of treatment. As daily health facility-based DOT for this long period is not feasible for the patient, nor for the health system, Tanzania introduced patient centred treatment (PCT). PCT allows patients to choose for daily DOT at a health facility or at their home by a supporter of choice. The introduction of fixed dose combinations in the intensive and continuation phase made PCT feasible by eliminating the risk of selective drug taking by patients and reducing the number of tablets to be taken. The approach was tested in three districts with the objective to assess the effect of this strategy on TB treatment outcomes</p> <p>Methods</p> <p>Cohort analysis comparing patients treated under the PCT strategy (registered April-September 2006) with patients treated under health-facility-based DOT (registered April-September 2005). The primary outcome was the cure rate. Differences were assessed by calculating the risk ratios. Associations between characteristics of the supporters and treatment outcomes in the group of patients opting for home-based DOT were assessed through logistic regression.</p> <p>Results</p> <p>In the PCT cohort there were 1208 patients and 1417 were included in the historic cohort. There was no significant difference in cure rates between the cohorts (risk ratio [RR]: 1.06; 95% confidence interval [CI]: 0.96-1.16). In the PCT cohort, significantly more patients had successful treatment (cure or treatment completed; RR: 1.10; 95%CI: 1.01-1.15). There were no characteristics of supporters that were associated with treatment outcome.</p> <p>Conclusion</p> <p>The PCT approach showed similar cure rates and better treatment success rates compared to daily health-facility DOT. The results indicate that there are no specific prerequisites for the supporter chosen by the patient. The programmatic setting of the study lends strong support for scaling-up of TB treatment observation outside the health facility.</p

Transcriptome Analysis and SNP Development Can Resolve Population Differentiation of Streblospio benedicti, a Developmentally Dimorphic Marine Annelid

Next-generation sequencing technology is now frequently being used to develop genomic tools for non-model organisms, which are generally important for advancing studies of evolutionary ecology. One such species, the marine annelid Streblospio benedicti, is an ideal system to study the evolutionary consequences of larval life history mode because the species displays a rare offspring dimorphism termed poecilogony, where females can produce either many small offspring or a few large ones. To further develop S. benedicti as a model system for studies of life history evolution, we apply 454 sequencing to characterize the transcriptome for embryos, larvae, and juveniles of this species, for which no genomic resources are currently available. Here we performed a de novo alignment of 336,715 reads generated by a quarter GS-FLX (Roche 454) run, which produced 7,222 contigs. We developed a novel approach for evaluating the site frequency spectrum across the transcriptome to identify potential signatures of selection. We also developed 84 novel single nucleotide polymorphism (SNP) markers for this species that are used to distinguish coastal populations of S. benedicti. We validated the SNPs by genotyping individuals of different developmental modes using the BeadXPress Golden Gate assay (Illumina). This allowed us to evaluate markers that may be associated with life-history mode

Long-term metapopulation study of the Glanville fritillary butterfly (Melitaea cinxia): survey methods, data management, and long-term population trends

Peer reviewe

There or not there? A multidisciplinary review and research agenda on the impact of transparent barriers on human perception, action, and social behavior

Contains fulltext : 145066.pdf (publisher's version ) (Open Access)Through advances in production and treatment technologies, transparent glass has become an increasingly versatile material and a global hallmark of modern architecture. In the shape of invisible barriers, it defines spaces while simultaneously shaping their lighting, noise, and climate conditions. Despite these unique architectural qualities, little is known regarding the human experience with glass barriers. Is a material that has been described as being simultaneously there and not there from an architectural perspective, actually there and/or not there from perceptual, behavioral, and social points of view? In this article, we review systematic observations and experimental studies that explore the impact of transparent barriers on human cognition and action. In doing so, the importance of empirical and multidisciplinary approaches to inform the use of glass in contemporary architecture is highlighted and key questions for future inquiry are identified.17 p

The role of fungal RNA biology during plant infection.

<p>Model of a filamentous pathogen (left) interacting with its plant host (right). RNA-dependent processes crucial for infection are numbered as follows: <b>1</b> translational regulation of <i>clp1</i> mRNA (ribosomal subunits in orange, mRNA in green); <b>2</b> 3′ end processing by the RNA-binding protein RBP35 in the nucleus (gray oval); <b>3</b> modulation of mRNA stability in processing bodies (PB, blue: accessory factors); <b>4</b> natural antisense transcripts (NAT) regulate mRNA stability; <b>5</b> endosomal mRNA transport along microtubule (black line, brown: endosome with motor proteins attached); <b>6</b> alternative splicing of <i>gapdh</i> mRNA to generate an enzyme with a peroxisomal targeting sequence; <b>7</b> translational read-through adding a peroxisomal targeting sequence; <b>8</b> antimicrobial peptide (AMP) Wheatwin1(Wwin1) with RNase activity; <b>9</b> ribosome-inactivating protein (RIP) alters rRNA; <b>10</b> pathogen effectors target host splice factors (SF) as shown for the bacterial effector HopU1 inactivating AtGRP7; <b>11</b> pathogen effectors interfere with the generation of small RNAs in the host as shown for oomycetes effectors. Further details are given in the text.</p

How do patients with systemic autoimmune rheumatic disease perceive the use of their medications: a systematic review and thematic synthesis of qualitative research

Background: Pharmacotherapy is paramount to the management of systemic autoimmune rheumatic diseases (SARDs), yet there is sub-optimal adherence and limited adherence interventions. To understand how to better support patients’ medication use, our two-fold objectives were: 1) to conduct a systematic review of qualitative research studies of medication taking among SARD patients; and 2) to thematically synthesize qualitative research studies to obtain SARD patients’ perspectives and experiences with medication use. Methods: We conducted a search of MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and Social Sciences Citation Index databases to identify qualitative research studies exploring views on medication use among patients with SARDs, their healthcare providers, or caregivers. We used thematic synthesis to combine data from selected studies, and identify analytical themes on SARD patients’ perspectives and experiences with medication use. Results: Our systematic review identified 18 studies. Thematic synthesis identified seven analytical themes: 1) effects of medications on emotional and social well-being, 2) impacts of healthcare provider relationships on treatment, 3) gaining control over treatment, 4) fear and concern with side effects of treatment, 5) understanding the importance of treatment, 6) practical barriers to taking medication, and 7) motivation towards adherence to treatment. Conclusion: This systematic review and thematic synthesis contributes to better understanding of SARDs patients’ perspectives on medication use. Given the paucity of existing adherence interventions targeting this patient population, our study has certain practical implications for care, namely the need to address emotional and social impacts of medication use and the necessity of establishing a meaningful and trusting professional relationship with patients.Medicine, Faculty ofPharmaceutical Sciences, Faculty ofOther UBCNon UBCMedicine, Department ofRheumatology, Division ofReviewedFacult