AT 009 / Affitech - LARVOL DELTA

Safety of Intravenous Arginine Therapy in Children with Sickle Cell Disease Hospitalized for Vaso-Occlusive Pain: A Randomized Placebo-Controlled Trial in Progress (ASH 2019) - P2; "This protocol utilizes IND#66943 (Sponsor-Morris), is registered with ClinicalTrials.gov (NCT02536170) & is funded by FDA-R01FD004814-01A2 & in part by NCCIH K24AT009893-01 (both to CRM)... All SAEs were expected events related to SCD. Additionally, SAE/AE rates were similar across study arms, providing further support for the safety of arginine therapy in children with SCD. Re-hospitalization rates within 72-hours are less than the ~20% previously reported in the literature."

Clinical

Sex Differences in Cannabinoid-Mediated Energy Homeostasis (CPDD 2022) - "Financial Support : R00AT009156 and MICHIGAN STATE UNIVERSITY Aim : The interplay of sex hormones and the cannabinoid system has been established in several physiological process... These data suggest that the cannabinoid system alters energy balance centrally and peripherally in a sex-specific way. Further analyses examining the sex-specific effects of CB1 receptor deletion on adipose tissue biology will be presented in June meeting."

Genetic Disorders • Obesity

LncRNA BIRF Promotes Brain Ischemic Tolerance Induced By Cerebral Ischemic Preconditioning Through Upregulating GLT-1 via Sponging miR-330-5p. (PubMed, Mol Neurobiol) - "The results of Cell-Counting Kit-8 (CCK-8) assay showed that a novel lncRNA, NONRATT009133.2, which we referred to as brain ischemia-related factor (BIRF), was highly correlated with BIT...Taken together, our results demonstrate the important roles of the BIRF/miR-330-5p/GLT-1 axis in the induction of BIT by CIPC. BIRF may be a potentially effective therapeutic strategy against stroke injury."

Journal • Cardiovascular

0D/2D Mixed Dimensional Lead-Free Caesium Bismuth Iodide Perovskite for Solar Cell Application. (PubMed, Materials (Basel)) - "The XRD pattern revealed additional characteristics peaks at 009, 012, 209 and 300, indicating the growth of another phase...When cells with and without solvent vapour annealing are compared, the power conversion efficiency of caesium bismuth iodide increases from 0.26% without solvent annealing to 0.98% with solvent vapour annealing. This study establishes a new route for future research on crystal configuration, nomenclature, film and morphology, quality tailoring and applications toward the goal of lead-free perovskite solar cells."

Journal

LncRNA NONRATT009773.2 promotes bone cancer pain progression through the miR-708-5p/CXCL13 axis. (PubMed, Eur J Neurosci) - "Moreover, NONRATT009773.2 functioned as a microRNA (miRNA) sponge to absorb miR-708-5p and up-regulated miRNA downstream target CXCL13, which plays fundamental roles in the initiation and maintenance of neuroinflammation and hyperalgesia. Collectively, our current findings indicated that NONRATT009773.2 could be employed as a new therapeutic target for BCP."

Journal • Immunology • Inflammation • Oncology • Osteosarcoma • Pain • Sarcoma • Solid Tumor • CXCL13

LncRNA NONHSAT009968 inhibits the osteogenic differentiation of hBMMSCs in SA-induced inflammation via Wnt3a. (PubMed, Biochem Biophys Res Commun) - "In sum, the results suggested that lncNONHSAT009968 inhibited osteogenic differentiation of hBMMSCs in SA-induced inflammation through Wnt3a, which may have affected the occurrence and development of osteomyelitis. This study might provide novel insights regarding osteomyelitis and infectious bone defects."

Journal • Immunology • Infectious Disease • Inflammation • Musculoskeletal Diseases • Orthopedics

Profiling and Molecular Mechanism Analysis of Long Non-Coding RNAs and mRNAs in Pulmonary Arterial Hypertension Rat Models. (PubMed, Front Pharmacol) - "In the end, lncRNA NONRATT009275.2 could facilitate macrophage polarization to M2 type and be involved in inflammatory immune response. In conclusion, this study provided candidate drug targets and potential roles on lncRNAs in the pathogenesis of PAH, and several key regulatory genes were identified, which laid the initial foundation for further mechanism study in PAH."

Journal • Preclinical • Hypertension • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • PDGFC • SERPINA1

[VIRTUAL] Pain Catastrophizing in Fibromyalgia is associated with insula and cingulate metabolite concentrations – a voxel-wise 3D MR Spectroscopic Imaging study (IASP 2021) - "Source of Financial Support for the Project: This work was funded by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R01-AR064367, National Center for Complementary and Integrative Health grants R01-AT007550, R61-AT009306, and P01-AT AT009965, and National Center for Research Resources grants P41-RR14075, S10-RR021110, and S10-RR023043)...Participants’ age and usage of medications known to affect Glx (gabapentin and pregabalin) were controlled for in this analysis... Pain catastrophizing in FM patients was associated with greater concentrations of metabolites known to be linked with excitatory neurotransmission (Glx) and neuroinflammation (mIno) in important pain and salience processing areas such as the insular cortex. Greater pain catastrophizing was also associated with metabolite concentrations in brain areas linked with both cognitive and emotional dimensions of pain processing such as anterior thalamus and anterior cingulate..."

Dermatology • Fibromyalgia • Immunology • Inflammation • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Rheumatology • AGER

[VIRTUAL] The Association of Prenatal Cannabis Use and Birth Outcomes in a Michigan Cohort (CPDD 2021) - "Financial Support: Michigan State University and NCCIH (R00AT009156) Aim: Cannabis use prevalence has doubled among pregnant women in the United States... In a Michigan cohort of pregnant women, we did not observe an association between cannabis use and birthweight, gestational age, Apgar score, or NICU admission. Small sample size was a limitation; larger prospective studies are warranted. Since prenatal cannabis use is increasing, clinicians should counsel patients to discontinue cannabis use during pregnancy."

Critical care

[VIRTUAL] Phone-Delivered Screening, Brief Intervention, and Referral to Treatment for Pain Management Among New England Veterans With Chronic Pain: A Pilot Study (CPDD 2021) - "Financial Support: UH3AT009758 (MIR/SM) Aim: Chronic pain puts sufferers at risk for substance misuse...Only one positive toxicology test (amphetamine, possible prescribed) was in someone who denied substance misuse... It was feasible to deliver SBIRT-PM by phone to Veterans across New England, and it was possible to track self-reported study outcomes over 12 weeks. Toxicological analysis of nail samples largely corroborated self-report but follow-up was sub-optimal. Preliminary results suggest SBIRT-PM has promise to engage Veterans in pain services and improve pain and substance use outcomes."

Clinical • Musculoskeletal Diseases • Pain

Bioinformatics-Based Analysis of the lncRNA-miRNA-mRNA Network and TF Regulatory Network to Explore the Regulation Mechanism in Spinal Cord Ischemia/Reperfusion Injury. (PubMed, Front Genet) - "Furthermore, qRT-PCR results showed that the NONRATT009530.2, NONRATT026999.2, Map3k8, Hfn4a, and SP1 were significantly upregulated in SCII of rats, while the miR-20b-5p was downregulated. Our results offer a new insight to understand the ceRNA regulation mechanism in SCII and identify highlighted lncRNA-miRNA-mRNA axes and two key TFs as potential targets for prevention and treatment of SCII."

Journal • Cardiovascular • Reperfusion Injury • HNF1A • MAP3K8 • MIR20B

[VIRTUAL] Impact of Oral Arginine Therapy on Global Arginine Bioavailability in Nigerian Children with Sickle Cell Anemia and Vaso-Occlusive Pain (ASH 2020) - "Arginine deficiency plays a role in acute pain requiring hospitalization in Nigerian children with SCA, similar to what has been reported in the US. Plasma arginine levels significantly increased with arginine supplementation, and improved global arginine bioavailability was inversely associated with total opioids used in VOE management. Lowest arginine levels were found in children with ACS, as previously reported in the US (Morris et al, 2000), a phenomenon that warrants further investigation."

Clinical • Anemia • Genetic Disorders • Hematological Disorders • Pain • Pediatrics • Sickle Cell Disease

Effectiveness and Reach of the Primary Palliative Care for Emergency Medicine (PRIM-ER) Pilot Study: a Qualitative Analysis. (PubMed, J Gen Intern Med) - P=N/A | "Capitalizing on strong institutional leadership support and established QI processes enhanced the reach and effectiveness of the PRIM-ER pilot. These findings will guide the PRIM-ER researchers in scaling up the intervention in the remaining 33 sites, as well as enhance the planning of other complex quality improvement interventions in clinical settings."

Clinical • Journal • Palliative care

Design and implementation of a clinical decision support tool for primary palliative Care for Emergency Medicine (PRIM-ER). (PubMed, BMC Med Inform Decis Mak) - P=N/A | "CDS can be an effective tool in the implementation of primary palliative care quality improvement best practices. Health systems should thoughtfully consider tailoring their CDSs in order to adapt to their unique workflows and environments. The findings of this research can assist health systems in effectively integrating a primary palliative care CDS system seamlessly into their processes of care."

Clinical • Journal • Palliative care

"Great advice. @hunter_reavis @Adam_Ferrari_ @MoreiraPharmD @Prawat2009Rawat @CAMBUpenn" (@ronny_drapkin)

Massage increases satellite cell number independent of the age-associated alterations in sarcolemma permeability. (PubMed, Physiol Rep) - "Data suggest that the load applied here, which was previously shown to induce immunomodulatory changes, does not induce overt muscle injury in young and old muscles but may result in muscle remodeling. Funded by NIH grant AG042699 and AT009268."

Journal • Immune Modulation • Inflammation

A six-microRNA signature predicts survival of patients with uterine corpus endometrial carcinoma. (PubMed, Curr Probl Cancer) - "Among them, 6 miRNAs (hsa-mir-15a.MIMAT0000068, hsa-mir-142.MIMAT0000433, hsa-mir-142.MIMAT0000434, hsa-mir-3170.MIMAT0015045, hsa-mir-1976.MIMAT0009451, and hsa-mir-146a.MIMAT0000449) were validated to be significantly correlated with the OS of patients with UCEC. The risk indictor established by the 6-microRNA signature was proved be an independent prognostic factor (Hazard ratio = 0.391; 95% CI: 0.195-0.783; P = 0.008). In conclusion, we identified miRNAs that were correlated with the occurrence and progression of UCEC and established a 6-microRNA expression signature as a predictor for the OS of patients with UCEC."

Clinical • Journal • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Uterine Cancer

Modulation of the Neural Circuitry Underlying Trait Hypnotizability Using Spaced Continuous Theta-Burst Stimulation (SOBP 2018) - "1R33AT009305-01 (Williams); Background: The neural trait of hypnotizability is a reflection of greater functional connectivity (fc) between the left dorsolateral prefrontal cortex (L-DLPFC) and the dorsal anterior cingulate cortex (dACC)... Spaced cTBS produced stable increases in hypnotizability over the course of an hour in 12 of 13 participants."

CNS Disorders

"Wonderful Journal Club for lab meeting. SOX17 and tumor angiogenesis and single-cell RNA-Seq and heterogeneity. Great job @MoreiraPharmD and @Prawat2009Rawat!" (@ronny_drapkin)

Heterogeneity

Effect of the traditional Chinese medicine Qi Teng Xiao Zhuo granules on chronic glomerulonephritis rats studied by using long noncoding RNAs expression profiling. (PubMed, Gene) - "The ten lncRNAs might play important roles in the Qi Teng Xiao Zhuo granules treatment of CGN. Key genes, such as Ptprc (protein tyrosine phosphatase, receptor type, C), TOP2a, Fos (FBJ osteosarcoma oncogene), Myc (myelocytomatosis oncogene), etc, may be crucial biomarkers for Qi Teng Xiao Zhuo granules."

Biomarker • Journal

LncRNAs expression in adriamycin-induced rats reveals the potential role of LncRNAs contributing to chronic glomerulonephritis pathogenesis. (PubMed, Gene) - "The ten LncRNAs were differentially expressed and might play important roles in the development of CGN. Key genes, such as Il6, Ptprc, TOP2a, Fos, Myc, etc., may be crucial biomarkers for CGN."

Biomarker • Journal