Methamphetamine use and depressive symptoms among heterosexual men and women

This study investigated the relationship between intensity of methamphetamine use and depressive symptoms in a sample of 182 heterosexually identified methamphetamine users. Perceived stigma and social and health problems were hypothesized as potential mediators of the relationship between methamphetamine use and depressive symptoms. Forty per cent of the sample met criteria for moderate to severe depression. As hypothesized, the greater the intensity of methamphetamine use, the higher the levels of depressive symptoms. Results of the mediation analyses failed to identify mediating effects for stigma, social problems or health problems. However, perceived stigma had a significant positive direct effect on depressive symptoms. Gender, age and marital status also predicted higher levels of depression. This research suggests the need for drug treatment programmes to: (1) identify and treat depressive symptoms among methamphetamine users; and (2) address social and psychological issues, such as perceived stigma, in an effort to decrease depressive symptomatology and ultimately enhance programme effectiveness.     

The quadricuspid truncal valve: Surgical management and outcomes

ObjectiveTo determine the outcomes of patients with a quadricuspid truncal valve (TV) and durability of TV repair.MethodWe reviewed 56 patients with truncus arteriosus and a quadricuspid TV who underwent complete repair between 1979 and 2018.ResultsTV insufficiency was present in 39 patients (mild, n = 22; moderate, n = 14; and severe, n = 3). Fourteen patients had concomitant TV surgery. Early mortality in patients who had concomitant TV surgery was 14% (2 out of 14 patients) and overall survival was 77.1% ± 11.7% at 15 years. Freedom from TV reoperation was 30.3% ± 14.6% at 15 years. Early mortality in patients who did not undergo concomitant TV surgery was 9.5% (4 out of 42 patients) and overall survival was 74.9% ± 6.9% at 15 years. Progression of TV insufficiency requiring TV surgery occurred in 16.7% (7 out of 42 patients). Freedom from TV reoperation was 77.1% ± 7.8% at 15 years. The most common method of repair was tricuspidization of the TV. Freedom from TV reoperation was 64.3% ± 21.0% at 10 years after tricuspidization and 0% at 6 years after other types of TV surgery. Overall follow-up was 97.6% (41 out of 42 patients) complete for survivors with median follow-up of 16.6 years. At last follow-up there was no TV insufficiency in 16 patients, mild insufficiency in 24 patients, and moderate insufficiency in 1 patient.ConclusionsMore than one-third of patients with a quadricuspid TV require TV surgery. Tricuspidization of the quadricuspid TV appears to be a durable repair option with good long-term outcomes.     

Factors impacting long-term pulmonary autograft durability after the Ross procedure

Objective

Although the Ross procedure provides excellent long-term survival and a high quality of life, its use has been limited to relatively few centers. In this study, we evaluated long-term Ross procedure results in adults to assess the predictors of pulmonary autograft durability.

Source apportionment of methane escaping the subsea permafrost system in the outer Eurasian Arctic Shelf

The East Siberian Arctic Shelf holds large amounts of inundated carbon and methane (CH₄). Holocene warming by overlying seawater, recently fortified by anthropogenic warming, has caused thawing of the underlying subsea permafrost. Despite extensive observations of elevated seawater CH₄ in the past decades, relative contributions from different subsea compartments such as early diagenesis, subsea permafrost, methane hydrates, and underlying thermogenic/ free gas to these methane releases remain elusive. Dissolved methane concentrations observed in the Laptev Sea ranged from 3 to 1,500 nM (median 151 nM; oversaturation by ∼3,800%). Methane stable isotopic composition showed strong vertical and horizontal gradients with source signatures for two seepage areas of δ¹³C-CH₄ = (−42.6 ± 0.5)/(−55.0 ± 0.5) ‰ and δD-CH₄ = (−136.8 ± 8.0)/(−158.1 ± 5.5) ‰, suggesting a thermogenic/natural gas source. Increasingly enriched δ¹³C-CH₄ and δD-CH₄ at distance from the seeps indicated methane oxidation. The Δ¹⁴C-CH₄ signal was strongly depleted (i.e., old) near the seeps (−993 ± 19/−1050 ± 89‰). Hence, all three isotope systems are consistent with methane release from an old, deep, and likely thermogenic pool to the outer Laptev Sea. This knowledge of what subsea sources are contributing to the observed methane release is a prerequisite to predictions on how these emissions will increase over coming decades and centuries.

The East Siberian Arctic Shelf (ESAS) is the world’s largest and shallowest shelf sea system, formed through inundation of northeast Siberia during sea level transgression in the early Holocene. The ESAS holds substantial but poorly constrained amounts of organic carbon and methane (CH₄). These carbon/methane stores are contained in unknown partitions as gas hydrates, unfrozen sediment, subsea permafrost, gas pockets within and below the subsea permafrost, and as underlying thermogenic gas (1–3). Methane release to the atmosphere from these compartments could potentially have significant effects on the global climate (4, 5), yet there are large uncertainties regarding the size and the vulnerability toward remobilization of these inaccessible and elusive subsea carbon/methane pools. Conceptual development and modeling have predicted that warming of the ESAS system by a combination of geothermal heat and climate-driven Holocene heat flux from overlying seawater, recently further enhanced by Anthropocene warming, may lead to thawing of subsea permafrost (6, 7). Subsea permafrost drilling in the Laptev Sea, in part at the same sites as 30 y ago, has recently confirmed that the subsea permafrost has indeed come near the point of thawing (8). In addition to mobilization of the carbon/methane stored within the subsea permafrost, its degradation can also lead to the formation of pathways for gaseous methane from underlying reservoirs, allowing further methane release to the overlying water column (3, 9).Near-annual ship-based expeditions to the ESAS over the past two decades have documented widespread seep locations with extensive methane releases to the water column (3, 10). Methane levels are often found to be 10 to 100 times higher than the atmospheric equilibrium and are particularly elevated in areas of strong ebullition from subsea gas seeps (“methane hotspots”). Similarly, elevated dissolved methane concentrations in bottom waters appear to be spatially related to the thermal state of subsea permafrost as deduced from modeling results and/or geophysical surveys (7, 9). Currently, we lack critical knowledge on the quantitative or even relative contributions of the different subsea pools to the observed methane release, a prerequisite for robust predictions on how these releases will develop. An important distinction needs to be made between pools that release methane gradually, such as methane produced microbially in shallow sediments during early diagenesis or in thawing subsea permafrost, versus pools with preformed methane that may release more abruptly once pathways are available, such as from disintegrating methane hydrates and pools of thermogenic (natural) gas below the subsea permafrost. Multidimensional isotope analysis offers a useful means to disentangle the relative importance of these different subsea sources of methane to the ESAS: Stable isotope data (δ¹³C-CH₄ and δD-CH₄) provide useful information on methane formation and removal pathways, and the radiocarbon content of methane (Δ¹⁴C-CH₄) helps to determine the age and methane source reservoir (see SI Appendix, text S1 for details on these isotope systematics and typical isotopic signatures for the ESAS subsea system).Here, we present triple-isotope–based source apportionment of methane conducted as part of the Swedish–Russian–US investigation of carbon–climate–cryosphere interactions in the East Siberian Arctic Ocean (SWERUS-C3) program. To this end, the distribution of dissolved methane, its stable carbon and hydrogen isotope composition, as well as natural radiocarbon abundance signature, were investigated with a focus on the isotopic fingerprint of methane escaping the seabed to pinpoint the subsea sources of elevated methane in the outer Laptev Sea.     

CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling

RAF kinase functions in the mitogen-activated protein kinase (MAPK) pathway to transmit growth signals to the downstream kinases MEK and ERK. Activation of RAF catalytic activity is facilitated by a regulatory complex comprising the proteins CNK (Connector enhancer of KSR), HYP (Hyphen), and KSR (Kinase Suppressor of Ras). The sterile alpha-motif (SAM) domain found in both CNK and HYP plays an essential role in complex formation. Here, we have determined the x-ray crystal structure of the SAM domain of CNK in complex with the SAM domain of HYP. The structure reveals a single-junction SAM domain dimer of 1:1 stoichiometry in which the binding mode is a variation of polymeric SAM domain interactions. Through in vitro and in vivo mutational analyses, we show that the specific mode of dimerization revealed by the crystal structure is essential for RAF signaling and facilitates the recruitment of KSR to form the CNK/HYP/KSR regulatory complex. We present two docking-site models to account for how SAM domain dimerization might influence the formation of a higher-order CNK/HYP/KSR complex.     

Quality of life in bridge-to-transplant patients with chronic heart failure after implantation of an axial flow ventricular assist device

Research suggests that ventricular assist devices improve quality of life for congestive heart failure patients awaiting heart transplantation. Axial flow ventricular assist devices like the Jarvik 2000 (Jarvik Heart, Inc., New York, NY) represent the newest type of ventricular assist device technology, but their effects on quality of life are not well understood. Therefore, the authors administered the Minnesota Living with Heart Failure Questionnaire to patients who had the Jarvik 2000 implanted as a bridge to heart transplantation. Patients completed the Minnesota Living with Heart Failure Questionnaire immediately before device implantation, 1 month after implantation, immediately before heart transplantation, and 1 month after transplantation. One month after implantation of the device, the nine patients who completed the study showed significant improvements in physical (p<0.008), emotional (p<0.02), and overall (p<0.008) quality of life. These improvements were maintained until the device was explanted. The authors conclude that implantation of the Jarvik 2000 ventricular assist device can substantially improve quality of life for patients awaiting heart transplantation.     

Body mass index and nine-year mortality in disabled and nondisabled older U.S. individuals

OBJECTIVES: To investigate the relationship between body mass index (BMI) and 9-year mortality in older (≥65) Americans with and without disability.
DESIGN: Cohort study.
SETTING: The unique disability-focused National Long Term Care Survey (NLTCS) data that assessed the health and well-being of older individuals in 1994 were analyzed.
PARTICIPANTS: Four thousand seven hundred ninety-one individuals in the 1994 survey.
MEASUREMENTS: BMI (kg/m²) was calculated from self- or proxy reports of height and weight. The analysis was adjusted for 1-year change in BMI and demographic and health-related factors, as well as reports by proxies, and death occurring during the first 2 years after the interview.
RESULTS: The relative risk of death as a function of BMI formed a nonsymmetric U-shaped pattern, with larger risks associated with lower BMI (<22.0) and minimal risks for BMI of 25.0 to 34.9. (BMI 22.0–24.9 was the reference.) Adjustments for demographic and health-related factors had little effect on this pattern. Nondisabled individuals exhibited a similar U-shaped pattern but with lower risks associated with lower BMI. For disabled individuals, the mortality–risk pattern was higher for lower BMI (<22.0) and flat for higher BMI, thus exhibiting an inverse J shape. BMI patterns were age sensitive, with disability status affecting sensitivity.
CONCLUSION: Overweight or mild (grade 1) obesity was not a risk factor for 9-year mortality in older Americans participating in the 1994 NLTCS. A flatter BMI pattern of the relative risk of death for disabled than for nondisabled individuals suggests that optimal body weight can be sensitive to age and health and well-being.