The effects of the DASH dietary pattern on clinical outcomes and quality of life in adults with uncontrolled asthma: Design and methods of the ALOHA Trial.

BACKGROUND: Poor diet quality is an important risk factor for increased asthma prevalence and poor asthma control. To address the question of whether adults with asthma can benefit from following a healthy diet, this trial will test the efficacy and mechanisms of action of a behavioral intervention promoting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern with sodium reduction among patients with uncontrolled asthma. METHODS: In this 2-arm randomized clinical trial, 320 racially/ethnically and socioeconomically diverse adults with uncontrolled asthma on standard controller therapy will be randomized to either a control or an intervention group and assessed at baseline, 3, 6 and 12 months. Control and intervention participants will receive education on lung health, asthma, and other general health topics; additionally, the intervention group will receive DASH behavioral counseling over 12 months. The primary hypothesis is that the DASH behavioral intervention, compared with the education-only control, will lead to significantly more participants with minimum clinically important improvement (responders) in asthma-specific quality of life at 12 months. Secondary hypotheses will test the intervention effects on other asthma (e.g., asthma control, lung function) and non-asthma outcomes (e.g., quality of life). Additionally, therapeutic (e.g., short chain fatty acids, cytokines) and nutritional biomarkers (e.g., dietary inflammatory index, carotenoids) will be assessed to understand the mechanisms of the intervention effect. CONCLUSION: This trial can substantially advance asthma care by providing rigorous evidence on the benefits of a behavioral dietary intervention and mechanistic insights into the role of diet quality in asthma. CLINICALTRIALS: gov #: NCT05251402.

Mineral and biological ice-nucleating particles above the South East of the British Isles.

A small fraction of aerosol particles known as Ice-Nucleating Particles (INPs) have the potential to trigger ice formation in cloud droplets at higher temperatures than homogeneous freezing. INPs can strongly reduce the water content and albedo of shallow mixed-phase clouds and also influence the development of convective clouds. Therefore, it is important to understand which aerosol types serve as INPs and how effectively they nucleate ice. Using a combination of INP measurements and Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM-EDS), we quantify both the INP concentrations over a range of activation temperatures and the size-resolved composition. We show that the INP population of aerosol samples collected from an aircraft over the UK during July of 2017 is consistent with ice-nucleation on mineral dust below about -20 °C, but some other INP type must account for ice-nucleation at higher temperatures. Biological aerosol particles above ∼2 µm were detected based on visual detection of their morphological features in all the analysed samples at concentrations of at least 10 to 100 L-1 in the boundary layer. We suggest that given the presence of biological material, it could substantially contribute to the enhanced ice-nucleation ability of the samples at above -20 °C. Organic material attached to mineral dust could be responsible for at least part of this enhancement. These results are consistent with a growing body of data which suggests mineral dust alone cannot explain the INP population in the mid-latitude terrestrial atmosphere and that biological ice nucleating particles are most likely important for cloud glaciation.

Iceland is an episodic source of atmospheric ice-nucleating particles relevant for mixed-phase clouds.

Ice-nucleating particles (INPs) have the potential to remove much of the liquid water in climatically important mid- to high-latitude shallow supercooled clouds, markedly reducing their albedo. The INP sources at these latitudes are very poorly defined, but it is known that there are substantial dust sources across the high latitudes, such as Iceland. Here, we show that Icelandic dust emissions are sporadically an important source of INPs at mid to high latitudes by combining ice-nucleating active site density measurements of aircraft-collected Icelandic dust samples with a global aerosol model. Because Iceland is only one of many high-latitude dust sources, we anticipate that the combined effect of all these sources may strongly contribute to the INP population in the mid- and high-latitude northern hemisphere. This is important because these emissions are directly relevant for the cloud-phase climate feedback and because high-latitude dust emissions are expected to increase in a warmer climate.

Contributions of biogenic material to the atmospheric ice-nucleating particle population in North Western Europe.

A minute fraction of atmospheric particles exert a disproportionate effect on the phase of mixed-phase clouds by acting as ice-nucleating particles (INPs). To understand the effects of these particles on weather and climate, both now and into the future, we must first develop a quantitative understanding of the major INP sources worldwide. Previous work has demonstrated that aerosols such as desert dusts are globally important INPs, but the role of biogenic INPs is unclear, with conflicting evidence for their importance. Here, we show that at a temperate site all INPs active above -18 °C at concentrations >0.1 L-1 are destroyed on heating, consistent with these INPs being of biological origin. Furthermore, we show that a global model of desert dust INPs dramatically underestimates the measured INP concentrations, but is consistent with the thermally-stable component. Notably, the heat sensitive INPs are active at temperatures where shallow cloud layers in Northern Europe are frequently observed to glaciate. Hence, we suggest that biogenic material is important for primary ice production in this region. The prevalence of heat sensitive, most likely biogenic, INPs in this region highlights that, as a community, we need to quantify the sources and transport of these particles as well as determine their atmospheric abundance across the globe and at cloud altitudes.

Expression of E6 and E7 papillomavirus oncogenes in the outer root sheath of hair follicles extends the growth phase and bypasses resting at telogen.

Hair follicle growth cycle proceeds through a series of stages in which strict control of cell proliferation, differentiation, and cell death occurs. Transgenic mice expressing human papillomavirus type 16 E6/E7 papillomavirus oncogenes in the outer root sheath (ORS) display a fur phenotype characterized by lower hair density and the ability to regenerate hair much faster than wild-type mice. Regenerating hair follicles of transgenic mice show a longer growth phase (anagen), and although bulb regression (catagen) occurs, rest at telogen was not observed. No abnormalities were detected during the first cycle of hair follicle growth, but by the second cycle, initiation of catagen was delayed, and rest at telogen was again not attained, even in the presence of estradiol, a telogen resting signal. In conclusion, expression of E6/E7 in the ORS delays entrance to catagen and makes cells of the ORS insensitive to telogen resting signals bearing to a continuous hair follicle cycling in transgenic mice.

Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes.

The purpose of this study was to examine the response of pancreatic beta-cells to changes in insulin sensitivity in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and frequently sampled intravenous glucose tolerance tests (FSIGTs) were conducted on Latino women with impaired glucose tolerance and a history of gestational diabetes before and after 12 weeks of treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12). Insulin sensitivity was assessed by minimal model analysis, and beta-cell insulin release was assessed as acute insulin responses to glucose (AIRg) and tolbutamide (AIRt) during FSIGTs and as the 30-min incremental insulin response (30-min dINS) during OGTTs. Beta-cell compensation for insulin resistance was assessed as the product (disposition index) of minimal model insulin sensitivity and each of the 3 measures of beta-cell insulin release. In the placebo group, there was no significant change in insulin sensitivity or in any measure of insulin release, beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone treatment resulted in a significant increase in insulin sensitivity, as reported previously. In response, AIRg did not change significantly, so that the disposition index for AIRg increased significantly from baseline (P = 0.004) and compared with placebo (P = 0.02). AIRt (P = 0.001) and 30-min dINS (P = 0.02) fell with improved insulin sensitivity during troglitazone treatment, so that the disposition index for each of these measures of beta-cell function did not change significantly from baseline (P > 0.20) or compared with placebo (P > 0.3). Minimal model analysis revealed that 89% of the change from baseline in insulin sensitivity during troglitazone treatment was accounted for by lowered plasma insulin concentrations. Neither oral nor intravenous glucose tolerance changed significantly from baseline or compared with placebo during troglitazone treatment. The predominant response of beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes was a reduction in insulin release to maintain nearly constant glucose tolerance.

[Mesenteric lymph node cavitation: a rare complication of celiac disease in the adult]. / Cavitación ganlionar mesentérica: una rara complicación de la enfermedad celíaca del adulto.

A case of coeliac disease (CD) and mesenteric lymph node cavitation (MLNC) in a 42-years-old female is presented. The other cases reported in the literature are also reviewed. The most important ganglionar histological features are described and a pathogenic explanation is suggested.

Epidemiología molecular de cánceres de alta incidencia en México / Molecular epidemiology of high incidence cancers in Mexico

En este trabajo presentamos la situación epidemiológica molecular actual en México con respecto a la presencia de secuencias de ADN de virus de papiloma humano (VPH) en pacientes afectadas por cáncer cérvicouterino (CaCu) y en mujeres asintomáticas clínicamente normales. Encontramos, por PCR, que en un 82-85 por ciento de las neoplasias cervicales y en el 31 por ciento de las mujeres normales están presentes dichas secuencias. En cuanto a leucemias, otro cáncer de muy alta incidencia en México, investigamos la frecuencia de los rearreglos brc-abl y e2a-pbxl en pacientes con Leucemia Linfoblástica Aguda (LLA) y Leucemia Granulocítica Crónica (LGC) mediante la tecnología de RT-PCR. Encontramos que un 66 por ciento de los niños con pre B-LLA presentan el rearreglo e2a-pbxl, un 46 por ciento de los adultos con LLA CALLA(+) presentan el rearreglo bcr-abl y el 100 por ciento de los pacientes con LGC tuvieron el rearreglo bor-abl. Esta tecnología y los resultados presentados permiten un mejor diagnóstico, pronóstico y terapia de las mencionadas neoplasias

Effect of troglitazone on insulin sensitivity and pancreatic beta-cell function in women at high risk for NIDDM.

We conducted a randomized placebo-controlled study to determine the effects of the thiazolidinedione compound troglitazone on whole-body insulin sensitivity (SI), pancreatic beta-cell function, and glucose tolerance in 42 Latino women with impaired glucose tolerance (IGT) and a history of gestational diabetes mellitus (GDM), characteristics that carry an 80% risk of developing NIDDM within 5 years. After baseline oral (OGTT) and intravenous (IVGTT) glucose tolerance testing, subjects were assigned to take placebo or 200 or 400 mg troglitazone daily for 12 weeks (14 subjects per treatment group). An OGTT and IVGTT were repeated during the 12th week of treatment. Five subjects failed to complete the trial for personal reasons, and medication compliance averaged 90% in the remaining subjects, none of whom experienced a serious adverse event. SI, calculated by minimal model analysis of IVGTT results, changed by only 4 +/- 14% during 12 weeks of placebo administration, but increased 40 +/- 22 and 88 +/- 22% above basal during treatment with 200 and 400 mg troglitazone, respectively (P = 0.01 among groups). Troglitazone administration was also associated with a dose-dependent reduction in the total insulin area during IVGTTs, which was highly significant (P < 0.001), and with a reduction during OGTTs, which approached statistical significance (P = 0.09). Glucose tolerance improved slightly in all groups, but the magnitude of change did not differ significantly among groups, whether it was assessed as the number of subjects who continued to manifest IGT at 12 weeks (P = 0.64 among groups), the change in total glucose area during OGTTs (P = 0.58), or the change in fractional glucose disappearance rates during IVGTTs (P = 0.28). Among the women who received troglitazone, the greatest improvement in SI occurred in the women who had the highest diastolic blood pressures and the best IVGTT insulin responses during baseline testing. Our findings indicate that troglitazone improved whole-body insulin sensitivity and lowered circulating insulin concentrations in women with prior GDM who are at very high risk for NIDDM. The lack of improvement in glucose tolerance despite improved insulin sensitivity may be a manifestation of the beta-cell defect that predisposes the women to NIDDM. The overall pattern of response to troglitazone in our high-risk patients indicates that the drug is an ideal agent with which to test whether the amelioration of insulin resistance can delay or prevent diabetes in women with limited beta-cell reserve.