Effect of Hypoxia Preconditioning on the Regenerative Capacity of Adipose Tissue Derived Mesenchymal Stem Cells in a Model of Renal Artery Stenosis.

Atherosclerotic renal artery stenosis (ARAS) is associated with irreversible parenchymal renal disease and regenerative stem cell therapies may improve renal outcomes. Hypoxia preconditioning (HPC) may improve the regenerative functions of adipose tissue-derived mesenchymal stem cells (AMSC) by affecting DNA 5-hydroxymethylcytosine (5hmC) marks in angiogenic genes. Here, we investigated using a porcine ARAS model, whether growth of ARAS AMSCs in hypoxia (Hx) versus normoxia (Nx) would enhance renal tissue repair, and comprehensively analyze how HPC modifies DNA hydroxymethylation compared to untreated ARAS and healthy/normal pigs (n=5 each). ARAS pigs exhibited elevated serum cholesterol, serum creatinine and renal artery stenosis, with a concomitant decrease in renal blood flow (RBF) and increased blood pressure (BP) compared to healthy pigs. Renal artery injection of either autologous Nx or Hx AMSCs improved diastolic BP, reduced kidney tissue fibrosis, and inflammation (CD3+ T-cells) in ARAS pigs. In addition, renal medullary hypoxia significantly lowered with Nx but not Hx AMSC treatment. Mechanistically, levels of epigenetic 5hmC marks (which reflect gene activation) estimated using DNA immunoprecipitation technique were elevated in profibrotic and inflammatory genes in ARAS compared with normal AMSCs. HPC significantly reduced 5hmC levels in cholesterol biosynthesis and oxidative stress response pathways in ARAS AMSCs. Thus, autologous AMSCs improve key renovascular parameters and inflammation in ARAS pigs, with HPC mitigating pathological molecular effects on inflammatory and profibrotic genes which may play a role in augmenting regenerative capacity of AMSCs.

Police shootings, violent crime, race and socio-economic factors in municipalities in the United States of America.

BACKGROUND: Both police shootings and violent crime remain high in the United States of America compared to other developed nations but debates continue about whether race, mental health or other social factors are related to them. AIMS: Our aim was to test relationships between community factors indicative of socio-economic status, racial demographics, police shootings, and violent crime. METHODS: Data on police shootings, violent crime and community sociodemographic factors were drawn from two publicly accessible datasets: health and police records of 100 US municipalities and relationships between them explored using regression analyses. RESULTS: Data were from the 100 largest US municipalities as designated by the mapping police violence database. The median per capital violent crime rate was 5.94 and median killings by police per 10 thousand arrests was 13.7. Violent crime was found to be related mainly to income inequality and lower academic achievement in the community. Race was unrelated to violent crime after controlling for other factors. Police shootings were found to be related to community level mental health concerns, food insecurity and the municipality's violent crime rate. CONCLUSION: The evidence suggests that socio-economic factors are the primary drivers of both violent crime perpetration and police shootings. Policy approaches aimed at improving education and reducing poverty are likely to mitigate both violent crime and police shootings. However, it is important to recognise that being Black is an indicator of particular disadvantage within this context. This underscores the need for comprehensive strategies that address the systemic issues of racial disparities and socio-economic inequality, while also acknowledging the complex interplay of race, poverty and policing in the context of violent crime and police shootings.

Effects of obesity on reparative function of human adipose tissue-derived mesenchymal stem cells on ischemic murine kidneys.

INTRODUCTION: Obesity is a health burden that impairs cellular processes. Mesenchymal stem/stromal cells (MSCs) are endowed with reparative properties and can ameliorate renal injury. Obesity impairs human MSC function in-vitro, but its effect on their in-vivo reparative potency remains unknown. SUBJECTS AND METHODS: Abdominal adipose tissue-derived MSC were harvested from patients without ('lean') or with obesity ('obese') (body mass index <30 or ≥30 kg/m2, respectively) during kidney donation or bariatric surgery, respectively. MSC (5 × 105/200 µL) or vehicle were then injected into 129S1 mice 2 weeks after renal artery stenosis (RAS) or sham surgery (n = 8/group). Two weeks later, mice underwent magnetic resonance imaging to assess renal perfusion and oxygenation in-vivo, and kidneys then harvested for ex-vivo studies. RESULTS: Similar numbers of lean and obese-MSCs engrafted in stenotic mouse kidneys. Vehicle-treated RAS mice had reduced stenotic-kidney cortical and medullary perfusion and oxygenation. Lean (but not obese) MSC normalized ischemic kidney cortical perfusion, whereas both effectively mitigated renal hypoxia. Serum creatinine and blood pressure were elevated in RAS mice and lowered only by lean-MSC. Both types of MSCs alleviated stenotic-kidney fibrosis, but lean-MSC more effectively than obese-MSC. MSC senescence-associated beta-gal activity, and gene expression of p16, p21, and vascular endothelial growth factor correlated with recipient kidney perfusion and tissue injury, linking MSC characteristics with their in-vivo reparative capacity. DISCUSSION: Human obesity impairs the reparative properties of adipose-tissue-derived MSCs, possibly by inducing cellular senescence. Dysfunction and senescence of the endogenous MSC repair system in patients with obesity may warrant targeting interventions to restore MSC vitality.

Microvascular remodeling and altered angiogenic signaling in human kidneys distal to occlusive atherosclerotic renal artery stenosis.

BACKGROUND: Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large-vessel occlusive disease on the microcirculation within human kidneys. METHOD: This study included five patients who underwent nephrectomy due to renovascular occlusion and seven nonstenotic discarded donor kidneys (four deceased donors). Micro-computed tomography was performed to assess microvascular spatial densities and tortuosity, an index of microvascular immaturity. Renal protein expression, gene expression and histology were studied in vitro using immunoblotting, polymerase chain reaction and staining. RESULTS: RAS demonstrated a loss of medium-sized vessels (0.2-0.3 mm) compared with donor kidneys (P = 0.037) and increased microvascular tortuosity. RAS kidneys had greater protein expression of angiopoietin-1, hypoxia-inducible factor-1α and thrombospondin-1 but lower protein expression of vascular endothelial growth factor (VEGF) than donor kidneys. Renal fibrosis, loss of peritubular capillaries (PTCs) and pericyte detachment were greater in RAS, yet they had more newly formed PTCs than donor kidneys. Therefore, our study quantified significant microvascular remodeling in the poststenotic human kidney. RAS induced renal microvascular loss, vascular remodeling and fibrosis. Despite downregulated VEGF, stenotic kidneys upregulated compensatory angiogenic pathways related to angiopoietin-1. CONCLUSIONS: These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis and support therapeutic strategies directly targeting the poststenotic kidney microcirculation in patients with RAS.

Improving Postoperative Acute Kidney Injury Rates Following Primary Total Joint Arthroplasty.

BACKGROUND: Perioperative hip and knee arthroplasty complications remain a significant clinical and financial burden. Our institution has shifted to developing protocols to decrease these perioperative complications. This study focuses on acute kidney injury (AKI) rate status post primary total joint arthroplasty (TJA). Current literature demonstrates a 2%-15% incidence of AKI following TJA. However, there is a paucity of published literature on protocols that have effectively reduced AKI rates following TJA. The purpose of this study is to evaluate the effect that our institutionally developed perioperative renal protocol had on the postoperative AKI rates. METHODS: A retrospective cohort study was performed. Patient demographics, baseline creatinine, and postoperative creatinine values during the patient's hospitalization were collected and analyzed. The preintervention cohort data contained all patients at our institution who underwent a primary TJA from November 1, 2016 to January 1, 2018. The postintervention cohort included all primary TJA patients from July 1, 2018 to February 2, 2020. AKI was defined using the AKI Network classification system comparing baseline and postoperative creatinine values. A multivariate analysis was performed to determine the statistical significance of our results. RESULTS: Before intervention 1013 patients underwent a primary TJA with 68 patients developing an AKI postoperatively. After intervention 2169 patients underwent primary TJA with 90 patients developing an AKI (6.71% vs 4.15%; P = .0015, odds ratio = 0.59, 95% confidence interval = 0.42-0.82). CONCLUSION: This study demonstrated that implementation of a perioperative renal protocol can significantly reduce AKI rates. A reduction in AKI rates following TJA will result in improved outcomes and secondarily decrease the financial impact of postoperative complications seen following TJA.

Prosocial Video Game Content, Empathy and Cognitive Ability in a Large Sample of Youth.

Whether playing video games with prosocial content has an influence on empathy among players remains contentious in the research literature. Some evidence suggests playing cooperatively with other gamers enhances empathy, but data have not conclusively linked prosocial content with empathy. Further, mechanisms of this potential relationship are unclear, and little work has been conducted on how cognitive skills, such as fluid reasoning, may mediate this relationship. The current study examines these relationships with a large sample of 3034 youth (27.2% female, Mage = 11.2; range 8-17 at time 1) in Singapore. Data were considered longitudinally across two years in three waves. Ultimately, no evidence emerged that prosocial content in video games had any impact on empathy related outcomes, nor was fluid reasoning a mediator variable for any relationship. However, variables such as social competence and depression and anxiety symptoms were highly related to empathy measures. This evidence adds to the growing debate in the field that video games may not dramatically alter, whether positively or negatively, the development of emotional and behavioral outcomes for youth.

Social, health and ethnicity correlates of complaints of excessive police force.

BACKGROUND: Following several high-profile police shootings of Black Americans, renewed debate has focused on race as a predictor of police violence. Past research has been inconsistent on this score. Some scholars argue that socioeconomic issues are better predictors of police-related violence than are race and ethnicity. AIMS: To test relationships between complaints of excessive use of police violence and racial/ethnic population demographics, allowing for social and mental health variables. METHODS: We examined records from all 195 municipal police departments in California to identify complaints of excessive force by police and tested for associations between such complaints and health, socio-economic and demographic data from county records, using multivariate analyses. RESULTS: There was no difference in reporting between communities according to Black or White American residency proportions; communities with more Latino Americans were less likely to complain formally of excessive use of police force. The strongest associate of complaints to police departments that their employees had used excessive force was experiencing mental distress in the community. CONCLUSIONS: Our findings are limited by reliance on complaints to police authorities rather than actual incidence of police use of excessive force and by having to map municipal data on to county data, but the finding that factors other than or in addition to any inherent police problems may contribute to excessive use of force by the police offers new lines for remedying the problem. In particular, our findings suggest that more training for police in recognising and managing mental distress and more provision of mental health experts to work alongside police would be worth evaluating as a next step.

Percutaneous transluminal renal angioplasty attenuates poststenotic kidney mitochondrial damage in pigs with renal artery stenosis and metabolic syndrome.

Percutaneous transluminal renal angioplasty (PTRA) has been used to treat renovascular disease (RVD), a chronic condition characterized by renal ischemia and metabolic abnormalities. Mitochondrial injury has been implicated as a central pathogenic mechanism in RVD, but whether it can be reversed by PTRA remains uncertain. We hypothesized that PTRA attenuates mitochondrial damage, renal injury, and dysfunction in pigs with coexisting renal artery stenosis (RAS) and metabolic syndrome (MetS). Four groups of pigs (n = 6 each) were studied after 16 weeks of diet-induced MetS and RAS (MetS + RAS), MetS + RAS treated 4 weeks earlier with PTRA, and Lean and MetS Sham controls. Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed in vivo with multidetector computed tomography, and renal tubular mitochondrial structure and function and renal injury ex vivo. PTRA successfully restored renal artery patency, but mean arterial pressure remained unchanged. Stenotic kidney RBF and GFR, which fell in MetS + RAS compared to MetS, rose after PTRA. PTRA attenuated MetS + RAS-induced mitochondrial structural abnormalities in tubular cells and peritubular capillary endothelial cells, decreased mitochondrial H2 02 production, and increased renal cytochrome-c oxidase-IV activity and ATP production. PTRA also improved cortical microvascular and peritubular capillary density and ameliorated tubular injury and tubulointerstitial fibrosis in the poststenotic kidney. Importantly, renal mitochondrial damage correlated with poststenotic injury and dysfunction. Renal revascularization attenuated mitochondrial injury and improved renal hemodynamics and function in swine poststenotic kidneys. This study suggests a novel mechanism by which PTRA might be relatively effective in ameliorating mitochondrial damage and improving renal function in coexisting MetS and RAS.

Links between screen use and depressive symptoms in adolescents over 16 years: Is there evidence for increased harm?

Recent scholarship has been divided on whether an observed increase in suicides in the United States among teenagers and preteens (12-18) can be attributed to an increased use in social screen media beginning in 2009. If these concerns are accurate effect sizes for the relationship between screen use and suicide should increase over the 16 years since 2001. The current study used the Florida Youth Risk Behavior Survey data (n = 45,992) from 2001 to 2017, to track effect sizes for screen/depression correlations, controlling for age and gender. A second dataset from the UK Understanding Society dataset (ns for each wave ranged between 3,536 and 4,850) was used to study associations between time spent on social media and emotional problems. Metaregression was be used to examine whether effect sizes increase across time. Results generally did not support the hypothesis that effect sizes between screen and social media use are increasing over time. Aside from the trends over time, for any given year, most effect sizes were below the r = .10 threshold used for interpretation with the exception of computer use which was just at that threshold. It is concluded that screens and social media use are unlikely to bear major responsibility for youth suicide trends. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=76S7cxiaU88.

Examining homicides and suicides cross-nationally: Economic factors, guns and video games.

Understanding why different nations have different homicide and suicide rates has been of interest to scholars, policy makers and the general public for years. Multiple theories have been offered, related to the economy, presence of guns and even exposure to violence in video games. In the current study, several factors were considered in combination across a sample of 92 countries. These included income inequality (Gini index), Human Capital Index (education and employment), per capita gun ownership and per capita expenditure on video games. Results suggest that economic factors primarily were related to homicide and suicide cross-nationally. Video game consumption was not a major indicative factor (other than a small negative relationship with homicides). More surprisingly, per capita gun ownership was not an indicator factor cross-nationally. The results suggest that a focus on economic factors and income inequality are most likely to bear fruit regarding reduction of violence and suicide.

Transplanted senescent renal scattered tubular-like cells induce injury in the mouse kidney.

Cellular senescence, a permanent arrest of cell proliferation, is characterized by a senescence-associated secretory phenotype (SASP), which reinforces senescence and exerts noxious effects on adjacent cells. Recent studies have suggested that transplanting small numbers of senescent cells suffices to provoke tissue inflammation. We hypothesized that senescent cells can directly augment renal injury. Primary scattered tubular-like cells (STCs) acquired from pig kidneys were irradiated by 10 Gy of cesium radiation, and 3 wk later cells were characterized for levels of senescence and SASP markers. Control or senescent STCs were then prelabeled and injected (5 × 105 cells) into the aorta of C57BL/6J mice. Four weeks later, renal oxygenation was studied in vivo using 16.4-T magnetic resonance imaging and function by plasma creatinine level. Renal markers of SASP, fibrosis, and microvascular density were evaluated ex vivo. Per flow cytometry, irradiation induced senescence in 80-99% of STCs, which showed increased gene expression of senescence and SASP markers, senescence-associated ß-galactosidase staining, and cytokine levels (especially IL-6) secreted in conditioned medium. Four weeks after injection, cells were detected engrafted in the mouse kidneys with no evidence for rejection. Plasma creatinine and renal tissue hypoxia increased in senescent compared with control cells. Senescent kidneys were more fibrotic, with fewer CD31+ endothelial cells, and showed upregulation of IL-6 gene expression. Therefore, exogenously delivered senescent renal STCs directly injure healthy mouse kidneys. Additional studies are needed to determine the role of endogenous cellular senescence in the pathogenesis of kidney injury and evaluate the utility of senolytic therapy.

In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure.

Atherosclerotic renovascular disease (ARVD) reduces tissue perfusion and eventually leads to loss of kidney function with limited therapeutic options. Here we describe results of Phase 1a escalating dose clinical trial of autologous mesenchymal stem cell infusion for ARVD. Thirty-nine patients with ARVD were studied on two occasions separated by three months. Autologous adipose-derived mesenchymal stem cells were infused through the renal artery in 21 patients at three different dose levels (1, 2.5 and 5.0 × 105 cells/kg) in seven patients each. We measured renal blood flow, glomerular filtration rate (GFR) (iothalamate and estimated GFR), renal vein cytokine levels, blood pressure, and tissue oxygenation before and three months after stem cell delivery. These indices were compared to those of 18 patients with ARVD matched for age, kidney function and blood pressure receiving medical therapy alone that underwent an identical study protocol. Cultured mesenchymal stem cells were also studied in vitro. For the entire stem cell treated-cohort, mean renal blood flow in the treated stenotic kidney significantly increased after stem cell infusion from (164 to 190 ml/min). Hypoxia, renal vein inflammatory cytokines, and angiogenic biomarkers significantly decreased following stem cell infusion. Mean systolic blood pressure significantly fell (144 to 136 mmHg) and the mean two-kidney GFR (Iothalamate) modestly but significantly increased from (53 to 56 ml/min). Changes in GFR and blood pressure were largest in the high dose stem cell treated individuals. No such changes were observed in the cohort receiving medical treatment alone. Thus, our data demonstrate the potential for autologous mesenchymal stem cell to increase blood flow, GFR and attenuate inflammatory injury in post-stenotic kidneys. The observation that some effects are dose-dependent and related to in-vitro properties of mesenchymal stem cell may direct efforts to maximize potential therapeutic efficacy.

Selective intrarenal delivery of mesenchymal stem cell-derived extracellular vesicles attenuates myocardial injury in experimental metabolic renovascular disease.

Extracellular vesicles (EVs) deliver genes and proteins to recipient cells, and mediate paracrine actions of their parent cells. Intrarenal delivery of mesenchymal stem cell (MSC)-derived EVs preserves stenotic-kidney function and reduces release of pro-inflammatory cytokines in a swine model of coexisting metabolic syndrome (MetS) and renal artery stenosis (RAS). We hypothesized that this approach is also capable of blunting cardiac injury and dysfunction. Five groups of pigs were studied after 16 weeks of diet-induced MetS and RAS (MetS + RAS), MetS and MetS + RAS treated 4 weeks earlier with a single intrarenal delivery of EVs-rich fraction harvested from autologous adipose tissue-derived MSCs, and lean and MetS Shams. Cardiac structure, function, and myocardial oxygenation were assessed in vivo using imaging, and cardiac inflammation, senescence, and fibrosis ex vivo. Inflammatory cytokine levels were measured in circulating and renal vein blood. Intrarenal EV delivery improved stenotic-kidney glomerular filtration rate and renal blood flow, and decreased renal release of monocyte-chemoattractant protein-1 and interleukin-6. Furthermore, despite unchanged systemic hemodynamics, intrarenal EV delivery in MetS + RAS normalized cardiac diastolic function, attenuated left ventricular remodeling, cellular senescence and inflammation, and improved myocardial oxygenation and capillary density in MetS + RAS. Intrarenal delivery of MSC-derived EVs blunts myocardial injury in experimental MetS + RAS, possibly related to improvement in renal function and systemic inflammatory profile. These observations underscore the central role of inflammation in the crosstalk between the kidney and heart, and the important contribution of renal function to cardiac structural and functional integrity in coexisting MetS and RAS.

Quantitative Magnetization Transfer Detects Renal Fibrosis in Murine Kidneys With Renal Artery Stenosis.

BACKGROUND: Renal fibrosis is a common pathway in tubulointerstitial injury and a major determinant of renal insufficiency. Collagen deposition, a key feature of renal fibrosis, may serve as an imaging biomarker to differentiate scarred from healthy kidneys. PURPOSE: To test the feasibility of using quantitative magnetization transfer (qMT), which assesses tissue macromolecule content, to measure renal fibrosis. STUDY TYPE: Prospective. ANIMAL MODEL: Fifteen 129S1 mice were studied 4 weeks after either sham (n = 7) or unilateral renal artery stenosis (RAS, n = 8) surgeries. FIELD STRENGTH/SEQUENCE: Magnetization transfer (MT)-weighted images were acquired at 16.4T using an MT-prepared fast-low-angle-shot sequence. Renal B0, B1, and T1 maps were also acquired, using a dual-echo gradient echo, an actual flip angle, and inversion recovery method, respectively. ASSESSMENT: A two-pool model was used to estimate the bound water fraction (f) and other tissue imaging biomarkers. Masson's trichrome staining was subsequently performed ex vivo to evaluate renal fibrosis. STATISTICAL TESTS: Comparisons of renal parameters between sham and RAS were performed using independent samples t-tests. Pearson's correlation was conducted to investigate the relationship between renal fibrosis by histology and the qMT-derived bound pool fraction f. RESULTS: The two-pool model provided accurate fittings of measured MT signal. The qMT-derived f of RAS kidneys was significantly increased compared to sham in all kidney zones (renal cortex [CO], 7.6 ± 2.4% vs. 4.6 ± 0.6%; outer medulla [OM], 8.2 ± 4.2% vs. 4.2 ± 0.9%; inner medulla [IM] + P, 5.8 ± 1.6% vs. 2.9 ± 0.6%, all P < 0.05). Measured f correlated well with histological fibrosis in all kidney zones (CO, Pearson's correlation coefficient r = 0.95; OM, r = 0.93; IM + P, r = 0.94, all P < 0.05). DATA CONCLUSION: The bound pool fraction f can be quantified using qMT at 16.4T in murine kidneys, increases significantly in fibrotic RAS kidneys, and correlates well with fibrosis by histology. Therefore, qMT may constitute a valuable tool for measuring renal fibrosis in RAS. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3.

Sexualised video games, sexist attitudes and empathy towards victims of rape: Correlational evidence for a relationship is minimal in an online study.

BACKGROUND: There is continued debate about whether sexualisation in games can influence sexist attitudes and reduced empathy towards women in real life. There is research evidence both supporting and refuting the possibility. AIMS: Our aim was to examine the relationship between sexualised content in video games and players' sexist attitudes and empathy. Our research question was, do any such relationships exist once other factors including gender and trait aggression are controlled? METHODS: An online sample of 125 participants were recruited and asked to rate their video game playing experience, complete a trait aggression scale and record responses to a vignette about rape. Scores were first correlated, and then hierarchical multiple regression was employed followed by PROCESS examination of interactions between sexualised game content and trait aggression. RESULTS: Exposure to sexualised content in video games was neither correlated with higher sexist attitude ratings nor with lower empathy scores. Sexualised content in games was associated with slightly lower sexist belief scores for those with higher scores on trait aggression (the 12.8% of our current sample at one standard deviation above the mean). No effects were observed for those low in trait aggression. CONCLUSIONS AND IMPLICATIONS: While it is natural to be concerned about the impact of potentially arousing video games, actual effects may be counterintuitive, so if seeking to regulate, it is important to act from actual information. Further research with groups of particular concern will be important.

Child Abuse, Spanking and Adult Dating Violence: A Replication Study of Temple et al., 2018.

The issue of whether spanking does or does not contribute to later aggression remains controversial despite public policy statements by the American Academy of Pediatrics and other groups opposing spanking. Studies have remained inconsistent regarding whether spanking does or does not contribute to later aggression. One study, Temple et al., 2018, released results from an adult retrospective study suggesting that spanking and related corporal punishment could predict adult dating violence, but that actual physical child abuse exposure did not. This current study attempted to replicate this unusual finding using similar methodologies. Current results did not replicate the findings of Temple et al., 2018. Exposure to child physical abuse predicted adult dating violence, but exposure to spanking and related corporal punishment did not. These results suggest it may be premature to link spanking to aggression in adulthood.

Tissue hypoxia, inflammation, and loss of glomerular filtration rate in human atherosclerotic renovascular disease.

The relationships between renal blood flow (RBF), tissue oxygenation, and inflammatory injury in atherosclerotic renovascular disease (ARVD) are poorly understood. We sought to correlate RBF and tissue hypoxia with glomerular filtration rate (GFR) in 48 kidneys from patients with ARVD stratified by single kidney iothalamate GFR (sGFR). Oxygenation was assessed by blood oxygenation level dependent magnetic resonance imaging (BOLD MRI), which provides an index for the levels of deoxyhemoglobin within a defined volume of tissue (R2*). sGFR correlated with RBF and with the severity of vascular stenosis as estimated by duplex velocities. Higher cortical R2* and fractional hypoxia and higher levels of renal vein neutrophil-gelatinase-associated-lipocalin (NGAL) and monocyte-chemoattractant protein-1 (MCP-1) were observed at lower GFR, with an abrupt inflection below 20 ml/min. Renal vein MCP-1 levels correlated with cortical R2* and with fractional hypoxia. Correlations between cortical R2* and RBF in the highest sGFR stratum (mean sGFR 51 ± 12 ml/min; R = -0.8) were degraded in the lowest sGFR stratum (mean sGFR 8 ± 3 ml/min; R = -0.1). Changes in fractional hypoxia after furosemide were also absent in the lowest sGFR stratum. These data demonstrate relative stability of renal oxygenation with moderate reductions in RBF and GFR but identify a transition to overt hypoxia and inflammatory cytokine release with severely reduced GFR. Tissue oxygenation and RBF were less correlated in the setting of reduced sGFR, consistent with variable oxygen consumption or a shift to alternative mechanisms of tissue injury. Identifying transitions in tissue oxygenation may facilitate targeted therapy in ARVD.

Aggressive Video Games are Not a Risk Factor for Future Aggression in Youth: A Longitudinal Study.

The issue of whether video games with aggressive or violent content (henceforth aggressive video games) contribute to aggressive behavior in youth remains an issue of significant debate. One issue that has been raised is that some studies may inadvertently inflate effect sizes by use of questionable researcher practices and unstandardized assessments of predictors and outcomes, or lack of proper theory-driven controls. In the current article, a large sample of 3034 youth (72.8% male Mage = 11.2) in Singapore were assessed for links between aggressive game play and seven aggression or prosocial outcomes 2 years later. Theoretically relevant controls for prior aggression, poor impulse control, gender and family involvement were used. Effect sizes were compared to six nonsense outcomes specifically chosen to be theoretically unrelated to aggressive game play. The use of nonsense outcomes allows for a comparison of effect sizes between theoretically relevant and irrelevant outcomes, to help assess whether any statistically significant outcomes may be spurious in large datasets. Preregistration was employed to reduce questionable researcher practices. Results indicate that aggressive video games were unrelated to any of the outcomes using the study criteria for significance. It would take 27 h/day of M-rated game play to produce clinically noticeable changes in aggression. Effect sizes for aggression/prosocial outcomes were little different than for nonsense outcomes. Evidence from this study does not support the conclusion that aggressive video games are a predictor of later aggression or reduced prosocial behavior in youth.

Pathological Gaming in Young Adolescents: A Longitudinal Study Focused on Academic Stress and Self-Control in South Korea.

With the increase in social concern regarding pathological gaming among adolescents, the WHO (World Health Organization) included "gaming disorder" in the International Classification of Disorders, 11th version (ICD-11). However, little longitudinal research has been conducted examining social influences on pathological gaming, particularly in Asian countries (e.g., South Korea, China). With 4-year panel data from young adolescents (N = 968, 50.7% girls; Mage = 13.3 years) in South Korea, this study examined the effects of cultural environmental factors (parents' excessive interference, communication with parents, and friends' and teachers' support) on pathological gaming through academic stress and self-control. The results showed the critical role of academic stress and self-control in the effects of environmental factors on pathological gaming. Parents' excessive interference increased the degree to which youth experienced academic stress while the degree of communication with parents decreased this stress. Increased academic stress damaged self-control, which finally increased the degree of pathological gaming. Self-control affected the degree of pathological gaming stronger than gaming time did. The theoretical and practical implications from the study findings are discussed.

A Preregistered Longitudinal Analysis of Aggressive Video Games and Aggressive Behavior in Chinese Youth.

Whether aggressive video games (AVGs) promote aggression in youth remains a matter of debate despite decades of research. Longitudinal studies to date have provided mixed results, with effect sizes, overall, being quite low. However, few longitudinal studies have preregistered their analyses. The current article presents a preregistered analysis of AVG influences on later youth aggression. With several other variables controlled (age, sex, family income, moral disengagement, Time 1 aggression) AVG exposure did not predict Time 2 aggression. Evidence from this sample did not support the common belief that AVG exposure is a risk factor for future aggression in youth.