Epidemiological time series studies of PM2.5 and daily mortality and hospital admissions: a systematic review and meta-analysis

Background Short-term exposure to outdoor fine particulate matter (particles with a median aerodynamic diameter <2.5 μm (PM2.5)) air pollution has been associated with adverse health effects. Existing literature reviews have been limited in size and scope. Methods We conducted a comprehensive, systematic review and meta-analysis of 110 peer-reviewed time series studies indexed in medical databases to May 2011 to assess the evidence for associations between PM2.5 and daily mortality and hospital admissions for a range of diseases and ages. We stratified our analyses by geographical region to determine the consistency of the evidence worldwide and investigated small study bias. Results Based upon 23 estimates for all-cause mortality, a 10 µg/m3 increment in PM2.5 was associated with a 1.04% (95% CI 0.52% to 1.56%) increase in the risk of death. Worldwide, there was substantial regional variation (0.25% to 2.08%). Associations for respiratory causes of death were larger than for cardiovascular causes, 1.51% (1.01% to 2.01%) vs 0.84% (0.41% to 1.28%). Positive associations with mortality for most other causes of death and for cardiovascular and respiratory hospital admissions were also observed. We found evidence for small study bias in single-city mortality studies and in multicity studies of cardiovascular disease. Conclusions The consistency of the evidence for adverse health effects of short-term exposure to PM2.5 across a range of important health outcomes and diseases supports policy measures to control PM2.5 concentrations. However, reasons for heterogeneity in effect estimates in different regions of the world require further investigation. Small study bias should also be considered in assessing and quantifying health risks from PM2.

Irritable bowel syndrome and risk of glaucoma: An analysis of two independent population-based cohort studies

Objective: Irritable bowel syndrome (IBS) is a chronic disorder associated with an abnormal gastrointestinal microbiome. Microbiome–host interactions are known to influence organ function including in the central nervous system; thus, we sought to identify whether IBS may be a risk factor for the development of glaucoma. Design: Two prospective cohort studies. Subjects: The 1958 United Kingdom Birth Cohort (UKBC; 9091 individuals) and the Danish National Registry of Patients (DNRP; 62,541 individuals with IBS and 625,410 matched general population cohort members). Methods: In the UKBC, participants were surveyed throughout life (including at ages 42 and 50). The DNRP contains records of hospital-based contacts and prescription data from the national prescription database. Main Outcome Measure: The main outcome measure was incidence of glaucoma. In the UKBC, incident glaucoma at age 50 (n = 48) was determined through comparison of survey responses at ages 42 and 50 years. In the DNRP, glaucoma was assessed by hospital diagnosis (n = 1510), glaucoma surgery (n = 582) and initiation of glaucoma medications (n = 1674). Results: In the UKBC, the odds ratio (OR) of developing glaucoma between ages 42 and 50 in persons with a chronic IBS diagnosis was increased [OR: 5.84, 95% confidence interval (CI): 2.26–15.13]. People with an IBS diagnosis in the DNRP had a hazard ratio (HR) of 1.35 for developing physician-diagnosed glaucoma (95% CI: 1.16–1.56), an HR of 1.35 for undergoing glaucoma surgery (95% CI: 1.06–1.70) and an HR of 1.19 for initiating glaucoma medication (95% CI: 1.03–1.38). Conclusions: In two large European cohort studies, IBS is a risk factor for glaucoma

A two-domain elevator mechanism for sodium/proton antiport

Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general

Evaluation of preoperative intra-aortic balloon pump in coronary patients with severe left ventricular dysfunction undergoing OPCAB surgery: early and mid-term outcomes

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to evaluate the safety and the cost-effectiveness of using preoperative IABP as support compared with postoperative IABP treatment in coronary patients with severe left ventricular dysfunction (SLVD) who is undergoing off-pump coronary artery bypass surgery (OPCAB), including early outcomes, hospital mortality and morbidity, and mid-term follow-up outcomes.</p> <p>Methods</p> <p>Between March 2000 and December 2008, we prospectively and randomly studied the insertion of preoperative IABP in 115 (7.4%) and postoperative IABP in 106 (6.8%) of the 1560 consecutive patients. Group A is preoperative IABP therapy. Group B is postoperative IABP therapy.</p> <p>Results</p> <p>There was no significant difference in the number of grafts used between the two groups. Completeness of revascularization did not differ between the two groups. The statistically significant difference was hospital mortality (2.6% in group A vs. 3.8% in group B) (<it>p </it>< 0.05). And there was significant reduction in postoperative low cardiac output, malignant arrhythmia, acute renal failure and length of stay in ICU in group A, compared with group B (<it>p </it>< 0.05). In the two groups, six-, 12-, 24- and 48-month survival rates were similar. In the study the degree of improvement in angina and quality of life did not differ significantly between the two groups.</p> <p>Conclusion</p> <p>The use of preoperative IABP in SLVD patients undergoing OPCAB is of safety and effectiveness. The combined use of preoperative IABP and OPCAB allows complete revascularization in SLVD patients with an important reduction in operative mortality and excellent mid-term results.</p

Natural Form of Noncytolytic Flexible Human Fc as a Long-Acting Carrier of Agonistic Ligand, Erythropoietin

Human IgG1 Fc has been widely used as a bioconjugate, but exhibits shortcomings, such as antibody- and complement-mediated cytotoxicity as well as decreased bioactivity, when applied to agonistic proteins. Here, we constructed a nonimmunogenic, noncytolytic and flexible hybrid Fc (hyFc) consisting of IgD and IgG4, and tested its function using erythropoietin (EPO) conjugate, EPO-hyFc. Despite low amino acid homology (20.5%) between IgD Fc and IgG4 Fc, EPO-hyFc retained “Y-shaped” structure and repeated intravenous administrations of EPO-hyFc into monkeys did not generate EPO-hyFc-specific antibody responses. Furthermore, EPO-hyFc could not bind to FcγR I and C1q in contrast to EPO-IgG1 Fc. In addition, EPO-hyFc exhibited better in vitro bioactivity and in vivo bioactivity in rats than EPO-IgG1 Fc, presumably due to the high flexibility of IgD. Moreover, the mean serum half-life of EPO-hyFc(H), a high sialic acid content form of EPO-hyFc, was approximately 2-fold longer than that of the heavily glycosylated EPO, darbepoetin alfa, in rats. More importantly, subcutaneous injection of EPO-hyFc(H) not only induced a significantly greater elevation of serum hemoglobin levels than darbepoetin alfa in both normal rats and cisplatin-induced anemic rats, but also displayed a delayed time to maximal serum level and twice final area-under-the-curve (AUClast). Taken together, hyFc might be a more attractive Fc conjugate for agonistic proteins/peptides than IgG1 Fc due to its capability to elongate their half-lives without inducing host effector functions and hindering bioactivity of fused molecules. Additionally, a head-to-head comparison demonstrated that hyFc-fusion strategy more effectively improved the in vivo bioactivity of EPO than the hyperglycosylation approach

HFR1 Is Crucial for Transcriptome Regulation in the Cryptochrome 1-Mediated Early Response to Blue Light in Arabidopsis thaliana

Cryptochromes are blue light photoreceptors involved in development and circadian clock regulation. They are found in both eukaryotes and prokaryotes as light sensors. Long Hypocotyl in Far-Red 1 (HFR1) has been identified as a positive regulator and a possible transcription factor in both blue and far-red light signaling in plants. However, the gene targets that are regulated by HFR1 in cryptochrome 1 (cry1)-mediated blue light signaling have not been globally addressed. We examined the transcriptome profiles in a cry1- and HFR1-dependent manner in response to 1 hour of blue light. Strikingly, more than 70% of the genes induced by blue light in an HFR1-dependent manner were dependent on cry1, and vice versa. High overrepresentation of W-boxes and OCS elements were found in these genes, indicating that this strong cry1 and HFR1 co-regulation on gene expression is possibly through these two cis-elements. We also found that cry1 was required for maintaining the HFR1 protein level in blue light, and that the HFR1 protein level is strongly correlated with the global gene expression pattern. In summary, HFR1, which is fine-tuned by cry1, is crucial for regulating global gene expression in cry1-mediated early blue light signaling, especially for the function of genes containing W-boxes and OCS elements

Difference of clinical features in childhood Mycoplasma pneumoniae pneumonia

<p>Abstract</p> <p>Background</p> <p><it>M. pneumoniae </it>pneumonia (MP) has been reported in 10-40% of community-acquired pneumonia cases. We aimed to evaluate the difference of clinical features in children with MP, according to their age and chest radiographic patterns.</p> <p>Methods</p> <p>The diagnosis of MP was made by examinations at both admission and discharge and by two serologic tests: the indirect microparticle agglutinin assay (≥1:40) and the cold agglutinins titer (≥1:32). A total of 191 children with MP were grouped by age: ≤2 years of age (29 patients), 3-5 years of age (81 patients), and ≥6 years of age (81 patients). They were also grouped by pneumonia pattern: bronchopneumonia group (96 patients) and segmental/lobar pneumonia group (95 patients).</p> <p>Results</p> <p>Eighty-six patients (45%) were seroconverters, and the others showed increased antibody titers during hospitalization. Among the three age groups, the oldest children showed the longest duration of fever, highest C-reactive protein (CRP) values, and the most severe pneumonia pattern. The patients with segmental/lobar pneumonia were older and had longer fever duration and lower white blood cell (WBC) and lymphocyte counts, compared with those with bronchopneumonia. The patient group with the most severe pulmonary lesions had the most prolonged fever, highest CRP, highest rate of seroconverters, and lowest lymphocyte counts. Thrombocytosis was observed in 8% of patients at admission, but in 33% of patients at discharge.</p> <p>Conclusions</p> <p>In MP, older children had more prolonged fever and more severe pulmonary lesions. The severity of pulmonary lesions was associated with the absence of diagnostic IgM antibodies at presentation and lymphocyte count. Short-term paired IgM serologic test may be mandatory for early and definitive diagnosis of MP.</p

Lrp Acts as Both a Positive and Negative Regulator for Type 1 Fimbriae Production in Salmonella enterica Serovar Typhimurium

Leucine-responsive regulatory protein (Lrp) is known to be an indirect activator of type 1 fimbriae synthesis in Salmonella enterica serovar Typhimurium via direct regulation of FimZ, a direct positive regulator for type 1 fimbriae production. Using RT-PCR, we have shown previously that fimA transcription is dramatically impaired in both lrp-deletion (Δlrp) and constitutive-lrp expression (lrpC) mutant strains. In this work, we used chromosomal PfimA-lacZ fusions and yeast agglutination assays to confirm and extend our previous results. Direct binding of Lrp to PfimA was shown by an electrophoretic mobility shift assay (EMSA) and DNA footprinting assay. Site-directed mutagenesis revealed that the Lrp-binding motifs in PfimA play a role in both activation and repression of type 1 fimbriae production. Overproduction of Lrp also abrogates fimZ expression. EMSA data showed that Lrp and FimZ proteins independently bind to PfimA without competitive exclusion. In addition, both Lrp and FimZ binding to PfimA caused a hyper retardation (supershift) of the DNA-protein complex compared to the shift when each protein was present alone. Nutrition-dependent cellular Lrp levels closely correlated with the amount of type 1 fimbriae production. These observations suggest that Lrp plays important roles in type 1 fimbriation by acting as both a positive and negative regulator and its effect depends, at least in part, on the cellular concentration of Lrp in response to the nutritional environment

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur