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We aimed to better understand emergency department (ED) use, admission patterns, and demographics for substance use disorder in pregnancy and postpartum (SUDPP).In this longitudinal study, the United States Nationwide Emergency Department Sample was queried for all ED visits by 15- to 50-year-old women with a primary diagnosis defined by International Classification of Diseases, 9th or 10th edition Clinical Modification, codes of SUDPP between 2006 and 2016. Patterns of ED visit counts, rates, admissions, and ED charges were analyzed.Annual national estimated ED visits for SUDPP increased from 2,919 to 9,497 between 2006 and 2016 (a 12.4% annual average percentage change), whereas admission rates decreased (from 41.9% to 32.0%). ED visits were more frequent among women who were 20-29 years old, using Medicaid insurance, in the lowest income quartile, living in the South, and in metropolitan areas. Compared with the proportion of ED visits, 15- to 19-year-olds had significantly lower admission rates, whereas women with Medicaid and in the lowest income quartile had higher admission rates (p .001). Opioid use, tobacco use, and mental health disorders were most commonly associated with SUDPP. The ED average inflation-adjusted charges for SUDPP increased from $1,486 to $3,085 between 2006 and 2016 (7.1% annual average percentage change; p .001), yielding total annual charges of $4.02 million and $28.53 million.Despite the decrease in admissions, the number and charges for ED visits for SUDPP increased substantially between 2006 and 2016. These increasing numbers suggest a continuous need to implement preventive public health measures and provide adequate outpatient care for this condition in this population specifically.

Purpose: The associations between longitudinal physical activity (PA) patterns across childhood and physical literacy have not been studied. The purpose of this study was to identify PA trajectories from preschool to school-age, and to determine if trajectory group membership was associated with school-age physical literacy. Methods: Participants (n = 279, 4.5 [0.9] y old, 48% girls) enrolled in this study and completed annual assessments of PA with accelerometry over 6 timepoints. Physical literacy was assessed at timepoint 6 (10.8 [1.0] y old). Group-based trajectory analysis was applied to identify trajectories of total volume of PA and of moderate to vigorous PA and to estimate group differences in physical literacy. Results: Three trajectories of total volume of PA and of moderate to vigorous PA were identified. Groups 1 (lowest PA) included 40% to 53% of the sample, groups 2 included 39% to 44% of the sample, and groups 3 (highest PA) included 8% to 16% of the sample. All trajectories declined from timepoint 1 to timepoint 6. School-age physical literacy was lowest in trajectory groups with the lowest total volume of PA or moderate to vigorous PA over time (P Conclusions: PA should be promoted across early and middle childhood, as it may play a formative role in the development of school-age physical literacy.

International audience; The European Space Agency (ESA) launched the SMOS (Soil Moisture Ocean Salinity) mission in 2009; currently, multiple global soil moisture (SM) products are based on the measurements of its L-band (1.4 GHz) radiometer. We compared four SMOS products with each other: Level 2, Level 3, IC (INRA-CESBIO), and Near Real Time products. The comparisons focused on core validation sites (CVS), whose spatial representativeness errors allow the estimation of the SM product performance for bias-insensitive metrics (unbiased root mean square error (ubRMSE) and correlation (R), and anomaly R) with negligible uncertainty and for bias-sensitive metrics (mean difference (MD) and root mean square difference or RMSD) with acceptable uncertainty. When the products were compared with CVS independently, the results showed that the ubRMSE, R, and anomaly R of the IC product were better than those of the other products, while the MD was larger. However, the differences between the performances were smaller when the products were assessed using only the data points when each product had a valid retrieval. This indicates that the algorithms have similar performance and that data screening and quality flagging of the retrievals markedly affects the performance. The NASA Soil Moisture Active Passive (SMAP) mission produces a similar SM product as SMOS using an L-band radiometer. The closeness of the ubRMSE, R, and anomaly R performance of the IC product and the SMAP product (0.039 m 3 /m 3 vs. 0.041 m 3 /m 3 , 0.80 vs. 0.81, and 0.75 vs. 0.75) demonstrate that the SMOS and SMAP radiometers can achieve similar SM sensitivity.

Health Promoting Schools (HPS) is a whole-school approach that shapes the conditions necessary to support student health and well-being. Youth engagement is recognized as key to HPS implementation, yet research related to the involvement of youth voice in school health promotion initiatives is limited. The purpose of this study was to understand youth perspectives on HPS and school youth engagement. Ten youth (grades 9-10, ages 14-16) were trained as peer researchers using a Youth Participatory Action Research approach. The peer researchers interviewed 23 of their peers (grades 7-10, ages 12-16) on perspectives related to HPS and school youth engagement. All interviews were audio-recorded, transcribed and data were analysed using inductive 'codebook' thematic analysis. Themes related to a healthy school community were mapped onto the pillars of HPS: (i) Social and Physical Environment, (ii) Teaching and Learning, (iii) Partnerships and Services and (iv) School Policies. Participants placed more importance on the social and physical environment of the school including respect, inclusivity, supportive relationships and the design of spaces. Key factors for youth engagement were: (i) safe and supportive spaces, (ii) passion and interest, (iii) using their voice, (iv) power dynamics, (v) accessibility and (vi) awareness. With recognition that youth engagement is a crucial part of HPS, this work provides relevant and applicable information on areas of the healthy school community that are important to youth, and if/how they are meaningfully engaged in school decision-making.Schools are a place for students to develop and learn about health. Schools in Nova Scotia have applied Health Promoting Schools (HPS) activities since 2005. HPS activities support students’ health and well-being by developing safe spaces, offering healthy food options and increasing time for physical activity. There is a lack of research outlining what youth think about HPS or how they are involved. We trained youth to interview their peers to find out what parts of the school they think are healthy, and how they are involved in school decision-making. We found that youth wanted to be part of a school where they felt safe, included and respected. Students also described a healthy school as welcoming, and clean. Youth felt their involvement in decision-making was important. Youth shared that teacher support and personal interest helped them be involved in decision-making. Fear of sharing their opinions and not knowing how to be involved made it harder for youth to be part of decision-making. Our research identified what parts of the school youth think are important for their health, and what makes it easier or harder for them to be engaged. The results of this research can support HPS activities moving forward.

Inspired by Fiset-Laniel et al.'s (2020) article entitled "Public health investments: neglect or wilful omission? Historical trends in Quebec and implications for Canada", we assessed public health investments since the establishment of the Nova Scotia provincial health authority in 2015. We analyzed Nova Scotia Department of Health and Wellness budgets from 2015-2016 to 2019-2020 and observed that less than 1% of funding was budgeted for public health annually, an amount well below the recommendation that 5-6% of healthcare funding be spent on public health. Healthcare spending has increased annually since 2015-2016, but proportions of funding to different programs and services have remained static. Specifically, we did not observe a change in investment in public health over time, suggesting that while the government does not necessarily spend too much or too little on healthcare, it spends far too little on public health. This chronic under-funding is problematic given the high rates of non-communicable diseases in Nova Scotia and health inequities experienced within the population. The 2020 COVID-19 pandemic has highlighted the importance of public health work, and the need for a pandemic recovery plan that prioritizes investment in all areas of public health in Nova Scotia.RéSUMé: Inspirés par l’article de Fiset-Laniel et coll. (2020) intitulé « Public health investments: neglect or wilful omission? Historical trends in Quebec and implications for Canada », nous avons évalué les investissements en santé publique depuis la fondation de l’autorité sanitaire provinciale de la Nouvelle-Écosse en 2015. Nous avons analysé les budgets du ministère de la Santé et du Mieux-Être de la Nouvelle-Écosse de 2015−2016 à 2019−2020 et nous avons observé que moins de 1 % du financement était prévu pour la santé publique annuellement, un montant bien inférieur à la recommandation que 5−6 % du financement pour les soins de santé soit dépensé sur la santé publique. Les dépenses de santé ont augmenté annuellement depuis 2015−2016, mais les proportions du financement consacrés à différents programmes et services ont demeuré statiques. Spécifiquement, nous n’avons pas observé de changement dans l’investissement en santé publique au fil du temps, indiquant que tandis que le gouvernement ne dépense pas nécessairement trop ou trop peu sur les soins de santé, il dépense bien trop peu sur la santé publique. Ce sous-financement chronique est problématique étant donné les hauts taux de maladies non transmissibles en Nouvelle-Écosse et les inégalités en matière de santé qui existent au sein de la population. La pandémie de la COVID-19 de 2020 a souligné l’importance du travail lié à la santé publique, ainsi que la nécessité d’un plan de rétablissement suite à une pandémie qui priorise l’investissement dans tous les domaines de santé publique en Nouvelle-Écosse.

Introduction:We evaluated primary testicular tumor characteristics associated with nongerm cell tumor histology and potential appropriateness for testis sparing surgery in selected patients...

KEY POINTS: Oral sulphonylureas, widely prescribed in diabetes, inhibit pancreatic ATP-sensitive K+ (KATP ) channels to increase insulin release. However, KATP channels are also located within vascular (endothelium and smooth muscle) and muscle (cardiac and skeletal) tissue. We evaluated left ventricular function at rest, maximal aerobic capacity (VI‡O2 max) and submaximal exercise tolerance (i.e. speed-duration relationship) during treadmill running in rats, before and after systemic KATP channel inhibition via glibenclamide. Glibenclamide impaired critical speed proportionally more than VI‡O2 max but did not alter resting cardiac output. Vascular KATP channel function (topical glibenclamide superfused onto hindlimb skeletal muscle) resolved a decreased blood flow and interstitial PO2 during twitch contractions reflecting impaired O2 delivery-to-utilization matching. Our findings demonstrate that systemic KATP channel inhibition reduces VI‡O2 max and critical speed during treadmill running in rats due, in part, to impaired convective and diffusive O2 delivery, and thus VI‡O2 , especially within fast-twitch oxidative skeletal muscle. ABSTRACT: Vascular ATP-sensitive K+ (KATP ) channels support skeletal muscle blood flow and microvascular oxygen delivery-to-utilization matching during exercise, however, oral sulphonylurea treatment in diabetes inhibits pancreatic KATP channels to enhance insulin release. Herein we tested the hypotheses that i) systemic KATP channel inhibition via glibenclamide (GLI; 10 mg kg-1 i.p.) would decrease cardiac output at rest (echocardiography), maximal aerobic capacity (VI‡O2 max) and the speed-duration relationship (i.e. lower critical speed (CS)) during treadmill running and ii) local KATP channel inhibition (5 mg kg-1 GLI superfusion) would decrease blood flow (15 µm microspheres), interstitial space oxygen pressures (PO2 is; phosphorescence quenching) and convective and diffusive O2 transport (QI‡O2 and DO2 , respectively; Fick Principle and Law of Diffusion) in contracting fast-twitch oxidative mixed gastrocnemius muscle (MG: 9% type I+IIa fibres). At rest, GLI slowed LV relaxation (2.11 ± 0.59 vs. 1.70 ± 0.23 cm s-1 ) and decreased heart rate (321 ± 23 vs. 304 ± 22 bpm, both P 0.05). During exercise, GLI reduced VI‡O2 max (71.5 ± 1.0 vs. 68.0 ± 1.5 ml kg-1 min-1 ) and CS (35.9 ± 0.9 vs. 31.9 ± 1.1 m min-1 , both P

While many children with renal tumors require long term venous access (VA) for adjuvant chemotherapy, certainly not all do. This study develops and tests a VA decision tree (DT) to direct the placement of VA in patients with renal tumors.Utilizing data readily available at surgery a VADT was developed. The VADT was tested retrospectively by 2 independent reviewers on a historic cohort. The ability of the VADT to appropriately select which patients would benefit from VA placement was tested.160 patients underwent renal tumor surgery between 2005 and 2018. 70 (43.8%) patients met study criteria with median age of 45.1 months (range 1.1-224); 73% required VA. Using the VADT, VA placement was "needed" in 67.1% of patients and "deferred" in 32.9%. Interrater reliability was very high (kappa = 0.97, 95% CI 0.91-1, p 0.001). The sensitivity and specificity of the VADT to correctly decide on VA placement were 0.92 (0.8-0.98) and 1 (0.79-1). Using the VADT, no patient would have undergone unnecessary VA placement. In reality, 4.3% of patients had an unnecessary VA placed which required a subsequent removal.These preliminary data support the continued study of this VADT to guide intraoperative decisions regarding VA placement in patients with renal tumors.III - Study of diagnostic test.

High dietary sodium intake is a risk factor for arterial hypertension; given that the ability to overcome sympathetically mediated vasoconstriction (functional sympatholysis) is attenuated in individuals with hypertension, we investigated the cardiovascular responses to high salt (HS) intake in healthy humans. We hypothesized that a HS intake of 15 g/day for 7 days would attenuate functional sympatholysis and augment the blood pressure response to handgrip exercise (HGE). Thirteen participants (6 males, 7 females) underwent 2 individual days of testing. Beat-by-beat blood pressure and heart rate were recorded throughout the trial on the non-exercising limb. Forearm blood flow was derived from ultrasonography on the brachial artery of the exercising limb. Participants then underwent a flow-mediated dilation (FMD) test. Next, a submaximal HGE was performed for 7 min with lower body negative pressure initiated during minutes 5–7. A single spot urine sample revealed a significant increase in sodium excretion during the HS conditions (p < 0.01). FMD was reduced during the HS condition. Mean arterial pressure was significantly higher during HS intake. No alteration to functional sympatholysis was found between conditions (p > 0.05). In summary, HS intake increases blood pressure without impacting functional sympatholysis or blood pressure responsiveness during HGE. These findings indicate that brachial artery dysfunction precedes an inefficient functional sympatholysis. Novelty Functional sympatholysis was not impacted by 1 week of high sodium intake. High sodium intake augmented the rate pressure product during handgrip exercise in healthy humans.

Neighborhood conditions are associated with health outcomes, but whether individual health behaviors are independent of or associated with the settings are not clear. We analyzed the California Health Interview Survey (CHIS) (N = 11,152) data to determine if the perceptions and behaviors of similar individuals with an income low enough to be eligible for SNAP-Ed services differed based on whether they lived in high- or low-income neighborhoods. We found that SNAP-Ed eligible individuals living in low-income neighborhoods walked for transportation more frequently (3.04 times versus 2.38 times, p = 0.001), drank sugary beverages more frequently in the past month (2.93 times versus 1.69 times, p = 0.000), and had a higher risk of obesity than similar low-income individuals living in high-income neighborhoods (0.34 versus 0.26, p = 0.012). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11524-020-00433-x) contains supplementary material, which is available to authorized users.

OBJECTIVES: Blacks and Hispanics face a higher incidence rate of end-stage renal disease (ESRD) and tend to experience poorer access to quality health care compared with Whites. Income, education, and insurance coverage differentials are typically identified as risk factors, but neighborhood-level analyses may provide additional insights. We examine whether neighborhood racial composition contributes to racial/ethnic inequities in access to high-quality dialysis care in Chicago. METHODS: Data are drawn from the United States Renal Data System merged to the ESRD Quality Incentive Program file and the American Community Survey (2005–2009) for facility and neighborhood characteristics (N = 2797). Outcomes included (1) spatial access (travel time to dialysis facilities) and (2) realized access (actual use of quality care). Neighborhood racial/ethnic composition was categorized into four types: predominantly White, Black, and Hispanic neighborhoods, and racially integrated neighborhoods. RESULTS: Blacks lived closer to a dialysis facility but traveled the same distance to their own dialysis compared with Whites. Hispanics had longer travel time to any dialysis than Whites, and the difference between Hispanics and Whites became no longer significant after adjusting for neighborhood racial/ethnic composition. Blacks and Hispanics had better access to a high-quality facility if they lived in integrated neighborhoods (OR = 1.85 and 3.77, respectively, p < 0.01) or in neighborhoods with higher concentrations of their own race/ethnicity (OR = 1.68 for Blacks in Black neighborhoods and 1.92 for Hispanics in Hispanic neighborhoods, p < 0.05) compared with Whites in predominantly White neighborhoods. CONCLUSION: Expanding opportunities for Blacks and Hispanics to gain access to racially integrated and minority neighborhoods may help alleviate racial/ethnic inequities in access to quality care among kidney disease patients.

This study explores: 1) provider narratives of their contraceptive counseling practices with Latina patients within the context of patient-centered care (PCC); and 2) provider perceptions about the barriers to the provision of patient-centered contraceptive counseling in general and more specifically, with Latina patients in Baltimore, MD.We conducted 25 semi-structured qualitative interviews with physicians (MD/DO) and nurse practitioners from four specialties (family medicine, internal medicine, pediatrics, obstetrics/gynecology) who provide contraceptive care to Latinas in Baltimore, MD. We analyzed data using a directed content analysis approach. We discuss findings with attention to major constructs of PCC, applying a reproductive justice framework.Providers described a contraceptive counseling approach focused on pregnancy prevention as the primary goal during contraceptive encounters with Latina patients. Most respondents described using a tiered-effectiveness approach when counseling even while noting the importance of PCC and its main tenets. Providers noted both health system and patient-attributed barriers to PCC. Health system barriers to PCC included time constraints and insurance status. Patient-attributed barriers reported by providers included low patient education/health literacy, culturally-attributed misconceptions about contraception, and the language barrier.Providers described knowledge of and intention to practice PCC during contraceptive care but had limited integration of it in their own counseling practices with Latinas. Provider responses suggest tension between an expressed desire to provide PCC and paternalistic counseling paradigms that prioritize the prevention of unintended pregnancy over patient preferences. Moreover, inequitable health system barriers also interfere with true implementation of contraceptive PCC.Translating contraceptive PCC into practice, especially for marginalized communities, is paramount. Training should teach clinicians to recognize systems of structural inequity and discrimination that have informed approaches to counseling but are not reflective of PCC. Institutional policies must address health system barriers (e.g., time constraints; insurance) that also hamper PCC.

In non-cancer populations, inorganic dietary nitrate (NO

The COVID-19 pandemic has changed healthcare utilization patterns and clinical practice, including pediatric mTBI evaluation and management. Providers treating pediatric mTBI, including neuropsychologists, have a unique role in evaluating and managing an already complex injury in the context of the COVID-19 pandemic with limited empirically based guidelines. In the present paper, we review usual, evidence-based pediatric mTBI care, highlight changes experienced by healthcare providers since the onset of the pandemic, and provide possible considerations and solutions. Three primary challenges to usual care are discussed, including changes to post-injury evaluation, management, and treatment of persistent symptoms. Changing patterns of healthcare utilization have created unique differences in mTBI identification and evaluation, including shifting injury frequency and mechanism, reluctance to seek healthcare, and increasing access to telemedicine. Typical injury management has been compromised by limited access to usual systems/activities (i.e., school, sports, social/leisure activities). Patients may be at higher risk for prolonged recovery due to pre-injury baseline elevations in acute and chronic stressors and reduced access to rehabilitative services targeting persistent symptoms. Considerations and solutions for addressing each of the three challenges are discussed. Neuropsychologists and other pediatric healthcare providers will need to continue to flexibly adapt to the changing needs of youth recovering from mTBI through the duration of the pandemic and beyond. Consistent with pre-pandemic consensus statements, neuropsychologists remain uniquely qualified to evaluate and manage mTBI and provide an increasingly integral role as members of multidisciplinary teams in the context of the global pandemic.Abbreviations: AAP: American Academy of Pediatrics; CDC: Centers for Disease Control and Prevention; COVID-19: coronavirus disease 19; ED: emergency department; mTBI: Mild traumatic brain injury.

Diabetic kidney disease (DKD) remains the number one cause of end-stage renal disease in the western world. In experimental diabetes, mitochondrial dysfunction in the kidney precedes the development of DKD. Reactive 1,2-dicarbonyl compounds, such as methylglyoxal, are generated from sugars both endogenously during diabetes and exogenously during food processing. Methylglyoxal is thought to impair the mitochondrial function and may contribute to the pathogenesis of DKD. Here, we sought to target methylglyoxal within the mitochondria using MitoGamide, a mitochondria-targeted dicarbonyl scavenger, in an experimental model of diabetes. Male 6-week-old heterozygous Akita mice (C57BL/6-Ins2-Akita/J) or wildtype littermates were randomized to receive MitoGamide (10 mg/kg/day) or a vehicle by oral gavage for 16 weeks. MitoGamide did not alter the blood glucose control or body composition. Akita mice exhibited hallmarks of DKD including albuminuria, hyperfiltration, glomerulosclerosis, and renal fibrosis, however, after 16 weeks of treatment, MitoGamide did not substantially improve the renal phenotype. Complex-I-linked mitochondrial respiration was increased in the kidney of Akita mice which was unaffected by MitoGamide. Exploratory studies using transcriptomics identified that MitoGamide induced changes to olfactory signaling, immune system, respiratory electron transport, and post-translational protein modification pathways. These findings indicate that targeting methylglyoxal within the mitochondria using MitoGamide is not a valid therapeutic approach for DKD and that other mitochondrial targets or processes upstream should be the focus of therapy.

ImportanceAdult sexual assault (SA) survivors experience numerous emergent health problems, yet few seek emergency medical care. Quantifying the number and types of survivors presenting to US emergency departments (EDs) after SA can inform health care delivery strategies to reduce survivor morbidity and mortality.ObjectiveTo quantify ED use and factors that influenced seeking ED care for adult SA from 2006 through 2019.Design, Setting, and ParticipantsThis cross-sectional study used SA data from the Nationwide Emergency Department Sample from 2006 through 2019, which includes more than 35.8 million observations of US ED visits from 989 hospitals, a 20% stratified sample of hospital-based EDs. The study also used the Federal Bureau of Investigation’s Uniform Crime Reporting Program, which includes annual crime data from more than 18 000 law enforcement agencies representing more than 300 million US inhabitants. The study sample included any adult aged 18 to 65 years with an ED visit in the Nationwide Emergency Department Sample coded as SA. The data were analyzed between January 2020 and June 2022.Main Outcomes and MeasuresAnnual SA-related ED visits, subsequent hospital admissions, and associated patient-related factors (age, sex, race and ethnicity, income quartile, and insurance) were analyzed using descriptive statistics.ResultsData were from 120 to 143 million weighted ED visits reported annually from 2006 through 2019. Sexual assault–related ED visits increased more than 1533.0% from 3607 in 2006 to 55 296 in 2019. Concurrently, admission rates for these visits declined from 12.6% to 4.3%. Female, younger, and lower-income individuals were more likely to present to the ED after SA. Older and Medicaid-insured patients were more likely to be admitted. Overall, the rate of ED visits for SA outpaced law enforcement reporting.Conclusions and RelevanceThis cross-sectional study found that US adult SA ED visits increased from 2006 through 2019 and highlighted the populations who access emergency care most frequently and who more likely need inpatient care. These data can inform policies and the programming needed to support this vulnerable population.

OBJECTIVE The purpose of this review is to describe how health service and delivery systems support health equity and to identify strategies and indicators being used to measure health equity. INTRODUCTION It is widely acknowledged that a population health and equity approach is needed to improve the overall health of the population. The health service and delivery system plays an important role in this approach. Despite this, system transformation to address health inequities has been slow. This is due, in part, to the lack of evidence-based guidance on how health service and delivery systems can address and measure health equity integration. Most studies focus on health equity integration in the public health sector at a provincial or national level, but less is known about integration within the health service and delivery system. More information is needed to understand how that transformation is occurring, or could occur, to make a meaningful contribution toward improving population health outcomes. INCLUSION CRITERIA This scoping review will identify studies that describe the strategies and indicators that health service and delivery systems are using to integrate health equity and how progress is measured. Evidence from qualitative, quantitative, mixed method studies, and gray literature will be included. METHODS This review will be conducted in accordance with JBI methodology for scoping reviews. A comprehensive search strategy, developed with a librarian scientist, will be used to identify relevant sources. Titles, abstracts, and full texts will be evaluated against inclusion criteria. Information will be extracted by two independent reviewers. Data will be synthesized and presented narratively, with tables and figures where appropriate.

Photouncaging delivers compounds with high spatial and temporal control to induce or inhibit biological processes but the released compounds may diffuse out. We here demonstrate that sulfonate anions can be photocaged so that a membrane impermeable compound can enter cells, be uncaged by photoirradiation and trapped within the cell., Photocaged sulfonate delivers membrane impermeant compounds to cells.

Purpose Methylglyoxal, a by-product of glycolysis and a precursor in the formation of advanced glycation end-products, is significantly elevated in the diabetic myocardium. Therefore, we sought to investigate the mitochondria-targeted methylglyoxal scavenger, MitoGamide, in an experimental model of spontaneous diabetic cardiomyopathy. Methods Male 6-week-old Akita or wild type mice received daily oral gavage of MitoGamide or vehicle for 10 weeks. Several morphological and systemic parameters were assessed, as well as cardiac function by echocardiography. Results Akita mice were smaller in size than wild type counterparts in terms of body weight and tibial length. Akita mice exhibited elevated blood glucose and glycated haemoglobin. Total heart and individual ventricles were all smaller in Akita mice. None of the aforementioned parameters was impacted by MitoGamide treatment. Echocardiographic analysis confirmed that cardiac dimensions were smaller in Akita hearts. Diastolic dysfunction was evident in Akita mice, and notably, MitoGamide treatment preferentially improved several of these markers, including e′/a′ ratio and E/e′ ratio. Conclusions Our findings suggest that MitoGamide, a novel mitochondria-targeted approach, offers cardioprotection in experimental diabetes and therefore may offer therapeutic potential for the treatment of cardiomyopathy in patients with diabetes.

During heart transplantation, storage in cold preservation solution is thought to protect the organ by slowing metabolism; by providing osmotic support; and by minimising ischaemia-reperfusion (IR) injury upon transplantation into the recipient1,2. Despite its widespread use our understanding of the metabolic changes prevented by cold storage and how warm ischaemia leads to damage is surprisingly poor. Here, we compare the metabolic changes during warm ischaemia (WI) and cold ischaemia (CI) in hearts from mouse, pig, and human. We identify common metabolic alterations during WI and those affected by CI, thereby elucidating mechanisms underlying the benefits of CI, and how WI causes damage. Succinate accumulation is a major feature within ischaemic hearts across species, and CI slows succinate generation, thereby reducing tissue damage upon reperfusion caused by the production of mitochondrial reactive oxygen species (ROS)3,4. Importantly, the inevitable periods of WI during organ procurement lead to the accumulation of damaging levels of succinate during transplantation, despite cooling organs as rapidly as possible. This damage is ameliorated by metabolic inhibitors that prevent succinate accumulation and oxidation. Our findings suggest how WI and CI contribute to transplant outcome and indicate new therapies for improving the quality of transplanted organs.

Patients with multiple sclerosis (MS) develop a variety of lower urinary tract symptoms (LUTS). We previously characterized a murine model of neurogenic bladder dysfunction induced by a neurotropic strain of a coronavirus. In the present study, we further study the role of long-lasting neurodegeneration on the development of neurogenic bladder dysfunction in mice with corona-virus induced encephalitis (CIE). Long-term follow up study revealed three phenotypes of neurodegenerative symptom development: recovery (REC group), chronic progression (C-PRO group) and chronic disease with relapsing-remitting episodes (C-RELAP group). The levels of IL-1β in REC group, IL-10 in C-RELAP group, and IL-1β, IL-6, IL-10 and TNF-α in C-PRO group were diminished in the brain. The levels of TNF-α in REC group and INF-γ, IL-2, TGF-β and TNF-α in the C-PRO group were also diminished in the urinary bladder. Mice in C-RELAP group showed a delayed recovery of voiding function. In vitro contractility studies determined a decreased basal detrusor tone and reduced amplitude of nerve-mediated contractions in C-RELAP group, whereas C-PRO group had elevated muscle-mediated contractions. In conclusion, mice with CIE developed three phenotypes of neurologic impairment mimicking different types of MS progression in humans and showed differential mechanisms driving neurogenic bladder dysfunction.