Retinal imaging for the assessment of stroke risk: a systematic review.

BACKGROUND: Stroke is a leading cause of morbidity and mortality. Retinal imaging allows non-invasive assessment of the microvasculature. Consequently, retinal imaging is a technology which is garnering increasing attention as a means of assessing cardiovascular health and stroke risk. METHODS: A biomedical literature search was performed to identify prospective studies that assess the role of retinal imaging derived biomarkers as indicators of stroke risk. RESULTS: Twenty-four studies were included in this systematic review. The available evidence suggests that wider retinal venules, lower fractal dimension, increased arteriolar tortuosity, presence of retinopathy, and presence of retinal emboli are associated with increased likelihood of stroke. There is weaker evidence to suggest that narrower arterioles and the presence of individual retinopathy traits such as microaneurysms and arteriovenous nicking indicate increased stroke risk. Our review identified three models utilizing artificial intelligence algorithms for the analysis of retinal images to predict stroke. Two of these focused on fundus photographs, whilst one also utilized optical coherence tomography (OCT) technology images. The constructed models performed similarly to conventional risk scores but did not significantly exceed their performance. Only two studies identified in this review used OCT imaging, despite the higher dimensionality of this data. CONCLUSION: Whilst there is strong evidence that retinal imaging features can be used to indicate stroke risk, there is currently no predictive model which significantly outperforms conventional risk scores. To develop clinically useful tools, future research should focus on utilization of deep learning algorithms, validation in external cohorts, and analysis of OCT images.

A Phase I Dose-Escalation Clinical Trial to Assess the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stromal Cells in Knee Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease. Mesenchymal stromal cells (MSC) are promising cell-based therapy for OA. However, there is still a need for additional randomized, dose-dependent studies to determine the optimal dose and tissue source of MSC for improved clinical outcomes. Here, we performed a dose-dependant evaluation of umbilical cord (UC)-derived MSC (Celllistem) in a murine model and in knee OA patients. For the preclinical study, a classical dose (200.000 cells) and a lower dose (50.000 cells) of Cellistem were intra-articularly injected into the mice knee joints. The results showed a dose efficacy response effect of Cellistem associated with a decreased inflammatory and degenerative response according to the Pritzker OARSI score. Following the same approach, the dose-escalation phase I clinical trial design included 3 sequential cohorts: low-dose group (2 × 106 cells), medium-dose group (20 × 106), and high-dose group (80 × 106). All the doses were safe, and no serious adverse events were reported. Nonetheless, 100% of the patients injected with the high-dose experienced injection-related swelling in the knee joint. According to WOMAC total outcomes, patients treated with all doses reported significant improvements in pain and function compared with baseline after 3 and 6 months. However, the improvements were higher in patients treated with both medium and low dose as compared to high dose. Therefore, our data demonstrate that the intra-articular injection of different doses of Cellistem is both safe and efficient, making it an interesting therapeutic alternative to treat mild and symptomatic knee OA patients. Trial registration ClinicalTrials.gov NCT03810521.

Chitinase induction in Trichoderma harzianum: a solid-state fermentation approach using shrimp waste and wheat bran/commercial chitin for chitooligosaccharides synthesis.

This study innovatively employed solid-state fermentation (SSF) to evaluate chitinase induction in Trichoderma harzianum. Solid-state fermentation minimizes water usage, a crucial global resource, and was applied using shrimp waste chitin and a mixture of commercial chitin with wheat bran as substrates. Shrimp waste and wheat bran were pretreated and characterized for SSF, and the fungus's utilization of the substrates was assessed using spectrophotometric and microscopic methods. The resulting enzymes' ability to produce chitooligosaccharides (COS) mixtures was studied. Wheat bran/commercial chitin demonstrated superior performance, with a 1.8-fold increase in chitinase activity (76.3 U/mg protein) compared to shrimp waste chitin (41.8 U/mg protein). Additionally, the COS mixture obtained from wheat bran/commercial chitin showed a higher concentration of reducing sugars, reaching 87.85 mM, compared to shrimp waste chitin (14.87 mM). The COS profile from wheat bran/commercial chitin included monomers to heptamers, while the profile from shrimp waste chitin was predominantly composed of monomers. These results highlight the advantages of SSF for chitinase induction and COS production in T. harzianum, offering potential applications as dietary fiber, antioxidants, and antimicrobial agents. The findings contribute to by-product valorization, waste reduction, and the sustainable generation of valuable products through SSF-based enzyme production.

3-min All-out Test to Evaluate Aerobic and Anaerobic Indexes in Court Team Sports.

This study aimed to test the reproducibility of the 3-min all-out effort applied using shuttle running and compare its values to aerobic parameters. On the first day, 14 futsal players underwent an exhaustive test to determine the maximal incremental speed (MIS) and anaerobic threshold (AnT). On the second day, the participants performed the 3-min all-out effort (n=14), which was repeated after 48 h (third day) to test its reproducibility (n=11). Peak oxygen consumption (V̇ O2PEAK) and peak blood lactate concentrations ([La-]) were determined from 3-min all-out efforts performed through a 20-m shuttle run on the official court. The distance covered, mean speed, and critical speed (CS) during the 3-min all-out presented direct relationships with aerobic parameters determined through the incremental test (r>0.62). The distance covered above CS (D') presented a direct relationship with peak lactate concentrations induced by a 3-min all-out effort (r=0.81). Despite the acceptable levels of reproducibility observed for most of the 3-min all-out variables, the minimal detectable change for D' was high (72%). Our results demonstrated the potential use of mean speed to evaluate aerobic fitness. However, the applicability of the 3-min all-out shuttle run test to monitor training adaptations should be avoided, at least in nonexperienced athletes.

CR5/CCL5 axis is linked to a poor outcome, and inhibition reduces metastasis in oral squamous cell carcinoma.

PURPOSE: The CCR5/CCL5 axis is essential for interactions between malignant cells and microenvironment components, promoting tumor progression in oral squamous cell carcinoma (OSCC). This study aims to evaluate the association of CCL5 and CCR5 with the behavior of oral cancer and assess the therapeutic potential of a CCR5 antagonist. METHODS: A retrospective study to analyze CCR5 and CCL5 expression on paraffin-embedded tissues was performed. In cell lines, rhCCL5 was added to induce CCR5-related pathways, and Maraviroc and shRNA against CCR5 were used to neutralize the receptor. Finally, an in vivo murine orthotopic xenograft model of tongue cancer was used to evaluate Maraviroc as an oncologic therapy. After 15 days, the mice were killed, and the primary tumors and cervical lymph nodes were analyzed. RESULTS: The expression of CCR5 was associated with clinical stage and metastasis, and CCL5 was related to overall survival. Adding rhCCL5 induced cell proliferation, while shRNA and Maraviroc reduced it in a dose-dependent manner. Maraviroc treatment also increased apoptosis and modified cytoskeletal organization. In vivo, Maraviroc reduced neck metastasis. CONCLUSIONS: The effects of CCR5 antagonists in OSCC have been poorly studied, and this study reports in vitro and in vivo evidence for the effects of Maraviroc in OSCC. Our results suggest that the CCR5/CCL5 axis plays a role in oral cancer behavior, and that its inhibition is a promising new therapy alternative.

Role of microRNA Shuttled in Small Extracellular Vesicles Derived From Mesenchymal Stem/Stromal Cells for Osteoarticular Disease Treatment.

Osteoarticular diseases (OD), such as rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic autoimmune/inflammatory and age-related diseases that affect the joints and other organs for which the current therapies are not effective. Cell therapy using mesenchymal stem/stromal cells (MSCs) is an alternative treatment due to their immunomodulatory and tissue differentiation capacity. Several experimental studies in numerous diseases have demonstrated the MSCs' therapeutic effects. However, MSCs have shown heterogeneity, instability of stemness and differentiation capacities, limited homing ability, and various adverse responses such as abnormal differentiation and tumor formation. Recently, acellular therapy based on MSC secreted factors has raised the attention of several studies. It has been shown that molecules embedded in extracellular vesicles (EVs) derived from MSCs, particularly those from the small fraction enriched in exosomes (sEVs), effectively mimic their impact in target cells. The biological effects of sEVs critically depend on their cargo, where sEVs-embedded microRNAs (miRNAs) are particularly relevant due to their crucial role in gene expression regulation. Therefore, in this review, we will focus on the effect of sEVs derived from MSCs and their miRNA cargo on target cells associated with the pathology of RA and OA and their potential therapeutic impact.

The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming.

Mesenchymal stem cells (MSCs) are multipotent adult stromal cells widely studied for their regenerative and immunomodulatory properties. They are capable of modulating macrophage plasticity depending on various microenvironmental signals. Current studies have shown that metabolic changes can also affect macrophage fate and function. Indeed, changes in the environment prompt phenotype change. Therefore, in this review, we will discuss how MSCs orchestrate macrophage's metabolic plasticity and the impact on their function. An improved understanding of the crosstalk between macrophages and MSCs will improve our knowledge of MSC's therapeutic potential in the context of inflammatory diseases, cancer, and tissue repair processes in which macrophages are pivotal.

Comunicación en el consultorio de medicina familiar: trabajo multicéntrico, cualitativo cuantitativo, en los meses de abril a julio de 2014, en Buenos Aires, Rosario y Tucumán / Communication in Family Medicine practice: multicenter research trial, qualitative and quantitative, from April to June 2014. in the City of Buenos Aires, Rosario and Tucumán

Introducción: la comunicación es trascendental para la vida en sociedad. El éxito de cualquier entrevista clínica depende de la calidad de la comunicación entre el médico y el paciente. Distintos factores pueden interferir en esta, como el ambiente, el tiempo y las interrupciones. Objetivo: Evaluar el grado de comprensión del mensaje transmitido por el médico hacia el paciente. Material y método: Trabajo multicéntrico, cualitativo cuantitativo. Componente cuantitativo: descriptivo de corte transversal de abril a julio de 2014. Se incluyeron 1200 adultos de ambos sexos, que asistieron a los Ce.M.A.P y 40 médicos de familia. Componente cualitativo: Muestreo no probabilístico, intencional, hasta saturación de datos. Triangulación y convergencia de datos. Resultados y discusión: Respecto al componente cuantitativo, se encontró que nuestras hipótesis acerca de la falta de comprensión del mensaje (indicaciones y problema de salud) no pudieron comprobarse. Ya que las indicaciones realizadas por el médico tuvieron una adecuación total del 60% y comprendieron el problema de salud un 77% de los pacientes entrevistados. Para el componente cualitativo luego del análisis temático se obtuvieron barreras (tiempo, paciente polidemandante, ideas previas, omisión de indicaciones no farmacológicas) y facilitadores (conocimiento previo del problema de salud, longitudinalidad, paciente acompañado) para la comprensión del mensaje. Conclusiones: Los pacientes entienden el mensaje de sus médicos de familia, ya que contamos con herramientas concretas como la escucha empática, el proceso clínico centrado en la persona y la longitudinalidad en la atención (AU)

Introduction: communication is important for life in a society. Success in any clinical interview depends on the quality of patient-doctor communication. Different factors may interfere, like the environment, time and interruptions. Objective: Asses the level of understanding of the message given to the patient by the doctor. Material and method: Multicenter research trial, qualitative and quantitative. Quantitative component: cross sectional descriptive from April to June 2014. 1200 adults of both sexes who assisted to the primary health care center: "Ce.M.A.P." in the City of Buenos Aires, Rosario and Tucumán and 40 family practitioners. Qualitative component: nonprobability, intentional sampling upon data saturation. Data triangulation and convergence. Results and discussion: as regards the quantitative component, we found out that our hypothesis in relation to the lack of understanding in the message (indications and health problem) could not be proven. Since 60% of the practitioner's indications were followed and 77% of the interviewed patients understood the health problem. Considering the qualitative component after the thematic analysis, barriers (time, highly demanding patient, previous knowledge, omission of non-pharmacological indications) and facilitators were obtained (previous knowledge of health problem, longitudinality, accompanied patient) to understand the message. Conclusion: patients understand their family practitioner's message since we have specific tools like empathic listening, patient centered healthcare and longitudinality in attention (AU)

Increased systemic and peritoneal oxidative stress biomarkers in endometriosis are not related to retrograde menstruation.

Objetives: The goal of this study was to determine if systemic and peritoneal oxidative stress biomarkers are related to each other and to retrograde menstruation in endometriosis. Methods: Plasma and peritoneal fluid oxidative stress biomarkers and hemoglobin and erythrocytes in peritoneal fluid as retrograde menstruation indicators, were measured in 28 patients with endometriosis and 23 without endometriosis. Results: In the peritoneal fluid, carbonyls and lipohydroperoxides, indicative of protein and lipid oxidative damage, were higher in endometriosis group (21%, p = 0.016 and 46%, p = 0.009, respectively). However, these biomarkers were not different in the blood plasma of both groups, and only protein dityrosine, was increased in the plasma of endometriosis group (31%, p = 0.04). The peritoneal fluid hemoglobin content was not higher in the endometriosis group, nor related to carbonyls and lipohydroperoxides. Additionally, the peritoneal fluid oxidative biomarkers were not correlated with the blood plasma ones, and only malondialdehyde, and ischemia-modified albumin were almost two times higher in peritoneal fluid. Discussion: Our results show a peritoneal and systemic oxidative stress biomarkers increase in endometriosis, but not related to each other, and do not support the hypothesis of an increase in hemoglobin-iron supply towards the peritoneal cavity that causes oxidative damage.

Long-Term Exposure to Ozone and Cause-Specific Mortality Risk in the United States.

Rationale: Many studies have linked short-term exposure to ozone (O3) with morbidity and mortality, but epidemiologic evidence of associations between long-term O3 exposure and mortality is more limited.Objectives: To investigate associations of long-term (annual or warm season average of daily 8-h maximum concentrations) O3 exposure with all-cause and cause-specific mortality in the NIH-AARP Diet and Health Study, a large prospective cohort of U.S. adults with 17 years of follow-up from 1995 to 2011.Methods: The cohort (n = 548,780) was linked to census tract-level estimates for O3. Associations between long-term O3 exposure (averaged values from 2002 to 2010) and multiple causes of death were evaluated using multivariate Cox proportional hazards models, adjusted for individual- and census tract-level covariates, and potentially confounding copollutants and temperature.Measurements and Main Results: Long-term annual average exposure to O3 was significantly associated with deaths caused by cardiovascular disease (per 10 ppb; hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.06), ischemic heart disease (HR, 1.06; 95% CI, 1.02-1.09), respiratory disease (HR, 1.04; 95% CI, 1.00-1.09), and chronic obstructive pulmonary disease (HR, 1.09; 95% CI, 1.03-1.15) in single-pollutant models. The results were robust to alternative models and adjustment for copollutants (fine particulate matter and nitrogen dioxide), although some evidence of confounding by temperature was observed. Significantly elevated respiratory disease mortality risk associated with long-term O3 exposure was found among those living in locations with high temperature (Pinteraction < 0.05).Conclusions: This study found that long-term exposure to O3 is associated with increased risk for multiple causes of mortality, suggesting that establishment of annual and/or seasonal federal O3 standards is needed to more adequately protect public health from ambient O3 exposures.

Impact of exposure of crude oil and dispersant (Corexit) on aggregation of extracellular polymeric substances.

Spilled oil treated with Corexit dispersant can cause unintended impacts on marine environment systems including altering marine organic matter dynamics; however, impacts on microgels and marine oil snow (MOS) formation are still debated and remain to be fully understood. Extracellular polymeric substances (EPS) are a major source of marine organic carbon for MOS and microgel formation. EPS initial aggregation plays key roles in the oil degrading process and various biogeochemical reactions. Here we used four types of EPS with water accommodated fraction (WAF), chemically-enhanced WAF (CEWAF) and Corexit, to represent potential situations during oil spills and post-application of Corexit. We found that Corexit alone can inhibit EPS aggregation and disperse pre-existing microgels. CEWAF can enhance EPS aggregation with efficiency by up to 80%-100% and more aggregates accumulated within the air-water interface. Additionally, more hydrophobic EPS aggregates showed high resistance to Corexit dispersion while hydrophilic EPS were more sensitive. Effects of oil spills on marine gel particle formation are primarily determined by chemical characteristics (hydrophobicity and protein content) of the constituent EPS. This study offers unique insights for organic particle dynamics and identifies controlling factors for MOS or gel particles associated with oil spills and Corexit dispersant used.

Preferencias alimentarias durante el recreo escolar: Niños de primaria de 9 a 10 años / Food preferences during lunch break: Elementary school children from 9 to 10 years

Resumen La alimentación de los niños durante el horario escolar es fundamental, por lo que a fin de adecuar la oferta alimentaria, es indispensable conocer cuáles son las preferencias alimentarias del alumnado. Así, el propósito de este estudio fue identificar los motivos de las preferencias y el consumo de alimentos durante el recreo escolar. Participaron 38 niños de 9-10 años de edad (55% niñas y 45% niños), alumnos de una escuela primaria pública de tiempo completo. Este estudio etnográfico comprendió el registro de alimentos consumidos y preferidos habitualmente, así como las narrativas de los niños, a través de observación dirigida, entrevistas no estructuradas y elaboración de dibujos. Se encontró que las preferencias alimentarias de los niños están estrechamente vinculadas al contexto familiar y los sentimientos ligados a éste. No obstante, en dichas preferencias influyen también la educación alimentaria recibida (escolar y extra-escolar), así como la disponibilidad-restricción de alimentos dentro de la escuela. En conclusión, aunque las y los niños podían no consumir en el recreo escolar su alimento favorito, adaptaban sus preferencias en función de los alimentos disponibles en la escuela, de modo que la selección variaba en función de la percepción y ponderación de las propiedades organolépticas del alimento (e.g., sabor, consistencia, temperatura).

Abstract Feeding children during school hours is essential, so to adapt the food supply, it is necessary to know what students' food preferences are. Thus, the purpose of this study was to identify the reasons for preferences and food consumption during school breaks. Thirty-eight children with an age range of 9 to 10 years (55% girls and 45% boys), from a full-time public primary school participated. This ethnographic study comprised the recording of commonly consumed and preferred foods, as well as children's narratives, through directed observation, unstructured interviews and drawings. It was found that children's food preferences are closely linked to the family context and the feelings linked to them. However, these preferences also influence the food education received (school and extra-school), as well as the availability-restriction of food within the school. In conclusion, although children could not consume their favorite food at school, they adapted their preferences according to the foods available at school, so the selection varied based on the perception and weighting of the organoleptic properties of the food (e.g., taste, consistency, temperature).

Association between long-term exposure to ambient air pollution and diabetes mortality in the US.

OBJECTIVE: Recent mechanistic and epidemiological evidence implicates air pollution as a potential risk factor for diabetes; however, mortality risks have not been evaluated in a large US cohort assessing exposures to multiple pollutants with detailed consideration of personal risk factors for diabetes. RESEARCH DESIGN AND METHODS: We assessed the effects of long-term ambient air pollution exposures on diabetes mortality in the NIH-AARP Diet and Health Study, a cohort of approximately a half million subjects across the contiguous U.S. The cohort, with a follow-up period between 1995 and 2011, was linked to residential census tract estimates for annual mean concentration levels of PM2.5, NO2, and O3. Associations between the air pollutants and the risk of diabetes mortality (N = 3598) were evaluated using multivariate Cox proportional hazards models adjusted for both individual-level and census-level contextual covariates. RESULTS: Diabetes mortality was significantly associated with increasing levels of both PM2.5 (HR = 1.19; 95% CI: 1.03-1.39 per 10 µg/m3) and NO2 (HR = 1.09; 95% CI: 1.01-1.18 per 10 ppb). The strength of the relationship was robust to alternate exposure assessments and model specifications. We also observed significant effect modification, with elevated mortality risks observed among those with higher BMI and lower levels of fruit consumption. CONCLUSIONS: We found that long-term exposure to PM2.5 and NO2, but not O3, is related to increased risk of diabetes mortality in the U.S, with attenuation of adverse effects by lower BMI and higher fruit consumption, suggesting that air pollution is involved in the etiology and/or control of diabetes.

Eight Genome Sequences of Cluster BE1 Phages That Infect Streptomyces Species.

Cluster BE1 Streptomyces bacteriophages belong to the Siphoviridae, with genome sizes over 130 kbp, and they contain direct terminal repeats of approximately 11 kbp. Eight newly isolated closely related cluster BE1 phages contain 43 to 48 tRNAs, one transfer-messenger RNA (tmRNA), and 216 to 236 predicted open reading frames (ORFs), but few of their genes are shared with other phages, including those infecting Streptomyces species.

Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade.

Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe) and were compared to rolipram in functional studies of spontaneous phasic, K⁺-induced tonic, and Ca2+-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC), in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs). Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca2+-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC50 = 125 ± 13.72 and 98.45 ± 8.86 µM, respectively). Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05) and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers.

Air Pollution and Pulmonary Tuberculosis: A Nested Case-Control Study among Members of a Northern California Health Plan.

BACKGROUND: Ecologic analyses, case-case comparisons, and animal experiments suggest positive associations between air pollution and tuberculosis. OBJECTIVES: We evaluated this hypothesis in a large sample, which yielded results that are applicable to the general population. METHODS: We conducted a case-control study nested within a cohort of Kaiser Permanente of Northern California members. All active pulmonary tuberculosis (TB) cases newly diagnosed between 1996 and 2010 (n = 2,309) were matched to two controls (n = 4,604) by age, sex, and race/ethnicity on the index date corresponding with the case diagnosis date. Average individual-level concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) and 10 µm (PM10) for 2 years before diagnosis/entry into the study were estimated using measurements from the California Air Resources Board monitor closest to the participant's residence. RESULTS: In single-pollutant adjusted conditional logistic regression models, the pulmonary TB odds ratios (95% confidence intervals) for the highest quintile (vs. lowest) were 1.50 (95% CI: 1.15, 1.95) for CO and 1.42 (95% CI: 1.10, 1.84) for NO2. Corresponding estimates were higher among never [1.68 (95% CI: 1.26, 2.24)] than ever [1.19 (95% CI: 0.74, 1.92)] smokers for CO. In contrast, for NO2, estimates were higher among ever [1.81 (95% CI: 1.13, 2.91)] than never [1.29 (95% CI: 0.97, 1.71)] smokers. O3 was inversely associated for smokers [0.66 (95% CI: 0.43, 1.02)] and never smokers [0.65 (95% CI: 0.52, 0.81)]. No other consistent patterns were observed. CONCLUSIONS: In this first, to our knowledge, U.S. nested case-control study on air pollution and pulmonary TB, we observed positive associations with ambient CO and NO2, which require confirmation. CITATION: Smith GS, Van Den Eeden SK, Garcia C, Shan J, Baxter R, Herring AH, Richardson DB, Van Rie A, Emch M, Gammon MD. 2016. Air pollution and pulmonary tuberculosis: a nested case-control study among members of a Northern California health plan. Environ Health Perspect 124:761-768; http://dx.doi.org/10.1289/ehp.1408166.

Association of long-term PM2.5 exposure with mortality using different air pollution exposure models: impacts in rural and urban California.

Most PM2.5-associated mortality studies are not conducted in rural areas where mortality rates may differ when population characteristics, health care access, and PM2.5 composition differ. PM2.5-associated mortality was investigated in the elderly residing in rural-urban zip codes. Exposure (2000-2006) was estimated using different models and Poisson regression was performed using 2006 mortality data. PM2.5 models estimated comparable exposures, although subtle differences were observed in rate ratios (RR) within areas by health outcomes. Cardiovascular disease (CVD), ischemic heart disease (IHD), and cardiopulmonary disease (CPD), mortality was significantly associated with rural, urban, and statewide chronic PM2.5 exposures. We observed larger effect sizes in RRs for CVD, CPD, and all-cause (AC) with similar sizes for IHD mortality in rural areas compared to urban areas. PM2.5 was significantly associated with AC mortality in rural areas and statewide; however, in urban areas, only the most restrictive exposure model showed an association. Given the results seen, future mortality studies should consider adjusting for differences with rural-urban variables.

Effectiveness of residential wood-burning regulation on decreasing particulate matter levels and hospitalizations in the San Joaquin Valley Air Basin.

OBJECTIVES: We examined the impact of Rule 4901, aimed at reducing residential wood burning, on particulate matter levels and hospitalizations in the San Joaquin Valley Air Basin (SJVAB). METHODS: Using general linear mixed models and generalized estimating equation models, we compared levels of particulate matter and of hospital admissions (age groups = 45-64 and ≥ 65 years) in the SJVAB for cardiovascular disease (CVD), ischemic heart disease (IHD), and chronic obstructive pulmonary disease during the burn seasons before (2000-2003) and after (2003-2006) implementation. RESULTS: After implementation, we observed reductions of 12%, 11%, and 15% in particulate matter 2.5 micrometers in diameter or smaller (PM2.5), and 8%, 7%, and 11% in coarse particles, in the entire SJVAB and in rural and urban regions of the air basin, respectively. Among those aged 65 years and older, Rule 4901 was estimated to prevent 7%, 8%, and 5% of CVD cases, and 16%, 17%, and 13% of IHD cases, in the entire SJVAB and in rural and urban regions, respectively. CONCLUSIONS: The study suggests that Rule 4901 is effective at reducing wintertime ambient PM2.5 levels and decreasing hospital admissions for heart disease among people aged 65 years and older.

The adhesion GPCR Gpr56 regulates oligodendrocyte development via interactions with Gα12/13 and RhoA.

In the vertebrate central nervous system, myelinating oligodendrocytes are postmitotic and derive from proliferative oligodendrocyte precursor cells (OPCs). The molecular mechanisms that govern oligodendrocyte development are incompletely understood, but recent studies implicate the adhesion class of G protein-coupled receptors (aGPCRs) as important regulators of myelination. Here, we use zebrafish and mouse models to dissect the function of the aGPCR Gpr56 in oligodendrocyte development. We show that gpr56 is expressed during early stages of oligodendrocyte development. In addition, we observe a significant reduction of mature oligodendrocyte number and myelinated axons in gpr56 zebrafish mutants. This reduction results from decreased OPC proliferation, rather than increased cell death or altered neural precursor differentiation potential. Finally, we show that these functions are mediated by Gα12/13 proteins and Rho activation. Together, our data establish Gpr56 as a regulator of oligodendrocyte development.