The Interaction Effects of Temperature and Humidity on Emergency Room Visits for Respiratory Diseases in Beijing,China

Few epidemiological studies have been reported as to whether there was any interactive effect between temperature and humidity on respiratory morbidity, especially in Asian countries. The present study used time-series analysis to explore the modification effects of humidity on the association between temperature and emergency room (ER) visits for respiratory, upper respiratory tract infection (URI), pneumonia, and bronchitis in Beijing between 2009 and 2011. Results showed that an obvious joint effect of temperature and humidity was revealed on ER visits for respiratory, URI, pneumonia, and bronchitis. Below temperature threshold, the temperature effect was stronger in low humidity level and presented a trend fall with humidity level increase. The effect estimates per 1 °C increase in temperature in low humidity level were ?2.88 % (95 % confidence interval (CI) ?3.08, ?2.67) for all respiratory, ?3.24 % (?3.59, ?2.88) for URI, ?1.48 % (?1.93, ?1.03) for pneumonia, and ?3.79 % (?4.37, ?3.21) for bronchitis ER visits, respectively. However, above temperature threshold, temperature effect was greater in high humidity level and trending upward with humidity level increasing. In high humidity level, a 1 °C increase in temperature, the effect estimates were 1.84 % (1.55, 2.13) for all respiratory, 1.76 % (1.41, 2.11) for URI, and 7.48 % (4.41, 10.65) for bronchitis ER visits. But, there was no statistically significant for pneumonia. This suggests that the modifying effects of the humidity should be considered when analyzing health impacts of temperature.     

Comparative 2D-DIGE Proteomic Analysis of Bovine Mammary Epithelial Cells during Lactation Reveals Protein Signatures for Lactation Persistency and Milk Yield

Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-κB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling.     

Fingolimod Increases CD39-Expressing Regulatory T Cells in Multiple Sclerosis Patients

Background

Multiple sclerosis (MS) likely results from an imbalance between regulatory and inflammatory immune processes. CD39 is an ectoenzyme that cleaves ATP to AMP and has been suggested as a novel regulatory T cells (Treg) marker. As ATP has numerous proinflammatory effects, its degradation by CD39 has anti-inflammatory influence. The purpose of this study was to explore regulatory and inflammatory mechanisms activated in fingolimod treated MS patients.

Methods and Findings

Peripheral blood mononuclear cells (PBMCs) were isolated from relapsing-remitting MS patients before starting fingolimod and three months after therapy start. mRNA expression was assessed in ex vivo PBMCs. The proportions of CD8, B cells, CD4 and CD39-expressing cells were analysed by flow cytometry. Treg proportion was quantified by flow cytometry and methylation-specific qPCR. Fingolimod treatment increased mRNA levels of CD39, AHR and CYP1B1 but decreased mRNA expression of IL-17, IL-22 and FOXP3 mRNA in PBMCs. B cells, CD4⁺ cells and Treg proportions were significantly reduced by this treatment, but remaining CD4⁺ T cells were enriched in FOXP3⁺ cells and in CD39-expressing Tregs.

Conclusions

In addition to the decrease in circulating CD4⁺ T cells and CD19⁺ B cells, our findings highlight additional immunoregulatory mechanisms induced by fingolimod.     

CCR7 Expressing Mesenchymal Stem Cells Potently Inhibit Graft-versus-Host Disease by Spoiling the Fourth Supplemental Billingham’s Tenet

The clinical acute graft-versus-host disease (GvHD)-therapy of mesenchymal stem cells (MSCs) is not as satisfactory as expected. Secondary lymphoid organs (SLOs) are the major niches serve to initiate immune responses or induce tolerance. Our previous study showed that CCR7 guide murine MSC line C3H10T1/2 migrating to SLOs. In this study, CCR7 gene was engineered into murine MSCs by lentivirus transfection system (MSCs/CCR7). The immunomodulatory mechanism of MSCs/CCR7 was further investigated. Provoked by inflammatory cytokines, MSCs/CCR7 increased the secretion of nitric oxide and calmed down the T cell immune response in vitro. Immunofluorescent staining results showed that transfused MSCs/CCR7 can migrate to and relocate at the appropriate T cell-rich zones within SLOs in vivo. MSCs/CCR7 displayed enhanced effect in prolonging the survival and alleviating the clinical scores of the GvHD mice than normal MSCs. Owing to the critical relocation sites, MSCs/CCR7 co-infusion potently made the T cells in SLOs more naïve like, thus control T cells trafficking from SLOs to the target organs. Through spoiling the fourth supplemental Billingham’s tenet, MSCs/CCR7 potently inhibited the development of GvHD. The study here provides a novel therapeutic strategy of MSCs/CCR7 infusion at a low dosage to give potent immunomodulatory effect for clinical immune disease therapy.     

Viral Aetiology of Central Nervous System Infections in Adults Admitted to a Tertiary Referral Hospital in Southern Vietnam over 12 Years

Background

Central nervous system (CNS) infections are important diseases in both children and adults worldwide. The spectrum of infections is broad, encompassing bacterial/aseptic meningitis and encephalitis. Viruses are regarded as the most common causes of encephalitis and aseptic meningitis. Better understanding of the viral causes of the diseases is of public health importance, in order to better inform immunization policy, and may influence clinical management.

Methodology/Principal Findings

Study was conducted at the Hospital for Tropical Diseases in Ho Chi Minh City, a primary, secondary, and tertiary referral hospital for all southern provinces of Vietnam. Between December 1996 and May 2008, patients with CNS infections of presumed viral origin were enrolled. Laboratory diagnostics consisted of molecular and serological tests targeted at 14 meningitis/encephalitis-associated viruses.Of 291 enrolled patients, fatal outcome and neurological sequelae were recorded in 10% (28/291) and 27% (78/291), respectively. Mortality was especially high (9/19, 47%) amongst those with confirmed herpes simplex encephalitis which is attributed to the limited availability of intravenous acyclovir/valacyclovir. Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses were the most common viruses detected, responsible for 36 (12%), 19 (6.5%), 19 (6.5%) and 8 (2.7%) respectively, followed by rubella virus (6, 2%), varicella zoster virus (5, 1.7%), mumps virus (2, 0.7%), cytomegalovirus (1, 0.3%), and rabies virus (1, 0.3%).

Conclusions/Significance

Viral infections of the CNS in adults in Vietnam are associated with high morbidity and mortality. Despite extensive laboratory testing, 68% of the patients remain undiagnosed. Together with our previous reports, the data confirm that Japanese encephalitis virus, dengue virus, herpes simplex virus, and enteroviruses are the leading identified causes of CNS viral infections in Vietnam, suggest that the majority of morbidity/mortality amongst patients with a confirmed/probable diagnosis is preventable by adequate vaccination/treatment, and are therefore of public health significance.     

The Effect of Probiotics Supplementation on Helicobacter pylori Eradication Rates and Side Effects during Eradication Therapy: A Meta-Analysis

Background

Previous meta-analyses reported that probiotics improve the effectiveness of Helicobacter pylori (H. pylori) eradication during antibiotic therapy, while results regarding a possible reduction of side effects remained inconclusive. Moreover, the effectiveness of different strains of probiotics has not been studied so far. It is further conceivable that probiotics will produce additional effects only if antibiotics are relatively ineffective.

Methods

This meta-analysis includes eligible randomized controlled trials examining effects of probiotics supplementation on eradication rates (ER) and side effects, published up to May 2014. Sub-group analysis was performed to compare different probiotic strains and antibiotic therapies with different effectiveness in controls (ER <80% vs.>80%). Publication bias was assessed with funnel plots and Harbord''s test. The quality of the trials was assessed with the Cochrane risk of bias tool.

Results

Thirty-three RCTs involving a total of 4459 patients met the inclusion criteria in case of eradication rates of which 20 assessed total side effects in addition. Overall, the pooled eradication rate in probiotics supplementation groups was significantly higher than in controls (ITT analysis: RR 1.122, 95% CI 1.086–1.159, PP analysis: RR 1.114, 95% CI 1.070–1.159). Sub group-analysis could, however, confirm this finding only for four individual strains (Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri, and Bifidobacterium infantis 2036) and for relatively ineffective antibiotic therapies. There was a significant difference between groups in the overall incidence of side effects (RR 0.735, 95% CI 0.598–0.902). This result was, however, only confirmed for non-blinded trials.

Conclusions

The pooled data suggest that supplementation with specific strains of probiotics compared with eradication therapy may be considered an option for increasing eradication rates, particularly when antibiotic therapies are relatively ineffective. The impact on side effects remains unclear and more high quality trials on specific probiotic strains and side effects are thus needed.     

CCN1 induces apoptosis in esophageal adenocarcinoma through p53-dependent downregulation of survivin

Many cancer drugs have been developed to control tumor growth by inducing cancer cell apoptosis. However, several intracellular barriers could fail this attempt. One of these barrier is high expression of survivin. Survivin can interfere caspase activation and thereby abort apoptosis. In this study, we found that CCN1 suppressed the survivin expression in tumor cells of esophageal adenocarcinoma (EAC) and thus allowed apoptosis to finish. Furthermore, we demonstrated that this downregulation was dependent on p53 phosphorylation at Ser20, and CCN1 induced EAC cell apoptosis through the activation of p53.     

Mutation of kri1l causes definitive hematopoiesis failure via PERK-dependent excessive autophagy induction

Dysregulation of ribosome biogenesis causes human diseases, such as Diamond-Blackfan anemia, del (5q-) syndrome and bone marrow failure. However, the mechanisms of blood disorders in these diseases remain elusive. Through genetic mapping, molecular cloning and mechanism characterization of the zebrafish mutant cas002, we reveal a novel connection between ribosomal dysfunction and excessive autophagy in the regulation of hematopoietic stem/progenitor cells (HSPCs). cas002 carries a recessive lethal mutation in kri1l gene that encodes an essential component of rRNA small subunit processome. We show that Kri1l is required for normal ribosome biogenesis, expansion of definitive HSPCs and subsequent lineage differentiation. Through live imaging and biochemical studies, we find that loss of Kri1l causes the accumulation of misfolded proteins and excessive PERK activation-dependent autophagy in HSPCs. Blocking autophagy but not inhibiting apoptosis by Bcl2 overexpression can fully rescue hematopoietic defects, but not the lethality of kri1l^cas002 embryos. Treatment with autophagy inhibitors (3-MA and Baf A1) or PERK inhibitor (GSK2656157), or knockdown of beclin1 or perk can markedly restore HSPC proliferation and definitive hematopoietic cell differentiation. These results may provide leads for effective therapeutics that benefit patients with anemia or bone marrow failure caused by ribosome disorders.     

Temporal variations of mobile carbohydrates in Abies fargesii at the upper tree limits

Low temperatures are associated high‐altitude treelines, but the functional mechanism of treeline formation remains controversial. The relative contributions of carbon limitation (source activity) and growth limitation (sink activity) require more tests across taxa and regions. We examined temporal variations of mobile carbon supply in different tissues of Abies fargesii across treeline ecotones on north‐ and south‐facing slopes of the Qinling Mountains, China. Non‐structural carbohydrate (NSC) concentrations in tissues along the altitudinal gradient on both slopes changed significantly in the early and late growing season, but not in the mid‐growing season, indicating the season‐dependent carbon supply status. Late in the growing season on both slopes, trees at the upper limits had the highest NSC concentrations and total soluble sugars and lowest starch concentrations compared to trees at the lower elevations. NSC concentrations tended to increase in needles and branches throughout the growing season with increasing elevation on both slopes, but declined in roots and stems. NSC concentrations across sampling dates also indicated increases in needles and branches, and decreases in roots and stem with increasing elevation. Overall altitudinal trends of NSC in A. fargesii revealed no depletion of mobile carbon reserves at upper elevation limits, suggesting limitation of sink activity dominates tree life across treeline ecotones in both north‐ and south‐facing slopes. Carbon reserves in storage tissues (especially roots) in the late growing season might also play an important role in winter survival and early growth in spring at upper elevations on both slopes, which define the uppermost limit of A. fargesii.     

Chemical Response of the Toxic Dinoflagellate Karenia mikimotoi Against Grazing by Three Species of Zooplankton

We investigated the toxicity of Karenia mikimotoi toward three model grazers, the cladoceran Moina mongolica, the copepod Pseudodiaptomus annandalei, and the crustacean Artemia salina, and explored its chemical response upon zooplankton grazing. An induction experiment, where K. mikimotoi was exposed to grazers or waterborne cues from the mixed cultures revealed that K. mikimotoi might be toxic or nutritionally inadequate toward the three grazers. In general, direct exposure to the three grazers induced the production of hemolytic toxins and the synthesis of eicosapentaenoic acid (EPA). Both EPA and the hemolytic toxins from K. mikimotoi decreased the survival rate of the three grazers. In addition, the survival rates of M. mongolica, P. annandalei, and A. salina in the presence of induced K. mikimotoi that had previously been exposed to a certain grazer were lower than their counterparts caused by fresh K. mikimotoi, suggesting that exposure to some grazers might increase the toxicity of K. mikimotoi. The chemical response and associated increased resistance to further grazing suggested that K. mikimotoi could produce deterrents to protect against grazing by zooplankton and that the substances responsible might be hemolytic toxins and EPA.