Understanding diet is critical for conservation of endangered predators. Southern Resident killer whales (SRKW) (Orcinus orca) are an endangered population occurring primarily along the outer coast ...and inland waters of Washington and British Columbia. Insufficient prey has been identified as a factor limiting their recovery, so a clear understanding of their seasonal diet is a high conservation priority. Previous studies have shown that their summer diet in inland waters consists primarily of Chinook salmon (Oncorhynchus tshawytscha), despite that species' rarity compared to some other salmonids. During other times of the year, when occurrence patterns include other portions of their range, their diet remains largely unknown. To address this data gap, we collected feces and prey remains from October to May 2004-2017 in both the Salish Sea and outer coast waters. Using visual and genetic species identification for prey remains and genetic approaches for fecal samples, we characterized the diet of the SRKWs in fall, winter, and spring. Chinook salmon were identified as an important prey item year-round, averaging ~50% of their diet in the fall, increasing to 70-80% in the mid-winter/early spring, and increasing to nearly 100% in the spring. Other salmon species and non-salmonid fishes, also made substantial dietary contributions. The relatively high species diversity in winter suggested a possible lack of Chinook salmon, probably due to seasonally lower densities, based on SRKW's proclivity to selectively consume this species in other seasons. A wide diversity of Chinook salmon stocks were consumed, many of which are also at risk. Although outer coast Chinook samples included 14 stocks, four rivers systems accounted for over 90% of samples, predominantly the Columbia River. Increasing the abundance of Chinook salmon stocks that inhabit the whales' winter range may be an effective conservation strategy for this population.
The lateral hypothalamus and the nucleus accumbens shell (AcbSh) are brain regions important for food intake. The AcbSh contains high levels of receptor for melanin-concentrating hormone (MCH), a ...lateral hypothalamic peptide critical for feeding and metabolism. MCH receptor (MCHR1) activation in the AcbSh increases food intake, while AcbSh MCHR1 blockade reduces feeding. Here biochemical and cellular mechanisms of MCH action in the rodent AcbSh are described. A reduction of phosphorylation of GluR1 at serine 845 (pSer(845)) is shown to occur after both pharmacological and genetic manipulations of MCHR1 activity. These changes depend upon signaling through G(i/o), and result in decreased surface expression of GluR1-containing AMPA receptors (AMPARs). Electrophysiological analysis of medium spiny neurons (MSNs) in the AcbSh revealed decreased amplitude of AMPAR-mediated synaptic events (mEPSCs) with MCH treatment. In addition, MCH suppressed action potential firing MSNs through K(+) channel activation. Finally, in vivo recordings confirmed that MCH reduces neuronal cell firing in the AcbSh in freely moving animals. The ability of MCH to reduce cell firing in the AcbSh is consistent with a general model from other pharmacological and electrophysiological studies whereby reduced AcbSh neuronal firing leads to food intake. The current work integrates the hypothalamus into this model, providing biochemical and cellular mechanisms whereby metabolic and limbic signals converge to regulate food intake.
Pancreatic ductal adenocarcinoma (PDAC) develops a pronounced stromal response reflecting an aberrant wound-healing process. This stromal reaction features transdifferentiation of tissue-resident ...pancreatic stellate cells (PSC) into activated cancer-associated fibroblasts, a process induced by PDAC cells but of unclear significance for PDAC progression. Here, we show that PSCs undergo a dramatic lipid metabolic shift during differentiation in the context of pancreatic tumorigenesis, including remodeling of the intracellular lipidome and secretion of abundant lipids in the activated, fibroblastic state. Specifically, stroma-derived lysophosphatidylcholines support PDAC cell synthesis of phosphatidylcholines, key components of cell membranes, and also facilitate production of the potent wound-healing mediator lysophosphatidic acid (LPA) by the extracellular enzyme autotaxin, which is overexpressed in PDAC. The autotaxin-LPA axis promotes PDAC cell proliferation, migration, and AKT activation, and genetic or pharmacologic autotaxin inhibition suppresses PDAC growth
. Our work demonstrates how PDAC cells exploit the local production of wound-healing mediators to stimulate their own growth and migration. SIGNIFICANCE: Our work highlights an unanticipated role for PSCs in producing the oncogenic LPA signaling lipid and demonstrates how PDAC tumor cells co-opt the release of wound-healing mediators by neighboring PSCs to promote their own proliferation and migration.
.
.
CONTEXT Despite the high prevalence and potentially serious outcomes associated
with concussion in athletes, there is little systematic research examining
risk factors and short- and long-term ...outcomes. OBJECTIVES To assess the relationship between concussion history and learning disability
(LD) and the association of these variables with neuropsychological performance
and to evaluate postconcussion recovery in a sample of college football players. DESIGN, SETTING, AND PARTICIPANTS A total of 393 athletes from 4 university football programs across the
United States received preseason baseline evaluations between May 1997 and
February 1999. Subjects who had subsequent football-related acute concussions
(n=16) underwent neuropsychological comparison with matched control athletes
from within the sample (n=10). MAIN OUTCOME MEASURES Clinical interview, 8 neuropsychological measures, and concussion symptom
scale ratings at baseline and after concussion. RESULTS Of the 393 players, 129 (34%) had experienced 1 previous concussion
and 79 (20%) had experienced 2 or more concussions. Multivariate analysis
of variance yielded significant main effects for both LD (P<.001) and concussion history (P=.009),
resulting in lowered baseline neuropsychological performance. A significant
interaction was found between LD and history of multiple concussions and LD
on 2 neuropsychological measures (Trail-Making Test, Form B P=.007 and Symbol Digit Modalities Test P=.009),
indicating poorer performance for the group with LD and multiple concussions
compared with other groups. A discriminant function analysis using neuropsychological
testing of athletes 24 hours after acute in-season concussion compared with
controls resulted in an overall 89.5% correct classification rate. CONCLUSIONS Our study suggests that neuropsychological assessment is a useful indicator
of cognitive functioning in athletes and that both history of multiple concussions
and LD are associated with reduced cognitive performance. These variables
may be detrimentally synergistic and should receive further study.
Significant mortality benefits have been documented in recipients of implantable cardioverter defibrillators (ICDs); however, the psychosocial distress created by the underlying arrhythmia and its ...potential treatments in patients and family members may be underappreciated by clinical care teams. The disentanglement of cardiac disease and device-related concerns is difficult. The majority of ICD patients and families successfully adjust to the ICD, but optimal care pathways may require additional psychosocial attention to all ICD patients and particularly those experiencing psychosocial distress. This state-of-the-science report was developed on the basis of an analysis and critique of existing science to (1) describe the psychological and quality-of-life outcomes after receipt of an ICD and describe related factors, such as patient characteristics; (2) describe the concerns and educational/informational needs of ICD patients and their family members; (3) outline the evidence that supports interventions for improving educational and psychological outcomes for ICD patients; (4) provide recommendations for clinical approaches for improving patient outcomes; and (5) identify priorities for future research in this area. The ultimate goal of this statement is to improve the precision of identification and care of psychosocial distress in ICD patients to maximize the derived benefit of the ICD.
BACKGROUND:High-risk patients with hypertrophic cardiomyopathy (HCM) are identified by contemporary risk stratification and effectively treated with implantable cardioverter-defibrillators (ICDs). ...However, long-term HCM clinical course after ICD therapy for ventricular tachyarrhythmias is incompletely understood.
METHODS AND RESULTS:Cohort of 486 high-risk HCM patients with ICDs was assembled from 8 international centers. Clinical course and device interventions were addressed, and survey questionnaires assessed patient anxiety level and psychological well-being related to ICD therapy. Of 486 patients, 94 (19%) experienced appropriate ICD interventions terminating ventricular tachycardia/ventricular fibrillation, 3.7% per year for primary prevention, over 6.4±4.7 years. Of 94 patients, 87 were asymptomatic or only mildly symptomatic at the time of appropriate ICD interventions; 74 of these 87 (85%) remained in classes I/II without significant change in clinical status over the subsequent 5.9±4.9 years (up to 22). Among the 94 patients, there was one sudden death (caused by device failure; 1.1%); 3 patients died from other HCM-related processes unrelated to arrhythmic risk (eg, end-stage heart failure). Post-ICD intervention, freedom from HCM mortality was 100%, 97%, and 92% at 1, 5, and 10 years, distinctly lower than in ischemic or nonischemic cardiomyopathy ICD trials. HCM patients with ICD interventions reported heightened anxiety in expectation of future shocks, but with intact general psychological well-being and quality of life.
CONCLUSIONS:In HCM, unlike ischemic heart disease, prevention of sudden death with ICD therapy is unassociated with significant increase in cardiovascular morbidity or mortality, or transformation to heart failure deterioration. ICD therapy does not substantially impair overall psychological and physical well-being.
An international initiative is developing a scientifically rigorous approach to evaluate the potential risks to nontarget arthropods (NTAs) posed by insect-resistant, genetically modified (IRGM) ...crops. It adapts the tiered approach to risk assessment that is used internationally within regulatory toxicology and environmental sciences. The approach focuses on the formulation and testing of clearly stated risk hypotheses, making maximum use of available data and using formal decision guidelines to progress between testing stages (or tiers). It is intended to provide guidance to regulatory agencies that are currently developing their own NTA risk assessment guidelines for IRGM crops and to help harmonize regulatory requirements between different countries and different regions of the world.
Background
Because as many as 46% of implantable cardioverter defibrillator (ICD) patients experience clinical symptoms of shock anxiety, this randomized controlled study evaluated the efficacy of ...adapted yoga (vs usual care) in reducing clinical psychosocial risks shown to impact morbidity and mortality in ICD recipients.
Methods
Forty‐six participants were randomized to a control group or an 8‐week adapted yoga group that followed a standardized protocol with weekly classes and home practice. Medical and psychosocial data were collected at baseline and follow‐up, then compared and analyzed.
Results
Total shock anxiety decreased for the yoga group and increased for the control group, t(4.43, 36), P < 0.0001, with significant differences between these changes. Similarly, consequential anxiety decreased for the yoga group but increased for the control group t(2.86,36) P = 0.007. Compared to the control, the yoga group had greater overall self‐compassion, t(–2.84,37), P = 0.007, and greater mindfulness, t(–2.10,37) P = 0.04, at the end of the study. Exploratory analyses utilizing a linear model (R2 = 0.98) of observed device‐treated ventricular (DTV) events revealed that the expected number of DTV events in the yoga group was significantly lower than in the control group (P < 0.0001). Compared to the control, the yoga group had a 32% lower risk of experiencing device‐related firings at end of follow‐up.
Conclusions
Our study demonstrated psychosocial benefits from a program of adapted yoga (vs usual care) for ICD recipients. These data support continued research to better understand the role of complementary medicine to address ICD‐specific stress in cardiac outcomes.
To define benchmark cutoffs for redo liver transplantation (redo-LT).
In the era of organ shortage, redo-LT is frequently discussed in terms of expected poor outcome and wasteful resources. However, ...there is a lack of benchmark data to reliably evaluate outcomes after redo-LT.
We collected data on redo-LT between January 2010 and December 2018 from 22 high-volume transplant centers. Benchmark cases were defined as recipients with model of end stage liver disease (MELD) score ≤25, absence of portal vein thrombosis, no mechanical ventilation at the time of surgery, receiving a graft from a donor after brain death. Also, high-urgent priority and early redo-LT including those for primary nonfunction (PNF) or hepatic artery thrombosis were excluded. Benchmark cutoffs were derived from the 75th percentile of the medians of all benchmark centers.
Of 1110 redo-LT, 373 (34%) cases qualified as benchmark cases. Among these cases, the rate of postoperative complications until discharge was 76%, and increased up to 87% at 1-year, respectively. One-year overall survival rate was excellent with 90%. Benchmark cutoffs included Comprehensive Complication Index CCI ® at 1-year of ≤72, and in-hospital and 1-year mortality rates of ≤13% and ≤15%, respectively. In contrast, patients who received a redo-LT for PNF showed worse outcomes with some values dramatically outside the redo-LT benchmarks.
This study shows that redo-LT achieves good outcome when looking at benchmark scenarios. However, this figure changes in high-risk redo-LT, as for example in PNF. This analysis objectifies for the first-time results and efforts for redo-LT and can serve as a basis for discussion about the use of scarce resources.
PDF
