Title: Vitamin E Helps Treat Common Liver Disease
Category: Health News
Created: 4/28/2010 6:10:00 PM
Last Editorial Review: 4/29/2010 12:00:00 AM

Title: TV Breakups: When a Show Ends, Fans May 'Mourn'
Category: Health News
Created: 4/23/2011 11:01:00 AM
Last Editorial Review: 4/25/2011 12:00:00 AM

Title: High Reps With Low Weights Builds Muscle, Too
Category: Health News
Created: 4/28/2012 11:01:00 AM
Last Editorial Review: 4/30/2012 12:00:00 AM

Title: 50 Years of Data Confirm Benefit of Antipsychotics
Category: Health News
Created: 5/3/2012 11:00:00 AM
Last Editorial Review: 5/3/2012 12:00:00 AM

Title: Health Tip: Be Alert for Signs of Preeclampsia
Category: Health News
Created: 5/3/2012 8:05:00 AM
Last Editorial Review: 5/3/2012 12:00:00 AM

Title: Psychopaths May Lack Capacity for Empathy
Category: Health News
Created: 4/26/2013 12:35:00 PM
Last Editorial Review: 4/29/2013 12:00:00 AM

Title: Lipsticks, Glosses Contain Toxic Metals: Report
Category: Health News
Created: 5/2/2013 10:35:00 AM
Last Editorial Review: 5/2/2013 12:00:00 AM

Title: Implanted Device May Predict Epilepsy Seizures, Study Suggests
Category: Health News
Created: 5/2/2013 10:35:00 AM
Last Editorial Review: 5/2/2013 12:00:00 AM

Title: Kelly the Robot Helps Kids Tackle Autism
Category: Health News
Created: 5/1/2013 12:36:00 PM
Last Editorial Review: 5/2/2013 12:00:00 AM

Title: Urologists' Group Issues Updated Guidelines on PSA Test
Category: Health News
Created: 5/3/2013 12:35:00 PM
Last Editorial Review: 5/3/2013 12:00:00 AM

Title: Longer Wait for Mammogram After Benign Breast Biopsy May Be Warranted
Category: Health News
Created: 5/2/2013 12:35:00 PM
Last Editorial Review: 5/3/2013 12:00:00 AM

Title: Nail Salons' Drying Lamps Carry Small Cancer Risk
Category: Health News
Created: 4/30/2014 7:36:00 PM
Last Editorial Review: 5/1/2014 12:00:00 AM

Title: Divorce May Increase Psychosomatic Symptoms in Teens: Study
Category: Health News
Created: 4/27/2015 12:00:00 AM
Last Editorial Review: 4/28/2015 12:00:00 AM

Title: 3D 'Printout' Device Keeps Very Ill Babies Breathing
Category: Health News
Created: 4/29/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM

Title: New Drug Kybella Zaps Double Chin: FAQ
Category: Health News
Created: 5/1/2015 12:00:00 AM
Last Editorial Review: 5/1/2015 12:00:00 AM

Title: Painkiller Addiction Relapse More Likely for Some
Category: Health News
Created: 4/22/2016 12:00:00 AM
Last Editorial Review: 4/25/2016 12:00:00 AM

Title: Skateboarding Mishaps Send 176 U.S. Kids to ERs Every Day
Category: Health News
Created: 4/26/2016 12:00:00 AM
Last Editorial Review: 4/27/2016 12:00:00 AM

Title: Psoriasis Tied to Obesity, Type 2 Diabetes
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM

Title: Health Tip: Smart Swaps at Mealtime
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/1/2017 12:00:00 AM

Title: Seizure Control Eases Life for Young Adults With Epilepsy
Category: Health News
Created: 4/28/2017 12:00:00 AM
Last Editorial Review: 5/1/2017 12:00:00 AM

Title: Psychiatric Scars of Wartime Brain Injury May Linger for Years
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/2/2017 12:00:00 AM

Title: Take These 5 Steps to Live 10 Extra Years
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM

Title: Study Debunks Idea That Epilepsy Can Hamper Fertility
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM

Title: 'What's That Word?' Fitness Helps Seniors Find It
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM

Title: Meal Swaps That Save 200 Calories
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM

Title: Health Tip: Protect Yourself From Sepsis
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Device Helps Doctors Select Lungs for Transplant
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: Health Tip: Understanding Breast Biopsy
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/1/2019 12:00:00 AM

Title: More Evidence CBD Can Help Ease a Form of Epilepsy in Kids
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 5/1/2019 12:00:00 AM

A new analysis suggests there may be a simple, noninvasive technique that could delay, or even eliminate, the need for ventilation in COVID-19 patients.

At some point, medical practices will reopen, but it will be anything but business as usual. Here are eight considerations for when it's time to unlock the doors and welcome patients back.

Two new reports suggest that the warm summer months will not significantly slow the novel coronavirus as it spreads around the globe.

KoreaMed Synapse, a digital archive and reference linking platform of Korean medical journals, is now using NCBI’s new PubReader presentation style to display their full-text journal articles. KoreaMed’s database of 122 journals now includes a blue ‘PubReader’ icon for each full-text article. NCBI launched PubReader in December 2012 as a convenient new way to view full-text articles in PubMed Central on desktops as well as tablets and mobile devices. In tandem with the launch, NCBI made the code used to create PubReader freely available on GitHub.

Title: How Many Steps Per Day to Lengthen Your Life?
Category: Health News
Created: 3/24/2020 12:00:00 AM
Last Editorial Review: 3/25/2020 12:00:00 AM

Title: Hantavirus Pulmonary Syndrome (HPS)
Category: Diseases and Conditions
Created: 4/21/2010 12:00:00 AM
Last Editorial Review: 3/24/2020 12:00:00 AM

Title: Religion Helps Protect Against 'Deaths of Despair': Study
Category: Health News
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/7/2020 12:00:00 AM

Title: Blood Pressure Dips Upon Standing Might Not Be as Dangerous as Thought
Category: Health News
Created: 1/28/2020 12:00:00 AM
Last Editorial Review: 1/29/2020 12:00:00 AM

Title: Up Your Steps to Lower Blood Pressure, Heart Study Suggests
Category: Health News
Created: 3/26/2020 12:00:00 AM
Last Editorial Review: 3/27/2020 12:00:00 AM

Title: Pick Summer Camps Carefully When Your Kid Has Allergies, Asthma
Category: Health News
Created: 2/29/2020 12:00:00 AM
Last Editorial Review: 3/2/2020 12:00:00 AM

Title: Allergy Med Singulair to Get 'Black Box' Warning Over Psych Side Effects: FDA
Category: Health News
Created: 3/4/2020 12:00:00 AM
Last Editorial Review: 3/5/2020 12:00:00 AM

Title: Heavy Drinking Into Old Age Ups Health Risks: Study
Category: Health News
Created: 4/7/2020 12:00:00 AM
Last Editorial Review: 4/8/2020 12:00:00 AM

Title: Therapy by Phone Helps Parkinson's Patients Manage Depression
Category: Health News
Created: 4/10/2020 12:00:00 AM
Last Editorial Review: 4/13/2020 12:00:00 AM

Title: Aftermath of Seizures Troubling for Those With Epilepsy
Category: Health News
Created: 4/17/2020 12:00:00 AM
Last Editorial Review: 4/20/2020 12:00:00 AM

Title: How Is a Transjugular Liver Biopsy Done?
Category: Procedures and Tests
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM

Title: Cough: 19 Tips on How to Stop a Cough
Category: Diseases and Conditions
Created: 5/24/2016 12:00:00 AM
Last Editorial Review: 4/14/2020 12:00:00 AM

ABSTRACT

Human genetics influence a range of pathological and clinical phenotypes in respiratory infections; however, the contributions of disease modifiers remain underappreciated. We exploited the Collaborative Cross (CC) mouse genetic-reference population to map genetic modifiers that affect the severity of Pseudomonas aeruginosa lung infection. Screening for P. aeruginosa respiratory infection in a cohort of 39 CC lines exhibits distinct disease phenotypes ranging from complete resistance to lethal disease. Based on major changes in the survival times, a quantitative-trait locus (QTL) was mapped on murine chromosome 3 to the genomic interval of Mb 110.4 to 120.5. Within this locus, composed of 31 protein-coding genes, two candidate genes, namely, dihydropyrimidine dehydrogenase (Dpyd) and sphingosine-1-phosphate receptor 1 (S1pr1), were identified according to the level of genome-wide significance and disease gene prioritization. Functional validation of the S1pr1 gene by pharmacological targeting in C57BL/6NCrl mice confirmed its relevance in P. aeruginosa pathophysiology. However, in a cohort of Canadian patients with cystic fibrosis (CF) disease, regional genetic-association analysis of the syntenic human locus on chromosome 1 (Mb 97.0 to 105.0) identified two single-nucleotide polymorphisms (rs10875080 and rs11582736) annotated to the Dpyd gene that were significantly associated with age at first P. aeruginosa infection. Thus, there is evidence that both genes might be implicated in this disease. Our results demonstrate that the discovery of murine modifier loci may generate information that is relevant to human disease progression.

IMPORTANCE Respiratory infection caused by P. aeruginosa is one of the most critical health burdens worldwide. People affected by P. aeruginosa infection include patients with a weakened immune system, such as those with cystic fibrosis (CF) genetic disease or non-CF bronchiectasis. Disease outcomes range from fatal pneumonia to chronic life-threatening infection and inflammation leading to the progressive deterioration of pulmonary function. The development of these respiratory infections is mediated by multiple causes. However, the genetic factors underlying infection susceptibility are poorly known and difficult to predict. Our study employed novel approaches and improved mouse disease models to identify genetic modifiers that affect the severity of P. aeruginosa lung infection. We identified candidate genes to enhance our understanding of P. aeruginosa infection in humans and provide a proof of concept that could be exploited for other human pathologies mediated by bacterial infection.

ABSTRACT

One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune system as they aid in the clearance of pathogens and can decrease pathogen virulence. It has also been recently reported that individual mucins and derived glycans can attenuate the virulence of the human pathogen Pseudomonas aeruginosa. Here, we show data indicating that mucins not only play a role in host defense but that they can also be subverted by P. aeruginosa to cause disease. We found that the mucin MUL-1 and mucin-derived monosaccharides N-acetyl-galactosamine and N-acetylglucosamine are required for P. aeruginosa killing of Caenorhabditis elegans. We also found that the defective adhesion of P. aeruginosa to human lung alveolar epithelial cells, deficient in the mucin MUC1, can be reversed by the addition of individual monosaccharides. The monosaccharides identified in this study are found in a wide range of organisms where they act as host factors required for bacterial pathogenesis. While mucins in C. elegans lack sialic acid caps, which makes their monosaccharides readily available, they are capped in other species. Pathogens such as P. aeruginosa that lack sialidases may rely on enzymes from other bacteria to utilize mucin-derived monosaccharides.

IMPORTANCE One of the first lines of defense present at mucosal epithelial tissues is mucus, which is a highly viscous material formed by mucin glycoproteins. Mucins serve various functions, but importantly they aid in the clearance of pathogens and debris from epithelial barriers and serve as innate immune factors. In this study, we describe a requirement of host monosaccharides, likely derived from host mucins, for the ability of Pseudomonas aeruginosa to colonize the intestine and ultimately cause death in Caenorhabditis elegans. We also demonstrate that monosaccharides alter the ability of bacteria to bind to both Caenorhabditis elegans intestinal cells and human lung alveolar epithelial cells, suggesting that there are conserved mechanisms underlying host-pathogen interactions in a range of organisms. By gaining a better understanding of pathogen-mucin interactions, we can develop better approaches to protect against pathogen infection.

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.

ABSTRACT

Recent global advocacy efforts have highlighted the importance of development of a vaccine against group A Streptococcus (GAS). Combo5 is a non-M protein-based vaccine that provides protection against GAS skin infection in mice and reduces the severity of pharyngitis in nonhuman primates. However, Combo5 with the addition of aluminum hydroxide (alum) as an adjuvant failed to protect against invasive GAS infection of mice. Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. SMQ, but not alum, generated strong interleukin-6 (IL-6), gamma interferon (IFN-), and tumor necrosis alpha (TNF-α) responses. This work highlights the importance of adjuvant selection for non-M protein-based GAS vaccines to optimize immune responses and protective efficacy.

IMPORTANCE Availability of a group A Streptococcus vaccine remains an unmet public health need. Here, we tested different adjuvant formulations to improve the protective efficacy of non-M protein vaccine Combo5 in an invasive disease model. We show that novel adjuvants can dramatically shape the type of immune response developed following immunization with Combo5 and significantly improve protection. In addition, protection afforded by Combo5 is not mediated by opsonizing antibodies, believed to be the main correlate of protection against GAS infections. Overall, this report highlights the importance of adjuvant selection in raising protective immune responses against GAS invasive infection. Adjuvants that can provide a more balanced Th1/Th2-type response may be required to optimize protection of GAS vaccines, particularly those based on non-M protein antigens.

ABSTRACT

The opportunistic bacterium Pseudomonas aeruginosa produces the fucose-specific lectin LecB, which has been identified as a virulence factor. LecB has a tetrameric structure with four opposing binding sites and has been shown to act as a cross-linker. Here, we demonstrate that LecB strongly binds to the glycosylated moieties of β1-integrins on the basolateral plasma membrane of epithelial cells and causes rapid integrin endocytosis. Whereas internalized integrins were degraded via a lysosomal pathway, washout of LecB restored integrin cell surface localization, thus indicating a specific and direct action of LecB on integrins to bring about their endocytosis. Interestingly, LecB was able to trigger uptake of active and inactive β1-integrins and also of complete α3β1-integrin–laminin complexes. We provide a mechanistic explanation for this unique endocytic process by showing that LecB has the additional ability to recognize fucose-bearing glycosphingolipids and causes the formation of membrane invaginations on giant unilamellar vesicles. In cells, LecB recruited integrins to these invaginations by cross-linking integrins and glycosphingolipids. In epithelial wound healing assays, LecB specifically cleared integrins from the surface of cells located at the wound edge and blocked cell migration and wound healing in a dose-dependent manner. Moreover, the wild-type P. aeruginosa strain PAO1 was able to loosen cell-substrate adhesion in order to crawl underneath exposed cells, whereas knockout of LecB significantly reduced crawling events. Based on these results, we suggest that LecB has a role in disseminating bacteria along the cell-basement membrane interface.

IMPORTANCE Pseudomonas aeruginosa is a ubiquitous environmental bacterium that is one of the leading causes of nosocomial infections. P. aeruginosa is able to switch between planktonic, intracellular, and biofilm-based lifestyles, which allows it to evade the immune system as well as antibiotic treatment. Hence, alternatives to antibiotic treatment are urgently required to combat P. aeruginosa infections. Lectins, like the fucose-specific LecB, are promising targets, because removal of LecB resulted in decreased virulence in mouse models. Currently, several research groups are developing LecB inhibitors. However, the role of LecB in host-pathogen interactions is not well understood. The significance of our research is in identifying cellular mechanisms of how LecB facilitates P. aeruginosa infection. We introduce LecB as a new member of the list of bacterial molecules that bind integrins and show that P. aeruginosa can move forward underneath attached epithelial cells by loosening cell-basement membrane attachment in a LecB-dependent manner.