2020-04-16 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Daily NM recap. Public Catholic masses resume. Chaplains stand down. Food delivered to tribal communities. Governors order face coverings use. Campfires restricted. NY hospitalizations fall. Nursing home probe in NJ. GOP call WHO Chief resignation. Africa cases up 51% and deaths up 60%. Sub-Saharan Africa prediction. Resurgence in Japan. UK conditions to reopen. France deaths up. UNMH protests over PPE. Med center financial stress. Hospitals bailout insufficient. 55% US healthcare worker cases hospital spread. Cruise ship transmission. Essential contact tracing. JAMA editors discuss policy. Guideline updates: treatment, emergency dep, ophthalmology, cath lab, telemedicine, liver disease, caregiver, health care facilities, FEMA, homeless services. Calcium channel blocker reduces fatality. Interferon lambda treatment. No benefit for lopinavir/ritonavir or arbidol in RCT. Donate plasma. Mixed results for antivirals on clearance. 37 new trials. Population-scale testing proposed. New rapid assay. Serology + RT-PCR needed. Hemoglobin monitoring. Co-infection of SARS-CoV-2. Urine glucose and proteinuria predict severity. Use damp cloth covers

2020-04-06 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NM case updates. Several NM policy and legislative actions. Federal vs. state conflict over medical supply lines. Healthcare workers sleep in cars to prevent family exposure. Same-day in-house testing at Cedars-Sinai. Debate over hydroxychloroquine Tx. Death rate differences: Germany and Italy. African innovations. Testing recommended with mild symptoms. CDC guidelines for law enforcement PPE. New WHO first responder training and CDC sign language resources. COVID-19 droplets can travel up to 27 feet. Transmission from the asymptomatic. Humidifiers help. Drug and vaccine progress

Proteomic comparisons of opaque and transparent variants of <i>Streptococcus pneumoniae</i> by two dimensional-differential gel electrophoresis

Streptococcus pneumoniae (the pneumococcus) is a human pathogen, accounting for massive global morbidity and mortality. Although asymptomatic colonization of the nasopharynx almost invariably precedes disease, the critical determinants enabling pneumococcal progression from this niche to cause invasive disease are poorly understood. One mechanism proposed to be central to this transition involves opacity phase variation, whereby pneumococci harvested from the nasopharynx are typically transparent, while those simultaneously harvested from the blood are opaque. Here, we used two dimensional-differential gel electrophoresis (2D-DIGE) to compare protein expression profiles of transparent and opaque variants of 3 pneumococcal strains, D39 (serotype 2), WCH43 (serotype 4) and WCH16 (serotype 6A) in vitro. One spot comprising a mixture of capsular polysaccharide biosynthesis protein and other proteins was significantly up-regulated in the opaque phenotype in all 3 strains; other proteins were differentially regulated in a strain-specific manner. We conclude that pneumococcal phase variation is a complex and multifactorial process leading to strain-specific pathogenicity.Melissa H. Chai, Florian Weiland, Richard M. Harvey, Peter Hoffmann, Abiodun D. Ogunniyi, James C. Pato

2020-04-14 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NMDOH county demographics online. NM emergency business loans. ABQ businesses violations. NM 5 new deaths 62 more cases. May 1 reopening too optimistic. MA contract tracing. Federal Ventilator Reserve. GM mass ventilator production. Ventilator-sharing device. $400M N-95 mask sterilization 60 sites. UNM PPE reprocessing online. Drug quality vulnerable. Managing urgent airway calls. Social distancing until 2022. SARS-Cov-2 blood supply. Contact tracing national blueprint. Mental health endangered. Successful surgical rapid response. Contact tracing medical ethics. Animal coronaviruses: human lessons. IDSA management guidelines. Ophthalmic practice. Pain management. Obstetrics management. Oncology practice. Forward triage. Scoring time-sensitive procedures. Outpatient structural heart disease. Thoracic surgery outcomes. Chest CT screening: epidemics. Sarcoma management. Endocrine diseases. Clinical pharmacists\u27 strategies. Non-invasive ventilation benefits. Essential laboratory testing. Psychiatric service. Hydroxychloroquine negative RCT. JAMA pharmacologic Tx review. Convalescent plasma. Promising antivirals. 55 clinical trials today. NYC hospitalization risk factors. Children milder disease. Blood morphology anomalies. No antimalarial consensus

2020-04-10 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Extra NM HSD SNAP benefits. NM cases \u3e1000. Meds supply chain threatened. Mass graves in NY. Surgeon General screening app. Presidential briefing. Italian healthcare worker deaths. Taiwan tiered care model. Communicating risks to public. French public demand hydroxychloroquine. Vaccination pause dangers. Retesting needed after discharge. CDC report geography and incidence. UW clinical informatics response. UW preparedness guidelines. Wuhan outbreak control. CDC asymptomatic exposed worker guidelines. Mask innovation. Unemployment spikes. Workforce gaps. Workspace modifications reduce transmission. Guidelines and recommendations: ER physician, surgery, cardiopulmonary resuscitation, chest imaging, geriatrics, critically ill children, postpyloric tube placement, genitourinary malignancies, obstetrics, and home work health. Remdesivir clinically promising. Hydroxychloroquine safe but higher mortality with azithromycin. Lockdown health risks. Post-ICU syndrome. Tetracyline therapy potential. ACE2 review. Repurposing candidates. Patient self-triage tool. Video of aerosol spread and lingering. Modeling challenges. 34 new clinical trials registered today

2020-04-15 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Daily NM recap. NM Hospital financial challenges. NM absentee voting. NM dairy farmers impact. 19-20 states open May 1? USA halts WHO funding. More NYC deaths. 250K tests AZ first responders. Global pandemic updates. Imported cases China. Masked South Korea elections. Danish children school return. PPE angiography. NYC cancels healthcare workers. GI shedding endoscopes. Blockade reduces transmission. Fever screening. Viral shedding post seroconversion. Radiology mitigations. Endoscopy units. Tracheostomy reduced transmission. Survivors plasma. Medical Imaging. Useful CTs. Electrophysiology procedures. Renin angiotensin blockers. Hemostasis. Dermatologic surgery. Pediatric gastroenterology. Autoimmune liver disease. Orthopedic surgical care. Updated treatment evidence. Asymptomatic detection. CVD pharmacology. Bleach disinfection. Arbidol beats lopinavir/ritonavir. IV immunoglobulin therapy. No HCQ clinical efficacy. Cepharantine inhibition pangolins. Machine learning antivirals. Eat bitter substances. 59 new trials. Combining RNA and antibody tests. No SARS-CoV-2 in patient ward air. Influenza impact prevention. Encephalitis. Low CD4+ and CD8+ severe. G6PD-deficient issues. Cytokine storm. Biosensor detection. Immunopathogenesis

2020-04-11/12 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: No NM church gatherings. NM a testing champ. Consolidation of elderly care. NM case update. 50-state disaster. Ventilator haggling. Economy reopening planning. PPE decontamination. Hospital ward contamination. Prolonged return to normal. FEMA projections. WHO tracking app. China SEIR model. Hubei epi. Mortality best measure. Covid-19 wave 2. Public should wear masks. Civil liberties. Safe grocery shopping. School closure impact. CDC caretaker guidelines. Psychiatric mobilization. Keep newborns with mom. C-section protocol. Italian obstetrics. Pediatric cardiac catherization. Chinese anesthesiology consensus. Cancer guidelines. Neuro-oncologic Tx. Radiology algorithm. Lung ultrasonography. ARF care. VTE common and predictable. Liver transplantation. Auto-immune treatments. Extracorporeal kidney involvement. Nutrition support. GI endoscopy. No stay-at-home for stroke. Intensive care collaboration. Supine swab collection. Lab tests for severity. Testing assay performance. False negative RT-PCR tests. IgM and IgG serum tests. FDA convalescent plasma. Blood purification device approval. Erythropoietin treatment. Tissue plasminogen activator. ECMO. Lopinavir/ritonavir study results. Immunotherapy review. Vaccine development. Hydroxychloroquine review. Candidates from in silico/virtual screening. Traditional Indian therapies. US trials update. Pathways and risk factors for death. ACE2 polymorphism. Severity in children. Lung tissue replication. Phylogenetic tracing. Text mining dataset. Risk by blood type

Structuring heterogeneous biological information using fuzzy clustering of k-partite graphs

<p>Abstract</p> <p>Background</p> <p>Extensive and automated data integration in bioinformatics facilitates the construction of large, complex biological networks. However, the challenge lies in the interpretation of these networks. While most research focuses on the unipartite or bipartite case, we address the more general but common situation of <it>k</it>-partite graphs. These graphs contain <it>k </it>different node types and links are only allowed between nodes of different types. In order to reveal their structural organization and describe the contained information in a more coarse-grained fashion, we ask how to detect clusters within each node type.</p> <p>Results</p> <p>Since entities in biological networks regularly have more than one function and hence participate in more than one cluster, we developed a <it>k</it>-partite graph partitioning algorithm that allows for overlapping (fuzzy) clusters. It determines for each node a degree of membership to each cluster. Moreover, the algorithm estimates a weighted <it>k</it>-partite graph that connects the extracted clusters. Our method is fast and efficient, mimicking the multiplicative update rules commonly employed in algorithms for non-negative matrix factorization. It facilitates the decomposition of networks on a chosen scale and therefore allows for analysis and interpretation of structures on various resolution levels. Applying our algorithm to a tripartite disease-gene-protein complex network, we were able to structure this graph on a large scale into clusters that are functionally correlated and biologically meaningful. Locally, smaller clusters enabled reclassification or annotation of the clusters' elements. We exemplified this for the transcription factor MECP2.</p> <p>Conclusions</p> <p>In order to cope with the overwhelming amount of information available from biomedical literature, we need to tackle the challenge of finding structures in large networks with nodes of multiple types. To this end, we presented a novel fuzzy <it>k</it>-partite graph partitioning algorithm that allows the decomposition of these objects in a comprehensive fashion. We validated our approach both on artificial and real-world data. It is readily applicable to any further problem.</p

Epistasis among Presynaptic Serotonergic System Components

Epistatic interactions among regulatory components of the serotonin (5-HT) neurotransmitter system may be an important aspect of 5-HT function. Because 5-HT dysregulation is associated with several common psychiatric disorders, the potential for epistasis among genetic variants in the 5-HT transporter (SERT), 5-HT 1B terminal autoreceptor and the 5-HT 1A somatodendritic autoreceptor should be examined. In this study, output from a dynamic minimal model of 5-HT function was compared to empirical results in the literature. Parameters representing extracellular 5-HT clearance rates (SERT), 5-HT release levels (5-HT 1B ) and inhibitory thresholds (the amount of extracellular 5-HT above which cell firing is inhibited, an indication of 5-HT 1A autoreceptor sensitivity) were varied to simulate genetic deletion (i.e. knockout) of each component singly, and in combination. Simulated knockout effects on extracellular 5-HT level and presynaptic neural firing rates were in the same direction and of similar relative magnitude as studies in the literature. Epistasis among presynaptic components appears to be important in the 5-HT system’s regulation of extracellular 5-HT levels, but not of firing rates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44113/1/10519_2004_Article_1019.pd

l-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells

This study tested the hypothesis that l-arginine (Arg) may stimulate cell proliferation and prevent lipopolysaccharide (LPS)-induced death of intestinal cells. Intestinal porcine epithelial cells (IPEC-1) were cultured for 4 days in Arg-free Dulbecco’s modified Eagle’s-F12 Ham medium (DMEM-F12) containing 10, 100 or 350 μM Arg and 0 or 20 ng/ml LPS. Cell numbers, protein concentrations, protein synthesis and degradation, as well as mammalian target of rapamycin (mTOR) and Toll-like receptor 4 (TLR4) signaling pathways were determined. Without LPS, IPEC-1 cells exhibited time- and Arg-dependent growth curves. LPS treatment increased cell death and reduced protein concentrations in IPEC-1 cells. Addition of 100 and 350 μM Arg to culture medium dose-dependently attenuated LPS-induced cell death and reduction of protein concentrations, in comparison with the basal medium containing 10 μM Arg. Furthermore, supplementation of 100 and 350 μM Arg increased protein synthesis and reduced protein degradation in both control and LPS-treated IPEC-1 cells. Consistent with the data on cell growth and protein turnover, addition of 100 or 350 μM Arg to culture medium increased relative protein levels for phosphorylated mTOR and phosphorylated ribosomal protein S6 kinase-1, while reducing the relative levels of TLR4 and phosphorylated levels of nuclear factor-κB in LPS-treated IPEC-1 cells. These results demonstrate a protective effect of Arg against LPS-induced enterocyte damage through mechanisms involving mTOR and TLR4 signaling pathways, as well as intracellular protein turnover