Long-term health care costs following COVID-19: implications for pandemic preparedness.

OBJECTIVES: To estimate excess health care costs in the 12 months following COVID-19 diagnosis. STUDY DESIGN: Retrospective cohort study using Blue Cross Blue Shield of Rhode Island claims incurred from January 1, 2019, to March 31, 2022, among commercial and Medicare Advantage members. METHODS: Difference-in-differences analyses were used to compare changes in health care spend between the 12 months before (baseline period) and the 12 months after (post period) COVID-19 diagnosis for COVID-19 cases and contemporaneous matched controls without COVID-19. RESULTS: Overall, there were 7224 commercial and 1630 Medicare Advantage members with a COVID-19 diagnosis on/before March 31, 2021, each with a matched control, yielding a sample of 14,448 commercial and 3260 Medicare Advantage members. Among commercial members, 51.9% were aged 25 to 54 years and 54.0% were female. Among Medicare Advantage members, 94.2% were 65 years or older and 62.0% were female. Among commercial members, from the baseline period to the post period, total health care spend increased $41.61 (7.7%) per member per month (PMPM) more among COVID-19 cases compared with their matched controls. Among Medicare Advantage members, the difference-in-differences was greater, with spend increasing $97.30 (13.1%) PMPM more among cases compared with controls. The difference-in-differences was greatest for outpatient and professional services (both populations) and prescription services (Medicare Advantage only). CONCLUSIONS: COVID-19 diagnosis was associated with excess health care spend PMPM over the subsequent 12 months, highlighting the importance of societal preparations to support individuals' long-term health care needs following COVID-19 and as a part of future pandemic preparedness.

Emotional intelligence: Its place in infection prevention and control.

Background: The Infection Prevention Societies Competency Framework is a detailed tool that recognises the multi factorial work of Infection Prevention and Control Teams. This work often takes place in complex, chaotic and busy environments where non-compliance with policies, procedures and guidelines is endemic. As reductions in Healthcare Associated Infection became a health service priority the tone of Infection Prevention and Control (IPC) became increasingly uncompromising and punitive. This can create conflict between IPC professionals and clinicians who may take a different view as to the reasons for sub optimum practice. If unresolved, this can create a tension that has a negative impact on working relationships and ultimately patient outcomes. Concepts and Context: Emotional Intelligence, that ability to recognise, understand and manage our own emotions and recognise, understand and influence the emotions of others, is not something, hitherto, that has been headlined as an attribute for individuals working in IPC. Individuals with higher level of Emotional Intelligence show a greater capacity for learning, deal with pressure more effectively, communicate in interesting and assertive ways and recognise the strengths and weaknesses of others. Overall, the trend is that they are more productive and satisfied in the workplace. Conclusion: Emotional Intelligence should be a much sought after trait in IPC as this will better equip a post holder to deliver challenging IPC programmes. When appointing to an IPC team, the candidates Emotional Intelligence should be considered and then developed through a process of education and reflection.

On the interdependence of ketone body oxidation, glycogen content, glycolysis and energy metabolism in the heart.

In heart, glucose and glycolysis are important for anaplerosis and potentially therefore for d-ß-hydroxybutyrate (ßHB) oxidation. As a glucose store, glycogen may also furnish anaplerosis. We determined the effects of glycogen content on ßHB oxidation and glycolytic rates, and their downstream effects on energetics, in the isolated rat heart. High glycogen (HG) and low glycogen (LG) containing hearts were perfused with 11 mM [5-3 H]glucose and/or 4 mM [14 C]ßHB to measure glycolytic rates or ßHB oxidation, respectively, then freeze-clamped for glycogen and metabolomic analyses. Free cytosolic [NAD+ ]/[NADH] and mitochondrial [Q+ ]/[QH2 ] ratios were estimated using the lactate dehydrogenase and succinate dehydrogenase reaction, respectively. Phosphocreatine (PCr) and inorganic phosphate (Pi ) concentrations were measured using 31 P-nuclear magnetic resonance spectroscopy. Rates of ßHB oxidation in LG hearts were half that in HG hearts, with ßHB oxidation directly proportional to glycogen content. ßHB oxidation decreased glycolysis in all hearts. Glycogenolysis in glycogen-replete hearts perfused with ßHB alone was twice that of hearts perfused with ßHB and glucose, which had significantly higher levels of the glycolytic intermediates fructose 1,6-bisphosphate and 3-phosphoglycerate, and higher free cytosolic [NAD+ ]/[NADH]. ßHB oxidation increased the Krebs cycle intermediates citrate, 2-oxoglutarate and succinate, the total NADP/H pool, reduced mitochondrial [Q+ ]/[QH2 ], and increased the calculated free energy of ATP hydrolysis (∆GATP ). Although ßHB oxidation inhibited glycolysis, glycolytic intermediates were not depleted, and cytosolic free NAD remained oxidised. ßHB oxidation alone increased Krebs cycle intermediates, reduced mitochondrial Q and increased ∆GATP . We conclude that glycogen facilitates cardiac ßHB oxidation by anaplerosis. KEY POINTS: Ketone bodies (d-ß-hydroxybutyrate, acetoacetate) are increasingly recognised as important cardiac energetic substrates, in both healthy and diseased hearts. As 2-carbon equivalents they are cataplerotic, causing depletion of Krebs cycle intermediates; therefore their utilisation requires anaplerotic supplementation, and intra-myocardial glycogen has been suggested as a potential anaplerotic source during ketone oxidation. It is demonstrated here that cardiac glycogen does indeed provide anaplerotic substrate to facilitate ß-hydroxybutyrate oxidation in isolated perfused rat heart, and this contribution was quantified using a novel pulse-chase metabolic approach. Further, using metabolomics and 31 P-MR, it was shown that glycolytic flux from myocardial glycogen increased the heart's ability to oxidise ßHB, and ßHB oxidation increased the mitochondrial redox potential, ultimately increasing the free energy of ATP hydrolysis.

Copy rats: Learning by observation during a foraging task by rats.

In two experiments, rats observed expert foragers in a laboratory foraging task. In both experiments, 12 towers with a food cup on top of each tower were placed in a circle. Six towers, marked with black and white stripes, had cups baited with cheese, and were located in randomly selected positions on successive trials. The other six towers were white with food cups that were sham baited with inaccessible food. In both experiments, during Phase 1, demonstrator rats eventually learned to find the baited towers, making approximately 90% correct choices in their first six choices. In Phase 2, observer rats each had an opportunity to observe, from a cage located inside the circle of towers, a now-expert demonstrator forage. Half of the observers were able to observe a cage mate, whereas the other half of the observers were able to observe a non-cage mate. After a delay of about 2 min (Experiment 1) or about 24 h (Experiment 2), the observers were allowed to forage among the rebaited towers. In both experiments, the observers performed better during their 20 Phase 2 trials than the demonstrators had performed during their first 20 Phase 1 trials. But, in both experiments, there was no clearly significant difference between the performance of observers able to watch cage mates as opposed to non-cage mates. Because the observational effect seen in both experiments survived a 24-h delay between observation and performance, it was deemed to have been based on learning.

Footwear characteristics and foot problems in community dwelling people with stroke: a cross-sectional observational study.

PURPOSE: To explore footwear characteristics and foot problems in community dwelling people with stroke as most research to date focused on the general elderly population. METHODS: Thirty people with mild to moderate stroke (nine men, mean age 68, mean time since onset 67 months) attended a single session to assess footwear and foot problems using established podiatry foot (wear) and ankle assessments. RESULTS: Most participants wore slippers indoors (n = 17, 57%) and walking shoes outdoors (n = 11, 37%). Over half wore unsupportive ill-fitting shoes indoors and 47% of outdoor shoes fitted badly. All participants had foot problems (mean 6.5 (3.1), 95% CI: 5.4-7.7), including impaired single limb heel raise (93%), reduced range of movement (77%), sensation (47%), and muscle strength (43%). Many had foot-pain, hallux valgus (both 50%), or swollen feet (40%). Foot problems were associated with reduced balance confidence, activity, and community participation (all p < 0.05). A greater proportion of fallers (13/16) than non-fallers (4/14) reported foot problems (p = 0.029). CONCLUSIONS: Many community-dwelling people with stroke wore poorly fitting shoes; all had foot problems. Foot problems were linked to reduced mobility. Finding more effective pathways to support people with stroke to select supportive, well-fitting indoor and outdoor footwear is indicated.Implications for rehabilitationPeople with stroke often wear unsupportive ill-fitting shoes and experience foot problems.Assessment of foot problems and footwear advice should be considered during stroke rehabilitation particularly when interventions target fall prevention or improvements in balance and mobility.Information on appropriate footwear and signposting that new shoe purchases should include measuring feet to ensure a good fit is recommended.

Potential role for pyruvate kinase M2 in the regulation of murine cardiac glycolytic flux during in vivo chronic hypoxia.

Carbohydrate metabolism in heart failure shares similarities to that following hypoxic exposure, and is thought to maintain energy homoeostasis in the face of reduced O2 availability. As part of these in vivo adaptations during sustained hypoxia, the heart up-regulates and maintains a high glycolytic flux, but the underlying mechanism is still elusive. We followed the cardiac glycolytic responses to a chronic hypoxic (CH) intervention using [5-3H]-glucose labelling in combination with detailed and extensive enzymatic and metabolomic approaches to provide evidence of the underlying mechanism that allows heart survivability. Following 3 weeks of in vivo hypoxia (11% oxygen), murine hearts were isolated and perfused in a retrograde mode with function measured via an intraventricular balloon and glycolytic flux quantified using [5-3H]-glucose labelling. At the end of perfusion, hearts were flash-frozen and central carbon intermediates determined via liquid chromatography tandem mass spectrometry (LC-MS/MS). The maximal activity of glycolytic enzymes considered rate-limiting was assessed enzymatically, and protein abundance was determined using Western blotting. Relative to normoxic hearts, CH increased ex vivo cardiac glycolytic flux 1.7-fold with no effect on cardiac function. CH up-regulated cardiac pyruvate kinase (PK) flux 3.1-fold and cardiac pyruvate kinase muscle isoenzyme M2 (PKM2) protein content 1.4-fold compared with normoxic hearts. CH also augmented cardiac pentose phosphate pathway (PPP) flux, reflected by higher ribose-5-phosphate (R5P) content. These findings support an increase in the covalent (protein expression) and allosteric (flux) control of PKM2 as being central to the sustained up-regulation of the glycolytic flux in the chronically hypoxic heart.

The use of military planning techniques to manage outbreaks of novel infections in acute inpatient settings: development of an 'infection control estimate' (ICE).

Outbreaks of infection create unique challenges to healthcare leaders and members of infection control teams who lead efforts to manage, control and resolve outbreaks. This is especially true during outbreaks of novel pathogens which may require atypical control methods reflecting the unknowns inherent in such situations. Healthcare providers within the UK have adopted various structures and models of infection prevention and control (IPC) service reflecting the individual needs of different organisations. As such, the roles and responsibilities of IPC practitioners vary between organisations. Variations in models of care combined with challenges created by outbreaks of novel infections may make algorithm based approaches to outbreak management less effective and potentially prone to missing key actions or considerations which may improve outcomes. Here we suggest the application of a widely established military planning technique, developed to aid decision making in combat environments, to the management of outbreaks of novel infection in acute hospital settings. The technique can be applied at all levels within an IPC hierarchy regardless of role or responsibility and may improve the coherency and efficacy of outbreak management efforts made by IPC teams. The technique may also be applied to outbreaks of known infections; however, in order to demonstrate the flexibility of the model, a novel infection has been used to illustrate its potential value in outbreak management when knowledge is limited.

Recognition and management of sepsis: the nurse's role.

Caring for a patient with suspected sepsis is a challenging nursing role. Early recognition and appropriate management of a patient with sepsis saves lives. Nurses play a fundamental role in detecting changes in physiological observations that could indicate the onset of sepsis. Additionally, an awareness of the pathophysiology of sepsis allows the nurse to better understand how rapid intervention prevents the onset of septic shock. Furthermore, knowledge and use of clinical guidelines and sepsis screening tools are established methods to help reduce patient mortality. Nurse familiarity with 'red flag' criteria for sepsis and thorough completion of early warning scores facilitate earlier recognition and time critical intervention. Delivery of the 'sepsis six' within 1 hour of suspected sepsis saves lives.

The trouble with footwear following stroke: a qualitative study of the views and experience of people with stroke.

Purpose: Foot problems and suboptimal footwear are risk factors for falls among the elderly. Footwear choice may, therefore, be important for people with balance impairment following stroke, but little is known about their experience. This study explored foot problems experienced following stroke, factors influencing footwear choices and views of footwear in use.Methods: Semi-structured interviews with 15 people with stroke, purposively sampled from respondents to a screening survey.Results: Participants typically experienced impaired mobility with balance problems and felt at risk of falling. Stroke related foot problems, including altered sensation, edema, and foot drop, predominantly on the stroke affected side, influenced footwear priorities. Footwear choices prioritized comfort, security, and convenience, sometimes in tension with concern about appearance. Challenges included choosing appropriate indoor footwear and finding shoes to accommodate their orthoses and edema. Participants highlighted perceived lack of footwear advice from health care professionals and variable experience of shoe shopping.Conclusions: Foot problems, as well as gait and balance impairment, have implications for footwear priorities following stroke, but people felt unsupported in making healthy footwear choices. Health care professionals could be trained to routinely deliver footwear assessment and advice and facilitate referrals to podiatrist, when appropriate.Implications for rehabilitationFoot problems, as well as gait and balance impairment, have implications for footwear priorities following stroke.People with stroke perceive a lack of professional advice about footwear and feel unsupported making healthy footwear choices.Health care professionals could be trained to routinely deliver an initial footwear assessment and advice as part of stroke rehabilitation.A greater transparency and knowledge of referral pathways into podiatry services for Health care professionals and patients would give access to specialist advice where appropriate.

Organ donation: reducing the risk of health care-associated infection.

Health care-associated infection is a real and relative risk within the realm of organ donation. Despite detailed guidance from the Advisory Committee on the Safety of Blood, Tissues and Organs on the microbiological safety of human organs, tissues and cells used in transplantation, the topic has received limited exposure in the literature. This paper will give a context to the Safety of Blood, Tissues and Organs guidance, outline the key recommendations for mandatory/recommended screening and provide a summary of infections that may be present at the time of donation that require careful risk assessment. This does not detract from national guidelines and cannot replace expert advice but will raise awareness and complement safe and effective care delivery.

Domesticated dogs (Canis familiaris) tend to follow repeated deceptive human cues even when food is visible.

There is abundant evidence that domestic dogs (Canis familiaris) readily follow pointing and other cues given by humans. But there has been much less research into the question of whether dogs can learn to discriminate between different humans giving repeated honest or dishonest cues as to food location, by ignoring the information imparted by the deceiver. Prior research has demonstrated that even after repeated exposures to deceptive cues with respect to food location, dogs failed to learn to ignore those cues completely. Kundey, De Los Reyes, Arbuthnot, Coshun, Molina, and Royer (2010) found the same outcome in a similar experiment. The purpose of the current experiment was to determine if dogs could learn to discriminate between an honest and a deceptive human by ignoring the deceiver's cues even when it was obvious that the container being pointed at was not baited by using two transparent containers. Eight dogs were tested. On 20 cooperator trials, the experimenter stood behind the baited container and cued the dog, located midway between the containers and 3 m away, to approach it. On 20 deceiver trials, a different experimenter stood behind the empty container and cued the dog to approach that container. Results replicated prior research in that, even though the containers were transparent, the dogs failed to learn to distrust the deceiver completely and went to the empty and indicated container on more than half of the deceiver trials.

Increasing cardiac pyruvate dehydrogenase flux during chronic hypoxia improves acute hypoxic tolerance.

KEY POINTS: The cardiac metabolic reprogramming seen in heart diseases such as myocardial infarction and hypertrophy shares similarities with that seen in chronic hypoxia, but understanding of how the hypoxic heart responds to further hypoxic challenge - hypoxic tolerance - is limited. The pyruvate dehydrogenase complex serves to control irreversible decarboxylation of pyruvate within mitochondria, and is a key regulator of substrate metabolism, potentially regulating hypoxic tolerance. Acute activation of the pyruvate dehydrogenase complex did not improve cardiac function during acute hypoxia; however, simultaneous activation of the pyruvate dehydrogenase complex during chronic hypoxic exposure improved tolerance to subsequent acute hypoxia. Activation of the pyruvate dehydrogenase complex during chronic hypoxia stockpiled cardiac acetylcarnitine, and this was used during acute hypoxia. This maintained cardiac ATP and glycogen, and improved hypoxic tolerance as a result. These findings demonstrate that pyruvate dehydrogenase complex activation can improve cardiac function under hypoxia. ABSTRACT: The pattern of metabolic reprogramming in chronic hypoxia shares similarities with that following myocardial infarction or hypertrophy; however, the response of the chronically hypoxic heart to subsequent acute injury, and the role of metabolism is not well understood. Here, we determined the myocardial tolerance of the chronically hypoxic heart to subsequent acute injury, and hypothesised that activation of a key regulator of myocardial metabolism, the pyruvate dehydrogenase complex (PDC), could improve hypoxic tolerance. Mouse hearts, perfused in Langendorff mode, were exposed to 30 min of hypoxia, and lost 80% of pre-hypoxic function (P = 0.001), with only 51% recovery of pre-hypoxic function with 30 min of reoxygenation (P = 0.046). Activation of the PDC with infusion of 1 mm dichloroacetate (DCA) during hypoxia and reoxygenation did not alter function. Acute hypoxic tolerance was assessed in hearts of mice housed in hypoxia for 3 weeks. Chronic hypoxia reduced cardiac tolerance to subsequent acute hypoxia, with recovery of function 22% of pre-acute hypoxic levels vs. 39% in normoxic control hearts (P = 0.012). DCA feeding in chronic hypoxia (per os, 70 mg kg-1  day-1 ) doubled cardiac acetylcarnitine content, and this fell following acute hypoxia. This acetylcarnitine use maintained cardiac ATP and glycogen content during acute hypoxia, with hypoxic tolerance normalised. In summary, chronic hypoxia renders the heart more susceptible to acute hypoxic injury, which can be improved by activation of the PDC and pooling of acetylcarnitine. This is the first study showing functional improvement of the chronically hypoxic heart with activation of the PDC, and offers therapeutic potential in cardiac disease with a hypoxic component.

A survey exploring self-reported indoor and outdoor footwear habits, foot problems and fall status in people with stroke and Parkinson's.

BACKGROUND: Ill-fitting shoes have been implicated as a risk factor for falls but research to date has focused on people with arthritis, diabetes and the general older population; little is known about people with neurological conditions. This survey for people with stroke and Parkinson's explored people's choice of indoor and outdoor footwear, foot problems and fall history. METHODS: Following ethical approval, 1000 anonymous postal questionnaires were distributed to health professionals, leads of Parkinson's UK groups and stroke clubs in the wider Southampton area, UK. These collaborators handed out survey packs to people with a confirmed diagnosis of stroke or Parkinson's. RESULTS: Three hundred and sixty three completed surveys were returned (218 from people with Parkinson's and 145 from people with stroke). Most respondents wore slippers indoors and walking shoes outdoors and considered comfort and fit the most important factors when buying footwear. Foot problems were reported by 43 % (95 % confidence intervals 36 to 52 %; stroke) and 53 % (95 % confidence interval 46 to 59 %; Parkinson's) of respondents; over 50 % had never accessed foot care support. Fifty percent of all respondents reported falls. In comparison to non-fallers, a greater proportion of fallers reported foot problems (57 %), with greater proportions reporting problems impacting on balance and influencing choice of footwear (p < 0.01) in comparison to non-fallers in each case. Forty-seven percent of fallers with foot problems had not accessed foot care support. CONCLUSIONS: Many people with stroke and Parkinson's wear slippers indoors. A high percentage of these individuals reported both foot problems and falls impacting on footwear habits and choice of footwear; however many did not receive foot care support. These findings highlight that further exploration of footwear and foot problems in these populations is warranted to provide evidence based advice on safe and appropriate footwear to support rehabilitation and fall prevention.

Novel ketone diet enhances physical and cognitive performance.

Ketone bodies are the most energy-efficient fuel and yield more ATP per mole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, low-carbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson's disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)-3-hydroxybutyl (R)-3-hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a treadmill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palm oil (P < 0.05). Ketone-fed rats completed an 8-arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P < 0.05). Isolated, perfused hearts from rats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [31P]-NMR spectroscopy. The novel ketone diet, therefore, improved physical performance and cognitive function in rats, and its energy-sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.-Murray, A. J., Knight, N. S., Cole, M. A., Cochlin, L. E., Carter, E., Tchabanenko, K., Pichulik, T., Gulston, M. K., Atherton, H. J., Schroeder, M. A., Deacon, R. M. J., Kashiwaya, Y., King, M. T., Pawlosky, R., Rawlins, J. N. P., Tyler, D. J., Griffin, J. L., Robertson, J., Veech, R. L., Clarke, K. Novel ketone diet enhances physical and cognitive performance.

The von Hippel-Lindau Chuvash mutation in mice alters cardiac substrate and high-energy phosphate metabolism.

Hypoxia-inducible factor (HIF) appears to function as a global master regulator of cellular and systemic responses to hypoxia. HIF pathway manipulation is of therapeutic interest; however, global systemic upregulation of HIF may have as yet unknown effects on multiple processes. We used a mouse model of Chuvash polycythemia (CP), a rare genetic disorder that modestly increases expression of HIF target genes in normoxia, to understand what these effects might be within the heart. An integrated in and ex vivo approach was employed. Compared with wild-type controls, CP mice had evidence (using in vivo magnetic resonance imaging) of pulmonary hypertension, right ventricular hypertrophy, and increased left ventricular ejection fraction. Glycolytic flux (measured using [(3)H]glucose) in the isolated contracting perfused CP heart was 1.8-fold higher. Net lactate efflux was 1.5-fold higher. Furthermore, in vivo (13)C-magnetic resonance spectroscopy (MRS) of hyperpolarized [(13)C1]pyruvate revealed a twofold increase in real-time flux through lactate dehydrogenase in the CP hearts and a 1.6-fold increase through pyruvate dehydrogenase. (31)P-MRS of perfused CP hearts under increased workload (isoproterenol infusion) demonstrated increased depletion of phosphocreatine relative to ATP. Intriguingly, no changes in cardiac gene expression were detected. In summary, a modest systemic dysregulation of the HIF pathway resulted in clear alterations in cardiac metabolism and energetics. However, in contrast to studies generating high HIF levels within the heart, the CP mice showed neither the predicted changes in gene expression nor any degree of LV impairment. We conclude that the effects of manipulating HIF on the heart are dose dependent.

Pattern Cue and Visual Cue Competition in a Foraging Task by Rats.

In 4 experiments, rats searched for food located on top of 4 of 16 towers which were arranged in a 4 × 4 matrix. The location of the baited towers was cued by visual landmark cues (the baited towers were striped, the others white) and by pattern cues (the baited towers were located in a 2 × 2 pattern within the larger 4 × 4 matrix) or simply by pattern cues without visual landmark cues. In 3 of the experiments, visual cues, after being paired with pattern cues, were removed altogether (Experiment 1), put into competition with pattern cues (Experiment 2), or made noninformative (Experiment 3). In Experiment 4, it was the pattern cues that were made noninformative. Collectively, the data suggest strongly that whereas the pattern is learned, even when presumably more salient visual cues are present, the connection between pattern and food location is much weaker than that between visual cue and food location. These data are more easily explained by a model of learning that includes dedicated modules than by a single-system associative model.

On the pivotal role of PPARα in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury.

The role of peroxisome proliferator-activated receptor α (PPARα)-mediated metabolic remodeling in cardiac adaptation to hypoxia has yet to be defined. Here, mice were housed in hypoxia for 3 wk before in vivo contractile function was measured using cine MRI. In isolated, perfused hearts, energetics were measured using (31)P magnetic resonance spectroscopy (MRS), and glycolysis and fatty acid oxidation were measured using [(3)H] labeling. Compared with a normoxic, chow-fed control mouse heart, hypoxia decreased PPARα expression, fatty acid oxidation, and mitochondrial uncoupling protein 3 (UCP3) levels, while increasing glycolysis, all of which served to maintain normal ATP concentrations ([ATP]) and thereby, ejection fractions. A high-fat diet increased cardiac PPARα expression, fatty acid oxidation, and UCP3 levels with decreased glycolysis. Hypoxia was unable to alter the high PPARα expression or reverse the metabolic changes caused by the high-fat diet, with the result that [ATP] and contractile function decreased significantly. The adaptive metabolic changes caused by hypoxia in control mouse hearts were found to have occurred already in PPARα-deficient (PPARα(-/-)) mouse hearts and sustained function in hypoxia despite an inability for further metabolic remodeling. We conclude that decreased cardiac PPARα expression is essential for adaptive metabolic remodeling in hypoxia, but is prevented by dietary fat.-Cole, M. A., Abd Jamil, A. H., Heather, L. C., Murray, A. J., Sutton, E. R., Slingo, M., Sebag-Montefiore, L., Tan, S. C., Aksentijevic, D., Gildea, O. S., Stuckey, D. J., Yeoh, K. K., Carr, C. A., Evans, R. D., Aasum, E., Schofield, C. J., Ratcliffe, P. J., Neubauer, S., Robbins, P. A., Clarke, K. On the pivotal role of PPARα in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury.

How language choice can affect HCAI prevention.

The financial and human costs of healthcare-associated infections have prompted many local and national policies/guidelines aimed at controlling or preventing infection. However, the language used in the discourse of this are of practice tends to lack objectivity and may make unachievable demands of staff. This article explores how such language can negatively affect staff behaviour and drive poor practice underground.

Increased oxidative metabolism following hypoxia in the type 2 diabetic heart, despite normal hypoxia signalling and metabolic adaptation.

KEY POINTS: Adaptation to hypoxia makes the heart more oxygen efficient, by metabolising more glucose. In contrast, type 2 diabetes makes the heart metabolise more fatty acids. Diabetes increases the chances of the heart being exposed to hypoxia, but whether the diabetic heart can adapt and respond is unknown. In this study we show that diabetic hearts retain the ability to adapt their metabolism in response to hypoxia, with functional hypoxia signalling pathways. However, the hypoxia-induced changes in metabolism are additive to abnormal baseline metabolism, resulting in hypoxic diabetic hearts metabolising more fat and less glucose than controls. This stops the diabetic heart being able to recover its function when stressed. These results demonstrate that the diabetic heart retains metabolic flexibility to adapt to hypoxia, but is hindered by the baseline effects of the disease. This increases our understanding of how the diabetic heart is affected by hypoxia-associated complications of the disease. ABSTRACT: Hypoxia activates the hypoxia-inducible factor (HIF), promoting glycolysis and suppressing mitochondrial respiration. In the type 2 diabetic heart, glycolysis is suppressed whereas fatty acid metabolism is promoted. The diabetic heart experiences chronic hypoxia as a consequence of increased obstructive sleep apnoea and cardiovascular disease. Given the opposing metabolic effects of hypoxia and diabetes, we questioned whether diabetes affects cardiac metabolic adaptation to hypoxia. Control and type 2 diabetic rats were housed for 3 weeks in normoxia or 11% oxygen. Metabolism and function were measured in the isolated perfused heart using radiolabelled substrates. Following chronic hypoxia, both control and diabetic hearts upregulated glycolysis, lactate efflux and glycogen content and decreased fatty acid oxidation rates, with similar activation of HIF signalling pathways. However, hypoxia-induced changes were superimposed on diabetic hearts that were metabolically abnormal in normoxia, resulting in glycolytic rates 30% lower, and fatty acid oxidation 36% higher, in hypoxic diabetic hearts than hypoxic controls. Peroxisome proliferator-activated receptor α target proteins were suppressed by hypoxia, but activated by diabetes. Mitochondrial respiration in diabetic hearts was divergently activated following hypoxia compared with controls. These differences in metabolism were associated with decreased contractile recovery of the hypoxic diabetic heart following an acute hypoxic insult. In conclusion, type 2 diabetic hearts retain metabolic flexibility to adapt to hypoxia, with normal HIF signalling pathways. However, they are more dependent on oxidative metabolism following hypoxia due to abnormal normoxic metabolism, which was associated with a functional deficit in response to stress.