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JBL Professional EON ONE Compact Portable PA System Makes Its 2020 NAMM and CES Shows Debut

NORTHRIDGE, Calif.—HARMAN Professional Solutions, the global leader in audio, video, lighting and control systems, today announced the new JBL EON ONE Compact portable PA system will be making its 2020 tradeshow season debut at the 2020 NAMM show in...




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Powerful HARMAN Solutions That Create a Comfortable and Productive At-Home Setup

All around the world, parents, students and professionals alike are adjusting to a new reality that involves strict quarantine, social distancing and work from home measures. Without a doubt, the COVID-19 pandemic has changed the way people lead their...




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HARMAN Celebrates Earth Month by Announcing the Launch of its First Eco-Friendly Portable Bluetooth Speaker

Special-Edition JBL Flip 5 Eco is made from 90% Recycled Plastic and Features an Eco-Friendly Case By Andy Tsui    April 22nd marks the 50th anniversary of Earth Day, so environmental stewardship is top of mind for consumers, companies and...




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JBL’s Beloved Portable, the Flip 5 Now Available with Eco-friendly Materials

Stamford, CT – May 5, 2020–JBL is now offering its first portable Bluetooth speaker made of recyclable plastic and packaging with the new Flip 5 - Eco edition. The popular Bluetooth speaker is back with the same superb sound and cool tech as before -...




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Take the call on the patio with HARMAN's portable conference speaker




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Le son Signature de JBL et un streaming musical facile : Découvrez l’enceinte Link Portable et la Link Music JBL®

Nouvelles lignes de basse percutantes et solos de guitare à tomber : les enceintes JBL Link Portable et Link Music viennent de sortir. Avec leur son signature 360 JBL, le Wi-Fi et le Bluetooth, Chromecast et Google Assistant intégrés, les enceintes sont aussi belles qu’intelligentes.




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JBL Sound und bequemes Musik-Streaming: Hier kommen die neuen JBL® Link Portable und Link Music

Satte Bässe oder heiße Gitarrensolos! Die neuen JBL Link Portable und JBL Link Music sind ab sofort verfügbar. Mit 360°-JBL Signature Sound, WLAN und Bluetooth-Konnektivität, integriertem Chromecast und Google Assistant klingen die beiden Lautsprecher genauso gut wie sie aussehen.




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JBL réalise un nouveau record avec 100 millions d’enceintes portables livrées

HARMAN International, filiale à 100% de Samsung Electronics Co. Ltd, spécialisée dans les technologies connectées pour les marchés de l'automobile, des particuliers et des entreprises, annonce un nouveau record de sa marque JBL avec 100 millions d'enceintes portables livrées dans le monde entier. JBL consolide ainsi sa position de leader dans le domaine de l'audio portable et de créateur de catégories. La marque repousse les limites de l'innovation en donnant vie à la musique, afin que tout le monde puisse la ressentir. Aujourd'hui, JBL équipe les musiciens, les athlètes, les sites et les voitures les plus épiques du monde, tout en étant le leader du marché des enceintes portables avec 34,2% de parts de marché.




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JBL geluid én gemakkelijk muziek streamen: Maak kennis met de JBL® Link Portable en Link Music

Van knallende baslijnen tot vloeiende gitaarsolo’s, JBL introduceert de JBL Link Portable en Link Music. Ze zijn net zo handig als ze mooi zijn, de speakers zijn voorzien van 360 graden JBL’s kenmerkende sound, Wifi- en Bluetooth-connectiviteit en ingebouwde Chromecast en Google assistent.




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JBL sound plus easy music streaming: Meet JBL® Link Portable and Link Music

From heart-thumping basslines to face-melting guitar solos, the new JBL Link Portable and Link Music have arrived. With 360 JBL Signature Sound, Wi-Fi and Bluetooth connectivity, Chromecast and Google Assistant built-in, they’ve got brains to match their beauty.




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JBL Sets New Record with 100 Million Portable Speakers

HARMAN International, a wholly-owned subsidiary of Samsung Electronics Co., Ltd. focused on connected technologies for automotive, consumer and enterprise markets, is delighted to announce that its JBL brand has reached the tremendous milestone of 100 million portable speakers shipped worldwide, cementing its position as the portable audio leader and category shaper. JBL pushes the boundaries of innovation, bringing music to life in ways that audiences everywhere can feel. Today, not only does JBL power the world’s most epic musicians, athletes, venues and automobiles, JBL is the market leader in portable speakers with 34.2% volume share.




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JBL Sets New Record with 100 Million Portable Speakers

HARMAN International, a wholly-owned subsidiary of Samsung Electronics Co., Ltd. focused on connected technologies for automotive, consumer and enterprise markets, is delighted to announce that its JBL brand has reached the tremendous milestone of 100 million portable speakers shipped worldwide, cementing its position as the portable audio leader and category shaper. JBL pushes the boundaries of innovation, bringing music to life in ways that audiences everywhere can feel. Today, not only does JBL power the world’s most epic musicians, athletes, venues and automobiles, JBL is the market leader in portable speakers with 34.2% volume share.




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Mazda and Aha by HARMAN Enter into Global Partnership to Provide Connected Entertainment System in Redesigned 2014 Mazda3 Worldwide including Japan

Palo Alto, CA – Aha™ by HARMAN today announced that the new 2014 Mazda3 to be launched in Japan, the United States, and a number of additional North American and Asian Countries this fall will offer access to the Aha free service with the ability to select presets from more than 40,000* audio and information stations from Japan and other countries.




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In the quantum world, uncertainty reigns – or is it all in the mind?

Schrödinger's dead-and-alive cat embodies the uncertainty of the quantum world. But whether parallel realities truly exist is a question less of science than belief




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Why fun is so important and how we benefit from play

How do you get to be a professor of play? Paul Ramchandani on fun, why playing is good for people of all ages and what games he plays with his kids




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Military now controls Myanmar’s scientifically important amber mines

Hundreds of scientifically priceless fossils are extracted in horrendous conditions in Myanmar’s amber mines and smuggled over the border for sale in China




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Covid-19: The science of uncertainty can help us make better choices

As the coronavirus outbreak continues, why do some people stockpile and others shrug? The psychology of uncertainty explains what's going on, says Rachel McCloy




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In the quantum world, uncertainty reigns – or is it all in the mind?

Schrödinger's dead-and-alive cat embodies the uncertainty of the quantum world. But whether parallel realities truly exist is a question less of science than belief




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Tamoxifen Protects Certain Women at High Risk for Breast Cancer

Title: Tamoxifen Protects Certain Women at High Risk for Breast Cancer
Category: Health News
Created: 5/3/2007 2:00:00 AM
Last Editorial Review: 5/3/2007 12:00:00 AM




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MRSA More Likely to Lurk in Certain Patients

Title: MRSA More Likely to Lurk in Certain Patients
Category: Health News
Created: 4/23/2010 4:10:00 PM
Last Editorial Review: 4/26/2010 12:00:00 AM




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Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?

Title: Could Certain Fatty Foods Be Linked to Aggressive Prostate Cancer?
Category: Health News
Created: 4/22/2016 12:00:00 AM
Last Editorial Review: 4/25/2016 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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Building Muscle Could Boost the Body's Most Important Muscle

Title: Building Muscle Could Boost the Body's Most Important Muscle
Category: Health News
Created: 4/28/2016 12:00:00 AM
Last Editorial Review: 4/29/2016 12:00:00 AM




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U.S. Moves to Avert Shortage of Yellow Fever Vaccine

Title: U.S. Moves to Avert Shortage of Yellow Fever Vaccine
Category: Health News
Created: 4/28/2017 12:00:00 AM
Last Editorial Review: 5/1/2017 12:00:00 AM




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The Other Opioid Crisis: Shortages at U.S. Hospitals

Title: The Other Opioid Crisis: Shortages at U.S. Hospitals
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/2/2018 12:00:00 AM




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After Trump Hypes Use of a Lupus Med Against COVID-19, Lupus Patients Face Shortages

Title: After Trump Hypes Use of a Lupus Med Against COVID-19, Lupus Patients Face Shortages
Category: Health News
Created: 4/25/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM




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Certain Gene Might Help Shield At-Risk People From Alzheimer's

Title: Certain Gene Might Help Shield At-Risk People From Alzheimer's
Category: Health News
Created: 4/13/2020 12:00:00 AM
Last Editorial Review: 4/14/2020 12:00:00 AM




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The Hypercomplex Genome of an Insect Reproductive Parasite Highlights the Importance of Lateral Gene Transfer in Symbiont Biology

ABSTRACT

Mobile elements—plasmids and phages—are important components of microbial function and evolution via traits that they encode and their capacity to shuttle genetic material between species. We here report the unusually rich array of mobile elements within the genome of Arsenophonus nasoniae, the son-killer symbiont of the parasitic wasp Nasonia vitripennis. This microbe’s genome has the highest prophage complement reported to date, with over 50 genomic regions that represent either intact or degraded phage material. Moreover, the genome is predicted to include 17 extrachromosomal genetic elements, which carry many genes predicted to be important at the microbe-host interface, derived from a diverse assemblage of insect-associated gammaproteobacteria. In our system, this diversity was previously masked by repetitive mobile elements that broke the assembly derived from short reads. These findings suggest that other complex bacterial genomes will be revealed in the era of long-read sequencing.

IMPORTANCE The biology of many bacteria is critically dependent on genes carried on plasmid and phage mobile elements. These elements shuttle between microbial species, thus providing an important source of biological innovation across taxa. It has recently been recognized that mobile elements are also important in symbiotic bacteria, which form long-lasting interactions with their host. In this study, we report a bacterial symbiont genome that carries a highly complex array of these elements. Arsenophonus nasoniae is the son-killer microbe of the parasitic wasp Nasonia vitripennis and exists with the wasp throughout its life cycle. We completed its genome with the aid of recently developed long-read technology. This assembly contained over 50 chromosomal regions of phage origin and 17 extrachromosomal elements within the genome, encoding many important traits at the host-microbe interface. Thus, the biology of this symbiont is enabled by a complex array of mobile elements.




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Lipid Anchoring of Archaeosortase Substrates and Midcell Growth in Haloarchaea

ABSTRACT

The archaeal cytoplasmic membrane provides an anchor for many surface proteins. Recently, a novel membrane anchoring mechanism involving a peptidase, archaeosortase A (ArtA), and C-terminal lipid attachment of surface proteins was identified in the model archaeon Haloferax volcanii. ArtA is required for optimal cell growth and morphogenesis, and the S-layer glycoprotein (SLG), the sole component of the H. volcanii cell wall, is one of the targets for this anchoring mechanism. However, how exactly ArtA function and regulation control cell growth and morphogenesis is still elusive. Here, we report that archaeal homologs to the bacterial phosphatidylserine synthase (PssA) and phosphatidylserine decarboxylase (PssD) are involved in ArtA-dependent protein maturation. Haloferax volcanii strains lacking either HvPssA or HvPssD exhibited motility, growth, and morphological phenotypes similar to those of an artA mutant. Moreover, we showed a loss of covalent lipid attachment to SLG in the hvpssA mutant and that proteolytic cleavage of the ArtA substrate HVO_0405 was blocked in the hvpssA and hvpssD mutant strains. Strikingly, ArtA, HvPssA, and HvPssD green fluorescent protein (GFP) fusions colocalized to the midcell position of H. volcanii cells, strongly supporting that they are involved in the same pathway. Finally, we have shown that the SLG is also recruited to the midcell before being secreted and lipid anchored at the cell outer surface. Collectively, our data suggest that haloarchaea use the midcell as the main surface processing hot spot for cell elongation, division, and shape determination.

IMPORTANCE The subcellular organization of biochemical processes in space and time is still one of the most mysterious topics in archaeal cell biology. Despite the fact that haloarchaea largely rely on covalent lipid anchoring to coat the cell envelope, little is known about how cells coordinate de novo synthesis and about the insertion of this proteinaceous layer throughout the cell cycle. Here, we report the identification of two novel contributors to ArtA-dependent lipid-mediated protein anchoring to the cell surface, HvPssA and HvPssD. ArtA, HvPssA, and HvPssD, as well as SLG, showed midcell localization during growth and cytokinesis, indicating that haloarchaeal cells confine phospholipid processing in order to promote midcell elongation. Our findings have important implications for the biogenesis of the cell surface.




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Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study

The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.

All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.

In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.146-17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755-8.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL–1 (OR 3.982, 95% CI 1.132-14.006; p<0.001) and cardiac troponin I ≥0.05 ng·mL–1 (OR 4.077, 95% CI 1.166-14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age- and comorbid illness-matched case–control study, CD3+CD8+ T-cells ≤75 cells·μL–1 and cardiac troponin I ≥0.05 ng·mL–1 remained as predictors for high mortality from COVID-19 pneumonia.

We identified four risk factors: age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL–1 and cardiac troponin I ≥0.05 ng·mL–1. The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.




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Unusual and important cause of acute neck pain: Longus colli calcific tendinitis

Early recognition of longus colli calcific tendinitis can prevent unnecessary interventions including antibiotics and surgical procedures.




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Ames SG, Davis BS, Marin JR, L. Fink EL, Olson LM, Gausche-Hill M, Kahn JM. Emergency Department Pediatric Readiness and Mortality in Critically Ill Children. Pediatrics. 2019;144(3):e20190568




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Every Child Counts: The Importance of the 2020 Census for Pediatric Health Equity




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Breastfeeding and Mortality Under 2 Years of Age in Sub-Saharan Africa

BACKGROUND:

Several studies have investigated the association of breastfeeding status with offspring mortality in Africa, but most studies were from one center only or had limited statistical power to draw robust conclusions.

METHODS:

Data came from 75 nationally representative cross-sectional Demographic and Health Surveys in 35 countries in sub-Saharan Africa conducted between 2000 and 2016. Our study relied on 217 112 individuals aged 4 days to 23 months for breastfeeding pattern analysis, 161 322 individuals aged 6 to 23 months for breastfeeding history analysis, and 104 427 individuals aged 12 to 23 months for breastfeeding duration analysis.

RESULTS:

Compared with children aged 4 days to 23 months exclusively breastfed in the first 3 days of life, those not breastfed had a high risk of mortality at <2 years of age (odds ratio [OR] = 13.45; 95% confidence interval [CI] = 11.43–15.83). Young children who were predominantly breastfed or partially breastfed had moderately increased risk of mortality at <2 years of age (OR = 1.11, 95% CI = 1.03–1.21 for predominant pattern; OR = 1.12, 95% CI = 0.99–1.27 for partial pattern). Compared with children aged 6 to 23 months who were breastfed within the first 6 months of life, those not breastfed had a high risk of mortality (OR = 5.65; 95% CI = 4.27–7.47). Compared with children aged 12 to 23 months who were breastfed for ≥6 months, those who were breastfed for shorter periods had a higher risk of mortality (OR = 2.78, 95% CI = 1.45–5.32 for duration of <3 months; OR = 5.28, 95% CI = 3.24–8.61 for those who were not breastfed).

CONCLUSIONS:

Our findings support exclusive breastfeeding during the first 6 months of life and continued breastfeeding up to 2 years of age recommended by the World Health Organization for reducing mortality of children <2 years old in sub-Saharan Africa.




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Long Noncoding RNA NRAV Promotes Respiratory Syncytial Virus Replication by Targeting the MicroRNA miR-509-3p/Rab5c Axis To Regulate Vesicle Transportation [Virus-Cell Interactions]

Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long noncoding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from the lncRNA database, and we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. Quantitative PCR (qPCR) detection indicated that the expression of lncRNA negative regulator of antiviral response (NRAV) in RSV-positive patients was significantly lower than that in uninfected patients, but lncRNA psoriasis-associated non-protein coding RNA induced by stress (PRINS), nuclear paraspeckle assembly transcript 1 (NEAT1), and Nettoie Salmonella pas Theiler’s (NeST) showed no difference in vivo and in vitro. Meanwhile, overexpression of NRAV promoted RSV proliferation in A549 and BEAS-2B cells, and vice versa, indicating that the downregulation of NRAV was part of the host antiviral defense. RNA fluorescent in situ hybridization (FISH) confirmed that NRAV was mainly located in the cytoplasm. Through RNA sequencing, we found that Rab5c, which is a vesicle transporting protein, showed the same change trend as NRAV. Subsequent investigation revealed that NRAV was able to favor RSV production indirectly by sponging microRNA miR-509-3p so as to release Rab5c and facilitate vesicle transportation. The study provides a new insight into virus-host interaction through noncoding RNA, which may contribute to exploring potential antivirus targets for respiratory virus.

IMPORTANCE The mechanism of interaction between RSV and host noncoding RNAs is not fully understood. In this study, we found that the expression of long noncoding RNA (lncRNA) negative regulator of antiviral response (NRAV) was reduced in RSV-infected patients, and overexpression of NRAV facilitated RSV production in vitro, suggesting that the reduction of NRAV in RSV infection was part of the host antiviral response. We also found that NRAV competed with vesicle protein Rab5c for microRNA miR509-3p in cytoplasm to promote RSV vesicle transport and accelerate RSV proliferation, thereby improving our understanding of the pathogenic mechanism of RSV infection.




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An Interrater Reliability Study of Pulmonary Function Assessment With a Portable Spirometer

BACKGROUND:In this study, we aimed to validate the agreement between pulmonary function measurements obtained with a portable spirometer and measurements obtained with conventional spirometry in Chinese pediatric and adult populations.METHODS:Pulmonary function testing was performed to evaluate subjects enrolled at Shanghai Zhongshan Hospital (n = 104) and Shanghai Children's Medical Center (n = 103). The portable spirometers and conventional devices were applied to each subject with a 20-min quiescent period between each measurement. Pulmonary function parameters of FVC, FEV1, peak expiratory flow, maximum expiratory flow at 25%, 50%, and 75% of FVC (MEF25, MEF50, and MEF75, respectively), and FEV1/FVC% were compared with intraclass correlation and Bland-Altman methods.RESULTS:A satisfactory concordance of pulmonary function was observed between spirometry measurements obtained with portable versus conventional spirometers. Intraclass correlation indicated excellent reliability (>0.75) for all pulmonary function indicators in pediatric and adult subjects. Significant positive correlations of all variables measured with different spirometers were observed (all P < .001). No significant bias was observed in either group, although limits of agreement varied. Funnel effects were observed for peak expiratory flow in pediatric subjects and for FVC, FEV1, MEF50, and MEF25 in adult subjects.CONCLUSIONS:The portable spirometer is an alternative to the conventional device for the measurement of pulmonary function. Compared with the conventional device, the portable spirometer is expected to provide convenient, operational, and financial advantages.




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The Most Important Thing We Give to People Is Hope: Overcoming Stigma in Diabetes and Obesity

Editor’s Note: This article is adapted from the address Ms. Valentine delivered as the recipient of the American Diabetes Association’s (ADA’s) Outstanding Educator in Diabetes Award for 2019. She delivered the address in June 2019 at the Association’s 79th Scientific Sessions in San Francisco, CA. A webcast of this speech is available for viewing at the ADA website (professional.diabetes.org/webcast/outstanding-educator-diabetes-award-lecture%E2%80%94-most-important-thing-we-give-people-hope).




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High cytomegalovirus serology and subsequent COPD-related mortality: a longitudinal study

Background

Positive serology for cytomegalovirus (CMV) has been associated with all-cause mortality risk but its role in COPD mortality is unknown. The objective of the present study was to assess the relationship between CMV serology and COPD mortality.

Methods

We analysed data from 806 participants in the Tucson Epidemiological Study of Airway Obstructive Disease who, at enrolment, were aged 28–70 years and had completed lung function tests. We tested CMV serology in sera from enrolment and defined "high CMV serology" as being in the highest tertile. Vital status, date and cause of death were assessed through death certificates and/or linkage with the National Death Index up to January 2017. The association of CMV serology with all-cause and cause-specific mortality risk was tested in Cox models adjusted for age, sex, level of education, body mass index, smoking status and pack-years.

Results

High CMV serology was marginally associated with all-cause mortality (p=0.071) but the effect was inversely dependent on age, with the association being much stronger among participants <55 years than among participants ≥55 years at enrolment (p-value for CMV-by-age interaction <0.001). Compared with low CMV serology, high CMV serology was associated with mortality from COPD among all subjects (adjusted hazard ratio (HR) 2.38, 95% CI 1.11–5.08; p=0.025) and particularly in subjects <55 years old at enrolment (HR 5.40, 95% CI 1.73–16.9; p=0.004). Consistent with these results, high CMV serology also predicted mortality risk among subjects who already had airflow limitation at enrolment (HR 2.10, 95% CI 1.20–3.68; p=0.009).

Conclusions

We report a strong relationship between CMV serology and the risk of dying from COPD, and thus identify a novel risk factor for COPD mortality.




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New developments in field-portable geochemical techniques and on-site technologies and their place in mineral exploration

This paper focuses on handheld and top-of-hole techniques which have appeared since 2007 or have undergone major improvements, and discusses their benefits, challenges and pitfalls, why we use them and what to expect from them. There is an ongoing need to be innovative with the way we undertake mineral exploration. Recent technological advances that have been applied to successful mineral exploration include on-site or portable instruments, on-site laboratory technologies, various core scanners, and technologies for fluid analysis. Portable or field technologies such as pXRF, pXRD, pNIR-SWIR, µRaman and LIBS aid in obtaining chemical and mineralogical information. Spectral gamma tools, a well-known technology, recently took advantage of improved ground and airborne (drone) instruments, to complement hyperspectral imagery. At mine and exploration sites, top-of-hole sensing technologies, such as Lab-at-Rig® and various core scanners (both spectral- and XRF-based) have become useful tools to analyse metres of core as it is being drilled. Fluid analyses are not as common as analyses of solid materials, but there are advances in such technologies as anodic stripping voltammetry, polarography and ion-exchange electrodes aiming for analysis of commodity or environmentally important elements.

Field-portable geochemical techniques and on-site technologies now offer instant response and flexibility for most exploration tasks. By providing relevant data within minutes, they allow safer field decisions and focus on the most promising finds, while saving valuable resources in sampling grids or drilling. More efficient laboratory analysis programs are supported by sample screening and homogeneity checking on-site. Field analyses are not always as accurate as laboratory ones, but most of the time can be correlated with them, enabling reliable decisions. The level of confidence in field-made decisions needs to be compared between later and less numerous laboratory analyses, and less precise but more abundant and immediate field analyses. It may be demonstrated that, in many cases, the fit–for-purpose nature of the latter allows a better confidence level. Quality compromises associated with field analyses can be reduced by the application of better sample preparation and quality assurance/quality control (QA/QC) procedures. Most of the further development of on-site chemical analysis is expected to be based on its integration with lab methods and on sound QA/QC practice, allowing a precise evaluation of its confidence level and uncertainties. Mineralogical analyses are constrained by our ability to interpret the data in near-real time but offer promising approaches in both surface and drilling exploration campaigns.

Thematic collection: This article is part of the Exploration 17 collection available at: https://www.lyellcollection.org/cc/exploration-17




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The M Protein of Streptococcus pyogenes Strain AP53 Retains Cell Surface Functional Plasminogen Binding after Inactivation of the Sortase A Gene [Article]

Streptococcus pyogenes (Lancefield group A Streptococcus [GAS]) is a β-hemolytic human-selective pathogen that is responsible for a large number of morbid and mortal infections in humans. For efficient infection, GAS requires different types of surface proteins that provide various mechanisms for evading human innate immune responses, thus enhancing pathogenicity of the bacteria. Many such virulence-promoting proteins, including the major surface signature M protein, are translocated after biosynthesis through the cytoplasmic membrane and temporarily tethered to this membrane via a type 1 transmembrane domain (TMD) positioned near the COOH terminus. In these proteins, a sorting signal, LPXTG, is positioned immediately upstream of the TMD, which is cleaved by the membrane-associated transpeptidase, sortase A (SrtA), leading to the covalent anchoring of these proteins to newly emerging l-Ala–l-Ala cross-bridges of the growing peptidoglycan cell wall. Herein, we show that inactivation of the srtA gene in a skin-tropic pattern D GAS strain (AP53) results in retention of the M protein in the cell membrane. However, while the isogenic AP53 srtA strain is attenuated in overall pathogenic properties due to effects on the integrity of the cell membrane, our data show that the M protein nonetheless can extend from the cytoplasmic membrane through the cell wall and then to the surface of the bacteria and thereby retain its important properties of productively binding and activating fluid-phase host plasminogen (hPg). The studies presented herein demonstrate an underappreciated additional mechanism of cell surface display of bacterial virulence proteins via their retention in the cell membrane and extension to the GAS surface.

IMPORTANCE Group A Streptococcus pyogenes (GAS) is a human-specific pathogen that produces many surface factors, including its signature M protein, that contribute to its pathogenicity. M proteins undergo specific membrane localization and anchoring to the cell wall via the transpeptidase sortase A. Herein, we explored the role of sortase A function on M protein localization, architecture, and function, employing, a skin-tropic GAS isolate, AP53, which expresses a human plasminogen (hPg)-binding M (PAM) Protein. We showed that PAM anchored in the cell membrane, due to the targeted inactivation of sortase A, was nonetheless exposed on the cell surface and functionally interacted with host hPg. We demonstrate that M proteins, and possibly other sortase A-processed proteins that are retained in the cell membrane, can still function to initiate pathogenic processes by this underappreciated mechanism.




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Differential Health Care Use, Diabetes-Related Complications, and Mortality Among Five Unique Classes of Patients With Type 2 Diabetes in Singapore: A Latent Class Analysis of 71,125 Patients

OBJECTIVE

With rising health care costs and finite health care resources, understanding the population needs of different type 2 diabetes mellitus (T2DM) patient subgroups is important. Sparse data exist for the application of population segmentation on health care needs among Asian T2DM patients. We aimed to segment T2DM patients into distinct classes and evaluate their differential health care use, diabetes-related complications, and mortality patterns.

RESEARCH DESIGN AND METHODS

Latent class analysis was conducted on a retrospective cohort of 71,125 T2DM patients. Latent class indicators included patient’s age, ethnicity, comorbidities, and duration of T2DM. Outcomes evaluated included health care use, diabetes-related complications, and 4-year all-cause mortality. The relationship between class membership and outcomes was evaluated with the appropriate regression models.

RESULTS

Five classes of T2DM patients were identified. The prevalence of depression was high among patients in class 3 (younger females with short-to-moderate T2DM duration and high psychiatric and neurological disease burden) and class 5 (older patients with moderate-to-long T2DM duration and high disease burden with end-organ complications). They were the highest tertiary health care users. Class 5 patients had the highest risk of myocardial infarction (hazard ratio [HR] 12.05, 95% CI 10.82–13.42]), end-stage renal disease requiring dialysis initiation (HR 25.81, 95% CI 21.75–30.63), stroke (HR 19.37, 95% CI 16.92–22.17), lower-extremity amputation (HR 12.94, 95% CI 10.90–15.36), and mortality (HR 3.47, 95% CI 3.17–3.80).

CONCLUSIONS

T2DM patients can be segmented into classes with differential health care use and outcomes. Depression screening should be considered for the two identified classes of patients.




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The Synergic Association of hs-CRP and Serum Amyloid P Component in Predicting All-Cause Mortality in Patients With Type 2 Diabetes

OBJECTIVE

Type 2 diabetes is characterized by increased death rate. In order to tackle this dramatic event, it becomes essential to discover novel biomarkers capable of identifying high-risk patients to be exposed to more aggressive preventive and treatment strategies. hs-CRP and serum amyloid P component (SAP) are two acute-phase inflammation proteins, which interact physically and share structural and functional features. We investigated their combined role in associating with and improving prediction of mortality in type 2 diabetes.

RESEARCH DESIGN AND METHODS

Four cohorts comprising 2,499 patients with diabetes (643 all-cause deaths) were analyzed. The improvement of mortality prediction was addressed using two well-established prediction models, namely, EstimatioN oF mORtality risk in type 2 diabetiC patiEnts (ENFORCE) and Risk Equations for Complications of Type 2 Diabetes (RECODe).

RESULTS

Both hs-CRP and SAP were independently associated with all-cause mortality (hazard ratios [HRs] [95% CIs]: 1.46 [1.34–1.58] [P < 0.001] and 0.82 [0.76–0.89] [P < 0.001], respectively). Patients with SAP ≤33 mg/L were at increased risk of death versus those with SAP >33 mg/L only if hs-CRP was relatively high (>2 mg/L) (HR 1.96 [95% CI 1.52–2.54] [P < 0.001] and 1.20 [0.91–1.57] [P = 0.20] in hs-CRP >2 and ≤2 mg/L subgroups, respectively; hs-CRP-by-SAP strata interaction P < 0.001). The addition of hs-CRP and SAP significantly (all P < 0.05) improved several discrimination and reclassification measures of both ENFORCE and RECODe all-cause mortality prediction models.

CONCLUSIONS

In type 2 diabetes, hs-CRP and SAP show opposite and synergic associations with all-cause mortality. The use of both markers, possibly in combination with others yet to be unraveled, might improve the ability to predict the risk of death in the real-life setting.




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HRD1, an Important Player in Pancreatic {beta}-Cell Failure and Therapeutic Target for Type 2 Diabetic Mice

Inadequate insulin secretion in response to glucose is an important factor for β-cell failure in type 2 diabetes (T2D). Although HMG-CoA reductase degradation 1 (HRD1), a subunit of the endoplasmic reticulum–associated degradation complex, plays a pivotal role in β-cell function, HRD1 elevation in a diabetic setting contributes to β-cell dysfunction. We report in this study the excessive HRD1 expression in islets from humans with T2D and T2D mice. Functional studies reveal that β-cell–specific HRD1 overexpression triggers impaired insulin secretion that will ultimately lead to severe hyperglycemia; by contrast, HRD1 knockdown improves glucose control and response in diabetic models. Proteomic analysis results reveal a large HRD1 interactome, which includes v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), a master regulator of genes implicated in the maintenance of β-cell function. Furthermore, mechanistic assay results indicate that HRD1 is a novel E3 ubiquitin ligase that targets MafA for ubiquitination and degradation in diabetic β-cells, resulting in cytoplasmic accumulation of MafA and in the reduction of its biological function in the nucleus. Our results not only reveal the pathological importance of excessive HRD1 in β-cell dysfunction but also establish the therapeutic importance of targeting HRD1 in order to prevent MafA loss and suppress the development of T2D.




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Identifying Outcomes Important to Patients with Glomerular Disease and Their Caregivers

Background and objectives

Shared decision making in patients with glomerular disease remains challenging because outcomes important to patients remain largely unknown. We aimed to identify and prioritize outcomes important to patients and caregivers and to describe reasons for their choices.

Design, setting, participants, & measurements

We purposively sampled adult patients with glomerular disease and their caregivers from Australia, Hong Kong, the United Kingdom, and the United States. Participants identified, discussed, and ranked outcomes in focus groups using the nominal group technique; a relative importance score (between zero and one) was calculated. Qualitative data were analyzed thematically.

Results

Across 16 focus groups, 134 participants (range, 19–85 years old; 51% women), including 101 patients and 33 caregivers, identified 58 outcomes. The ten highest-ranked outcomes were kidney function (importance score of 0.42), mortality (0.29), need for dialysis or transplant (0.22), life participation (0.18), fatigue (0.17), anxiety (0.13), family impact (0.12), infection and immunity (0.12), ability to work (0.11), and BP (0.11). Three themes explained the reasons for these rankings: constraining day-to-day experience, impaired agency and control over health, and threats to future health and family.

Conclusions

Patients with glomerular disease and their caregivers highly prioritize kidney health and survival, but they also prioritize life participation, fatigue, anxiety, and family impact.




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Deprivation and mortality related to pediatric respiratory tract infection: a cohort study in 3 high-income jurisdictions

Background:

Deaths from respiratory tract infections (RTIs) in children are preventable through timely access to public health and medical interventions. We aimed to assess whether socioeconomic disparities in mortality related to pediatric RTI persisted after accounting for health status at birth.

Methods:

We compared the prevalence of and risk factors for RTI-related death in singletons aged 28 days to 4 years across Ontario (Canada), Scotland and England (jurisdictions with universal health care) using linked administrative data for 2003–2013. We estimated rates of RTI-related mortality for children living in deprived areas and those born to teenage girls; we estimated both crude rates and those adjusted for health status at birth.

Results:

A total of 1 299 240 (Ontario), 547 556 (Scotland) and 3 910 401 (England) children were included in the study. Across all jurisdictions, children born in the most deprived areas experienced the highest rates of RTI-related mortality. After adjustment for high-risk chronic conditions and prematurity, we observed differences in mortality according to area-level deprivation in Ontario and England but not in Scotland. In Ontario, teenage motherhood was also an independent risk factor for RTI-related mortality.

Interpretation:

Socioeconomic disparities played a substantial role in child mortality related to RTI in all 3 jurisdictions. Context-specific investigations around the mechanisms of this increased risk and development of programs to address socioeconomic disparities are needed.




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Emergence of a Novel Coronavirus Disease (COVID-19) and the Importance of Diagnostic Testing: Why Partnership between Clinical Laboratories, Public Health Agencies, and Industry Is Essential to Control the Outbreak




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Lung cancer incidence and mortality with extended follow-up in the National Lung Screening Trial

Since lung cancer (LC) is still the leading cause of cancer deaths worldwide [1], early detection through screening represents an important opportunity to improve LC survival and is a priority area for cancer care. The National Lung Screening Trial (NLST) aimed to compare low-dose helical computed tomography (LDCT) with chest radiography in LC screening of current or former heavy smokers. The trial found a relative reduction in mortality from LC of 20% in those who had undergone LDCT screening. LC screening has regained prominence in the thoracic oncology literature with the completion of NELSON and other European trials, which support the role of LC screening in achieving early diagnosis and reducing mortality. A growing number of implementation pilots are providing an impetus towards organised, national programmes for LC screening, which are in need of long-term follow-up data such as those presented in this study.




rta

Lung cancer incidence and mortality with extended follow-up in the National LungScreening Trial

A 78-year-old male presented at the emergency room complaining of dry cough, fever up to 38.5 °C and malaise for 1 month. He had visited a general practitioner and received amoxicillin 500 mg three times a day for 7 days for a presumed chest infection, without improvement. He had a history of diabetes and arterial blood hypertension, for which he was receiving metformin 1000 mg twice a day and amlodipine 10 mg a day for 7 years. He reported no alcohol abuse and was an ex-smoker of 20 pack-years (quit 30 years ago). He had no recent hospitalisations or any medical interventions.




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Importation of Extensively Drug-Resistant Salmonella enterica Serovar Typhi Cases in Ontario, Canada [Susceptibility]

A strain of extensively drug-resistant (XDR) Salmonella enterica serovar Typhi has caused a large ongoing outbreak in Pakistan since 2016. In Ontario, Canada, 10 cases of mainly bloodstream infections (n = 9) were identified in patients who traveled to Pakistan. Whole-genome sequencing showed that Canadian cases were genetically related to the Pakistan outbreak strain. The appearance of XDR typhoid cases in Ontario prompted a provincial wide alert to physicians to recommend treatment with carbapenems or azithromycin in suspected typhoid cases with travel history to Pakistan.




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Objectively-Measured Light-Intensity Physical Activity and Risk of Cancer Mortality: A Meta-analysis of Prospective Cohort Studies

Background:

The impact of light-intensity physical activity (LPA) in preventing cancer mortality has been questioned. To address this concern, the present meta-analysis aimed to quantify the association between objectively-measured LPA and risk of cancer mortality.

Methods:

We conducted a systematic literature search in PubMed and Scopus to January 2020. Prospective cohort studies reporting the association between objectively-measured LPA using activity monitors (e.g., accelerometers) and risk of cancer mortality in the general population were included. The summary hazard ratios (HR) per 30 min/day of LPA and 95% confidence intervals (CI) were obtained using a random-effects model. Dose–response analysis was used to plot their relationship.

Results:

Five prospective cohort studies were included, in which the definition of LPA based on accelerometer readings was mainly set within 100 to 2,100 counts/min. The summary HR for cancer mortality per 30 min/day of LPA was 0.86 (95% CI, 0.79–0.95; I2 < 1%), and the association between LPA and risk reduction in cancer mortality was linearly shaped (Pnonlinearity = 0.72). LPA exhibited a comparable magnitude of risk reduction in cancer mortality of moderate-to-vigorous physical activity regardless of equal time-length (0.87 per 30 min/day vs. 0.94 per 30 min/day, Pinteraction = 0.46) or equal amount (0.74 vs. 0.94 per 150 metabolic equivalents-min/day, Pinteraction = 0.11). Furthermore, replacing sedentary time by LPA of 30 min/day decreased the risk of cancer mortality by 9%.

Conclusions:

Objectively-measured LPA conferred benefits in decreasing the risk of cancer mortality.

Impact:

LPA should be considered in physical activity guidelines to decrease the risk of cancer mortality.