Use of an interactive obesity treatment approach in individuals with severe mental illness: Feasibility, acceptability, and proposed engagement criteria

BACKGROUND: Digital and mobile health interventions are increasingly being used to support healthy lifestyle change, including in certain high-risk populations such as those with severe mental illnesses (SMIs). Life expectancy in this population lags 15 years behind counterparts in the general population, primarily due to obesity-related health conditions. OBJECTIVE: We tested the feasibility and usability of a 12-week interactive obesity treatment approach (iOTA) to adults with chronic SMIs (depression, bipolar disorder and schizophrenia spectrum disorder) receiving treatment in community settings. The iOTA incorporates short message service (SMS) text messages to supplement monthly in-person health coaching. METHODS: Factors hypothesized to be associated with weight change were illness severity and treatment engagement. Severe psychiatric symptoms were defined as baseline Clinical Global Impression severity score of \u3e5. Criterion engagement was defined as a text messaging response rate \u3e80% during the first 4 weeks of treatment. Disordered eating, assessed with the Loss of Control Over Eating Scores, was also evaluated. Participants provided qualitative data, further informing assessment of intervention feasibility, usability, and acceptability. RESULTS: A total of 26 participants were enrolled. The mean age was 48.5 (SD 15.67) years; 40% (10/26) were Black and 60% (15/26) female. Participants with lower symptom severity and adequate engagement demonstrated significantly decreased weight (F CONCLUSIONS: These results demonstrate the feasibility of delivering an adapted iOTA to SMI patients receiving care in community settings and suggest testable criteria for defining sufficient treatment engagement and psychiatric symptom severity, two factors known to impact weight loss outcomes. These important findings suggest specific adaptations may be needed for optimal treatment outcomes in individuals with SMI

Effect of Cu substitution on anion redox behaviour in P3-type sodium manganese oxides

This work was supported by the Faraday Institution (Grant No. FIRG018). The authors gratefully acknowledge support from the Engineering and Physical Sciences Research Council (EPSRC), Grant Nos. EP/L017008/1, EP/R023751/1 and EP/T019298/1.Sodium layered oxides which display oxygen anion redox behaviour are considered promising positive electrodes for sodium-ion batteries because they offer increased specific capacities. However, they suffer from irreversible structural changes resulting in significant capacity loss and limited oxygen redox reversibility. Here the effect of Cu substitution on the electrochemical performance of P3-type sodium manganese oxide is examined by evaluating the structural and electronic structural evolution upon cycling, supported by density functional theory (DFT) calculations. Over the voltage range 1.8–3.8 V vs. Na/Na+, where the redox reactions of the transition metal ions contribute entirely towards the charge compensation mechanism, stable cycling performance is maintained, showing a capacity retention of 90% of the initial discharge capacity of 166 mA h g−1 after 40 cycles at 10 mA g−1. Over an extended voltage range of 1.8–4.3 V vs. Na/Na+, oxygen anion redox is invoked, with a voltage hysteresis of 110 mV and a greater initial discharge capacity of 195 mA h g−1 at 10 mA g−1 is reached. Ex-situ powder x-ray diffraction patterns reveal distortion of the P3 structure to P'3 after charge to 4.3 V, and then transformation to O'3 upon discharge to 1.8 V, which contributes towards the capacity fade observed between the voltage range 1.8–4.3 V. DFT with projected density of states calculations reveal a strong covalency between the copper and oxygen atoms which facilitate both the cationic and anionic redox reactions in P3-type Na0.67Mn0.9Cu0.1O2.Publisher PDFPeer reviewe

Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasis

<p>Abstract</p> <p>Background</p> <p>Transforming Growth Factor β (TGF-β) plays an important role in tumor invasion and metastasis. We set out to investigate the possible clinical utility of TGF-β antagonists in a human metastatic basal-like breast cancer model. We examined the effects of two types of the TGF-β pathway antagonists (1D11, a mouse monoclonal pan-TGF-β neutralizing antibody and LY2109761, a chemical inhibitor of TGF-β type I and II receptor kinases) on sublines of basal cell-like MDA-MB-231 human breast carcinoma cells that preferentially metastasize to lungs (4175TR, 4173) or bones (SCP2TR, SCP25TR, 2860TR, 3847TR).</p> <p>Results</p> <p>Both 1D11 and LY2109761 effectively blocked TGF-β-induced phosphorylation of receptor-associated Smads in all MDA-MB-231 subclones <it>in vitro</it>. Moreover, both antagonists inhibited TGF-β stimulated <it>in vitro </it>migration and invasiveness of MDA-MB-231 subclones, indicating that these processes are partly driven by TGF-β. In addition, both antagonists significantly reduced the metastatic burden to either lungs or bones <it>in vivo</it>, seemingly independently of intrinsic differences between the individual tumor cell clones. Besides inhibiting metastasis in a tumor cell autonomous manner, the TGF-β antagonists inhibited angiogenesis associated with lung metastases and osteoclast number and activity associated with lytic bone metastases. In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer.</p> <p>Conclusions</p> <p>In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer.</p

Bluefin Tuna Larvae in Oligotrophic Ocean Foodwebs, Investigations of Nutrients to Zooplankton: Overview of the BLOOFINZ-Gulf of Mexico program

Western Atlantic bluefin tuna (ABT) undertake long-distance migrations from rich feeding grounds in the North Atlantic to spawn in oligotrophic waters of the Gulf of Mexico (GoM). Stock recruitment is strongly affected by interannual variability in the physical features associated with ABT larvae, but the nutrient sources and food-web structure of preferred habitat, the edges of anticyclonic loop eddies, are unknown. Here, we describe the goals, physical context, design and major findings of an end-to-end process study conducted during peak ABT spawning in May 2017 and 2018. Mesoscale features in the oceanic GoM were surveyed for larvae, and five multi-day Lagrangian experiments measured hydrography and nutrients; plankton biomass and composition from bacteria to zooplankton and fish larvae; phytoplankton nutrient uptake, productivity and taxon-specific growth rates; micro- and mesozooplankton grazing; particle export; and ABT larval feeding and growth rates. We provide a general introduction to the BLOOFINZ-GoM project (Bluefin tuna Larvae in Oligotrophic Ocean Foodwebs, Investigation of Nitrogen to Zooplankton) and highlight the finding, based on backtracking of experimental waters to their positions weeks earlier, that lateral transport from the continental slope region may be more of a key determinant of available habitat utilized by larvae than eddy edges per se.Postprint1,74

2020-05-08 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: UNM drug repurposing. NM cases. Doctors Without Borders. SNAP benefits online. NM 7th highest unemployment. Virtual LemonAid tonight. New N98 masks. Healthcare supply chain challenge. EMS lack resources. Infection risk in healthcare workers. COVID-19 on medical education. Human disinfectant chambers. Evidence of seroconversion. Dangers of considering herd immunity. Wastewater-based surveillance. More youths infected. Reconstructing ship spread. Pharmacoepidemiologic analysis. Clinicopathologic characteristics. Cancer treatment impact. Reduced voluntary psychiatric admission in Italy. Operating room management. Humidifiers reduce transmission. Phone contact tracing ethics. Call for patient database. Immunity certification program. Guidelines on tracheostomy, IBD, nose bleeding, pituitary tumors, and hematopoietic stem cells transplantation, benefits of low-PEEP, and of molecular diagnostics. FDA authorizes at-home test. Cephid Xpert test. MRSA nasal swabs. NIH remdesivir+barictinib RCT. Corticosteroid caution. Arbidol active in vitro. ACE/ARB systematic review. In silico phytochemical and virus protease candidates. Potential zinc benefit. 31 new clinical trials. Glycemic control benefit. Psychological effects meta-analysis and survey. Disease course model. Liver injury. Environmental and health perspectives. Olfactory and gustatory dysfunction. Vitamin D. Disease map

Preclinical Evaluation of AZ12601011 and AZ12799734, Inhibitors of Transforming Growth Factor β Superfamily Type 1 Receptors.

The transforming growth factor β (TGFβ) superfamily includes TGFβ, activins, inhibins, and bone morphogenetic proteins (BMPs). These extracellular ligands have essential roles in normal tissue homeostasis by coordinately regulating cell proliferation, differentiation, and migration. Aberrant signaling of superfamily members, however, is associated with fibrosis as well as tumorigenesis, cancer progression, metastasis, and drug-resistance mechanisms in a variety of cancer subtypes. Given their involvement in human disease, the identification of novel selective inhibitors of TGFβ superfamily receptors is an attractive therapeutic approach. Seven mammalian type 1 receptors have been identified that have context-specific roles depending on the ligand and the complex formation with the type 2 receptor. Here, we characterize the biologic effects of two transforming growth factor β receptor 1 (TGFBR1) kinase inhibitors designed to target TGFβ signaling. AZ12601011 [2-(2-pyridinyl)-4-(1H-pyrrolo[3,2-c]pyridin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine]; structure previously undisclosed] and AZ12799734 [4-({4-[(2,6-dimethyl-3-pyridinyl)oxy]-2-pyridinyl}amino)benzenesulfonamide] (IC50 = 18 and 47 nM, respectively) were more effective inhibitors of TGFβ-induced reporter activity than SB-431542 [4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzamide] (IC50 = 84 nM) and LY2157299 [4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide monohydrate]] (galunisertib) (IC50 = 380 nM). AZ12601011 inhibited phosphorylation of SMAD2 via the type 1 receptors activin A receptor type 1B (ALK4), TGFBR1, and activin A receptor type 1C (ALK7). AZ12799734, however, is a pan TGF/BMP inhibitor, inhibiting receptor-mediated phosphorylation of SMAD1 by activin A receptor type 1L, bone morphogenetic protein receptor type 1A, and bone morphogenetic protein receptor type 1B and phosphorylation of SMAD2 by ALK4, TGFBR1, and ALK7. AZ12601011 was highly effective at inhibiting basal and TGFβ-induced migration of HaCaT keratinocytes and, furthermore, inhibited tumor growth and metastasis to the lungs in a 4T1 syngeneic orthotopic mammary tumor model. These inhibitors provide new reagents for investigating in vitro and in vivo pathogenic processes and the contribution of TGFβ- and BMP-regulated signaling pathways to disease states

Behavioral Weight Loss Treatment for Youth Treated With Antipsychotic Medications

Background: Youth who are being treated with antipsychotic medications are at increased risk for the development of obesity and type 2 diabetes. Behavioral weight loss treatments show promise for reducing obesity and diabetes risk among adults treated with these drugs, but such treatments have not previously been studied in youth. Objective: We describe a rationale for behavioral weight loss intervention for high-weight youth being treated with antipsychotic medications. We report behavioral, anthropomorphic, and metabolic findings from a case series of obese adolescents taking antipsychotic medications who participated in a short-term, family-based behavioral weight loss intervention. Methods: We adapted the Traffic Light Plan, a 16-week family-based weight loss intervention that promotes healthy energy balance using the colors of the traffic light to categorize the nutritional value of foods and the intensity of physical activity. We then added a social and ecological framework to address health behavior change in multiple social contexts. The intervention was administered to three obese adolescents with long-term antipsychotic medication exposure. The efficacy of the intervention was evaluated with a battery of anthropomorphic and metabolic assessments, including weight, body mass index percentile, whole body adiposity, liver fat content, and fasting plasma glucose and lipid levels. Participants and their parents also filled out a treatment satisfaction questionnaire after study completion. Results: Two boys and one girl, all of whom were 14 years old, participated in this study. All three participants attended all 16 sessions of the intervention and experienced beneficial changes in adiposity, fasting lipid levels, and liver fat content associated with weight stabilization or weight loss. Adolescents and their parents all reported a high level of satisfaction with the treatment. Conclusions: Family-based behavioral weight loss treatment can be feasibly delivered and is acceptable to youth taking antipsychotic medications and their families. Randomized controlled trials are needed to fully evaluate the effectiveness and acceptability of these treatments for these individuals

2020-04-30 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NM residential facility deaths. NM case update. NM TriCore testing antibodies. Navajo nation cases. May 10 Navajo peak. Udall funding push. El Paso shopping discouraged. NM budget shortfall. Santa Fe furlough. Ethanol sanitizer safety. LA free testing for all. Michigan protest. NM Batelle N95 decontamination. Hospital revenue decline. Wastewater early detection. German herd immunity. 60-day viral shedding possible. Temporary infected “ark”. Prison release preparedness. Low quality research. Phased long-term care. Suicide prevention. Corticosteroid tradeoffs. Cloth mask guidelines. SARS-CoV-2 assays compared. IgG and viral loads. Better testing reporting. Dubious testing vendors. Promising oral drug. Hydroxychloroquine prophylaxis dosing. Umifenovir ineffective. Multi-drug nanoparticles. Drug discovery new targets. 38 new COVID-19 trials. Cancer research review. Attenuated SARS-CoV-2