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FDA Panel Backs 2 Hepatitis C Drugs

Title: FDA Panel Backs 2 Hepatitis C Drugs
Category: Health News
Created: 4/29/2011 11:01:00 AM
Last Editorial Review: 4/29/2011 12:00:00 AM




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Afinitor Approval Expanded to Include Benign Kidney Tumors

Title: Afinitor Approval Expanded to Include Benign Kidney Tumors
Category: Health News
Created: 4/27/2012 2:05:00 PM
Last Editorial Review: 4/30/2012 12:00:00 AM




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Diamond Pet Food Recall Expands

Title: Diamond Pet Food Recall Expands
Category: Health News
Created: 5/2/2012 11:00:00 AM
Last Editorial Review: 5/2/2012 12:00:00 AM




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Once-Banned Bird Flu Study Suggests Pandemic Threat Is Real

Title: Once-Banned Bird Flu Study Suggests Pandemic Threat Is Real
Category: Health News
Created: 5/2/2012 4:05:00 PM
Last Editorial Review: 5/3/2012 12:00:00 AM




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Companies to Donate Prosthetic Legs to Boston Bombing Victims in Need

Title: Companies to Donate Prosthetic Legs to Boston Bombing Victims in Need
Category: Health News
Created: 4/30/2013 8:35:00 PM
Last Editorial Review: 5/1/2013 12:00:00 AM




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Testicular Cancer on Rise in U.S., Especially Among Hispanic Men

Title: Testicular Cancer on Rise in U.S., Especially Among Hispanic Men
Category: Health News
Created: 5/3/2013 12:35:00 PM
Last Editorial Review: 5/3/2013 12:00:00 AM




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Spanking May Be More Common Than Parents Admit

Title: Spanking May Be More Common Than Parents Admit
Category: Health News
Created: 4/29/2014 7:36:00 PM
Last Editorial Review: 4/30/2014 12:00:00 AM




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Japan Quake Shows How Stress Alters the Brain

Title: Japan Quake Shows How Stress Alters the Brain
Category: Health News
Created: 4/29/2014 12:35:00 PM
Last Editorial Review: 4/30/2014 12:00:00 AM




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Company to Destroy 265 Tons of Ice Cream Over Listeria Contamination

Title: Company to Destroy 265 Tons of Ice Cream Over Listeria Contamination
Category: Health News
Created: 4/28/2015 12:00:00 AM
Last Editorial Review: 4/29/2015 12:00:00 AM




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Cloudy Climes May Up Risk of Pancreatic Cancer: Study

Title: Cloudy Climes May Up Risk of Pancreatic Cancer: Study
Category: Health News
Created: 4/30/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM




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Hispanic Women's Upbeat Outlook May Boost Heart Health

Title: Hispanic Women's Upbeat Outlook May Boost Heart Health
Category: Health News
Created: 4/29/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM




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Certain Cancers Seem Less Likely for Kids of Hispanic Moms Born Outside U.S.

Title: Certain Cancers Seem Less Likely for Kids of Hispanic Moms Born Outside U.S.
Category: Health News
Created: 4/25/2016 12:00:00 AM
Last Editorial Review: 4/26/2016 12:00:00 AM




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Spanking: More Harm Than Good?

Title: Spanking: More Harm Than Good?
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM




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Tobacco Companies Must Put New Warnings on Packaging, Court Says

Title: Tobacco Companies Must Put New Warnings on Packaging, Court Says
Category: Health News
Created: 5/1/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM




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Calm Parenting Will Help Children Through Coronavirus Pandemic

Title: Calm Parenting Will Help Children Through Coronavirus Pandemic
Category: Health News
Created: 4/26/2020 12:00:00 AM
Last Editorial Review: 4/26/2020 12:00:00 AM




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Isolation During Coronavirus Pandemic a Trigger for Depression

Title: Isolation During Coronavirus Pandemic a Trigger for Depression
Category: Health News
Created: 4/27/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM




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Have Heart Failure? Take Precautions During Pandemic

Title: Have Heart Failure? Take Precautions During Pandemic
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM




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Don't Let the Coronavirus Pandemic Rob You of Your Sleep

Title: Don't Let the Coronavirus Pandemic Rob You of Your Sleep
Category: Health News
Created: 4/29/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM




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Pandemic Delaying Medical Care of Older Americans

Title: Pandemic Delaying Medical Care of Older Americans
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM




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During Coronavirus Pandemic, Don't Ignore Symptoms of Heart Attack, Stroke

Title: During Coronavirus Pandemic, Don't Ignore Symptoms of Heart Attack, Stroke
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 4/30/2020 12:00:00 AM




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Company Selling Direct-to-Consumer Coronavirus Antibody Test

Title: Company Selling Direct-to-Consumer Coronavirus Antibody Test
Category: Health News
Created: 4/30/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM




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Best Ways to Help Kids Through the Pandemic

Title: Best Ways to Help Kids Through the Pandemic
Category: Health News
Created: 5/1/2020 12:00:00 AM
Last Editorial Review: 5/1/2020 12:00:00 AM




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Pregnancy Guidelines During COVID-19 Pandemic

Title: Pregnancy Guidelines During COVID-19 Pandemic
Category: Health News
Created: 4/2/2020 12:00:00 AM
Last Editorial Review: 4/2/2020 12:00:00 AM




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Pangolins Hold Clues to How COVID-19 Began -- and Might End

Title: Pangolins Hold Clues to How COVID-19 Began -- and Might End
Category: Health News
Created: 5/8/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM




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COVID-19 Pandemic May Lead to 75,000 'Deaths of Despair'

Title: COVID-19 Pandemic May Lead to 75,000 'Deaths of Despair'
Category: Health News
Created: 5/8/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM




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Baby Boom After Pandemic Lockdowns? Maybe Not

Title: Baby Boom After Pandemic Lockdowns? Maybe Not
Category: Health News
Created: 5/8/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM




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Inhaler Use Up During Coronavirus Pandemic

Between the first seven days of January 2020 and the last seven days of March, mean daily controller inhaler use rose 14.5%.




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COVID-19 Daily: ER Docs Procure PPE, Earlier Pandemic Start

These are the coronavirus stories you need to know about today.




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Don't Expect a Baby Boom After Pandemic Lockdowns

Researchers conducted nearly 1,500 online interviews and found that nearly 82% of those surveyed said they didn't plan to conceive during the coronavirus pandemic.




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Pangolins May Hold Clues to How COVID-19 Began

Learning more about this evolutionary advantage in pangolins may suggest possible treatments for coronavirus in humans, the team said.




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Mental Health an Emerging Crisis of COVID Pandemic

Americans are reporting high levels of emotional distress from the coronavirus pandemic – levels that some experts warn may lead to national mental health crisis.




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Public Access Expansion and PMC

Last month marked the third anniversary of the White House’s Office of Science and Technology Policy (OSTP) memorandum directing Federal agencies with more than $100 million in annual research and development (R&D) expenditures to develop plans for increasing public access to the results of the research they support, including scholarly publications. As a result of this directive, in 2015, PMC started providing support as a public access repository for funding agencies beyond the National Institutes of Health (NIH) and Howard Hughes Medical Institute (HHMI).

As of March 2015, the following additional agencies are using the NIH Manuscript Submission (NIHMS) system to facilitate the deposit in PMC of peer-reviewed manuscripts that fall under their public access policies:

  • Agency for Healthcare Research Quality (AHRQ/HHS)
  • Centers for Disease Control and Prevention (CDC/HHS),
  • Food and Drug Administration (FDA/HHS),
  • National Institute of Standards and Technology (NIST), and
  • U.S. Department of Veterans Affairs (VA)

Additionally, the following additional HHS and other federal agencies have announced public access plans and committed to using PMC as the repository for agency-funded publications:

  • Administration for Community Living (ACL/HHS)
  • Assistant Secretary for Preparedness and Response (ASPR/HHS)
  • Environmental Protection Agency (EPA)
  • National Aeronautics and Space Administration (NASA)

PMC will continue to update the list of participating funding agencies at Public Access and PMC as these agencies begin implementation of their policies.

More information about the current status of public access expansion as a result of the OSTP memo can be found on the White House blog.




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PMC Continues to Expand its Role as a Repository for Federally and Privately-funded Research

Since March 2016, the NIH Manuscript Submission (NIHMS) system has added support for researchers from the following federal agencies to deposit in PMC any manuscripts that fall under the agency’s public access policy:

  • Assistant Secretary for Preparedness and Response (ASPR/HHS; intramural only at this time)
  • Environmental Protection Agency (EPA; intramural only at this time)
  • National Aeronautics and Space Administration (NASA; intramural/civil servants and grantees)

Manuscript deposit support for all Administration for Community Living (ACL/HHS) researchers will be available in NIHMS by October 2017 and for Department of Homeland Security researchers in early 2018.

Additionally, the Bill & Melinda Gates Foundation Open Access Policy now requires their grantees to make their published research results available in PMC immediately upon publication under a Creative Commons Attribution (CC-BY) license. Manuscript deposit support is not provided in NIHMS for Gates-funded researchers; rather the final published version of any Gates-funded article is to be deposited directly to PMC by the publisher or a funder-supported data provider without author involvement. More information on this open access policy is available on the Gates Foundation website.

PMC will continue to update the list of participating funding agencies at Public Access and PMC as support is implemented.




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Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti-c-Met Antibody, in Patients with Advanced Solid Tumors

This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose escalation (3+3 design), 3 to 6 patients with advanced solid tumors were enrolled into four dose cohorts (5–25 mg/kg). In the dose-expansion phase, a subset of patients was prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every 21 days. For dose expansion, 15 mg/kg was chosen as the dose on the basis of safety, pharmacokinetics, and other data from the escalation cohorts. Forty-five patients were enrolled and received at least one dose of telisotuzumab (dose escalation, n = 15; dose expansion, n = 30). Telisotuzumab showed a linear pharmacokinetics profile; peak plasma concentration was proportional to dose level. There were no acute infusion reactions and no dose-limiting toxicities were observed. The most common treatment-related adverse events included hypoalbuminemia (n = 9, 20.0%) and fatigue (n = 5, 11.1%). By Response Evaluation Criteria In Solid Tumors (RECIST), 4 of 10 (40.0%) patients with MET-amplified tumors had confirmed partial response in target lesions (one ovarian, two gastric, and one esophageal), two (20.0%) had stable disease, three (30.0%) had progressive disease; one patient was unable to be evaluated. Among patients with nonamplified tumors (n = 35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria. In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors.




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A Shift in Central Metabolism Accompanies Virulence Activation in Pseudomonas aeruginosa

ABSTRACT

The availability of energy has significant impact on cell physiology. However, the role of cellular metabolism in bacterial pathogenesis is not understood. We investigated the dynamics of central metabolism during virulence induction by surface sensing and quorum sensing in early-stage biofilms of the multidrug-resistant bacterium Pseudomonas aeruginosa. We established a metabolic profile for P. aeruginosa using fluorescence lifetime imaging microscopy (FLIM), which reports the activity of NADH in live cells. We identified a critical growth transition period during which virulence is activated. We performed FLIM measurements and direct measurements of NADH and NAD+ concentrations during this period. Here, planktonic (low-virulence) and surface-attached (virulence-activated) populations diverged into distinct metabolic states, with the surface-attached population exhibiting FLIM lifetimes that were associated with lower levels of enzyme-bound NADH and decreasing total NAD(H) production. We inhibited virulence by perturbing central metabolism using citrate and pyruvate, which further decreased the enzyme-bound NADH fraction and total NAD(H) production and suggested the involvement of the glyoxylate pathway in virulence activation in surface-attached populations. In addition, we induced virulence at an earlier time using the electron transport chain oxidase inhibitor antimycin A. Our results demonstrate the use of FLIM to noninvasively measure NADH dynamics in biofilms and suggest a model in which a metabolic rearrangement accompanies the virulence activation period.

IMPORTANCE The rise of antibiotic resistance requires the development of new strategies to combat bacterial infection and pathogenesis. A major direction has been the development of drugs that broadly target virulence. However, few targets have been identified due to the species-specific nature of many virulence regulators. The lack of a virulence regulator that is conserved across species has presented a further challenge to the development of therapeutics. Here, we identify that NADH activity has an important role in the induction of virulence in the pathogen P. aeruginosa. This finding, coupled with the ubiquity of NADH in bacterial pathogens, opens up the possibility of targeting enzymes that process NADH as a potential broad antivirulence approach.




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The Mitochondrial Calcium Uniporter Interacts with Subunit c of the ATP Synthase of Trypanosomes and Humans

ABSTRACT

Mitochondrial Ca2+ transport mediated by the uniporter complex (MCUC) plays a key role in the regulation of cell bioenergetics in both trypanosomes and mammals. Here we report that Trypanosoma brucei MCU (TbMCU) subunits interact with subunit c of the mitochondrial ATP synthase (ATPc), as determined by coimmunoprecipitation and split-ubiquitin membrane-based yeast two-hybrid (MYTH) assays. Mutagenesis analysis in combination with MYTH assays suggested that transmembrane helices (TMHs) are determinants of this specific interaction. In situ tagging, followed by immunoprecipitation and immunofluorescence microscopy, revealed that T. brucei ATPc (TbATPc) coimmunoprecipitates with TbMCUC subunits and colocalizes with them to the mitochondria. Blue native PAGE and immunodetection analyses indicated that the TbMCUC is present together with the ATP synthase in a large protein complex with a molecular weight of approximately 900 kDa. Ablation of the TbMCUC subunits by RNA interference (RNAi) significantly increased the AMP/ATP ratio, revealing the downregulation of ATP production in the cells. Interestingly, the direct physical MCU-ATPc interaction is conserved in Trypanosoma cruzi and human cells. Specific interaction between human MCU (HsMCU) and human ATPc (HsATPc) was confirmed in vitro by mutagenesis and MYTH assays and in vivo by coimmunoprecipitation. In summary, our study has identified that MCU complex physically interacts with mitochondrial ATP synthase, possibly forming an MCUC-ATP megacomplex that couples ADP and Pi transport with ATP synthesis, a process that is stimulated by Ca2+ in trypanosomes and human cells.

IMPORTANCE The mitochondrial calcium uniporter (MCU) is essential for the regulation of oxidative phosphorylation in mammalian cells, and we have shown that in Trypanosoma brucei, the etiologic agent of sleeping sickness, this channel is essential for its survival and infectivity. Here we reveal that that Trypanosoma brucei MCU subunits interact with subunit c of the mitochondrial ATP synthase (ATPc). Interestingly, the direct physical MCU-ATPc interaction is conserved in T. cruzi and human cells.




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A Chimeric Japanese Encephalitis Vaccine Protects against Lethal Yellow Fever Virus Infection without Inducing Neutralizing Antibodies

ABSTRACT

Recent outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being unprepared against future YFV epidemics. Here we report that a live attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D-mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific nonneutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV nonstructural (NS) proteins. Our findings reveal the potential of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev, could confer protection against two flaviviruses. This dual protection may have implications for the possible off-label use of JE-CVax in case of emergency and vaccine shortage during YFV outbreaks. In addition, populations in Asia that have been vaccinated with Imojev may already be protected against YFV should outbreaks ever occur on that continent, as several countries/regions in the Asia-Pacific are vulnerable to international spread of the YFV.

IMPORTANCE Efficient and safe vaccines against yellow fever (e.g., YFV-17D) that provide long-lasting protection by rapidly inducing neutralizing antibody responses exist. However, the vaccine supply cannot cope with an increasing demand posed by urban outbreaks in recent years. Here we report that JE-CVax/Imojev, a YFV-17D-based chimeric Japanese encephalitis vaccine, also efficiently protects against YFV infection in mice. In case of shortage of the YFV vaccine during yellow fever outbreaks, (off-label) use of JE-CVax/Imojev may be considered. Moreover, wider use of JE-CVax/Imojev in Asia may lower the risk of the much-feared YFV spillover to the continent. More generally, chimeric vaccines that combine surface antigens and replication machineries of two distinct flaviviruses may be considered dual vaccines for the latter pathogen without induction of surface-specific antibodies. Following this rationale, novel flavivirus vaccines that do not hold a risk for antibody-dependent enhancement (ADE) of infection (inherent to current dengue vaccines and dengue vaccine candidates) could be designed.




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Tracing the Evolutionary History and Global Expansion of Candida auris Using Population Genomic Analyses

ABSTRACT

Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris.

IMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.




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We need equity-oriented solutions to COVID-19: Asians facing stigma, discrimination, fear during pandemic

APHA member Elena Ong, PHN, MS, past president and founding CEO of the Asian & Pacific Islander Caucus for Public Health, a recent APHA Executive Board member, and a past vice president of the Southern California Public Health Association, discusses discrimination against Asians in the U.S. and beyond.




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Expanding the public health team: a cross-sector workforce

I’ve been talking a lot lately about the importance of working across sectors for public health — of not going it alone to tackle the imposing challenges before us. The ideal public health team is broad and includes not only public health professionals representing the essential services, but also professionals from other disciplines, the general public and students of all stripes.




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US public health meets COVID-19 head-on: Pandemic squeezes long-underfunded public health system

Forty miles from the state capital, Jackson County, West Virginia, is home to about 29,000 people and 25 hospital beds. Like much of the state, the rural county is reeling from the opioid epidemic.




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Expanding the phenotype of MTOR-related disorders and the Smith-Kingsmore syndrome

Heterozygous germline mutations in mammalian target of rapamycin (MTOR) (OMIM 601231) are known to underlie Smith-Kingsmore syndrome (SKS; OMIM 616638), an infrequent entity with autosomal dominant inheritance, also known as macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (ORPHA 457485).1 Among the clinical features of SKS, the most common features include intellectual disability, macrocephaly, epilepsy, and facial dysmorphism. The aim of this case is to raise awareness of a distinct phenotypical presentation of SKS manifesting with bilateral cataracts and no history of seizures.




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ACA Medicaid Expansion and Insurance Coverage Among New Mothers Living in Poverty

BACKGROUND:

Medicaid plays a critical role during the perinatal period, but pregnancy-related Medicaid eligibility only extends for 60 days post partum. In 2014, the Affordable Care Act’s (ACA’s) Medicaid expansions increased adult Medicaid eligibility to 138% of the federal poverty level in participating states, allowing eligible new mothers to remain covered after pregnancy-related coverage expires. We investigate the impact of ACA Medicaid expansions on insurance coverage among new mothers living in poverty.

METHODS:

We define new mothers living in poverty as women ages 19 to 44 with incomes below the federal poverty level who report giving birth in the past 12 months. We use 2010–2017 American Community Survey data and a difference-in-differences approach using parental Medicaid-eligibility thresholds to estimate the effect of ACA Medicaid expansions on insurance coverage among poor new mothers.

RESULTS:

A 100-percentage-point increase in parental Medicaid-eligibility is associated with an 8.8-percentage-point decrease (P < .001) in uninsurance, a 13.2-percentage-point increase (P < .001) in Medicaid coverage, and a 4.4-percentage-point decrease in private or other coverage (P = .001) among poor new mothers. The average increase in Medicaid eligibility is associated with a 28% decrease in uninsurance, a 13% increase in Medicaid coverage, and an 18% decline in private or other insurance among poor new mothers in expansion states. However, in 2017, there were ~142 000 remaining uninsured, poor new mothers.

CONCLUSIONS:

ACA Medicaid expansions are associated with increased Medicaid coverage and reduced uninsurance among poor new mothers. Opportunities remain for expansion and nonexpansion states to increase insurance coverage among new mothers living in poverty.




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A Novel Variation in the FRIZZLE PANICLE (FZP) Gene Promoter Improves Grain Number and Yield in Rice [Genetics of Complex Traits]

Secondary branch number per panicle plays a crucial role in regulating grain number and yield in rice. Here, we report the positional cloning and functional characterization for SECONDARY BRANCH NUMBER7 (qSBN7), a quantitative trait locus affecting secondary branch per panicle and grain number. Our research revealed that the causative variants of qSBN7 are located in the distal promoter region of FRIZZLE PANICLE (FZP), a gene previously associated with the repression of axillary meristem development in rice spikelets. qSBN7 is a novel allele of FZP that causes an ~56% decrease in its transcriptional level, leading to increased secondary branch and grain number, and reduced grain length. Field evaluations showed that qSBN7 increased grain yield by 10.9% in a temperate japonica variety, TN13, likely due to its positive effect on sink capacity. Our findings suggest that incorporation of qSBN7 can increase yield potential and improve the breeding of elite rice varieties.




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PNAS and the pandemic [Editorials]

On January 15, 1915, the first issue of PNAS, the official “organ of publication” of the National Academy of Sciences, appeared in print. It was, in some ways, a less than propitious time to launch a journal—just a little more than seven months after the start of what ultimately became...




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Correction for Dietz et al., "2019 Novel Coronavirus (COVID-19) Pandemic: Built Environment Considerations To Reduce Transmission"




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Membrane peroxidation index and maximum lifespan are negatively correlated in fish of genus Nothobranchius [SHORT COMMUNICATION]

Jorge de Costa, Gustavo Barja, and Pedro F. Almaida-Pagan

Lipid composition of cell membranes is linked to metabolic rate and lifespan in mammals and birds but very little information is available for fishes. In this study, three fish species of the short-lived annual genus Nothobranchius with different maximum lifespan potentials (MLSP) and the longer-lived outgroup species Aphyosemion australe were studied to test whether they conform to the predictions of the longevity-homeoviscous adaptation (LHA) theory of aging. Lipid analyses were performed in whole fish samples and peroxidation indexes (PIn) for every PL class and for the whole membrane, were calculated. Total PL content was significantly lower in A. australe and N. korthausae, the two species with the highest MLSP, and a negative correlation between membrane total PIn and fish MLSP was found, this meaning that the longer-lived fish species have more saturated membranes and therefore, a lower susceptibility to oxidative damage, as the LHA theory posits.




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Reply to Cosgrove: Non-enzymatic action of expansins [Letters to the Editor]

In our computational study, we use molecular simulations to substantiate a hypothetical mechanism for glycosidic bond cleavage in the presence of a single catalytic acid at the active site of the mutant D10N HiCel45A. In addition to discussing this plausible mechanism from the context of structurally related MltA lytic transglycosylase and subfamily C GH45s, we also suggest the implications of the plausible mechanism for our current understanding of the action of expansins and lytic transglycosylases. As correctly pointed out by Professor Cosgrove (1), there is large body of evidence, a significant portion of which was regrettably not discussed in our paper, that suggests that expansins are incapable of lytic action on polysaccharide substrates. Whereas these insights do not change the results or the conclusions of our article, we would like to thank Professor Cosgrove for these additional insights. In particular, our main point with respect to expansins is that our results suggest the possibility that expansins are capable of nonhydrolytic lytic activity. Our intention was not to suggest this was the mechanism of expansins, but that it should be considered based on our results and the similarity of the active sites.The molecular mechanisms of how expansins enable cell wall expansion remains to be fully understood. Whereas our proposed mechanism resulting in the formation of the 1,6-anhdro product might be found in expansins and might contribute to the mode of action of expansins, we would like to emphasize that the intent of this study was only to suggest this as a...




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Non-enzymatic action of expansins [Letters to the Editor]

From their simulations of endoglucanase Cel45A, Bharadwaj et al. (1) propose that structurally related expansins and MltA may cut glycan backbones without generating reducing ends. This is tenable for MltA, a peptidoglycan lytic transglycosylase whose action produces nonreducing 1,6-anhydro products, but is untenable for expansins.Expansins loosen plant cell walls and induce wall expansion. Contrary to the assertion by Bharadwaj et al., the conclusion that expansins are not lytic is not merely based on lack of new reducing ends but is supported by multiple (negative) tests for polysaccharide cleavage that do not rely on detection of reducing ends. At least eight studies with three divergent groups of expansins document this point. For instance, α-expansin did not reduce the viscosity of various wall polysaccharide solutions, an endolytic assay that does not rely on measuring reducing ends (e.g. see Ref. 2 and other studies).Walls treated with α-expansin did not release saccharide fragments, measured by pulsed amperometric detection, which can detect nonreducing saccharides (3).In the case of β-expansins, protein treatments did not cleave the backbones of a wide range of dye-coupled cross-linked wall polysaccharides; nor did they cleave backbones of polysaccharides extracted from plant cell walls, measured by gel permeation chromatography (4).For five microbial expansins, tests with a range of dye-coupled cross-linked polysaccharides likewise did not detect lytic activity (e.g. see Ref. 5). Thus, extensive published evidence argues against lytic action by expansins, as proposed by Bharadwaj (1), and attempts to identify 1,6-anhydro products seem unlikely to succeed.




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Evaluation of a Novel Multiplex PCR Panel Compared to Quantitative Bacterial Culture for Diagnosis of Lower Respiratory Tract Infections [Bacteriology]

Quantitative bacterial culture of bronchoalveolar lavage fluids (BALF) is labor-intensive, and the delay involved in performing culture, definitive identification, and susceptibility testing often results in prolonged use of broad-spectrum antibiotics. The Unyvero lower respiratory tract (LRT) panel (Curetis, Holzgerlingen, Germany) allows the multiplexed rapid detection and identification of 20 potential etiologic agents of pneumonia within 5 h of collection. In addition, the assay includes detection of gene sequences that confer antimicrobial resistance. We retrospectively compared the performance of the molecular panel to routine quantitative bacterial culture methods on remnant BALF. Upon testing 175 BALF, we were able to analyze positive agreement of 181 targets from 129 samples, and 46 samples were negative. The positive percent agreement (PPA) among the microbial targets was 96.5%, and the negative percent agreement (NPA) was 99.6%. The targets with a PPA of <100% were Staphylococcus aureus (34/37 [91.9%]), Streptococcus pneumoniae (10/11 [90.9%]), and Enterobacter cloacae complex (2/4 [50%]). For the analyzable resistance targets, concordance with phenotypic susceptibility testing was 79% (14/18). This study found the Unyvero LRT panel largely concordant with culture results; however, no outcome or clinical impact studies were performed.