Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). Tumour necrosis factor (TNF) family genes have been widely investigated ...but inconsistent results may lie either in the genetic heterogeneity of populations or in the poor phenotype definition. A genetic study was performed using a narrower phenotype of COPD. The authors studied 86 healthy smokers and 63 COPD subjects who were enrolled based on irreversible airflow obstruction (forced expiratory volume in one second/forced vital capacity <70% predicted) and a diffusing capacity for carbon monoxide <50% predicted (moderate-to-severe COPD associated with pulmonary emphysema). The following polymorphisms were investigated: TNF-308, the biallelic polymorphism located in the first intron of the lymphotoxin-alpha gene, and exon 1 and exon 6 of the TNF receptor 1 and 2 genes, respectively. No significant deviations were found concerning the four polymorphisms studied between the two populations. The authors confirm that the tumour necrosis factor family genes, at least for the polymorphisms investigated, are not major genetic risk factors for chronic obstructive pulmonary disease in Caucasians, either defined in terms of emphysema (this study) or airflow obstruction (previous studies). Nevertheless, the authors would like to emphasise the importance of narrowing the phenotype in the search for genetic risk factors in chronic obstructive pulmonary disease.
HIV and pathogenic SIV infection are characterized by mucosal dysfunction including epithelial barrier damage, loss of Th17 cells, neutrophil infiltration, and microbial translocation with ...accompanying inflammation. However, it is unclear how and when these contributing factors occur relative to one another. In order to determine whether any of these features initiates the cycle of damage, we longitudinally evaluated the kinetics of mucosal and systemic T-cell activation, microbial translocation, and Th17 cell and neutrophil frequencies following intrarectal SIV infection of rhesus macaques. We additionally assessed the colon proteome to elucidate molecular pathways altered early after infection. We demonstrate increased T-cell activation (HLA-DR+) beginning 3-14 days post-SIV challenge, reduced peripheral zonulin 3-14 days post-SIV, and evidence of microbial translocation 14 days post-SIV. The onset of mucosal dysfunction preceded peripheral and mucosal Th17 depletion, which occurred 14-28 days post-SIV, and gut neutrophil accumulation was not observed. Proteins involved in epithelial structure were downregulated 3 days post-SIV followed by an upregulation of immune proteins 14 days post-SIV. These data demonstrate that immune perturbations such as Th17 loss and neutrophil infiltration occur after alterations to epithelial structural protein pathways, suggesting that epithelial damage occurs prior to widespread immune dysfunction.
In order to determine the possible role of the cystic fibrosis transmembrane regulator (CFTR) gene in pulmonary diseases not due to cystic fibrosis, a complete screening of the CFTR gene was ...performed in 120 Italian patients with disseminated bronchiectasis of unknown cause (DBE), chronic bronchitis (CB), pulmonary emphysema (E), lung cancer (LC), sarcoidosis (S) and other forms of pulmonary disease. The 27 exons of the CFTR gene and their intronic flanking regions were analyzed by denaturing gradient gel electrophoresis and automatic sequencing. Mutations were detected in 11/23 DBE (P = 0.009), 7/25 E, 5/27 CB, 5/26 LC, 5/8 S (P = 0.013), 1/4 tuberculosis, and 1/5 pneumonia patients, and in 5/33 controls. Moreover, the IVS8-5T allele was detected in 6/25 E patients (P = 0.038). Four new mutations were identified: D651N, 2377C/T, E826K, and P1072L. These results confirm the involvement of the CFTR gene in disseminated bronchiectasis of unknown origin, and suggest a possible role for CFTR gene mutations in sarcoidosis, and for the 5T allele in pulmonary emphysema.
To evaluate the effects of early exercise training in patients recovering from acute respiratory failure needing mechanical ventilation (MV).
Prospective, randomized, and controlled study.
Three ...respiratory intermediate ICUs (RIICUs).
Of 228 patients admitted to an RIICU, 66 patients weaned from MV from > 48 to < 96 h were considered eligible and enrolled in the study.
Sixty-six patients were randomized to either supported arm exercise training plus general physiotherapy (gPT) group 1, 32 patients or to gPT alone (group 2, 34 patients).
Twenty-five patients in each group completed the protocol. Group 1 showed a greater improvement in exercise capacity, as assessed by an arm incremental test (IT) p = 0.003 and an endurance test (ET) p = 0.021, compared to group 2. Posttraining maximal inspiratory pressure (MIP) significantly improved in both groups (p < 0.001 and p = 0.003 in groups 1 and 2 respectively; not significant). IT isoworkload dyspnea improved significantly in both groups (p = 0.005 and p = 0.009 in groups 1 and 2, respectively; not significant between groups), whereas IT isoworkload peripheral muscle fatigue (p < 0.001), ET isotime dyspnea (p < 0.01), and ET isotime muscular fatigue (p < 0.005) improved significantly in group 1 but not in group 2. IT improvers (χ2 = 0.004) and ET improvers (χ2 = 0.047) were more frequently observed in group 1 than in group 2. Baseline MIP could discriminate for IT (p = 0.013; odds ratio OR, 1.116) and ET improvers (p = 0.022; OR, 1.067).
Early upper-limb exercise training is feasible in RIICU patients recently weaned from MV and can enhance the effects of gPT. Baseline inspiratory muscle function is related to exercise capacity improvement.
Tumor necrosis factor (TNF) is a potent proinflammatory cytokine with increased levels in the sputum of COPD subjects. Two biallelic TNF gene complex polymorphisms have been described: LtαNcoI, in ...the first intron of the lymphotoxin α (previously referred to as TNF-β) gene, and TNF-308, in the promoter region of the TNF-α gene. Higher levels of TNF production are associated with allele 1 of LtαNcoI (LtαNcoI*1) and with allele 2 of TNF-308 (TNF-308*2).
To study the frequencies of the two TNF gene complex polymorphisms in patients with COPD and bronchiectasis.
Association study.
We studied the frequencies of these polymorphisms in 66 subjects with COPD and in 23 subjects with disseminated bronchiectasis and compared them to the frequencies in 98 healthy control subjects and 45 subjects with nonobstructive pulmonary disease. Genomic DNA samples were extracted, and TNF-α and LtαNcoI polymorphisms were detected after polymerase chain reaction by restriction digestion.
We found the following frequencies: the TNF-308*2 allele was detected in 11% of COPD individuals, 15% of bronchiectasis patients, 10% of healthy control subjects, and 18% of subjects with nonobstructive pulmonary disease. The LtαNcoI*1 allele was detected in 28% of COPD individuals, 30% of bronchiectasis patients, 29% of healthy control subjects, and 29% of subjects with nonobstructive pulmonary disease. We found evidence of linkage disequilibrium between the two loci (Δ = 0.068).
We conclude that the TNF gene complex, at least in Caucasoid individuals and for the considered polymorphisms, does not seem to play a major role as genetic risk factor in COPD and bronchiectasis.
We assessed the levels of exhaled nitric oxide (eNO) in patients with chronic heart failure (CHF) according to the functional impairment and the use of nitrate-containing agents. Forty patients (age ...55±9 years) were classified according to the NYHA classes I–II (
n=18, group 1) and classes III–IV (
n=22, group 2), and to the use of nitrate-containing drugs (Nitrate+, Nitrate−). Twenty-two healthy age-related subjects served as controls (group 3). Respiratory function, symptom-limited incremental cycloergometry and resting eNO concentration at peak (FENOp) or plateau (FENOpl) of the single-breath exhalation curve were assessed in all subjects. FENOpl was significantly lower in patients than in controls (7.8±2.7 and 10.6±2.8 ppb, respectively,
P<0.005) and lower in most severe CHF patients (7.1±2.6 and 8.8±2.7 ppb in group 2 and group 1, respectively,
P<0.05). A significant correlation between peak V′O
2, Watts and FENOpl (
r=0.42,
P<0.013 and
r=0.46,
P=0.008, respectively) was found. Independent of NYHA class, Nitrate+ showed higher FENOp levels than Nitrate− patients (36.9±15.7 vs. 28.1±15.1 ppb,
P<0.05). Resting eNO was lower in the most compromised CHF patients and was significantly related to exercise capacity. Nitrate-containing agents might influence the levels of eNO in these patients.
Collection details including locality, date, and (as far as possible) habitat characteristics must also be provided, accompanied in parasitic and symbiotic taxa by an accurately identified host ...voucher or its DNA/tissue sample wherever this is available. ...the extracted DNA must be deposited in a recognized DNA bank or museum collection and cited with a unique identifier to allow checks and further genetic analyses. ...the large majority of protists are currently uncultivable by known means or not available in culture collections, and genetic data only exist for a very small fraction of described species. ...it is imperative to establish standard barcoding protocols for future protist barcoding projects that will substantially increase the number of collected, described, but uncultivable protists.
In the Samail Ophiolite of Oman, the geological process of serpentinization produces reduced, hydrogen rich, hyperalkaline (pH > 11) fluids. These fluids are generated through water reacting with ...ultramafic rock from the upper mantle in the subsurface. On Earth's continents, serpentinized fluids can be expressed at the surface where they can mix with circumneutral surface water and subsequently generate a pH gradient (∼pH 8 to pH > 11) in addition to variations in other chemical parameters such as dissolved CO
, O
, and H
. Globally, archaeal and bacterial community diversity has been shown to reflect geochemical gradients established by the process of serpentinization. It is unknown if the same is true for microorganisms of the domain Eukarya (eukaryotes). In this study, using 18S rRNA gene amplicon sequencing, we explore the diversity of microbial eukaryotes called protists in sediments of serpentinized fluids in Oman. We demonstrate that protist community composition and diversity correlate significantly with variations in pH, with protist richness being significantly lower in sediments of hyperalkaline fluids. In addition to pH, the availability of CO
to phototrophic protists, the composition of potential food sources (prokaryotes) for heterotrophic protists and the concentration of O
for anaerobic protists are factors that likely shape overall protist community composition and diversity along the geochemical gradient. The taxonomy of the protist 18S rRNA gene sequences indicates the presence of protists that are involved in carbon cycling in serpentinized fluids of Oman. Therefore, as we evaluate the applicability of serpentinization for carbon sequestration, the presence and diversity of protists should be considered.
The process of selecting students likely to complete science, technology, engineering and mathematics (STEM) doctoral programs has not changed greatly over the last few decades and still relies ...heavily on Graduate Record Examination (GRE) scores in most U.S. universities. It has been long debated whether the GRE is an appropriate selection tool and whether overreliance on GRE scores may compromise admission of students historically underrepresented in STEM. Despite many concerns about the test, there are few studies examining the efficacy of the GRE in predicting PhD completion and even fewer examining this question in STEM fields. For the present study, we took advantage of a long-lived collaboration among institutions in the Northeast Alliance for Graduate Education and the Professoriate (NEAGEP) to gather comparable data on GRE scores and PhD completion for 1805 U.S./Permanent Resident STEM doctoral students in four state flagship institutions. We found that GRE Verbal (GRE V) and GRE Quantitative (GRE Q) scores were similar for women who completed STEM PhD degrees and those who left programs. Remarkably, GRE scores were significantly higher for men who left than counterparts who completed STEM PhD degrees. In fact, men in the lower quartiles of GRE V or Q scores finished degrees more often than those in the highest quartile. This pattern held for each of the four institutions in the study and for the cohort of male engineering students across institutions. GRE scores also failed to predict time to degree or to identify students who would leave during the first year of their programs. Our results suggests that GRE scores are not an effective tool for identifying students who will be successful in completing STEM doctoral programs. Considering the high cost of attrition from PhD programs and its impact on future leadership for the U.S. STEM workforce, we suggest that it is time to develop more effective and inclusive admissions strategies.
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