High-intensity exercise training using a rotarod instrument (RotaHIIT) significantly improves exercise capacity in mice.

Voluntary or forced exercise training in mice is used to assess functional capacity as well as potential disease-modifying effects of exercise over a range of cardiovascular disease phenotypes. Compared to voluntary wheel running, forced exercise training enables precise control of exercise workload and volume, and results in superior changes in cardiovascular performance. However, the use of a shock grid with treadmill-based training is associated with stress and risk of injury, and declining compliance with longer periods of training time for many mouse strains. With these limitations in mind, we designed a novel, high-intensity interval training modality (HIIT) for mice that is carried out on a rotarod. Abbreviated as RotaHIIT, this protocol establishes interval workload intensities that are not time or resource intensive, maintains excellent training compliance over time, and results in improved exercise capacity independent of sex when measured by treadmill graded exercise testing (GXT) and rotarod specific acceleration and endurance testing. This protocol may therefore be useful and easily implemented for a broad range of research investigations. As RotaHIIT training was not associated cardiac structural or functional changes, or changes in oxidative capacity in cardiac or skeletal muscle tissue, further studies will be needed to define the physiological adaptations and molecular transducers that are driving the training effect of this exercise modality.

Mitral re-valve-in-valve as a new perspective for high-risk patients with prosthetic valve dysfunction: case reports.

Background: Mitral valve diseases are a common medical condition, and surgery is the most used therapeutic approach. The need for less invasive interventions led to the development of transcatheter valve implantation in high-risk patients. However, the treatment to the dysfunctions of these prosthetic valves is still uncertain, and the yield and safety of repeated transcatheter valve implantations remain unclear. Cases summary: A 69-year-old Caucasian woman with three previous mitral valve procedures performed due to rheumatic valve disease (currently with a biological prosthetic mitral valve) and a 76-year-old Latin woman with previous liver transplantation (due to metabolic-associated fatty liver disease) and biological mitral prosthesis due to mitral valve prolapse with severe regurgitation underwent mitral valve-in-valve (ViV) transcatheter implantation at the time of dysfunction of their surgical prostheses. Later, these patients developed prosthetic valve dysfunction and clinical worsening, requiring another invasive procedure. Due to maintained high-risk status and unfavourable clinical conditions for surgery, re-valve-in-valve (re-ViV) was performed. Discussion: Valve-in-valve transcatheter mitral valve implantation was approved in 2017, and, since then, it has been used in several countries, mainly in high-risk patients. Nevertheless, these prosthetic valves may complicate with stenosis or regurgitation, demanding reinterventions. Although there are favourable data for mitral ViV, re-ViV still lacks robust data to support its performance, with only case reports in the literature so far. It is possible that in high-risk patients, there is a greater benefit from re-ViV when compared with the surgical strategy. However, this hypothesis must be studied in future controlled trials.

Early or Late-Life Treatment With Acarbose or Rapamycin Improves Physical Performance and Affects Cardiac Structure in Aging Mice.

Pharmacological treatments can extend the life span of mice. For optimal translation in humans, treatments should improve health during aging, and demonstrate efficacy when started later in life. Acarbose (ACA) and rapamycin (RAP) extend life span in mice when treatment is started early or later in life. Both drugs can also improve some indices of healthy aging, although there has been little systematic study of whether health benefits accrue differently depending on the age at which treatment is started. Here we compare the effects of early (4 months) versus late (16 months) onset ACA or RAP treatment on physical function and cardiac structure in genetically heterogeneous aged mice. ACA or RAP treatment improve rotarod acceleration and endurance capacity compared to controls, with effects that are largely similar in mice starting treatment from early or late in life. Compared to controls, cardiac hypertrophy is reduced by ACA or RAP in both sexes regardless of age at treatment onset. ACA has a greater effect on the cardiac lipidome than RAP, and the effects of early-life treatment are recapitulated by late-life treatment. These results indicate that late-life treatment with these drugs provide at least some of the benefits of life long treatment, although some of the benefits occur only in males, which could lead to sex differences in health outcomes later in life.

[Sensitivity pattern of E. coli at the National Medical Center of Bajío]. / Patrón de sensibilidad de E. coli en el Centro Médico Nacional del Bajío.

Background: Antimicrobial resistance represents a serious public health problem that has caused an increase in the morbidity and mortality of infections, a greater use of antibiotics and excessive hospitalization costs. Objective: To describe the frequency of Escherichia coli and its pattern of bacterial susceptibility in cultures of blood, urine and other body fluids in a tertiary care hospital. Material and methods: A quantitative and retrospective test was designed to evaluate the sensitivity pattern of the data obtained in the Microbiology Department. Descriptive statistics were obtained from the sensitivity patterns of the microorganism studied in the period of time analyzed. Results: The sensitivity pattern of different samples evaluated in the unit (n = 694) was recovered. In the strains analyzed, it was found that about 50% have a positive phenotype for extended-spectrum beta-lactamases and that the sensitivity pattern shows that penicillins, cephalosporins and fluoroquinolones are not adequate antimicrobials to treat infections derived from this microorganism. Conclusions: The antimicrobial pattern obtained demonstrates the imperative need for rational and well-founded use of antibiotic therapy, highlighted by the great difference with reports in other scientific articles. Investment in mechanisms to confirm these patterns is necessary, which is why no expense should be spared for the identification, typification and classification of disease-causing microorganisms.

Introducción: la resistencia antimicrobiana representa un grave problema de salud pública que ha provocado un aumento en la morbimortalidad de las infecciones, un mayor uso de antibióticos y el exceso en gastos de hospitalización. Objetivo: describir la frecuencia de Escherichia coli y su patrón de susceptibilidad bacteriana en cultivos de sangre, orina y de otros fluidos corporales en un hospital de tercer nivel. Material y métodos: se diseñó un ensayo cuantitativo y retrospectivo para evaluar el patrón de sensibilidad de los datos obtenidos en el departamento de microbiología. Mediante estadística descriptiva se obtuvieron los patrones de sensibilidad del microorganismo estudiado en el periodo de tiempo analizado. Resultados: se recuperó el patrón de sensibilidad de diferentes muestras evaluadas en la unidad (n = 694). En las cepas analizadas, se encontró que cerca del 50% poseen un fenotipo positivo para betalactamasas de expectro extendido y que el patrón de sensibilidad demuestra que penicilinas, cefalosporinas y fluoroquinolonas no son antimicrobianos adecuados para tratar infecciones por este microorganismo. Conclusiones: el patrón antimicrobiano obtenido demuestra la imperiosa necesidad del uso racional y fundamentado de la terapia antibiótica puesto de manifiesto por la gran diferencia con los reportes en otros artículos científicos. Es necesaria la inversión en mecanismos para la confirmación de estos patrones, por lo que no debe escatimarse en gastos para la identificación, tipificación y clasificación de microorganismos causantes de enfermedades.

Animal Models of Exercise From Rodents to Pythons.

Acute and chronic animal models of exercise are commonly used in research. Acute exercise testing is used, often in combination with genetic, pharmacological, or other manipulations, to study the impact of these manipulations on the cardiovascular response to exercise and to detect impairments or improvements in cardiovascular function that may not be evident at rest. Chronic exercise conditioning models are used to study the cardiac phenotypic response to regular exercise training and as a platform for discovery of novel pathways mediating cardiovascular benefits conferred by exercise conditioning that could be exploited therapeutically. The cardiovascular benefits of exercise are well established, and, frequently, molecular manipulations that mimic the pathway changes induced by exercise recapitulate at least some of its benefits. This review discusses approaches for assessing cardiovascular function during an acute exercise challenge in rodents, as well as practical and conceptual considerations in the use of common rodent exercise conditioning models. The case for studying feeding in the Burmese python as a model for exercise-like physiological adaptation is also explored.

[Perception of working environment in the Laboratory of the Bajío's National Medical Center]. / Percepción del clima laboral en el Laboratorio del Centro Médico Nacional Bajío.

Background: Since the development of the concepts of organizational climate and working environment, at the beginning of the 20th century, very important advances have been made to improve and increase the quality of professional performance in the health area. Belonging to an emblematic institution in health services, it is necessary to establish how the working environment is perceived within it. Objective: To assess the perception of the working environment in the Clinical Analysis Laboratory of the Centro Médico Nacional del Bajío (Bajío's National Medical Center). Material and methods: The Working Environment Perception And Non-Discrimination Questionnaire was administered and a factorial analysis of variance (ANOVA) was performed to establish the relationship between the answers of the collaborators and the perception of the working environment. Results: The participation of 65 employees showed that in our work center there is a predominance of a positive general perception of the working environment (67%). Conclusions: The perception of the working environment in the Clinical analysis Laboratory is positive. The measurement and weighting of this environment allows the continuous improvement and the prevention and eradication of negative tendencies that violate the integrity of the collaborators.

Introducción: desde el desarrollo de los conceptos de clima organizacional y clima laboral, a principios del siglo XX, se han obtenido avances muy importantes para mejorar e incrementar la calidad del desempeño profesional en el área de la salud. Al pertenecer a una institución emblemática en los servicios de salud, es necesario establecer cómo se percibe el clima laboral dentro de ella. Objetivo: evaluar la percepción de clima laboral en el Laboratorio de Análisis Clínicos del Centro Médico Nacional del Bajío. Material y métodos: se aplicó el Cuestionario de percepción de clima laboral y no discriminación y se realizó la codificación de las variables para establecer el clima laboral en negativo, neutro o positivo, de acuerdo con el cuestionario. Resultados: se contó con la participación de 65 colaboradores, cuyos resultados reflejaron que en el centro de trabajo estudiado predomina una percepción positiva del clima laboral (67%). Conclusiones: la percepción del clima laboral en el Laboratorio de Análisis Clínicos es positiva. La medición y ponderación de este clima permite la mejora continua y la prevención y erradicación de tendencias negativas que vulneran la integridad de los colaboradores.

Acarbose has sex-dependent and -independent effects on age-related physical function, cardiac health, and lipid biology.

With an expanding aging population burdened with comorbidities, there is considerable interest in treatments that optimize health in later life. Acarbose (ACA), a drug used clinically to treat type 2 diabetes mellitus (T2DM), can extend mouse life span with greater effect in males than in females. Using a genetically heterogeneous mouse model, we tested the ability of ACA to ameliorate functional, pathological, and biochemical changes that occur during aging, and we determined which of the effects of age and drug were sex dependent. In both sexes, ACA prevented age-dependent loss of body mass, in addition to improving balance/coordination on an accelerating rotarod, rotarod endurance, and grip strength test. Age-related cardiac hypertrophy was seen only in male mice, and this male-specific aging effect was attenuated by ACA. ACA-sensitive cardiac changes were associated with reduced activation of cardiac growth-promoting pathways and increased abundance of peroxisomal proteins involved in lipid metabolism. ACA further ameliorated age-associated changes in cardiac lipid species, particularly lysophospholipids - changes that have previously been associated with aging, cardiac dysfunction, and cardiovascular disease in humans. In the liver, ACA had pronounced effects on lipid handling in both sexes, reducing hepatic lipidosis during aging and shifting the liver lipidome in adulthood, particularly favoring reduced triglyceride (TAG) accumulation. Our results demonstrate that ACA, already in clinical use for T2DM, has broad-ranging antiaging effects in multiple tissues, and it may have the potential to increase physical function and alter lipid biology to preserve or improve health at older ages.

Determining the primary sources of fecal pollution using microbial source tracking assays combined with land-use information in the Edwards Aquifer.

The Edwards Aquifer serves as a primary source of drinking water to more than 2 million people in south-central Texas, and as a karst aquifer, is vulnerable to human and animal fecal contamination which poses a serious risk to human and environmental health. A one-year study (Jan 2018 - Feb 2019) was conducted to determine the primary sources of fecal pollution along the Balcones and Leon Creek within the Edwards Aquifer recharge and contributing zones using general (E. coli, enterococci, and universal Bacteriodales) and host-associated (human-, dog-, cow- and chicken/duck-associated Bacteriodales) microbial source tracking (MST) assays. Additionally, sites were classified based on surrounding land use as a potential source predictor and marker levels were correlated with rain events and water quality parameters. Levels for the three general indicators were highest and exhibited similar trends across the sampling sites, suggesting that the sole use of these markers is not sufficient for specific fecal source identification. Among the host-associated markers, highest concentrations were observed for the dog marker (BacCan) in the Leon Creek area and the cow marker (BacCow) in the Balcones Creek area. Additionally, Chicken/Duck-Bac, BacCan and BacCow all exhibited higher concentrations during the spring season and the end of fall/early winter. Relatively lower concentrations were observed for the human-associated markers (HF183 and BacHum), however, levels were higher in the Leon Creek area and highest following rainfall events. Additionally, relatively higher levels in HF183 and BacHum were observed at sites having greater human population and septic tank density and may be attributed to leaks or breaks in these infrastructures. This study is the first to examine and compare fecal contamination at rural and urban areas in the recharge and contributing zones of the Edwards Aquifer using a molecular MST approach targeting Bacteroidales 16S rRNA gene-based assays. The Bacteroidales marker assays, when combined with land use and weather information, can allow for a better understanding of the sources and fluxes of fecal contamination, which can help devise effective mitigation measures to protect water quality.

17-α estradiol ameliorates age-associated sarcopenia and improves late-life physical function in male mice but not in females or castrated males.

Pharmacological treatments can extend mouse lifespan, but lifespan effects often differ between sexes. 17-α estradiol (17aE2), a less feminizing structural isomer of 17-ß estradiol, produces lifespan extension only in male mice, suggesting a sexually dimorphic mechanism of lifespan regulation. We tested whether these anti-aging effects extend to anatomical and functional aging-important in late-life health-and whether gonadally derived hormones control aging responses to 17aE2 in either sex. While 17aE2 started at 4 months of age diminishes body weight in both sexes during adulthood, in late-life 17aE2-treated mice better maintain body weight. In 17aE2-treated male mice, the higher body weight is associated with heavier skeletal muscles and larger muscle fibers compared with untreated mice during aging, while treated females have heavier subcutaneous fat. Maintenance of skeletal muscle in male mice is associated with improved grip strength and rotarod capacity at 25 months, in addition to higher levels of most amino acids in quadriceps muscle. We further show that sex-specific responses to 17aE2-metabolomic, structural, and functional-are regulated by gonadal hormones in male mice. Castrated males have heavier quadriceps than intact males at 25 months, but do not respond to 17aE2, suggesting 17aE2 promotes an anti-aging skeletal muscle phenotype similar to castration. Finally, 17aE2 treatment benefits can be recapitulated in mice when treatment is started at 16 months, suggesting that 17aE2 may be able to improve aspects of late-life function even when started after middle age.

Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy: A Randomized Clinical Trial.

Importance: Formulating exercise recommendations for patients with hypertrophic cardiomyopathy is challenging because of concern about triggering ventricular arrhythmias and because a clinical benefit has not been previously established in this population. Objective: To determine whether moderate-intensity exercise training improves exercise capacity in adults with hypertrophic cardiomyopathy. Design, Setting, and Participants: A randomized clinical trial involving 136 patients with hypertrophic cardiomyopathy was conducted between April 2010 and October 2015 at 2 academic medical centers in the United States (University of Michigan Health System and Stanford University Medical Center). Date of last follow-up was November 2016. Interventions: Participants were randomly assigned to 16 weeks of moderate-intensity exercise training (n = 67) or usual activity (n = 69). Main Outcomes and Measures: The primary outcome measure was change in peak oxygen consumption from baseline to 16 weeks. Results: Among the 136 randomized participants (mean age, 50.4 [SD, 13.3] years; 42% women), 113 (83%) completed the study. At 16 weeks, the change in mean peak oxygen consumption was +1.35 (95% CI, 0.50 to 2.21) mL/kg/min among participants in the exercise training group and +0.08 (95% CI, -0.62 to 0.79) mL/kg/min among participants in the usual-activity group (between-group difference, 1.27 [95% CI, 0.17 to 2.37]; P = .02). There were no occurrences of sustained ventricular arrhythmia, sudden cardiac arrest, appropriate defibrillator shock, or death in either group. Conclusions and Relevance: In this preliminary study involving patients with hypertrophic cardiomyopathy, moderate-intensity exercise compared with usual activity resulted in a statistically significant but small increase in exercise capacity at 16 weeks. Further research is needed to understand the clinical importance of this finding in patients with hypertrophic cardiomyopathy, as well as the long-term safety of exercise at moderate and higher levels of intensity. Trial Registration: clinicaltrials.gov Identifier: NCT01127061.

Interleukin 37 reverses the metabolic cost of inflammation, increases oxidative respiration, and improves exercise tolerance.

IL-1 family member interleukin 37 (IL-37) has broad antiinflammatory properties and functions as a natural suppressor of innate inflammation. In this study, we demonstrate that treatment with recombinant human IL-37 reverses the decrease in exercise performance observed during systemic inflammation. This effect was associated with a decrease in the levels of plasma and muscle cytokines, comparable in extent to that obtained upon IL-1 receptor blockade. Exogenous administration of IL-37 to healthy mice, not subjected to an inflammatory challenge, also improved exercise performance by 82% compared with vehicle-treated mice (P = 0.01). Treatment with eight daily doses of IL-37 resulted in a further 326% increase in endurance running time compared with the performance level of mice receiving vehicle (P = 0.001). These properties required the engagement of the IL-1 decoy receptor 8 (IL-1R8) and the activation of AMP-activated protein kinase (AMPK), because both inhibition of AMPK and IL-1R8 deficiency abrogated the positive effects of IL-37 on exercise performance. Mechanistically, treatment with IL-37 induced marked metabolic changes with higher levels of muscle AMPK, greater rates of oxygen consumption, and increased oxidative phosphorylation. Metabolomic analyses of plasma and muscles of mice treated with IL-37 revealed an increase in AMP/ATP ratio, reduced levels of proinflammatory mediator succinate and oxidative stress-related metabolites, as well as changes in amino acid and purine metabolism. These effects of IL-37 to limit the metabolic costs of chronic inflammation and to foster exercise tolerance provide a rationale for therapeutic use of IL-37 in the treatment of inflammation-mediated fatigue.

Neurochemical and behavioural indices of exercise reward are independent of exercise controllability.

Brain reward circuits are implicated in stress-related psychiatric disorders. Exercise reduces the incidence of stress-related disorders, but the contribution of exercise reward to stress resistance is unknown. Exercise-induced stress resistance is independent of exercise controllability; both voluntary running (VR) and forced running (FR) protect rats against the anxiety-like and depression-like behavioural consequences of stress. Voluntary exercise is a natural reward, but whether rats find FR rewarding is unknown. Moreover, the contribution of dopamine (DA) and striatal reward circuits to exercise reward is not well characterized. Adult, male rats were assigned to locked wheels, VR, or FR groups. FR rats were forced to run in a pattern resembling the natural wheel running behavior of rats. Both VR and FR increased the reward-related plasticity marker ΔFosB in the dorsal striatum and nucleus accumbens, and increased the activity of DA neurons in the lateral ventral tegmental area, as revealed by immunohistochemistry for tyrosine hydroxylase and pCREB. Both VR and FR rats developed conditioned place preference (CPP) to the side of a CPP chamber paired with exercise. Re-exposure to the exercise-paired side of the CPP chamber elicited conditioned increases in cfos mRNA in direct-pathway (dynorphin-positive) neurons in the dorsal striatum and nucleus accumbens in both VR and FR rats, and in tyrosine hydroxylase-positive neurons in the lateral ventral tegmental area of VR rats only. The results suggest that the rewarding effects of exercise are independent of exercise controllability and provide insight into the DA and striatal circuitries involved in exercise reward and exercise-induced stress resistance.

Exercise is More Effective at Altering Gut Microbial Composition and Producing Stable Changes in Lean Mass in Juvenile versus Adult Male F344 Rats.

The mammalian intestine harbors a complex microbial ecosystem that influences many aspects of host physiology. Exposure to specific microbes early in development affects host metabolism, immune function, and behavior across the lifespan. Just as the physiology of the developing organism undergoes a period of plasticity, the developing microbial ecosystem is characterized by instability and may also be more sensitive to change. Early life thus presents a window of opportunity for manipulations that produce adaptive changes in microbial composition. Recent insights have revealed that increasing physical activity can increase the abundance of beneficial microbial species. We therefore investigated whether six weeks of wheel running initiated in the juvenile period (postnatal day 24) would produce more robust and stable changes in microbial communities versus exercise initiated in adulthood (postnatal day 70) in male F344 rats. 16S rRNA gene sequencing was used to characterize the microbial composition of juvenile versus adult runners and their sedentary counterparts across multiple time points during exercise and following exercise cessation. Alpha diversity measures revealed that the microbial communities of young runners were less even and diverse, a community structure that reflects volatility and malleability. Juvenile onset exercise altered several phyla and, notably, increased Bacteroidetes and decreased Firmicutes, a configuration associated with leanness. At the genus level of taxonomy, exercise altered more genera in juveniles than in the adults and produced patterns associated with adaptive metabolic consequences. Given the potential of these changes to contribute to a lean phenotype, we examined body composition in juvenile versus adult runners. Interestingly, exercise produced persistent increases in lean body mass in juvenile but not adult runners. Taken together, these results indicate that the impact of exercise on gut microbiota composition as well as body composition may depend on the developmental stage during which exercise is initiated.

An ontology for microbial phenotypes.

BACKGROUND: Phenotypic data are routinely used to elucidate gene function in organisms amenable to genetic manipulation. However, previous to this work, there was no generalizable system in place for the structured storage and retrieval of phenotypic information for bacteria. RESULTS: The Ontology of Microbial Phenotypes (OMP) has been created to standardize the capture of such phenotypic information from microbes. OMP has been built on the foundations of the Basic Formal Ontology and the Phenotype and Trait Ontology. Terms have logical definitions that can facilitate computational searching of phenotypes and their associated genes. OMP can be accessed via a wiki page as well as downloaded from SourceForge. Initial annotations with OMP are being made for Escherichia coli using a wiki-based annotation capture system. New OMP terms are being concurrently developed as annotation proceeds. CONCLUSIONS: We anticipate that diverse groups studying microbial genetics and associated phenotypes will employ OMP for standardizing microbial phenotype annotation, much as the Gene Ontology has standardized gene product annotation. The resulting OMP resource and associated annotations will facilitate prediction of phenotypes for unknown genes and result in new experimental characterization of phenotypes and functions.

Wheel running alters patterns of uncontrollable stress-induced cfos mRNA expression in rat dorsal striatum direct and indirect pathways: A possible role for plasticity in adenosine receptors.

Emerging evidence indicates that adenosine is a major regulator of striatum activity, in part, through the antagonistic modulation of dopaminergic function. Exercise can influence adenosine and dopamine activity, which may subsequently promote plasticity in striatum adenosine and dopamine systems. Such changes could alter activity of medium spiny neurons and impact striatum function. The purpose of this study was twofold. The first was to characterize the effect of long-term wheel running on adenosine 1 (A1R), adenosine 2A (A2AR), dopamine 1 (D1R), and dopamine 2 (D2R) receptor mRNA expression in adult rat dorsal and ventral striatum structures using in situ hybridization. The second was to determine if changes to adenosine and dopamine receptor mRNA from running are associated with altered cfos mRNA induction in dynorphin- (direct pathway) and enkephalin- (indirect pathway) expressing neurons of the dorsal striatum following stress exposure. We report that chronic running, as well as acute uncontrollable stress, reduced A1R and A2AR mRNA levels in the dorsal and ventral striatum. Running also modestly elevated D2R mRNA levels in striatum regions. Finally, stress-induced cfos was potentiated in dynorphin and attenuated in enkephalin expressing neurons of running rats. These data suggest striatum adenosine and dopamine systems are targets for neuroplasticity from exercise, which may contribute to changes in direct and indirect pathway activity. These findings may have implications for striatum mediated motor and cognitive processes, as well as exercise facilitated stress-resistance.