Current Management of Heart Failure: When to Refer to Heart Failure Specialist and When Hospice is the Best Option.

Heart failure is a common syndrome caused by different abnormalities of the cardiovascular system that result in impairment of the ventricles in filling or ejecting blood. It is one of the most common causes of hospitalization in the United States, with a very high cost to the health care system. This article focuses on the causes of left ventricle dysfunction and the presentation and management of heart failure, both acute and chronic

Sepsis-induced cardiomyopathy: a review of pathophysiologic mechanisms.

Cardiac dysfunction is a well-recognized complication of severe sepsis and septic shock. Cardiac dysfunction in sepsis is characterized by ventricular dilatation, reduction in ejection fraction and reduced contractility. Initially, cardiac dysfunction was considered to occur only during the hypodynamic phase of shock. But we now know that it occurs very early in sepsis even during the hyperdynamic phase of septic shock. Circulating blood-borne factors were suspected to be involved in the evolution of sepsis induced cardiomyopathy, but it is not until recently that the cellular and molecular events are being targeted by researchers in a quest to understand this enigmatic process. Septic cardiomyopathy has been the subject of investigation for nearly half a century now and yet controversies exist in understanding it\u27s pathophysiology. Here, we discuss our understanding of the pathogenesis of septic cardiomyopathy and the complex roles played by nitric oxide, mitochondrial dysfunction, complements and cytokines

Obesity Alters Molecular and Functional Cardiac Responses to Ischemia-Reperfusion and Glucagon-Like Peptide-1 Receptor Agonism

This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-minutes coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect the blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca2+ binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion

Scalar cosmological perturbations from inflationary black holes

We study the correction to the scale invariant power spectrum of a scalar field on de Sitter space from small black holes that formed during a pre-inflationary matter dominated era. The formation probability of such black holes is estimated from primordial Gaussian density fluctuations. We determine the correction to the spectrum by first deriving the Keldysh propagator for a massless scalar field on Schwarzschild-de Sitter space. Our results suggest that the effect is strong enough to be tested -- and possibly even ruled out -- by observations.Comment: 41 pages, 11 figures, published versio

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

A randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents

Cognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings

Estimating the bispectrum of the Very Small Array data

We estimate the bispectrum of the Very Small Array data from the compact and extended configuration observations released in December 2002, and compare our results to those obtained from Gaussian simulations. There is a slight excess of large bispectrum values for two individual fields, but this does not appear when the fields are combined. Given our expected level of residual point sources, we do not expect these to be the source of the discrepancy. Using the compact configuration data, we put an upper limit of 5400 on the value of f_NL, the non-linear coupling parameter, at 95 per cent confidence. We test our bispectrum estimator using non-Gaussian simulations with a known bispectrum, and recover the input values.Comment: 17 pages, 16 figures, replaced with version accepted by MNRAS. Primordial bispectrum recalculated and figure 11 change

A non-coding insertional mutation of Grhl2 causes gene over-expression and multiple structural anomalies including cleft palate, spina bifida and encephalocele

Orofacial clefts, including cleft lip and palate (CL/P), and neural tube defects (NTDs) are among the most common congenital anomalies but knowledge of the genetic basis of these conditions remains incomplete. The extent to which genetic risk factors are shared between CL/P, NTDs and related anomalies is also unclear. While identification of causative genes has largely focused on coding and loss of function mutations, it is hypothesised that regulatory mutations account for a portion of the unidentified heritability. We found that excess expression of Grainyhead-like 2 (Grhl2) not only causes spinal NTDs in Axial defects (Axd) mice, but also multiple additional defects affecting the cranial region. These include orofacial clefts comprising midline cleft lip and palate, abnormalities of the craniofacial bones and frontal and/or basal encephalocele, in which brain tissue herniates through the cranium or into the nasal cavity. To investigate the causative mutation in the Grhl2Axd strain, whole genome sequencing identified an approximately 4 kb LTR retrotransposon insertion which disrupts the non-coding regulatory region, lying approximately 300 base pairs upstream of the 5' UTR. This insertion also lies within a predicted long non-coding RNA, oriented on the reverse strand, which like Grhl2 is over-expressed in Axd (Grhl2Axd) homozygous mutant embryos. Initial analysis of the GRHL2 upstream region in individuals with NTDs or cleft palate revealed rare or novel variants in a small number of cases. We hypothesise that mutations affecting the regulation of GRHL2 may contribute to craniofacial anomalies and NTDs in humans

ClassifyMe: A Field-Scouting Software for the Identification of Wildlife in Camera Trap Images

We present ClassifyMe a software tool for the automated identification of animal species from camera trap images. ClassifyMe is intended to be used by ecologists both in the field and in the office. Users can download a pre-trained model specific to their location of interest and then upload the images from a camera trap to a laptop or workstation. ClassifyMe will identify animals and other objects (e.g., vehicles) in images, provide a report file with the most likely species detections, and automatically sort the images into sub-folders corresponding to these species categories. False Triggers (no visible object present) will also be filtered and sorted. Importantly, the ClassifyMe software operates on the user's local machine (own laptop or workstation) - not via internet connection. This allows users access to state-of-the-art camera trap computer vision software in situ, rather than only in the office. The software also incurs minimal cost on the end-user as there is no need for expensive data uploads to cloud services. Furthermore, processing the images locally on the users' end-device allows them data control and resolves privacy issues surrounding transfer and third-party access to users' datasets