Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts

A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (IPC) or remote ischemic conditioning (RIC) on IR injury in isolated rat hearts. Moreover, we aimed to define the optimum timing of initiating hypothermia and evaluate underlying cardioprotective mechanisms. Compared to infarct size in normothermic controls (56 ± 4%), mild hypothermia during the entire or final 20 min of the ischemic period reduced infarct size (34 ± 2%, p < 0.01; 35 ± 5%, p < 0.01, respectively), while no reduction was seen when hypothermia was initiated at reperfusion (51 ± 4%, p = 0.90). In all groups with effect of mild hypothermia, IPC further reduced infarct size. In contrast, we found no additive effect on infarct size between hypothermic controls (20 ± 3%) and the combination of mild hypothermia and RIC (33 ± 4%, p = 0.09). Differences in temporal lactate dehydrogenase release patterns suggested an anti-ischemic effect by mild hypothermia, while IPC and RIC preferentially targeted reperfusion injury. In conclusion, additive underlying mechanisms seem to provide an additive effect of mild hypothermia and IPC, whereas the more clinically applicable RIC does not add cardioprotection beyond mild hypothermia

Translation of experimental cardioprotective capability of P2Y(12) inhibitors into clinical outcome in patients with ST-elevation myocardial infarction

We studied the translational cardioprotective potential of P2Y12 inhibitors against acute myocardial ischemia/reperfusion injury (IRI) in an animal model of acute myocardial infarction and in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). P2Y12 inhibitors may have pleiotropic effects to induce cardioprotection against acute myocardial IRI beyond their inhibitory effects on platelet aggregation. We compared the cardioprotective effects of clopidogrel, prasugrel, and ticagrelor on infarct size in an in vivo rat model of acute myocardial IRI, and investigated the effects of the P2Y12 inhibitors on enzymatic infarct size (48-h area-under-the-curve (AUC) troponin T release) and clinical outcomes in a retrospective study of STEMI patients from the CONDI-2/ERIC-PPCI trial using propensity score analyses. Loading with ticagrelor in rats reduced infarct size after acute myocardial IRI compared to controls (37 ± 11% vs 52 ± 8%, p  0.99 and 49 ± 9%, p > 0.99, respectively). Correspondingly, troponin release was reduced in STEMI patients treated with ticagrelor compared to clopidogrel (adjusted 48-h AUC ratio: 0.67, 95% CI 0.47–0.94). Compared to clopidogrel, the composite endpoint of cardiac death or hospitalization for heart failure within 12 months was reduced in STEMI patients loaded with ticagrelor (HR 0.63; 95% CI 0.42–0.94) but not prasugrel (HR 0.84, 95% CI 0.43–1.63), prior to PPCI. Major adverse cardiovascular events did not differ between clopidogrel, ticagrelor, or prasugrel. The cardioprotective effects of ticagrelor in reducing infarct size may contribute to the clinical benefit observed in STEMI patients undergoing PPCI

Demanding business travel:the evolution of the timespaces of business practice

To date, virtual ways of working have yet to substantially reduce demand for business travel. Emerging research claims that virtual and physical work compliment rather than substitute for one another. This suggests travel demand stems from business strategies and achieving business outcomes. In building on these ideas, this chapter draws upon Schatzki’s conception of timespace to capture changes in how two UK-based global construction and engineering consulting firms organise work and the implications in terms of demand for business travel. Overtime, particular forms of spatially stretched organisation which have developed are found to require the interweaving of timespaces through travel. As such, how each firm has evolved has in turn created the contemporary situation of significant and hard to reduce demand for travel

A cross-sectional study of the relation between symptoms and physical findings in computer operators

BACKGROUND: The character of upper limb disorder in computer operators is subject to debate. A peripheral nerve-involvement is suggested from the common presence of a triad of symptoms consisting of pain, paraestesiae and subjective weakness, and from physical findings suggesting neuropathy. This study aimed to examine the outcome of a detailed neurological examination in computer operators and to compare findings with the presence of symptoms. METHODS: 96 graphical computer operators answered a modified Nordic Questionnaire including information on perceived pain in the shoulder, elbow, and wrist/hand scored for each region on a VAS-scale 0 – 9. In addition, they underwent a physical examination including the subjective assessment of the individual function of 11 upper limb muscles, of algesia in five and vibratory threshold in three territories, respectively, and of mechanosensitivity of nerves at seven locations. In order to reflect an involvement of the brachial plexus (chord level), the posterior interosseous nerve and the median nerve at elbow level we defined three patterns of neurological findings illustrating the course of nerves and their innervation. The pain scores summarized for the three upper limb regions (min. = 0, max = 27) in the mouse-operating and contralateral limbs were compared by a Wilcoxon test and the relation to each physical item analyzed by Kendall's rank correlation. The relation of summarized pain to each pattern was studied by application of a test of the trend across ordered groups (patterns). RESULTS: Pain, paraestesiae and subjective weakness was reported for 67, 23, and 7 mouse-operating limbs, respectively, with the summarized pain scores exceeding 4 in 33 limbs. Abnormal physical findings were prevalent. The summarized pain was significantly related to a reduced function in five muscles, to mechanical allodynia at one location and to elevated threshold to vibration in two territories. Brachial plexopathy was diagnosed in 9/2, median neuropathy in 13/5 and posterior interosseous neuropathy in 13/8 mouse operating/contralateral limbs, respectively. The summarized pain was significantly higher in the mouse-operating limbs and in limbs with any of the defined patterns. There was a significant trend between the summarized pain and the summarized scores for the items contained in each pattern. CONCLUSION: This small-scale study of a group of computer-operators currently in work and with no or minor upper limb symptoms has indicated in symptomatic subjects the presence of peripheral nerve-afflictions with specific locations

Computer work and musculoskeletal disorders of the neck and upper extremity: A systematic review

<p>Abstract</p> <p>Background</p> <p>This review examines the evidence for an association between computer work and neck and upper extremity disorders (except carpal tunnel syndrome).</p> <p>Methods</p> <p>A systematic critical review of studies of computer work and musculoskeletal disorders verified by a physical examination was performed.</p> <p>Results</p> <p>A total of 22 studies (26 articles) fulfilled the inclusion criteria. Results show limited evidence for a causal relationship between computer work per se, computer mouse and keyboard time related to a diagnosis of wrist tendonitis, and for an association between computer mouse time and forearm disorders. Limited evidence was also found for a causal relationship between computer work per se and computer mouse time related to tension neck syndrome, but the evidence for keyboard time was insufficient. Insufficient evidence was found for an association between other musculoskeletal diagnoses of the neck and upper extremities, including shoulder tendonitis and epicondylitis, and any aspect of computer work.</p> <p>Conclusions</p> <p>There is limited epidemiological evidence for an association between aspects of computer work and some of the clinical diagnoses studied. None of the evidence was considered as moderate or strong and there is a need for more and better documentation.</p

Diminishing benefits of urban living for children and adolescents’ growth and development

AbstractOptimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.</jats:p

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining https://researchonline.ljmu.ac.uk/images/research_banner_face_lab_290.jpgunderweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity