Phagocytosis via complement receptor 3 enables microbes to evade killing by neutrophils.

CR3 (CD11b/CD18; αmβ2 integrin) is a conserved phagocytic receptor. The active conformation of CR3 binds the iC3b fragment of complement C3 as well as many host and microbial ligands, leading to actin-dependent phagocytosis. There are conflicting reports about how CR3 engagement affects the fate of phagocytosed substrates.

Dental school pathway programs: Best practices for increasing workforce diversity.

The chronic underrepresentation of racial/ethnic minority practitioners in the U.S. health professions workforce is an oft-cited factor for disparities in health and health-care access affecting communities of color.

The CHO Cell Clustering Response to Pertussis Toxin: History of Its Discovery and Recent Developments in Its Use.

Chinese hamster ovary (CHO) cells respond to pertussis toxin (PT) with a novel clustering pattern, which is dependent on biologically active PT. Since its description in 1983, this cellular response has been refined and used extensively for detection and quantification of PT activity, as well as anti-PT antibodies. There are limitations, however, in the use of this phenomenon as originally described.

Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin.

Secretion of pertussis toxin (PT) is the preeminent virulence trait of the human pathogen Bordetella pertussis, causing whooping cough. Bordetella bronchiseptica, although it harbors an intact 12-kb ptx-ptl operon, does not express PT due to an inactive ptx promoter (Pptx), which contains 18 SNPs (single nucleotide polymorphisms) relative to B. pertussis Pptx.

Patient-reported indicators in mental health care: towards international standards among members of the OECD.

Background: Achieving people-centred health care systems requires new and innovative strategies to capture information about whether, and to what degree, health care is successful in improving health from the perspective of the patient. Patient-reported outcome measures (PROMs) and Patient-reported experience measures (PREMs) can bring some of these new insights, and are increasingly used in research, clinical care, and policymaking.

Methods: This paper reflects the ongoing discussions and findings of the OECD PaRIS Working Group on Patient-reported Indicators for Mental Health Care.

Measuring patient voice matters: setting the scene for patient-reported indicators.

Background: Achieving people-centred health care systems requires new and innovative strategies to capture information about whether, and to what degree, health care is successful in improving health from the perspective of the patient. Patient-reported outcome measures (PROMs) and Patient-reported experience measures (PREMs) can bring some of these new insights, and are increasingly used in research, clinical care, and policymaking.

Methods: This paper reflects the ongoing discussions and findings of the OECD PaRIS Working Group on Patient-reported Indicators for Mental Health Care.

Novel allosteric PARP1 inhibitors for the treatment of BRCA-deficient leukemia.

The successful use of PARP1 inhibitors like olaparib (Loparza) in the treatment of BRCA1/2- deficient breast cancer has provided clinical proof of concept for applying personalized medicine based on synthetic lethality to the treatment of cancer. Unfortunately, all marketed PARP1 inhibitors act by competing with the cofactor NAD and resistance is already developing to this anti-cancer mechanism. Allosteric PARP1 inhibitors could provide a means of overcoming this resistance.

Pathogenesis, diagnosis and management of dentin hypersensitivity: an evidence-based overview for dental practitioners.

Though dentin hypersensitivity (DHS) is one of the most common complaints from patients in dental clinics, there are no universally accepted guidelines for differential diagnosis as well as selection of reliable treatment modalities for this condition. The neurosensory mechanisms underlying DHS remain unclear, but fluid movements within exposed dentinal tubules, i.e.

Coronary artery bypass grafting is associated with immunoparalysis of monocytes and dendritic cells.

Coronary artery bypass grafting (CABG) triggers a systemic inflammatory response that may contribute to adverse outcomes. Dendritic cells (DC) and monocytes are immunoregulatory cells potentially affected by CABG, contributing to an altered immune state. This study investigated changes in DC and monocyte responses in CABG patients at 5 time-points: admission, peri-operative, ICU, day 3 and day 5.

Gene Essentiality and Metabolism in Bordetella pertussis.

is the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms of growth and pathogenicity. While previous studies have provided insight into gene essentiality of this organism, very little is known about gene essentiality, a critical gap in knowledge, since has no previously identified environmental reservoir and is isolated from human respiratory tract samples.

Bordetella pertussis Can Be Motile and Express Flagellum-Like Structures.

encodes and expresses a flagellar apparatus. In contrast, , the causative agent of whooping cough, has historically been described as a nonmotile and nonflagellated organism. The previous statements that was a nonmotile organism were consistent with a stop codon located in the flagellar biosynthesis gene, , discovered when the Tohama I genome was sequenced and analyzed by Parkhill et al.

Analysis of the Transcriptome of Bordetella pertussis during Infection of Mice.

causes the disease whooping cough through coordinated control of virulence factors by the virulence gene system. Microarrays and, more recently, RNA sequencing (RNA-seq) have been used to describe gene expression profiles of and other pathogens. In previous studies, we have analyzed the gene expression profiles of , and we hypothesize that the infection transcriptome profile is significantly different from that under laboratory growth conditions.

Non-NAD-like PARP-1 inhibitors in prostate cancer treatment.

In our previous studies of the molecular mechanisms of poly(ADP-ribose) polymerase 1 (PARP-1)-mediated transcriptional regulation we identified a novel class of PARP-1 inhibitors targeting the histone-dependent route of PARP-1 activation. Because histone-dependent activation is unique to PARP-1, non-NAD-like PARP-1 inhibitors have the potential to bypass the off-target effects of classical NAD-dependent PARP-1 inhibitors, such as olaparib, veliparib, and rucaparib. Furthermore, our recently published studies demonstrate that, compared to NAD-like PARP-1 inhibitors that are used clinically, the non-NAD-like PARP-1 inhibitor 5F02 exhibited superior antitumor activity in cell and animal models of human prostate cancer (PC).

Evaluation of Adenylate Cyclase Toxoid Antigen in Acellular Pertussis Vaccines by Using a Bordetella pertussis Challenge Model in Mice.

is the primary causative agent of pertussis (whooping cough), which is a respiratory infection that leads to a violent cough and can be fatal in infants. There is a need to develop more effective vaccines because of the resurgence of cases of pertussis in the United States since the switch from the whole-cell pertussis vaccines (wP) to the acellular pertussis vaccines (aP; diphtheria-tetanus-acellular-pertussis vaccine/tetanus-diphtheria-pertussis vaccine). Adenylate cyclase toxin (ACT) is a major virulence factor of that is (i) required for establishment of infection, (ii) an effective immunogen, and (iii) a protective antigen.

New genotypes of Liao ning virus (LNV) in Australia exhibit an insect-specific phenotype.

Liao ning virus (LNV) was first isolated in 1996 from mosquitoes in China, and has been shown to replicate in selected mammalian cell lines and to cause lethal haemorrhagic disease in experimentally infected mice. The first detection of LNV in Australia was by deep sequencing of mosquito homogenates. We subsequently isolated LNV from mosquitoes of four genera (Culex, Anopheles, Mansonia and Aedes) in New South Wales, Northern Territory, Queensland and Western Australia; the earliest of these Australian isolates were obtained from mosquitoes collected in 1988, predating the first Chinese isolates.

Ross River virus in Australian blood donors: possible implications for blood transfusion safety.

Background: Emerging transfusion-transmissible pathogens, including arboviruses such as West Nile, Zika, dengue, and Ross River viruses, are potential threats to transfusion safety. The most prevalent arbovirus in humans in Australia is Ross River virus (RRV); however, prevalence varies substantially around the country. Modeling estimated a yearly risk of 8 to 11 potentially RRV-viremic fresh blood components nationwide.

Albumin, in the Presence of Calcium, Elicits a Massive Increase in Extracellular Bordetella Adenylate Cyclase Toxin.

Pertussis (whooping cough), caused by , is resurging in the United States and worldwide. Adenylate cyclase toxin (ACT) is a critical factor in establishing infection with and acts by specifically inhibiting the response of myeloid leukocytes to the pathogen. We report here that serum components, as discovered during growth in fetal bovine serum (FBS), elicit a robust increase in the amount of ACT, and ≥90% of this ACT is localized to the supernatant, unlike growth without FBS, in which ≥90% is associated with the bacterium.

Fine Epitope Mapping of Two Antibodies Neutralizing the Bordetella Adenylate Cyclase Toxin.

Adenylate cyclase toxin (ACT) is an important Bordetella pertussis virulence factor that is not included in current acellular pertussis vaccines. We previously demonstrated that immunization with the repeat-in-toxin (RTX) domain of ACT elicits neutralizing antibodies in mice and discovered the first two antibodies to neutralize ACT activities by occluding the receptor-binding site. Here, we fully characterize these antibodies and their epitopes.

Should Lecture Recordings Be Mandated in Dental Schools? Two Viewpoints: Viewpoint 1: Lecture Recordings Should Be Mandatory in U.S. Dental Schools and Viewpoint 2: Lecture Recordings Should Not Be Mandatory in U.S. Dental Schools.

Transcription or recording of lectures has been in use for many years, and with the availability of high-fidelity recording, the practice is now ubiquitous in higher education. Since technology has permeated education and today's tech-savvy students have expectations for on-demand learning, dental schools are motivated to record lectures, albeit with positive and negative implications. This Point/Counterpoint article addresses the question of whether lecture recording should be mandatory in U.

Modulation of Pertussis and Adenylate Cyclase Toxins by Sigma Factor RpoE in Bordetella pertussis.

Bordetella pertussis is a human pathogen that can infect the respiratory tract and cause the disease known as whooping cough. B. pertussis uses pertussis toxin (PT) and adenylate cyclase toxin (ACT) to kill and modulate host cells to allow the pathogen to survive and persist.

Bordetella adenylate cyclase toxin interacts with filamentous haemagglutinin to inhibit biofilm formation in vitro.

Bordetella pertussis, the causative agent of whooping cough, secretes and releases adenylate cyclase toxin (ACT), which is a protein bacterial toxin that targets host cells and disarms immune defenses. ACT binds filamentous haemagglutinin (FHA), a surface-displayed adhesin, and until now, the consequences of this interaction were unknown. A B.

Use of a Toxin Neutralization Assay To Characterize the Serologic Response to Adenylate Cyclase Toxin after Infection with Bordetella pertussis.

Adenylate cyclase toxin (ACT) is an essential virulence factor of Bordetella pertussis, and antibodies to ACT protect against B. pertussis infection in mice. The toxin is therefore a strong candidate antigen for addition to future acellular pertussis vaccines.

Sealants for Preventing and Arresting Pit-and-fissure Occlusal Caries in Primary and Permanent Molars.

Background: National Health and Nutrition Examination Survey 2011-2012 data indicated that, in the United States, nearly onefourth of children and over one-half of adolescents experienced dental caries in their permanent teeth. The purpose of this review was to summarize the available clinical evidence regarding the effect of dental sealants for the prevention and management of pit-and-fissure occlusal carious lesions in primary and permanent molars, compared with a control without sealants, with fluoride varnishes, or with other head-to head comparisons.

Type Of Studies Reviewed: The authors included parallel and split-mouth randomized controlled trials that included at least 2 years of follow-up, which they identified using MEDLINE (via PubMed), Embase, LILACS, the Cochrane Central Register of Controlled Trials, and registers of ongoing trials.

Evidence-based clinical practice guideline for the use of pit-and-fissure sealants: A report of the American Dental Association and the American Academy of Pediatric Dentistry.

Background: This article presents evidence-based clinical recommendations for the use of pit-and-fissure sealants on the occlusal surfaces of primary and permanent molars in children and adolescents. A guideline panel convened by the American Dental Association (ADA) Council on Scientific Affairs and the American Academy of Pediatric Dentistry conducted a systematic review and formulated recommendations to address clinical questions in relation to the efficacy, retention, and potential side effects of sealants to prevent dental caries; their efficacy compared with fluoride varnishes; and a head-to-head comparison of the different types of sealant material used to prevent caries on pits and fissures of occlusal surfaces.

Types Of Studies Reviewed: This is an update of the ADA 2008 recommendations on the use of pit-and-fissure sealants on the occlusal surfaces of primary and permanent molars.