Revised SED of the triple protostellar system VLA 1623-2417

VLA 1623$-$2417 is a triple protostellar system deeply embedded in Ophiuchus A. Sources A and B have a separation of 1.1", making their study difficult beyond the submillimeter regime. Lack of circumstellar gas emission suggested that VLA 1623$-$2417 B has a very cold envelope and is much younger than source A, generally considered the prototypical Class 0 source. We explore the consequences of new ALMA Band 9 data on the spectral energy distribution (SED) of VLA 1623$-$2417 and their inferred nature. Using dust continuum observations spanning from centimeter to near-infrared wavelengths, the SED of each component in VLA 1623$-$2417 is constructed and analysed. The ALMA Band 9 data presented here show that the SED of VLA 1623$-$2417 B does not peak at 850 $\mu$m as previously expected, but instead presents the same shape as VLA 1623$-$2417 A at wavelengths shorter than 450 $\mu$m. The results presented here indicate that the previous assumption that the flux in $Herschel$ and Spitzer observations is solely dominated by VLA 1623$-$2417 A is not valid, and instead, VLA 1623$-$2417 B most likely contributes a significant fraction of the flux at $\lambda~<$ 450 $\mu$m. These results, however, do not explain the lack of circumstellar gas emission and puzzling nature of VLA 1623$-$2417 B.Comment: 6 pages, 2 figures, accepted to A&A letters to the edito

Nobody Wants to Be Narcan\u27d: A Pilot Qualitative Analysis of Drug Users\u27 Perspectives on Naloxone

INTRODUCTION: Bystander naloxone distribution is an important component of public health initiatives to decrease opioid-related deaths. While there is evidence supporting naloxone distribution programs, the effects of increasing naloxone availability on the behavior of people who use drugs have not been adequately delineated. In this study we sought to 1) evaluate whether individuals\u27 drug use patterns have changed due to naloxone availability; and 2) explore individuals\u27 knowledge of, access to, experiences with, and perceptions of naloxone. METHODS: We conducted a pilot study of adults presenting to the emergency department whose medical history included non-medical opioid use. Semi-structured interviews were conducted with participants and thematic analysis was used to code and analyze interview transcripts. RESULTS: Ten participants completed the study. All were aware of naloxone by brand name (Narcan) and had been trained in its use, and all but one had either currently or previously possessed a kit. Barriers to naloxone administration included fear of legal repercussions, not having it available, and a desire to avoid interrupting another user\u27s high. Of the eight participants who reported being revived with naloxone at least once during their lifetime, all described experiencing a noxious physical response and expressed a desire to avoid receiving it again. Furthermore, participants did not report increasing their use of opioids when naloxone was available. CONCLUSIONS: Participants were accepting of and knowledgeable about naloxone, and were willing to administer naloxone to save a life. Participants tended to use opioids more cautiously when naloxone was present due to fears of experiencing precipitated withdrawal. This study provides preliminary evidence countering the unsubstantiated narrative that increased naloxone availability begets more high-risk opioid use and further supports increasing naloxone access

Generation of cloned transgenic pigs rich in omega-3 fatty acids

Meat products are generally low in omega-3 (n-3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty acids from n-6 analogs, and their tissues have a significantly reduced ratio of n-6/n-3 fatty acids (P < 0.001). © 2006 Nature Publishing Group

Effects of Exposure to Community Violence and Family Violence on School Functioning Problems among Urban Youth: The Potential Mediating Role of Posttraumatic Stress Symptoms

Adolescents who are exposed to violence during childhood are at an increased risk for developing posttraumatic stress (PTS) symptoms. The literature suggests that violence exposure might also have negative effects on school functioning, and that PTS might serve as a potential mediator in this association. The purpose of the current study was to replicate and extend prior research by examining PTS symptoms as a mediator of the relationship between two types of violence exposure and school functioning problems among ado- lescent youth from an urban setting. Participants included a sample of 121 junior high and high school students (M = 15 years; range = 13–16 years; 60 males, 61 females) within high-crime neighborhoods. Consistent with our hypotheses, community violence and fam- ily violence were associated with PTS symptoms and school functioning problems. Our data suggest that community and family violence were indirectly related to school func- tioning problems through PTS symptoms. Findings from this study demonstrate that PTS symptoms potentially mediate the relationship between violence exposure and school functioning problems across two settings (community and home). Future research should further examine protective factors that can prevent youth violence exposure as well as negative outcomes related to violence

A mouse chromosome 4 balancer ENU-mutagenesis screen isolates eleven lethal lines.

BACKGROUND: ENU-mutagenesis is a powerful technique to identify genes regulating mammalian development. To functionally annotate the distal region of mouse chromosome 4, we performed an ENU-mutagenesis screen using a balancer chromosome targeted to this region of the genome. RESULTS: We isolated 11 lethal lines that map to the region of chromosome 4 between D4Mit117 and D4Mit281. These lines form 10 complementation groups. The majority of lines die during embryonic development between E5.5 and E12.5 and display defects in gastrulation, cardiac development, and craniofacial development. One line displayed postnatal lethality and neurological defects, including ataxia and seizures. CONCLUSION: These eleven mutants allow us to query gene function within the distal region of mouse chromosome 4 and demonstrate that new mouse models of mammalian developmental defects can easily and quickly be generated and mapped with the use of ENU-mutagenesis in combination with balancer chromosomes. The low number of mutations isolated in this screen compared with other balancer chromosome screens indicates that the functions of genes in different regions of the genome vary widely

Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics

Constitutively activated STAT3 protein has been found to be a key regulator of pancreatic cancer and a target for molecular therapeutic intervention. In this study, PG-S3-001, a small molecule derived from the SH-4-54 class of STAT3 inhibitors, was found to inhibit patient-derived pancreatic cancer cell proliferation in vitro and in vivo in the low micromolar range. PG-S3-001 binds the STAT3 protein potently, Kd = 324 nmol/L by surface plasmon resonance, and showed no effect in a kinome screen (>100 cancer-relevant kinases). In vitro studies demonstrated potent cell killing as well as inhibition of STAT3 activation in pancreatic cancer cells. To better model the tumor and its microenvironment, we utilized three-dimensional (3D) cultures of patient-derived pancreatic cancer cells in the absence and presence of cancer-associated fibroblasts (CAF). In this coculture model, inhibition of tumor growth is maintained following STAT3 inhibition in the presence of CAFs. Confocal microscopy was used to verify tumor cell death following treatment of 3D cocultures with PG-S3-001. The 3D model was predictive of in vivo efficacy as significant tumor growth inhibition was observed upon administration of PG-S3-001. These studies showed that the inhibition of STAT3 was able to impact the survival of tumor cells in a relevant 3D model, as well as in a xenograft model using patient-derived cells

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Proteomic profiles for Alzheimer's disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma: An Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study.

INTRODUCTION: Previously generated serum and plasma proteomic profiles were examined among adults with Down syndrome (DS) to determine whether these profiles could discriminate those with mild cognitive impairment (MCI-DS) and Alzheimer's disease (DS-AD) from those cognitively stable (CS). METHODS: Data were analyzed on n = 305 (n = 225 CS; n = 44 MCI-DS; n = 36 DS-AD) enrolled in the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS). RESULTS: Distinguishing MCI-DS from CS, the serum profile produced an area under the curve (AUC) = 0.95 (sensitivity [SN] = 0.91; specificity [SP] = 0.99) and an AUC = 0.98 (SN = 0.96; SP = 0.97) for plasma when using an optimized cut-off score. Distinguishing DS-AD from CS, the serum profile produced an AUC = 0.93 (SN = 0.81; SP = 0.99) and an AUC = 0.95 (SN = 0.86; SP = 1.0) for plasma when using an optimized cut-off score. AUC remained unchanged to slightly improved when age and sex were included. Eotaxin3, interleukin (IL)-10, C-reactive protein, IL-18, serum amyloid A , and FABP3 correlated fractions at r2 > = 0.90. DISCUSSION: Proteomic profiles showed excellent detection accuracy for MCI-DS and DS-AD