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Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms. We identified numerous viruses and other microbial species that transmit to cohoused mice, including prospective new members of the Coronaviridae, Astroviridae, Picornaviridae, and Narnaviridae families, and uncovered pathogen interactions that promote or prevent virus transmission. We also evaluated transmission dynamics of murine astroviruses during transmission and spread within a new host. Finally, by cohousing our laboratory mice with the bedding of pet store rats, we identified cross-species transmission of a rat astrovirus. Overall, this model system allows for the analysis of transmission of natural rodent viruses and is a platform to further characterize barriers to zoonosis.

Background Habitual high-intensity endurance exercise is associated with increased atrial fibrillation (AF) risk and impaired cardiac conduction. It is unknown whether these observations extend to prior strength-type sports exposure. The primary aim of this study was to compare AF prevalence in former National Football League (NFL) athletes to population-based controls. The secondary aim was to characterize other conduction system parameters. Methods and Results This cross-sectional study compared former NFL athletes (n=460, age 56±12 years, black 47%) with population-based controls of similar age and racial composition from the cardiovascular cohort Dallas Heart Study-2 (n=925, age 54±9 years, black 53%). AF was present in 28 individuals (n=23 [5%] in the NFL group; n=5 [0.5%] in the control group). After controlling for other cardiovascular risk factors in multivariable regression analysis, former NFL participation remained associated with a 5.7 (95% CI: 2.1-15.9, P

Phagocytosis is required for a broad range of physiological functions, from pathogen defense to tissue homeostasis, but the mechanisms required for phagocytosis of diverse substrates remain incompletely understood. Here, we developed a rapid magnet-based phenotypic screening strategy, and performed eight genome-wide CRISPR screens in human cells to identify genes regulating phagocytosis of distinct substrates. After validating select hits in focused miniscreens, orthogonal assays and primary human macrophages, we show that (1) the previously uncharacterized gene NHLRC2 is a central player in phagocytosis, regulating RhoA-Rac1 signaling cascades that control actin polymerization and filopodia formation, (2) very-long-chain fatty acids are essential for efficient phagocytosis of certain substrates and (3) the previously uncharacterized Alzheimer's disease-associated gene TM2D3 can preferentially influence uptake of amyloid-β aggregates. These findings illuminate new regulators and core principles of phagocytosis, and more generally establish an efficient method for unbiased identification of cellular uptake mechanisms across diverse physiological and pathological contexts.

We explored the association between liver metastases, tumor CD8+ T-cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival [PFS; objective response rate (ORR), 30.6%; median PFS, 5.1 months] compared with patients without liver metastasis (ORR, 56.3%; median PFS, 20.1 months) P ≤ 0.0001, and confirmed in the validation cohort (P = 0.0006). The presence of liver metastasis significantly increased the likelihood of progression (OR, 1.852; P < 0.0001). In a subset of biopsied patients (n = 62), liver metastasis was associated with reduced CD8+ T-cell density at the invasive tumor margin (liver metastasis+ group, n = 547 ± 164.8; liver metastasis- group, n = 1,441 ± 250.7; P < 0.016). A reduced response rate and shortened PFS was also observed in NSCLC patients with liver metastasis [median PFS, 1.8 months; 95% confidence interval (CI), 1.4-2.0], compared with those without liver metastasis (n = 119, median PFS, 4.0 months; 95% CI, 2.1-5.1), P = 0.0094. Thus, liver metastatic patients with melanoma or NSCLC that had been treated with pembrolizumab were associated with reduced responses and PFS, and liver metastases were associated with reduced marginal CD8+ T-cell infiltration, providing a potential mechanism for this outcome. Cancer Immunol Res; 5(5); 417-24. ©2017 AACR.

The specific function of microglia, the tissue resident macrophages of the brain and spinal cord, has been difficult to ascertain because of a lack of tools to distinguish microglia from other immune cells, thereby limiting specific immunostaining, purification, and manipulation. Because of their unique developmental origins and predicted functions, the distinction of microglia from other myeloid cells is critically important for understanding brain development and disease; better tools would greatly facilitate studies of microglia function in the developing, adult, and injured CNS. Here, we identify transmembrane protein 119 (Tmem119), a cell-surface protein of unknown function, as a highly expressed microglia-specific marker in both mouse and human. We developed monoclonal antibodies to its intracellular and extracellular domains that enable the immunostaining of microglia in histological sections in healthy and diseased brains, as well as isolation of pure nonactivated microglia by FACS. Using our antibodies, we provide, to our knowledge, the first RNAseq profiles of highly pure mouse microglia during development and after an immune challenge. We used these to demonstrate that mouse microglia mature by the second postnatal week and to predict novel microglial functions. Together, we anticipate these resources will be valuable for the future study and understanding of microglia in health and disease.

War and asymmetrical conflicts are becoming increasingly prevalent in the modern world. Due to improvements in conflict medicine, survivable injuries are now more severe than they once were. Therefore, it is now more important than ever that there exist scientific and engineering methods for replicating wartime injuries in the context of the laboratory. We have developed one such method: a shock tube platform for testing ex vivo samples of the porcine respiratory system. Using this platform, we can, to some extent, simulate the pathophysiological consequences of blast lung. This is a condition commonly present in victims of explosive blasts, both those due to typical armaments and Improvised Explosive Devices (IEDs). Presented here are the results of experiments conducted using porcine bronchiole tissue as ex vivo organ cultures. Data presented show epithelial damage, consistent with known trauma-induced cell injury that can lead to acute respiratory distress syndrome (ARDS).

Non-native rusty crayfish are abundant egg predators on spawning reef habitats for lake trout and coregonines in northern Lake Michigan. To better understand rusty crayfish life-history on these unique habitats, we conducted monitoring in 2012 and 2013 at four locations previously identified as spawning areas for native fish. With the aid of a graphical causal model, we conducted an exploratory statistical analysis using a Bayesian multilevel modeling approach with model selection based on information criteria to identify important environmental variables for predicting rusty crayfish distribution and abundance on spawning reefs. We also compared seasonal trends in relative abundance, inferred from catch-per-unit-effort calculations from trapping, to previously reported accounts from a smaller inland lake. The results from our modeling provide evidence of size-class segregation across subtle changes in habitat characteristics of spawning reefs. Specifically, we found evidence that the distribution of >30 mm rusty crayfish was only weakly related to rock density (#/m2) relative to juveniles and smaller size classes. We also observed highest relative abundances from minnow trap monitoring in mid-October when water temperatures averaged 13.9 °C, which is later in the year and at cooler temperatures than similar monitoring from smaller inland lakes has reported. We hypothesize that unique environmental conditions elicit novel life-history responses from rusty crayfish on Lake Michigan spawning reefs and discuss our findings in the context of native fish restoration in the Laurentian Great Lakes. [ABSTRACT FROM AUTHOR]

Significant opportunities exist to connect more directly sexuality research to urbanisation research in the global South. This article considers such connections in relation to the informal sector, the state, and urban health. It highlights how such connections can help surface the strategic and pragmatic choices made by same-sex communities in the face of persistent urban challenges in the global South. The article draws on examples from sub-Saharan Africa, a region that exhibits significant sexuality-based discrimination and which has had significant urban research attention. [ABSTRACT FROM AUTHOR]

Abstract Photoquadrats and underwater video surveys are standard non-destructive monitoring methods in marine ecosystems and are becoming more common in freshwater systems. The high water clarity found in most of the Laurentian Great Lakes make them ideally suited for photoquadrat sampling. We compared the effectiveness of baited photoquadrats to monitor benthic fish communities of shallow, littoral habitats of northern Lake Michigan. We compared our results with baited minnow traps, a technique commonly used to monitor benthic fish communities in freshwater ecosystems. Photoquadrats baited with lake trout (Salvelinus namaycush) eggs, the most effective attractant, proved to be an efficient tool for sampling round goby (Neogobius melanostomus) relative abundance and resulted in higher round goby catches than in photoquadrats baited with a commercially available fish attractant or unbaited photoqudrats. This method allowed sites to be surveyed rapidly (requiring <1 h per site), and replicate samples produced data with low variability. In contrast, baited minnow traps produced highly variable catch per unit effort (CPUE) irrespective of soak time. Photoquadrat methods appear to be an improvement over traditional sampling with minnow traps for round goby and may also be better for other nearshore benthic fishes. [ABSTRACT FROM AUTHOR]

Background--Ascending aortic dimensions are slightly larger in young competitive athletes compared with sedentary controls, but rarely >40 mm. Whether this finding translates to aortic enlargement in older, former athletes is unknown. Methods and Results--This cross-sectional study involved a sample of 206 former National Football League (NFL) athletes compared with 759 male subjects from the DHS-2 (Dallas Heart Study-2; mean age of 57.1 and 53.6 years, respectively, P<0.0001; body surface area of 2.4 and 2.1 m², respectively, P<0.0001). Midascending aortic dimensions were obtained from computed tomographic scans performed as part of a NFL screening protocol or as part of the DHS. Compared with a population-based control group, former NFL athletes had significantly larger ascending aortic diameters (38±5 versus 34±4 mm; P<0.0001). A significantly higher proportion of former NFL athletes had an aorta of >40 mm (29.6% versus 8.6%; P<0.0001). After adjusting for age, race, body surface area, systolic blood pressure, history of hypertension, current smoking, diabetes mellitus, and lipid profile, the former NFL athletes still had significantly larger ascending aortas (P<0.0001). Former NFL athletes were twice as likely to have an aorta >40 mm after adjusting for the same parameters. Conclusions--Ascending aortic dimensions were significantly larger in a sample of former NFL athletes after adjusting for their size, age, race, and cardiac risk factors. Whether this translates to an increased risk is unknown and requires further evaluation. [ABSTRACT FROM AUTHOR]

The article discusses the issue of conflict of interest (COI) about the concept of sports medicine among physicians. Topics discussed include the clinical decision making and confidentiality as the areas for potential ground of conflict, the evolution of the relationships among professional team physician, and the role of physicians in protecting the long-term health of patient.

Previous findings suggest that professional American football players have higher blood pressures (BP) and a higher prevalence of pre–hypertension and hypertension than the general population. We sought to determine whether race is associated with differences in BP and prevalence of pre–hypertension and hypertension among a large sample of professional football players. BP was measured at 2009 team mini–camps for 1484 black (n = 1007) and white (n = 477) players from 27 National Football League (NFL) teams. Players were categorized into three position groups based on body mass index (BMI). There was no racial difference in mean systolic or diastolic BP in any of the three position groups. There were no racial differences in prevalence of hypertension (99 [9.8%] black players vs. 39 [8.2%] white players; P = .353) or pre–hypertension (557 [55.3%] black players vs. 264 [55.3%] white players; P = 1.0). Contrary to findings in the general population, BP and prevalence of pre–hypertension/hypertension did not vary with race in a large population of active NFL players. [ABSTRACT FROM AUTHOR]

Rational and Objectives The objective of this study was to compare the stationary digital breast tomosynthesis (s-DBT) system to a conventional mammography system in a study of breast specimens. Radiologist evaluation of image quality was assessed in a reader study. This study represents the first human tissue imaging with the novel carbon nanotube–based s-DBT device. Materials and Methods Thirty-nine patients, with known breast lesions (Breast Imaging Reporting and Data System 4 or 5) by conventional mammography and scheduled for needle localization biopsy, were recruited under an institutional review board–approved protocol. Specimen images were obtained using a two-dimensional (2D) mammography system with a ×1.8 magnification factor and an s-DBT system without a high magnification factor. A reader study was performed with four breast fellowship-trained radiologists over two separate sessions. Malignancy scores were recorded for both masses and microcalcifications (MCs). Reader preference between the two modalities for MCs, masses, and surgical margins was recorded. Results The s-DBT system was found to be comparable to magnified 2D mammography for malignancy diagnosis. Readers preferred magnified 2D mammography for MC visualization ( P < .05). However, readers trended toward a preference for s-DBT with respect to masses and surgical margin assessment. Conclusions Here, we report on the first human data acquired using a stationary digital breast tomosynthesis system. The novel s-DBT system was found to be comparable to magnified 2D mammography imaging for malignancy diagnosis. Given the trend of preference for s-DBT over 2D mammography for both mass visibility and margin assessment, s-DBT could be a viable alternative to magnified 2D mammography for imaging breast specimens. [ABSTRACT FROM AUTHOR]

The use of over-the-counter dietary supplements has risen dramatically, and adverse events can be severe. Physicians should recognize the dangers that ephedrine-containing supplements present and remain vigilant for sympathomimetic symptoms in young, otherwise healthy, patients. This case illustrates how the use of a popular weight-loss supplement by a 27-year-old professional football player apparently resulted in cardiac arrhythmia requiring direct cardioversion. [ABSTRACT FROM AUTHOR]