Single-cell transcriptional profiling reveals cellular diversity and intercommunication in the mouse heart

Characterization of the cardiac cellulome, the network of cells that form the heart, is essential for understanding cardiac development and normal organ function and for formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our understanding of cardiac cellular composition and highlighted important functional roles for non-myocyte cell types. In this study, we characterized single-cell transcriptional profiles of the murine non-myocyte cardiac cellular landscape using single-cell RNA sequencing (scRNA-seq). Detailed molecular analyses revealed the diversity of the cardiac cellulome and facilitated the development of techniques to isolate understudied cardiac cell populations, such as mural cells and glia. Our analyses also revealed extensive networks of intercellular communication and suggested prevalent sexual dimorphism in gene expression in the heart. This study offers insights into the structure and function of the mammalian cardiac cellulome and provides an important resource that will stimulate studies in cardiac cell biology

Capture the fracture: a best practice framework and global campaign to break the fragility fracture cycle

Summary The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world. Introduction FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk. Methods Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery. Results The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award ‘Capture the Fracture Best Practice Recognition’ to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities. Conclusion Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.</p

Cirsium species show disparity in patterns of genetic variation at their range-edge, despite similar patterns of reproduction and isolation

Genetic variation was assessed across the UK geographical range of Cirsium acaule and Cirsium heterophyllum. A decline in genetic diversity and increase in population divergence approaching the range edge of these species was predicted based on parallel declines in population density and seed production reported seperately. Patterns were compared with UK populations of the widespread Cirsium arvense.Populations were sampled along a latitudinal transect in the UK and genetic variation assessed using microsatellite markers. Cirsium acaule shows strong isolation by distance, a significant decline in diversity and an increase in divergence among range-edge populations. Geographical structure is also evident in C. arvense, whereas no such patterns are seen in C.heterophyllum. There is a major disparity between patterns of genetic variation in C. acaule and C. heterophyllum despite very similar patterns in seed production and population isolation in these species. This suggests it may be misleading to make assumptions about the geographical structure of genetic variation within species based solely on the present-day reproduction and distribution of populations

Aptamers for respiratory syncytial virus detection.

The identification of the infectious agents is pivotal for appropriate care of patients with viral diseases. Current viral diagnostics rely on selective detection of viral nucleic acid or protein components. In general, detection of proteins rather than nucleic acids is technically more suitable for rapid tests. However, protein-based virus identification methods depend on antibodies limiting the practical applicability of these approaches. Aptamers rival antibodies in target selectivity and binding affinity, and excel in terms of robustness and cost of synthesis. Although aptamers have been generated for virus identification in laboratory settings, their introduction into routine virus diagnostics has not been realized, yet. Here, we demonstrate that the rationally designed SELEX protocol can be applied on whole virus to select aptamers, which can potentially be applied for viral diagnostics. This approach does not require purified virus protein or complicated virus purification. The presented data also illustrate that corroborating the functionality of aptamers with various approaches is essential to pinpoint the most appropriate aptamer amongst the panel of candidates obtained by the selection. Our protocol yielded aptamers capable of detecting respiratory syncytial virus (RSV), an important pathogen causing severe disease especially in young infants, at clinically relevant concentrations in complex matrices

Interest in healthy living outweighs presumed cultural norms for obesity for Ghanaian women

BACKGROUND: Cultural norms indicate that obesity reflects increased wealth and prosperity. Yet obesity is linked to serious medical illnesses. The purpose of this study was to determine if Ghanaian women would change their body image if it meant a healthier life. METHODS: A questionnaire was administered to 305 Ghanaian women waiting for clinic appointments at Korle Bu Teaching Hospital, Accra Ghana. This survey included questions on current health, selection of figural stimuli, decision making on health and social determinants and 5 questions on self-perception of health from SF-36. Anthropometric measures were taken and body mass index calculated. Women were also provided with health related information at the conclusion of the interview. RESULTS: The majority of all women surveyed would reduce their current body image if it meant that they would have an overall healthier life and reduce the risks of obesity-linked illnesses and complications. Currently obese women were significantly more likely than non-obese women to reduce their body image to reduce the risk of hypertension (OR 2.03 [1.64 – 2.51],<0.001); cardiovascular accident (OR 1.96 [1.61 – 2.38],<0.001); diabetes (OR 2.00 [1.63 – 2.44],<0.001); myocardial infarction (OR 2.27 [1.80 – 2.86],<0.001); if requested by a spouse(OR 2.64 [1.98 – 3.52],<0.001); and to improve overall health (OR 1.95 [1.60 – 2.37], <0.001). There was no association with current body image and responses to SF-36. The decision to select a new body image was not influenced by education, income, marital status or parity. Age 50 years old and less was significantly associated with the body image size reduction to reduce the risk of hypertension, diabetes, and a cardiovascular accident. CONCLUSION: The Ghanaian women interviewed in this study are interested in living a healthy life and are willing to reduce their body size to reduce the risk of obesity-linked illnesses. The target group for any interventional studies and measures to reduce obesity appears to be women age 50 and younger

The prevalence of vertebral fracture amongst patients presenting with non-vertebral fractures

INTRODUCTION: Despite vertebral fracture being a significant risk factor for further fracture, vertebral fractures are often unrecognised. A study was therefore conducted to determine the proportion of patients presenting with a non-vertebral fracture who also have an unrecognised vertebral fracture. METHODS: Prospective study of patients presenting with a non-vertebral fracture in South Glasgow who underwent DXA evaluation with vertebral morphometry (MXA) from DV5/6 to LV4/5. Vertebral deformities (consistent with fracture) were identified by direct visualisation using the Genant semi-quantitative grading scale. RESULTS: Data were available for 337 patients presenting with low trauma non-vertebral fracture; 261 were female. Of all patients, 10.4% were aged 50–64 years, 53.2% were aged 65–74 years and 36.2% were aged 75 years or over. According to WHO definitions, 35.0% of patients had normal lumbar spine BMD (T-score −1 or above), 37.4% were osteopenic (T-score −1.1 to −2.4) and 27.6% osteoporotic (T-score −2.5 or lower). Humerus (n=103, 31%), radius–ulna (n=90, 27%) and hand/foot (n=53, 16%) were the most common fractures. For 72% of patients (n=241) the presenting fracture was the first low trauma fracture to come to clinical attention. The overall prevalence of vertebral deformity established by MXA was 25% (n=83); 45% (n=37) of patients with vertebral deformity had deformities of more than one vertebra. Of the patients with vertebral deformity and readable scans for grading, 72.5% (58/80) had deformities of grade 2 or 3. Patients presenting with hip fracture, or spine T-score ≤−2.5, or low BMI, or with more than one prior non-vertebral fracture were all significantly more likely to have evidence of a prevalent vertebral deformity (p<0.05). However, 19.8% of patients with an osteopenic T-score had a vertebral deformity (48% of which were multiple), and 16.1% of patients with a normal T-score had a vertebral deformity (26.3% of which were multiple). Following non-vertebral fracture, some guidelines suggest that anti-resorptive therapy should be reserved for patients with DXA-proven osteoporosis. However, patients who have one or more prior vertebral fractures (prevalent at the time of their non-vertebral fracture) would also become candidates for anti-resorptive therapy—which would have not been the case had their vertebral fracture status not been known. Overall in this study, 8.9% of patients are likely to have had a change in management by virtue of their underlying vertebral deformity status. In other words, 11 patients who present with a non-vertebral fracture would need to undergo vertebral morphometry in order to identify one patient who ought to be managed differently. CONCLUSIONS: Our results support the recommendation to perform vertebral morphometry in patients who are referred for DXA after experiencing a non-vertebral fracture. Treatment decisions will then better reflect any given patient’s future absolute fracture risk. The 'Number Needed to Screen' if vertebral morphometry is used in this way would be seven to identify one patient with vertebral deformity, and 14 to identify one patient with two or more vertebral deformities. Although carrying out MXA will increase radiation exposure for the patient, this increased exposure is significantly less than would be obtained if X-rays of the dorso-lumbar spine were obtained

Cue Reactivity in Active Pathological, Abstinent Pathological, and Regular Gamblers

Twenty-one treatment-seeking pathological gamblers, 21 pathological gamblers in recovery, and 21 recreational gamblers watched two video-taped exciting gambling scenarios and an exciting roller-coaster control scenario while their arousal (heart rate and subjective excitement) and urge to gamble were being measured. The gamblers did not differ significantly in cue-elicited heart rate elevations or excitement. However, the active pathological gamblers reported significantly greater urges to gamble across all cues compared to the abstinent pathological gamblers and, with marginal significance (p = 0.06), also compared to the social gamblers. Further exploration of these findings revealed that active pathological gamblers experience urges to gamble in response to exciting situations, whether or not they are gambling related, whereas abstinent and social gamblers only report urges to an exciting gambling-related cue. This suggests that for pathological gamblers excitement itself, irrespective of its source, may become a conditioned stimulus capable of triggering gambling behavior. Implications for treatment and future research are discussed

Immunogenicity and Protective Capacity of a Virosomal Respiratory Syncytial Virus Vaccine Adjuvanted with Monophosphoryl Lipid A in Mice

Respiratory Syncytial Virus (RSV) is a major cause of viral brochiolitis in infants and young children and is also a significant problem in elderly and immuno-compromised adults. To date there is no efficacious and safe RSV vaccine, partially because of the outcome of a clinical trial in the 1960s with a formalin-inactivated RSV vaccine (FI-RSV). This vaccine caused enhanced respiratory disease upon exposure to the live virus, leading to increased morbidity and the death of two children. Subsequent analyses of this incident showed that FI-RSV induces a Th2-skewed immune response together with poorly neutralizing antibodies. As a new approach, we used reconstituted RSV viral envelopes, i.e. virosomes, with incorporated monophosphoryl lipid A (MPLA) adjuvant to enhance immunogenicity and to skew the immune response towards a Th1 phenotype. Incorporation of MPLA stimulated the overall immunogenicity of the virosomes compared to non-adjuvanted virosomes in mice. Intramuscular administration of the vaccine led to the induction of RSV-specific IgG2a levels similar to those induced by inoculation of the animals with live RSV. These antibodies were able to neutralize RSV in vitro. Furthermore, MPLA-adjuvanted RSV virosomes induced high amounts of IFNγ and low amounts of IL5 in both spleens and lungs of immunized and subsequently challenged animals, compared to levels of these cytokines in animals vaccinated with FI-RSV, indicating a Th1-skewed response. Mice vaccinated with RSV-MPLA virosomes were protected from live RSV challenge, clearing the inoculated virus without showing signs of lung pathology. Taken together, these data demonstrate that RSV-MPLA virosomes represent a safe and efficacious vaccine candidate which warrants further evaluation