Patient-cost survey for tuberculosis in the context of patient-pathway modelling.

ETTING: Eight tuberculosis treatment sites in Cavite Province, the Philippines, including two sites specialising in management of multidrug-resistant tuberculosis (MDR-TB).OBJECTIVE: To evaluate costs incurred by TB patients and to determine the proportion of households that faced catastrophic costs, then to consider cost survey responses alongside results of detailed patient-pathway modelling.DESIGN: Clustered cross-sectional survey using a field testing version of the WHO TB patient-costing tool and protocol; face-to-face interviews with 194 patients conducted in May-August 2016. Costs included direct-medical, direct non-medical and indirect costs using the human capital approach. Patients were deemed to incur catastrophic expenditure if TB-related costs exceeded 20% of annual household income. Patient pathways were modelled following multiple health staff interviews.RESULTS: Estimated mean cost incurred by patients with drug-susceptible TB was US$321 vs.$2356 for MDR-TB patients. Catastrophic costs were suffered by 28% of drug-susceptible and 80% of MDR-TB patients, with lost income being the largest contributor. Patient-pathway modelling suggested most patients had under-reported health visits.CONCLUSION: Survey results indicate that patient costs are large for all patients in Cavite, particularly for MDR-TB patients. Patient-pathway modelling suggests these costs are an underestimate due to poor recollection of health visits, suggesting that the WHO instrument and protocol could be improved to better capture the diagnostic journey

Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6.

Endogenous sphingolipids (ceramide) and related synthetic molecules (FTY720, SH-BC-893) reduce nutrient access by decreasing cell surface expression of a subset of nutrient transporter proteins. Here, we report that these sphingolipids disrupt endocytic recycling by inactivating the small GTPase ARF6. Consistent with reported roles for ARF6 in maintaining the tubular recycling endosome, MICAL-L1-positive tubules were lost from sphingolipid-treated cells. We propose that ARF6 inactivation may occur downstream of PP2A activation since: (1) sphingolipids that fail to activate PP2A did not reduce ARF6-GTP levels; (2) a structurally unrelated PP2A activator disrupted tubular recycling endosome morphology and transporter localization; and (3) overexpression of a phosphomimetic mutant of the ARF6 GEF GRP1 prevented nutrient transporter loss. ARF6 inhibition alone was not toxic; however, the ARF6 inhibitors SecinH3 and NAV2729 dramatically enhanced the killing of cancer cells by SH-BC-893 without increasing toxicity to peripheral blood mononuclear cells, suggesting that ARF6 inactivation contributes to the anti-neoplastic actions of sphingolipids. Taken together, these studies provide mechanistic insight into how ceramide and sphingolipid-like molecules limit nutrient access and suppress tumor cell growth and survival

Measurements of differential cross sections of Z/gamma*+jets+X events in proton anti-proton collisions at sqrt{s}=1.96 TeV

We present cross section measurements for Z/gamma*+jets+X production, differential in the transverse momenta of the three leading jets. The data sample was collected with the D0 detector at the Fermilab Tevatron proton anti-proton collider at a center-of-mass energy of 1.96 TeV and corresponds to an integrated luminosity of 1 fb-1. Leading and next-to-leading order perturbative QCD predictions are compared with the measurements, and agreement is found within the theoretical and experimental uncertainties. We also make comparisons with the predictions of four event generators. Two parton-shower-based generators show significant shape and normalization differences with respect to the data. In contrast, two generators combining tree-level matrix elements with a parton shower give a reasonable description of the the shapes observed in data, but the predicted normalizations show significant differences with respect to the data, reflecting large scale uncertainties. For specific choices of scales, the normalizations for either generator can be made to agree with the measurements.Comment: Published in PLB. 11 pages, 3 figure

Relative rates of B meson decays into psi(2S) and J/psi mesons

We report on a study of the relative rates of B meson decays into psi(2S) and J/psi mesons using 1.3 fb^-1 of pbar p collisions at sqrt(s) = 1.96 TeV recorded by the D0 detector operating at the Fermilab Tevatron Collider. We observe the channels B^0_s -> psi(2S)phi, B^0_s -> J/psi phi, B^+/- -> psi(2S) K^+/-, and B^+/- -> J/psi K^+/- and we measure the relative branching fractions for these channels to be B(B^0_s -> psi(2S)phi)/B(B^0_s -> J/psi phi) = 0.55 +/- 0.11 (stat) +/- 0.07 (syst) +/- 0.06 (B), B(B^+/- -> psi(2S) K^+/-)/B(B^+/- -> J/psi K^+/-) = 0.65 +/- 0.04 (stat) +/- 0.03 (syst) +/- 0.07 (B) where the final error corresponds to the uncertainty in the J/psi and psi(2S) branching ratio into two muons.Comment: Published in Phys. Rev. D - Rapid Communicatio

Chemical composition of juice and antihyperglycemic studies in seed of the prehispanic fruit tunillo (Stenocereus stellatus) collected in Oaxaca, Mexico

580-584Tunillo, or pitaya of august (Stenocereus stellatus) is a prehispanic fruit, endemic to the Mixteca region in Mexico and to which a lot of medicinal properties have been associated. However, there are few scientific studies regarding its characterization and use. For these reasons, in this study we carried out a chemical characterization of the juice of four-color variants as well as determine the antihyperglycemic capacity of seed. Physical and chemical characterization were carried out in juice of fruits of Stenocereus after a preselection based on pulp color. Total soluble solids, pH, titratable acidity, organic acid and betalains were quantified in juice and antihyperglycemic capacity was measured in seed. Physicochemical parameters in juice were similar in the 4 variants; regarding the content of pigments, the red variant showed the highest values as well as the highest organic acids. However, the white, orange, and red variants showed better antihyperglycemic capacity. Red tunillo is the best candidate for obtaining pigments and its higher organic acids content correlates with its lower acceptance by the local population. The seeds of the white, orange, and red colors showed promising anhyperglycemic capacity, which suggest that they should be considered for the development of antidiabetic treatments. These results contribute to the use of compex matrices considered waste products of the fruits. This would undoubtedly increase their commercial value

Chemical composition of juice and antihyperglycemic studies in seed of the prehispanic fruit tunillo (Stenocereus stellatus) collected in Oaxaca, Mexico

Tunillo, or pitaya of august (Stenocereus stellatus) is a prehispanic fruit, endemic to the Mixteca region in Mexico and to which a lot of medicinal properties have been associated. However, there are few scientific studies regarding its characterization and use. For these reasons, in this study we carried out a chemical characterization of the juice of four-color variants as well as determine the antihyperglycemic capacity of seed. Physical and chemical characterization were carried out in juice of fruits of Stenocereus after a preselection based on pulp color. Total soluble solids, pH, titratable acidity, organic acid and betalains were quantified in juice and antihyperglycemic capacity was measured in seed. Physicochemical parameters in juice were similar in the 4 variants; regarding the content of pigments, the red variant showed the highest values as well as the highest organic acids. However, the white, orange, and red variants showed better antihyperglycemic capacity. Red tunillo is the best candidate for obtaining pigments and its higher organic acids content correlates with its lower acceptance by the local population. The seeds of the white, orange, and red colors showed promising anhyperglycemic capacity, which suggest that they should be considered for the development of antidiabetic treatments. These results contribute to the use of compex matrices considered waste products of the fruits. This would undoubtedly increase their commercial value

Geographic variations in the PARADIGM-HF heart failure trial

Aims: The globalization of clinical trials has highlighted geographic variations in patient characteristics, event rates, and treatment effects. We investigated these further in PARADIGM-HF, the largest and most globally representative trial in heart failure (HF) to date. Methods and results: We looked at five regions: North America (NA) 622 (8%), Western Europe (WE) 1680 (20%), Central/Eastern Europe/Russia (CEER) 2762 (33%), Latin America (LA) 1413 (17%), and Asia-Pacific (AP) 1487 (18%). Notable differences included: WE patients (mean age 68 years) and NA (65 years) were older than AP (58 years) and LA (63 years) and had more coronary disease; NA and CEER patients had the worst signs, symptoms, and functional status. North American patients were the most likely to have a defibrillating-device (53 vs. 2% AP) and least likely prescribed a mineralocorticoid receptor antagonist (36 vs. 61% LA). Other evidence-based therapies were used most frequently in NA and WE. Rates of the primary composite outcome of cardiovascular (CV) death or HF hospitalization (per 100 patient-years) varied among regions: NA 13.5 (95% CI 11.7–15.6), WE 9.6 (8.6–10.6), CEER 12.3 (11.4–13.2), LA 11.2 (10.0–12.5), and AP 12.5 (11.3–13.8). After adjustment for prognostic variables, relative to NA, the risk of CV death was higher in LA and AP and the risk of HF hospitalization lower in WE. The benefit of sacubitril/valsartan was consistent across regions. Conclusion: There were many regional differences in PARADIGM-HF, including in age, symptoms, comorbidity, background therapy, and event-rates, although these did not modify the benefit of sacubitril/valsartan

HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Background & aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated.Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764). Expression levels of HLA-DP on intestinal epithelial cells (IECs) in individuals with and without UC were quantified. Human intestinal 3-dimensional (3D) organoid cocultures with human NK cells were used to determine functional consequences of interactions between HLA-DP and NKp44.Results: These studies identified HLA-DPA1∗01:03-DPB1∗04:01 (HLA-DP401) as a risk haplotype and HLA-DPA1∗01:03-DPB1∗03:01 (HLA-DP301) as a protective haplotype for UC in European populations. HLA-DP expression was significantly higher on IECs of individuals with UC compared with controls. IECs in human intestinal 3D organoids derived from HLA-DP401pos individuals showed significantly stronger binding of NKp44 compared with HLA-DP301pos IECs. HLA-DP401pos IECs in organoids triggered increased degranulation and tumor necrosis factor production by NKp44+ NK cells in cocultures, resulting in enhanced epithelial cell death compared with HLA-DP301pos organoids. Blocking of HLA-DP401-NKp44 interactions (anti-NKp44) abrogated NK cell activity in cocultures.Conclusions: We identified an UC risk HLA-DP haplotype that engages NKp44 and activates NKp44+ NK cells, mediating damage to intestinal epithelial cells in an HLA-DP haplotype-dependent manner. The molecular interaction between NKp44 and HLA-DP401 in UC can be targeted by therapeutic interventions to reduce NKp44+ NK cell-mediated destruction of the intestinal epithelium in UC