Peripheral CD4+ cell prevalence and pleuropulmonary manifestations in systemic lupus erythematosus patients.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving several organs, including the lungs. Previous results confirmed changes of peripheral T cell subsets in lupus patients; however no data are available about their possible relationship with pulmonary involvement.

Objective: To determine pulmonary manifestations and potential relationship in changes of peripheral CD4+ T cell subsets.

Impact of climate change on global malaria distribution.

Malaria is an important disease that has a global distribution and significant health burden. The spatial limits of its distribution and seasonal activity are sensitive to climate factors, as well as the local capacity to control the disease. Malaria is also one of the few health outcomes that has been modeled by more than one research group and can therefore facilitate the first model intercomparison for health impacts under a future with climate change.

Girl power: estrogen promotes HSC self-renewal.

Although some hematopoietic cell types are known to respond to sex hormones, hematopoietic stem cells (HSCs) are generally thought to function similarly in both sexes. Recently in Nature, Nakada et al. (2014) show that HSCs respond to higher levels of estrogen in females, resulting in enhanced self-renewal and increased erythropoiesis.

Pharmacological and genomic profiling identifies NF-κB-targeted treatment strategies for mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an aggressive malignancy that is characterized by poor prognosis. Large-scale pharmacological profiling across more than 100 hematological cell line models identified a subset of MCL cell lines that are highly sensitive to the B cell receptor (BCR) signaling inhibitors ibrutinib and sotrastaurin. Sensitive MCL models exhibited chronic activation of the BCR-driven classical nuclear factor-κB (NF-κB) pathway, whereas insensitive cell lines displayed activation of the alternative NF-κB pathway.

The impact of climatic risk factors on the prevalence, distribution, and severity of acute and chronic trachoma.

Background And Objectives: Trachoma is the most common cause of infectious blindness. Hot, dry climates, dust and water scarcity are thought to be associated with the distribution of trachoma but the evidence is unclear. The aim of this study was to evaluate the epidemiological evidence regarding the extent to which climatic factors explain the current prevalence, distribution, and severity of acute and chronic trachoma.

Increased level of E protein activity during invariant NKT development promotes differentiation of invariant NKT2 and invariant NKT17 subsets.

E protein transcription factors and their natural inhibitors, Id proteins, play critical and complex roles during lymphoid development. In this article, we report that partial maintenance of E protein activity during positive selection results in a change in the cell fate determination of developing iNKT cells, with a block in the development of iNKT1 cells and a parallel increase in the iNKT2 and iNKT17 subsets. Because the expression levels of the transcription factors that drive these alternative functional fates (GATA-3, RORγT, T-bet, and Runx-3) are not altered, our results suggest that E protein activity controls a novel checkpoint that regulates the number of iNKT precursors that choose each fate.

Heat-related mortality risk model for climate change impact projection.

Objectives: We previously developed a model for projection of heat-related mortality attributable to climate change. The objective of this paper is to improve the fit and precision of and examine the robustness of the model.

Methods: We obtained daily data for number of deaths and maximum temperature from respective governmental organizations of Japan, Korea, Taiwan, the USA, and European countries.

Left ventricular untwisting in athlete's heart: key role in early diastolic filling?

Untwisting contributes to left ventricular filling through suction generation. We sought to investigate diastolic function and untwisting dynamics in different forms of left ventricular hypertrophy: in athlete's heart and hypertrophic cardiomyopathy. Elite athletes in kayaking, canoeing and rowing (n=28), patients with hypertrophic cardiomyopathy (HCM, n=15) and healthy sedentary volunteers (n=13) were compared.

An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide).

Unlabelled: Castration-resistant prostate cancer (CRPC) is the most aggressive, incurable form of prostate cancer. MDV3100 (enzalutamide), an antagonist of the androgen receptor (AR), was approved for clinical use in men with metastatic CRPC. Although this compound showed clinical efficacy, many initial responders later developed resistance.

The ecotoxicological evaluation of Cylindrospermopsis raciborskii from Lake Balaton (Hungary) employing a battery of bioassays and chemical screening.

Ecotoxicity of four Cylindrospermopsis raciborskii strains (ACT 9502, ACT 9503, ACT 9504, ACT 9505) isolated from Lake Balaton (Hungary) was evaluated in four aquatic bioassays including the Thamnocephalus platyurus acute lethality test; Daphnia magna acute immobilization assay; D. magna feeding inhibition assay and Danio rerio embryo developmental toxicity assay, assisted by chemical screening for known toxins by HPLC-MS. For reference, we analyzed in parallel the toxin content and toxic effects of two previously characterized toxin-producing strains: the Australian cylindrospermopsin producer AQS C.

Ecotoxicity and genotoxicity assessment of exhaust particulates from diesel-powered buses.

Diesel exhaust is one of the major sources of fine and ultra-fine particulate matter in urban air. Toxicity of diesel-powered engine emissions has been quite widely assessed; however, much less information is available on their ecotoxicity. In our study, the kinetic version of the Vibrio fischeri bioluminescence inhibition bioassay based on the ISO 21338:2010 standard was used to characterise the ecotoxicity of diesel-powered buses.

Time-series analysis of weather and mortality patterns in Nairobi's informal settlements.

Background: Many studies have established a link between weather (primarily temperature) and daily mortality in developed countries. However, little is known about this relationship in urban populations in sub-Saharan Africa.

Objectives: The objective of this study was to describe the relationship between daily weather and mortality in Nairobi, Kenya, and to evaluate this relationship with regard to cause of death, age, and sex.

IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation.

Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous infection, autoimmune disease, and vaccination. In this study, we investigated whether the development and migration of skin-resident DC were regulated by IFN regulatory factor 4 (IRF4), a transcription factor that is required for the development of CD11b(+) splenic DC. We found that the skin of naive IRF4(-/-) mice contained normal numbers of epidermal Langerhans cells (eLC) and increased numbers of CD11b(+) and CD103(+) dermal DC (dDC) populations, indicating that tissue DC development and skin residency is not disrupted by IRF4 deficiency.

Ecotoxicological characterisation of sedimentation in the Kis-Balaton Water Protection System.

The main function of the Kis-Balaton Water Protection System is to retain nutrients and total suspended solids, thus protecting the water quality of Lake Balaton. In this paper, the toxic nature of the sediment in the 2nd reservoir of the KBWPS has been characterised, using a battery of tests: Vibrio fischeri acute bioassay on whole sediment samples, and V. fischeri bioassay on pore water and elutriate samples.

Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and Orally Active CDK4/6 Inhibitors.

Herein, we describe the discovery of potent and highly selective inhibitors of both CDK4 and CDK6 via structure-guided optimization of a fragment-based screening hit. CDK6 X-ray crystallography and pharmacokinetic data steered efforts in identifying compound 6, which showed >1000-fold selectivity for CDK4 over CDKs 1 and 2 in an enzymatic assay. Furthermore, 6 demonstrated in vivo inhibition of pRb-phosphorylation and oral efficacy in a Jeko-1 mouse xenograft model.

[Pulmonary infections following solid organ transplantation].

Solid organ transplantation is the standard of care for selected patients with severe vital organ dysfunction. The need for immunosuppression to prevent organ rejection is a common characteristic of recipients. Immunosuppression increases the risk of infections, especially with low virulence opportunistic pathogens.

Temperature-related deaths in people with psychosis, dementia and substance misuse.

Background: Climate change is expected to have significant effects on human health, partly through an increase in extreme events such as heatwaves. People with mental illness may be at particular risk.

Aims: To estimate risk conferred by high ambient temperature on patients with psychosis, dementia and substance misuse.

Estrogen receptors regulate an inflammatory pathway of dendritic cell differentiation: mechanisms and implications for immunity.

Immune cells and hematopoietic progenitors express estrogen receptors (ER). As ligand-activated transcription factors that modulate chromatin structure, ER regulate transcriptional programs that direct the development or functional responses of immune cells. ER-regulated immune responses likely contribute to significant sex biases in infection, autoimmunity and other inflammatory diseases, and changes in immune function during the female hormonal cycle and pregnancy.

Tumor cell expression of heat shock protein (HSP) 72 is influenced by HSP72 [HSPA1B A(1267)G] polymorphism and predicts survival in small Cell lung cancer (SCLC) patients.

The inducible heat shock protein (HSP)72 plays a central role in antitumor immunomodulation. HSP72 expression was assessed on tumor samples of 43 patients with advanced and metastatic small cell lung cancer (SCLC) by immunohistochemistry and HSP72 [HSPA1B A(1267)G] polymorphism was determined. HSP72 expression of SCLC cells was significantly decreased in GG as compared to cells of AA or AG genotype patients, and was associated with significantly shorter survival in GG patients as compared to carriers of the A allele.