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While cardiac rehabilitation (CR) has been shown to be a beneficial form of secondary prevention for patients with cardiovascular disease, barriers of referral to CR still exist for patients. Barriers that specifically make it difficult for physicians to make the referral could be worthwhile to examine. This narrative review hypothesizes that increasing awareness and education on the various aspects of CR as well as simplifying the referral process could lead to increased referral rates as they target physician-related barriers. This narrative review seeks to further understand the physician-related barriers of low CR awareness and hindering referral processes. A search in Scopus was conducted with preference for articles examining CR referral strategies used by physicians; physicians’ awareness of CR programs; physicians’ perceptions, beliefs, or knowledge of the benefits of CR; or physicians’ experience with or understanding of the selection process of CR programs, including indications for referral. Two systematic reviews and two observational studies were selected for discussion. Three of the selected studies had findings supporting the notion that increasing physicians’ awareness of CR could impact referral rates. One of the studies evaluated the perceptions that physicians and CR programs had on various referral strategies. While more study is needed to assess the actual level of knowledge and awareness physicians have regarding CR, this review supports using educational interventions as well as targeting various aspects of the referral process for improving referral rates.

Chronic systemic skin disease and cardiovascular disease are multisystem disorders which have been associated with each other for centuries. Recent research has strengthened this association, particularly in systemic inflammatory disease. Here we explore the current literature on psoriasis, hidradenitis suppurativa, lupus erythematosus, acanthosis nigricans, atopic dermatitis, and bullous pemphigoid. Psoriasis is a chronic inflammatory disorder that has been labeled as a risk-modifier for hyperlipidemia and coronary artery disease by the American College of Cardiology ACC lipid guidelines. Cardiovascular disease is also found at a significantly higher rate in patients with hidradenitis suppurativa and lupus erythematosus. Some associations have even been noted between cardiovascular disease and acanthosis nigricans, atopic dermatitis, and bullous pemphigoid. While many of these associations have been attributed to a shared underlying disease process such as chronic systemic inflammation and shared underlying risk factors, these dermatologic manifestations can help to identify patients at higher risk for cardiovascular disease.

Objective Insulin signalling via phosphoinositide 3-kinase (PI3K) requires PIK3R1-encoded regulatory subunits. C-terminal PIK3R1 mutations cause SHORT syndrome, as well as lipodystrophy and insulin resistance (IR), surprisingly without fatty liver or metabolic dyslipidaemia. We sought to investigate this discordance. Methods The human pathogenic Pik3r1 Y657∗ mutation was knocked into mice by homologous recombination. Growth, body composition, bioenergetic and metabolic profiles were investigated on chow and high-fat diet (HFD). We examined adipose and liver histology, and assessed liver responses to fasting and refeeding transcriptomically. Results Like humans with SHORT syndrome, Pik3r1WT/Y657∗ mice were small with severe IR, and adipose expansion on HFD was markedly reduced. Also as in humans, plasma lipid concentrations were low, and insulin-stimulated hepatic lipogenesis was not increased despite hyperinsulinemia. At odds with lipodystrophy, however, no adipocyte hypertrophy nor adipose inflammation was found. Liver lipogenic gene expression was not significantly altered, and unbiased transcriptomics showed only minor changes, including evidence of reduced endoplasmic reticulum stress in the fed state and diminished Rictor-dependent transcription on fasting. Increased energy expenditure, which was not explained by hyperglycaemia nor intestinal malabsorption, provided an alternative explanation for the uncoupling of IR from dyslipidaemia. Conclusions Pik3r1 dysfunction in mice phenocopies the IR and reduced adiposity without lipotoxicity of human SHORT syndrome. Decreased adiposity may not reflect bona fide lipodystrophy, but rather, increased energy expenditure, and we suggest that further study of brown adipose tissue in both humans and mice is warranted., Highlights • SHORT syndrome features insulin resistance and reduced adiposity without dyslipidaemia and fatty liver. • A mouse model with a pathogenic human PI 3-Kinase mutation recapitulates this uncoupling. • Surprisingly, no adipose injury nor increased liver de novo lipogenesis is seen. • Energy expenditure is increased, causing resistance to diet-induced obesity. • This increases evidence for some beneficial metabolic effects of PI 3-Kinase inhibition.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder associated with venous or arterial thrombosis and with adverse pregnancy outcomes. The disorder is confirmed by the presence of antiphospholipid antibodies. Diagnosis of APS has important treatment implications insofar as newer direct

SummaryHeterodimeric class IA phosphatidylinositol-3-kinases (PI3K) transduce signals from many receptor tyrosine kinases including the insulin receptor. PI3K recruitment to phosphotyrosines is mediated by Pik3r1 gene products including the most intensely studied PI3K regulatory subunit, p85α, which also binds and regulates the PIP3 phosphatase Pten, and the lipogenic transcription factor Xbp1. Mutations in human PIK3R1 cause SHORT syndrome, featuring lipodystrophy and severe insulin resistance which, uniquely, are uncoupled from fatty liver and dyslipidemia. We describe a novel mouse model of SHORT syndrome made by knock in of the Pik3r1 Y657X mutation. Homozygous embryos die at E11.5, while heterozygous mice exhibit pre-and postnatal growth impairment with diminished placental vascularity. Adipose tissue accretion on high fat feeding was reduced, however adipocyte size was unchanged and preadipocyte differentiation ex vivo unimpaired. Despite severe insulin resistance, heterozygous mice were hypolipidemic, and plasma adiponectin, liver weight, cholesterol, glycogen and triglyceride content were unchanged. Mild downregulation of lipogenic Srebp1, Srebp2 and Chrebp transcriptional activity but no suppression of Xbp1 target genes was seen after fasting. These findings give new insights into the developmental role of Pik3r1, and establish a model of lipodystrophic insulin resistance dissociated from dyslipidemia as seen in SHORT syndrome.

MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes. There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were normal in skin fibroblasts. These findings suggest that specific MFN2 mutations cause tissue-selective mitochondrial dysfunction with increased adipocyte proliferation and survival, confirm a novel form of excess adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therapies. DOI: http://dx.doi.org/10.7554/eLife.23813.001, eLife digest Obesity and the diseases associated with it are among the biggest healthcare problems in developed countries. The word obesity means, simply, the accumulation of too much fat tissue in the body, but this ignores growing evidence that fat tissue is highly complex. Fat tissue is important for “mopping up” and storing excess calories safely, but also sends messages to the brain and other organs to report how full the body’s energy stores are. Understanding how fat tissues perform these roles will aid the development of strategies to treat or prevent obesity. A hormone called leptin acts as a signal of the status of the body’s fat stores. High levels of leptin in the blood tell the brain that the body has plenty of fat stored. On the other hand, if the levels of leptin in the blood become very low it tells the brain to prioritize finding food and shut down any nonessential processes. This helps to prevent the body from starving. It is not clear how the production of leptin is controlled, in part because fat tissues in different parts of the body behave very differently. Individuals who have a particular rare genetic mutation accumulate large amounts of fat tissue in their upper bodies and gradually lose fat tissue in their arms and legs. Despite accumulating a lot of fat tissue in the upper body, these individuals have extremely low levels of leptin in their blood. To investigate this genetic condition, Rocha et al. studied two children with the mutation and their healthy parents. The experiments show that this mutation alters a protein called mitofusin 2, which is found in cell compartments called mitochondria. Mitofusin 2 helps the mitochondria to bind to each other and to other parts of the cell, which is important for the mitochondria to generate the energy needed for vital cell processes. The mitochondria in the fat cells of the children are less closely linked to each other and have an unusual appearance compared to the mitochondria in the parents’ fat cells. Further experiments showed that some genes, including the one that produces leptin, are less active in the children compared to their parents – while other genes that are involved in starvation or stress responses are more active. This work suggests that mitochondria play an important role in regulating the production of leptin. Furthermore, it suggests that leptin or drugs that switch off stress-related genes may have the potential to be used to treat individuals with this particular mutation. DOI: http://dx.doi.org/10.7554/eLife.23813.002

Although referral to cardiac rehabilitation (CR) is considered the standard of care and demonstrably reduces both mortality rates and hospital admissions after cardiac events, rates of referral continue to be suboptimal. In fact, national reports reveal rates ranging from approximately 60% to 85% depending on the type of cardiac event. At an urban teaching hospital in Tennessee, efforts to increase referral rates were launched during the first quarter of 2018 as part of the Define, Measure, Analyze, Improve, Control (DMAIC) Project: Acute Myocardial Infarction (AMI) Transition of Care. The goal of this Action Plan is to review the interventions taken and the outcomes data from this project in order to propose future deliverables that can address areas of improvement within the DMAIC project. A list of the DMAIC project's interventions, which were varied and multidisciplinary, were obtained from the university hospital as well as the project's data. Data from the National Cardiovascular Data Registry (NCDR)-ACTION Registry show that referral rates at this hospital have been on the rise since the initiation of the DMAIC project. Peak referral rates in the year before the interventions were implemented were approximately 39%; whereas, the peak referral rate in the year these interventions were launched rose to 86.4%. While the interventions of the DMAIC project are hypothesized to have contributed to this increase in referral rates, based on their collaborative nature and the types of referral strategies employed, there are still opportunities for improvement and growth. Thus, this Action Plan proposes future projects to increase inclusivity of CR referral pathways, improve physician education, and establish support for outpatient CR programs.

Background Calculating Abraham descriptors from solubility values requires that the solute have the same form when dissolved in all solvents. However, carboxylic acids can form dimers when dissolved in non-polar solvents. For such compounds Abraham descriptors can be calculated for both the monomeric and dimeric forms by treating the polar and non-polar systems separately. We illustrate the method of how this can be done by calculating the Abraham descriptors for both the monomeric and dimeric forms of trans-cinnamic acid, the first time that descriptors for a carboxylic acid dimer have been obtained. Results Abraham descriptors were calculated for the monomeric form of trans-cinnamic acid using experimental solubility measurements in polar solvents from the Open Notebook Science Challenge together with a number of water-solvent partition coefficients from the literature. Similarly, experimental solubility measurements in non-polar solvents were used to determine Abraham descriptors for the trans-cinnamic acid dimer. Conclusion Abraham descriptors were calculated for both the monomeric and dimeric forms of trans-cinnamic acid. This allows for the prediction of further solubilities of trans-cinnamic acid in both polar and non-polar solvents with an error of about 0.10 log units.

The Internet represents a substantial advance in information exchange and presents the healthcare industry with a significant opportunity to fundamentally enhance the manner in which individuals manage their relative wellness. As the World Wide Web matures, usage patterns are becoming more precisely defined. These patterns can be examined and used to enhance accessibility and encourage user loyalty to a particular site. The internet, coupled with future technology advances, could enable healthcare providers to offer individually tailored disease management programmes, adapt to patient needs in real-time and deliver vast amounts of information with virtually no fulfilment costs. However, a planned and well co-ordinated approach is needed if the benefits of this new communication medium are to be fully realised. If this is achieved, Web-based disease management could be a cost-effective means of lowering patient health risk and an excellent asynchronous link between patient and provider.

Disease management is an approach to patient care that includes health promotion and disease prevention, diagnosis, treatment and rehabilitation, as well as long term care. Research indicates that providing health promotion, disease prevention and disease self-management information that is individually tailored to a patient's unique needs, interests and comprehension skills can have a significant impact on changes in the patient's health-related behaviours. This article provides an overview of disease management and tailored communication, and discusses potential uses for tailored communication to enhance the effectiveness of disease management curricula.

This book is a compilation of Ugi reactions attempted for the UsefulChem Project mainly in the Bradley laboratory at Drexel University. This includes failed, inconclusive or in progress reactions as well as those where a product was successfully isolated and characterized. The entries are sorted alphabetically based on reactants. Links are provided to the relevant lab notebook pages. Future editions will include contributions from other sources as well.

This article discusses the beneficial effects of setting goals in health behavior change and maintenance interventions. Goal setting theory predicts that, under certain conditions, setting specific difficult goals leads to higher performance when compared with no goals or vague, nonquantitative goals, such as "do your best." In contrast to the graduated, easy goals often set in health behavior change programs, goal setting theory asserts a positive linear relationship between degree of goal difficulty and level of performance. Research on goal setting has typically been conducted in organizational and laboratory settings. Although goal setting procedures are used in many health behavior change programs, they rarely have been the focus of systematic research. Therefore, many research questions still need to be answered regarding goal setting in the context of health behavior change. Finally, initial recommendations for the successful integration of goal setting theory in health behavior change programs are offered.