Age-Related Decline in Cardiorespiratory Fitness among Career Firefighters: Modification by Physical Activity and Adiposity

Firefighting is a very hazardous occupation, and strenuous fire duties require high levels of physical fitness. In the general adult population, cardiorespiratory fitness (CRF) declines with aging. We sought to investigate the effect of increasing age on CRF in male career firefighters as well as the modifying effects of physical activity and adiposity. We cross-sectionally examined 804 male career firefighters from two Midwestern states. CRF was determined from symptom-limited maximal treadmill exercise testing in metabolic equivalents (METS) following the Bruce protocol. Physical activity self-reports were extracted from responses to a health and lifestyle questionnaire. We found as expected that CRF declines with advancing age; however, the decline is greatly attenuated among leaner firefighters who report more physical activity. Furthermore, in a linear regression model including age, BMI, and variables describing physical activity behaviors, we could predict CRF (R2 = 0.6286). The total weekly duration of aerobic exercise as well as the duration of weight lifting sessions both had significant impacts on age-related decline. We conclude that firefighters are more likely to maintain the high levels of CRF needed to safely perform their duties if they engage in frequent exercise and maintain healthy weights

Les phlébotomes (Diptera-Psychodidae) de l'île de Chypre.II - Presence de Leishmania (Leishmania) infantum Nicolle, 1908 (zymodeme MON 1) chez Phlebotomus (Larroussius) tobbi Adler et Theodor, 1930

Dans le foyer leishmanien cypriote, les auteurs ont disseque 2910 femelles de phlebotomes appartenant a 11 especes : Phlebotomus papatasi, P. sergenti, P. jacusieli, P. alexandri, P. tobbi, P. galilaeus, P. mascittii, P. economidesi, Sergentomyia fallax, S. minuta et S. azizi . Les deux larroussius (P. galilaeus et P. tobbi ) sont les especes les plus abondantes. Elles representent plus de 60 % des captures realisees avec des pieges CDC. Des promastigotes ont ete observees chez un seul specimen appartenant a l'espece P. tobbi . Elles ont ete mises en culture puis identifiees selon la methode isoenzymatique. La souche de Leishmania isolee appartient a l'espece Leishmania infantum , zymodeme MON 1. Le meme zymodeme a ete aussi isole et identifie chez quatre chiens de l'ile. En l'absence des vecteurs habituels de L. infantum dans l'est mediterraneen (P. neglectus ef P. syriacus) et en raison de sa repartition a Chypre, P. tobbi constitue vraisemblablement un bon vecteur local. Sa faible anthropophilie expliquerait peut-etre le tres faible nombre de cas humains. Le role de P. galilaeus dans la transmission de la leishmaniose a Chypre reste a preciser

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

COVID-19 symptoms predictive of healthcare workers' SARS-CoV-2 PCR results

Background Coronavirus 2019 disease (COVID-19) is caused by the virus SARS-CoV-2, transmissible both person-to-person and from contaminated surfaces. Early COVID-19 detection among healthcare workers (HCWs) is crucial for protecting patients and the healthcare workforce. Because of limited testing capacity, symptom-based screening may prioritize testing and increase diagnostic accuracy. Methods and findings We performed a retrospective study of HCWs undergoing both COVID-19 telephonic symptom screening and nasopharyngeal SARS-CoV-2 assays during the period, March 9.April 15, 2020. HCWs with negative assays but progressive symptoms were re-tested for SARSCoV- 2. Among 592 HCWs tested, 83 (14%) had an initial positive SARS-CoV-2 assay. Fiftynine of 61 HCWs (97%) who were asymptomatic or reported only sore throat/nasal congestion had negative SARS-CoV-2 assays (P = 0.006). HCWs reporting three or more symptoms had an increased multivariate-adjusted odds of having positive assays, 1.95 (95% CI: 1.10.3.64), which increased to 2.61 (95% CI: 1.50.4.45) for six or more symptoms. The multivariate-adjusted odds of a positive assay were also increased for HCWs reporting fever and a measured temperature . 37.5°C (3.49 (95% CI: 1.95.6.21)), and those with myalgias (1.83 (95% CI: 1.04.3.23)). Anosmia/ageusia (i.e. loss of smell/loss of taste) was reported less frequently (16%) than other symptoms by HCWs with positive assays, but was associated with more than a seven-fold multivariate-adjusted odds of a positive test: OR = 7.21 (95% CI: 2.95.17.67). Of 509 HCWs with initial negative SARS-CoV-2 assays, nine had symptom progression and positive re-tests, yielding an estimated negative predictive value of 98.2% (95% CI: 96.8-99.0%) for the exclusion of clinically relevant COVID-19. Conclusions Symptom and temperature reports are useful screening tools for predicting SARS-CoV-2 assay results in HCWs. Anosmia/ageusia, fever, and myalgia were the strongest independent predictors of positive assays. The absence of symptoms or symptoms limited to nasal congestion/sore throat were associated with negative assays

Effects of a healthy lifestyle intervention and COVID-19-adjusted training curriculum on firefighter recruits

There are knowledge gaps regarding healthy lifestyle (HLS) interventions in fire academy settings and also concerning the impacts of the pandemic on training. We enrolled fire recruits from two fire academies (A and B) in New England in early 2019 as the historical control group, and recruits from academies in New England (B) and Florida (C), respectively, during the pandemic as the intervention group. The three academies have similar training environments and curricula. The exposures of interest were a combination of (1) an HLS intervention and (2) impacts of the pandemic on training curricula and environs (i.e. social distancing, masking, reduced class size, etc.). We examined the health/fitness changes throughout training. The follow-up rate was 78%, leaving 92 recruits in the historical control group and 55 in the intervention group. The results show an HLS intervention improved the effects of fire academy training on recruits healthy behaviors (MEDI-lifestyle score, 0.5 ± 1.4 vs. - 0.3 ± 1.7), systolic blood pressure (- 7.2 ± 10.0 vs. 2.9 ± 12.9 mmHg), and mental health (Beck Depression score, - 0.45 ± 1.14 vs. - 0.01 ± 1.05) (all P < 0.05). The associations remained significant after multivariable adjustments. Moreover, a 1-point MEDI-lifestyle increment during academy training is associated with about 2% decrement in blood pressures over time, after multivariable adjustments (P < 0.05). Nonetheless, the impacts of pandemic restrictions on academy procedures compromised physical fitness training, namely in percent body fat, push-ups, and pull-ups

Ambient temperature and subsequent COVID-19 mortality in the OECD countries and individual United States

Epidemiological studies have yielded conflicting results regarding climate and incident SARS-CoV-2 infection, and seasonality of infection rates is debated. Moreover, few studies have focused on COVD-19 deaths. We studied the association of average ambient temperature with subsequent COVID-19 mortality in the OECD countries and the individual United States (US), while accounting for other important meteorological and non-meteorological co-variates. The exposure of interest was average temperature and other weather conditions, measured at 25 days prior and 25 days after the first reported COVID-19 death was collected in the OECD countries and US states. The outcome of interest was cumulative COVID-19 mortality, assessed for each region at 25, 30, 35, and 40 days after the first reported death. Analyses were performed with negative binomial regression and adjusted for other weather conditions, particulate matter, sociodemographic factors, smoking, obesity, ICU beds, and social distancing. A 1 °C increase in ambient temperature was associated with 6% lower COVID-19 mortality at 30 days following the first reported death (multivariate-adjusted mortality rate ratio: 0.94, 95% CI 0.90, 0.99, p = 0.016). The results were robust for COVID-19 mortality at 25, 35 and 40 days after the first death, as well as other sensitivity analyses. The results provide consistent evidence across various models of an inverse association between higher average temperatures and subsequent COVID-19 mortality rates after accounting for other meteorological variables and predictors of SARS-CoV-2 infection or death. This suggests potentially decreased viral transmission in warmer regions and during the summer season

Human Metapneumovirus Inhibits IFN-β Signaling by Downregulating Jak1 and Tyk2 Cellular Levels

Human metapneumovirus (hMPV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN) signaling by an unidentified mechanism. In this study, we showed that infection of airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2 (Tyk2), due to enhanced proteosomal degradation and reduced gene transcription. In addition, hMPV infection also reduced the surface expression of type I IFN receptor (IFNAR). These inhibitory mechanisms are different from the ones employed by respiratory syncytial virus (RSV), which does not affect Jak1, Tyk2 or IFNAR expression, but degrades downstream signal transducer and activator of transcription proteins 2 (STAT2), although both viruses are pneumoviruses belonging to the Paramyxoviridae family. Our study identifies a novel mechanism by which hMPV inhibits STAT1 and 2 activation, ultimately leading to viral evasion of host IFN responses

Functional Role of Kallikrein 6 in Regulating Immune Cell Survival

Kallikrein 6 (KLK6) is a newly identified member of the kallikrein family of secreted serine proteases that prior studies indicate is elevated at sites of central nervous system (CNS) inflammation and which shows regulated expression with T cell activation. Notably, KLK6 is also elevated in the serum of multiple sclerosis (MS) patients however its potential roles in immune function are unknown. Herein we specifically examine whether KLK6 alters immune cell survival and the possible mechanism by which this may occur.Using murine whole splenocyte preparations and the human Jurkat T cell line we demonstrate that KLK6 robustly supports cell survival across a range of cell death paradigms. Recombinant KLK6 was shown to significantly reduce cell death under resting conditions and in response to camptothecin, dexamethasone, staurosporine and Fas-ligand. Moreover, KLK6-over expression in Jurkat T cells was shown to generate parallel pro-survival effects. In mixed splenocyte populations the vigorous immune cell survival promoting effects of KLK6 were shown to include both T and B lymphocytes, to occur with as little as 5 minutes of treatment, and to involve up regulation of the pro-survival protein B-cell lymphoma-extra large (Bcl-XL), and inhibition of the pro-apoptotic protein Bcl-2-interacting mediator of cell death (Bim). The ability of KLK6 to promote survival of splenic T cells was also shown to be absent in cell preparations derived from PAR1 deficient mice.KLK6 promotes lymphocyte survival by a mechanism that depends in part on activation of PAR1. These findings point to a novel molecular mechanism regulating lymphocyte survival that is likely to have relevance to a range of immunological responses that depend on apoptosis for immune clearance and maintenance of homeostasis

Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer

Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention. © 2014

Transcriptional upregulation of human tissue kallikrein 6 in ovarian cancer: clinical and mechanistic aspects

The human tissue kallikrein family (KLK for protein; KLK for gene) includes 15 members. Twelve kallikreins, including KLK6, are concurrently upregulated in ovarian cancer. However, the mechanism of this phenomenon remains unclear. In this study, we measured KLK6 expression in a large series of ovarian tissue cytosols and examined possible mechanisms of KLK6 up-regulation in ovarian cancer. Using a newly developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies, we quantified KLK6 expression in ovarian tissue cytosols, and confirmed the upregulation of KLK6 in ovarian cancer and its unfavourable prognostic value. We then examined KLK6 mRNA expression using reverse transcription–polymerase chain reaction and established its good concordance with KLK6 protein expression. This finding suggested that the KLK6 gene is under transcriptional regulation. We then scrutinised a few mechanisms that could explain KLK6 upregulation. The relative abundance of two KLK6 mRNA transcripts was studied; we found the same differential expression pattern in all samples, regardless of KLK6 levels. Genomic mutation screening of all exons and the 5′-flanking region of the KLK6 gene identified two linked single-nucleotide polymorphisms in the 5′-untranslated region, but neither correlated with KLK6 expression. Ovarian cell lines were separately treated with five steroid hormones. None of the treatments produced significant effects on KLK6 expression. We conclude that KLK6 is transcriptionally upregulated in ovarian cancer, but probably not through alternative mRNA transcript expression, genomic mutation, or steroid hormone induction