International volunteerism and urethral stricture disease: A review

Global health is an ever-expanding area of interest for many healthcare workers around the world. In recent years, it has become apparent that much of the global disease burden is surgical. Urologic disease is no exception-many international organizations send volunteers around the world to support Urologic services in countries that lack capacity and resources. Urethral stricture represents a unique opportunity for specialized surgical management that vastly improves long term morbidity. Here we review the prevalence, etiology, and management of urethral stricture from a global perspective while highlighting impact of international urologic volunteer efforts

Regulation of major histocompatibility complex class II gene expression in trophoblast cells

Trophoblast cells are unique because they are one of the few mammalian cell types that do not express major histocompatibility complex (MHC) class II antigens, either constitutively or after exposure to IFN-γ. The absence of MHC class II antigen expression on trophoblast cells has been postulated to be one of the essential mechanisms by which the semi-allogeneic fetus evades immune rejection reactions by the maternal immune system. Consistent with this hypothesis, trophoblast cells from the placentas of women suffering from chronic inflammation of unknown etiology and spontaneous recurrent miscarriages have been reported to aberrantly express MHC class II antigens. The lack of MHC class II antigen expression on trophoblast cells is due to silencing of expression of the class II transactivator (CIITA), a transacting factor that is essential for constitutive and IFN-γ-inducible MHC class II gene transcription. Transfection of trophoblast cells with CIITA expression vectors activates both MHC class II and class Ia antigen expression, which confers on trophoblast cells both the ability to activate helper T cells, and sensitivity to lysis by cytotoxic T lymphocytes. Collectively, these studies strongly suggest that stringent silencing of CIITA (and therefore MHC class II) gene expression in trophoblast cells is critical for the prevention of immune rejection responses against the fetus by the maternal immune system. The focus of this review is to summarize studies examining the novel mechanisms by which CIITA is silenced in trophoblast cells. The elucidation of the silencing of CIITA in trophoblast cells may shed light on how the semi-allogeneic fetus evades immune rejection by the maternal immune system during pregnancy

Brief bouts of device-measured intermittent lifestyle physical activity and its association with major adverse cardiovascular events and mortality in people who do not exercise: a prospective cohort study

BACKGROUND: Guidelines emphasise the health benefits of bouts of physical activity of any duration. However, the associations of intermittent lifestyle physical activity accumulated through non-exercise with mortality and major adverse cardiovascular events (MACE) remain unclear. We aimed to examine the associations of bouts of moderate-to-vigorous intermittent lifestyle physical activity (MV-ILPA) and the proportion of vigorous activity contributing within these bouts with mortality and MACE. METHODS: In this prospective cohort study, we used data from the UK Biobank on adults who do not exercise (ie, those who did not report leisure-time exercise) who had wrist-worn accelerometry data available. Participants were followed up until Nov 30, 2022, with the outcome of interest of all-cause mortality obtained through linkage with NHS Digital of England and Wales, and the NHS Central Register and National Records of Scotland, and MACE obtained from inpatient hospitalisation data provided by the Hospital Episode Statistics for England, the Patient Episode Database for Wales, and the Scottish Morbidity Record for Scotland. MV-ILPA bouts were derived using a two-level Random Forest classifier and grouped as short (<1 min), medium (1 to <3 min; 3 to <5 min), and long (5 to <10 min). We further examined the dose-response relationship of the proportion of vigorous physical activity contributing to the MV-ILPA bout. FINDINGS: Between June 1, 2013, and Dec 23, 2015, 103 684 Biobank participants wore an accelerometer on their wrist. 25 241 adults (mean age 61·8 years [SD 7·6]), of whom 14 178 (56·2%) were women, were included in our analysis of all-cause mortality. During a mean follow-up duration of 7·9 years (SD 0·9), 824 MACE and 1111 deaths occurred. Compared with bouts of less than 1 min, mortality risk was lower for bouts of 1 min to less than 3 min (hazard ratio [HR] 0·66 [0·53-0·81]), 3 min to less than 5 min (HR 0·56 [0·46-0·69]), and 5 to less than 10 min (HR 0·48 [0·39-0·59]). Similarly, compared with bouts of less than 1 min, risk of MACE was lower for bouts of 1 min to less than 3 min (HR 0·71 [0·54-0·93]), 3 min to less than 5 min (0·62 [0·48-0·81]), and 5 min to less than 10 min (0·59 [0·46-0·76]). Short bouts (<1 min) were associated with lower MACE risk only when bouts were comprised of at least 15% vigorous activity. INTERPRETATION: Intermittent non-exercise physical activity was associated with lower mortality and MACE. Our results support the promotion of short intermittent bouts of non-exercise physical activity of moderate-to-vigorous intensity to improve longevity and cardiovascular health among adults who do not habitually exercise in their leisure time. FUNDING: Australian National Health, Medical Research Council, and Wellcome Trust

Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic stiffening in old mice.

Aortic stiffening is a major independent risk factor for cardiovascular diseases, cognitive dysfunction, and other chronic disorders of aging. Mitochondria-derived reactive oxygen species are a key source of arterial oxidative stress, which may contribute to arterial stiffening by promoting adverse structural changes-including collagen overabundance and elastin degradation-and enhancing inflammation, but the potential for mitochondria-targeted therapeutic strategies to ameliorate aortic stiffening with primary aging is unknown. We assessed aortic stiffness [pulse-wave velocity (aPWV)], ex vivo aortic intrinsic mechanical properties [elastic modulus (EM) of collagen and elastin regions], and aortic protein expression in young (~6 mo) and old (~27 mo) male C57BL/6 mice consuming normal drinking water (YC and OC) or water containing mitochondria-targeted antioxidant MitoQ (250 µM; YMQ and OMQ) for 4 wk. Both baseline and postintervention aPWV values were higher in OC vs. YC (post: 482 ± 21 vs. 420 ± 5 cm/s, P < 0.05). MitoQ had no effect in young mice but decreased aPWV in old mice (OMQ, 426 ± 20, P < 0.05 vs. OC). MitoQ did not affect age-associated increases in aortic collagen-region EM, collagen expression, or proinflammatory cytokine expression, but partially attenuated age-associated decreases in elastin region EM and elastin expression. Our results demonstrate that MitoQ reverses in vivo aortic stiffness in old mice and suggest that mitochondria-targeted antioxidants may represent a novel, promising therapeutic strategy for decreasing aortic stiffness with primary aging and, possibly, age-related clinical disorders in humans. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation/reversal of age-related aortic elastin degradation. NEW & NOTEWORTHY We show that 4 wk of treatment with the mitochondria-specific antioxidant MitoQ in mice completely reverses the age-associated elevation in aortic stiffness, assessed as aortic pulse-wave velocity. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation of age-related aortic elastin degradation. Our results suggest that mitochondria-targeted therapeutic strategies may hold promise for decreasing arterial stiffening with aging in humans, possibly decreasing the risk of many chronic age-related clinical disorders

A feature-importance-aware and robust aggregator for GCN

Neighborhood aggregation is a key step in Graph Convolutional Networks (GCNs) for graph representation learning. Two commonly used aggregators, sum and mean, are designed with the homophily assumption that connected nodes are likely to share the same label. However, real-world graphs are noisy and adjacent nodes do not necessarily imply similarity.Learnable aggregators are proposed in Graph Attention Network (GAT) and Learnable Graph Convolutional Layer (LGCL). However, GAT considers node importance but not the importance of different features. The convolution aggregator in LGCL considers feature importance but it can not directly operate on graphs due to the irregular connectivity and lack of orderliness. In this paper, we firstly unify the current learnable aggregators in a framework: Learnable Aggregator for GCN (LA-GCN) by introducing a shared auxiliary model that provides a customized schema in neighborhood aggregation. Under this framework, we propose a new model called LA-GCNMask consisting of a new aggregator function,mask aggregator. The auxiliary model learns a specific mask for each neighbor of a given node, allowing both node-level and feature-level attention. This mechanism learns to assign different importance to both nodes and features for prediction, which provides interpretable explanations for prediction and increases the model robustness. Experiments on seven graphs for node classification and graph classification tasks show that LA-GCNMask outperforms the state-of-the-art methods. Moreover, our aggregator can identify both the important nodes and node features simultaneously, which provides a quantified understanding of the relationship between input nodes and the prediction. We further conduct experiments on noisy graphs to evaluate the robustness of our model. Experiments show that LA-GCNMask consistently outperforms the state-of-the-art methods, with up to 15% improvements in terms of accuracy compared to the second best

The Great Observatories All-Sky LIRG Survey: Herschel Image Atlas and Aperture Photometry

Far-infrared (FIR) images and photometry are presented for 201 Luminous and Ultraluminous Infrared Galaxies [LIRGs: log$(L_{\rm IR}/L_\odot) = 11.00 - 11.99$, ULIRGs: log$(L_{\rm IR}/L_\odot) = 12.00 - 12.99$], in the Great Observatories All-Sky LIRG Survey (GOALS) based on observations with the $Herschel$ $Space$ $Observatory$ Photodetector Array Camera and Spectrometer (PACS) and the Spectral and Photometric Imaging Receiver (SPIRE) instruments. The image atlas displays each GOALS target in the three PACS bands (70, 100, and 160 $\mu$m) and the three SPIRE bands (250, 350, and 500 $\mu$m), optimized to reveal structures at both high and low surface brightness levels, with images scaled to simplify comparison of structures in the same physical areas of $\sim$$100\times100$ kpc$^2$. Flux densities of companion galaxies in merging systems are provided where possible, depending on their angular separation and the spatial resolution in each passband, along with integrated system fluxes (sum of components). This dataset constitutes the imaging and photometric component of the GOALS Herschel OT1 observing program, and is complementary to atlases presented for the Hubble Space Telescope (Evans et al. 2017, in prep.), Spitzer Space Telescope (Mazzarella et al. 2017, in prep.), and Chandra X-ray Observatory (Iwasawa et al. 2011, 2017, in prep.). Collectively these data will enable a wide range of detailed studies of AGN and starburst activity within the most luminous infrared galaxies in the local Universe.Comment: Accepted for publication in ApJS, 270 pages, 216 figures, 4 table

Brief bouts of device-measured intermittent lifestyle physical activity and its association with major adverse cardiovascular events and mortality in people who do not exercise: a prospective cohort study

Background: Guidelines emphasise the health benefits of bouts of physical activity of any duration. However, the associations of intermittent lifestyle physical activity accumulated through non-exercise with mortality and major adverse cardiovascular events (MACE) remain unclear. We aimed to examine the associations of bouts of moderateto-vigorous intermittent lifestyle physical activity (MV-ILPA) and the proportion of vigorous activity contributing within these bouts with mortality and MACE. Methods: In this prospective cohort study, we used data from the UK Biobank on adults who do not exercise (ie, those who did not report leisure-time exercise) who had wrist-worn accelerometry data available. Participants were followed up until Nov 30, 2022, with the outcome of interest of all-cause mortality obtained through linkage with NHS Digital of England and Wales, and the NHS Central Register and National Records of Scotland, and MACE obtained from inpatient hospitalisation data provided by the Hospital Episode Statistics for England, the Patient Episode Database for Wales, and the Scottish Morbidity Record for Scotland. MV-ILPA bouts were derived using a two-level Random Forest classifier and grouped as short (&lt;1 min), medium (1 to &lt;3 min; 3 to &lt;5 min), and long (5 to &lt;10 min). We further examined the dose–response relationship of the proportion of vigorous physical activity contributing to the MV-ILPA bout. Findings: Between June 1, 2013, and Dec 23, 2015, 103 684 Biobank participants wore an accelerometer on their wrist. 25 241 adults (mean age 61·8 years [SD 7·6]), of whom 14 178 (56·2%) were women, were included in our analysis of all-cause mortality. During a mean follow-up duration of 7·9 years (SD 0·9), 824 MACE and 1111 deaths occurred. Compared with bouts of less than 1 min, mortality risk was lower for bouts of 1 min to less than 3 min (hazard ratio [HR] 0·66 [0·53–0·81]), 3 min to less than 5 min (HR 0·56 [0·46–0·69]), and 5 to less than 10 min (HR 0·48 [0·39–0·59]). Similarly, compared with bouts of less than 1 min, risk of MACE was lower for bouts of 1 min to less than 3 min (HR 0·71 [0·54–0·93]), 3 min to less than 5 min (0·62 [0·48–0·81]), and 5 min to less than 10 min (0·59 [0·46–0·76]). Short bouts (&lt;1 min) were associated with lower MACE risk only when bouts were comprised of at least 15% vigorous activity. Interpretation: Intermittent non-exercise physical activity was associated with lower mortality and MACE. Our results support the promotion of short intermittent bouts of non-exercise physical activity of moderate-to-vigorous intensity to improve longevity and cardiovascular health among adults who do not habitually exercise in their leisure time

Implications of extinction due to meteoritic smoke in the upper stratosphere

Recent optical observations of aerosols in the upper stratosphere and mesosphere show significant amounts of extinction at altitudes above about 40 km where the stratospheric sulfate aerosol layer ends. Recent modeling of this region reveals that meteoritic smoke settling from the mesosphere and its interaction with the upper part of the sulfate aerosol layer is the origin of the observed extinction. Extinction in this region has major implications for the interpretation and analysis of several kinds of aerosol data (satellite and lidar). We compare observations from the SAGE II satellite and from NOAA's lidar located at Mauna Loa, Hawaii to extinction profiles derived from the Whole Atmosphere Community Climate Model (WACCM) coupled with the Community Aerosol and Radiation Model for Atmospheres (CARMA). Our results show that a major source of extinction exists in the region above about 30 km that must be addressed by all remote sensing instruments that have traditionally used the stratosphere above about 30 km as an aerosol free region to estimate the molecular component of their total extinction. It is also shown that meteoritic smoke not only contributes to but also becomes the dominant source of aerosol extinction above 35 km and poleward of 30 degrees in latitude, as well as above 40 km in the tropics. After addressing the concerns described here, current and past observations of this region could be reanalyzed to further our understanding of meteoritic dust in the upper stratosphere