Age-dependent electrical and morphological remodeling of the Drosophila heart caused by hERG/seizure mutations.

Understanding the cellular-molecular substrates of heart disease is key to the development of cardiac specific therapies and to the prevention of off-target effects by non-cardiac targeted drugs. One of the primary targets for therapeutic intervention has been the human ether a go-go (hERG) K+ channel that, together with the KCNQ channel, controls the rate and efficiency of repolarization in human myocardial cells. Neither of these channels plays a major role in adult mouse heart function; however, we show here that the hERG homolog seizure (sei), along with KCNQ, both contribute significantly to adult heart function as they do in humans. In Drosophila, mutations in or cardiac knockdown of sei channels cause arrhythmias that become progressively more severe with age. Intracellular recordings of semi-intact heart preparations revealed that these perturbations also cause electrical remodeling that is reminiscent of the early afterdepolarizations seen in human myocardial cells defective in these channels. In contrast to KCNQ, however, mutations in sei also cause extensive structural remodeling of the myofibrillar organization, which suggests that hERG channel function has a novel link to sarcomeric and myofibrillar integrity. We conclude that deficiency of ion channels with similar electrical functions in cardiomyocytes can lead to different types or extents of electrical and/or structural remodeling impacting cardiac output.

RTX toxin plays a key role in Kingella kingae virulence in an infant rat model.

Kingella kingae is a human oral bacterium that can cause diseases of the skeletal system in children and infective endocarditis in children and adults. K. kingae produces a toxin of the RTX group, RtxA. To investigate the role of RtxA in disease pathogenesis in vivo, K. kingae strain PYKK081 and its isogenic RtxA-deficient strain KKNB100 were tested for their virulence and pathological consequences upon intraperitoneal injections in 7-day-postnatal (PN 7) rats. At the doses above 8.0 × 10(6) cells/animal, PYKK081 was able to cause a fatal illness, resulting in rapid weight loss, bacteremia, and abdominal necrotic lesion formation. Significant histopathology was observed in thymus, spleen, and bone marrow. Strain KKNB100 was less toxic to animals. Neither weight loss, bacteremia, nor histopathological changes were evident. Animals injected with KKNB100 exhibited a significantly elevated circulating white blood cell (WBC) count, whereas animals injected with PYKK081 had a WBC count that resembled that of the uninfected control. This observation parallels the subtleties associated with clinical presentation of K. kingae disease in humans and suggests that the toxin contributes to WBC depletion. Thus, our results demonstrate that RtxA is a key K. kingae virulence factor. Furthermore, our findings suggest that the PN 7 rat can serve as a useful model for understanding disease caused by K. kingae and for elucidating diagnostic parameters in human patients.

Characterization of TEM-1 ß-Lactamase-Producing Kingella kingae Clinical Isolates.

Kingella kingae is a human pathogen that causes pediatric osteoarticular infections and infective endocarditis in children and adults. The bacterium is usually susceptible to ß-lactam antibiotics, although ß-lactam resistance has been reported in rare isolates. This study was conducted to identify ß-lactam-resistant strains and to characterize the resistance mechanism. Screening of a set of 90 K. kingae clinical isolates obtained from different geographic locations revealed high-level resistance to penicillins among 25% of the strains isolated from Minnesota and Iceland. These strains produced TEM-1 ß-lactamase and were shown to contain additional ≥50-kb plasmids. Ion Torrent sequencing of extrachromosomal DNA from a ß-lactamase-producing strain confirmed the plasmid location of the blaTEM gene. An identical plasmid pattern was demonstrated by multiplex PCR in all ß-lactamase producers. The porin gene's fragments were analyzed to investigate the relatedness of bacterial strains. Phylogenetic analysis revealed 27 single-nucleotide polymorphisms (SNPs) in the por gene fragment, resulting in two major clusters with 11 allele types forming bacterial-strain subclusters. ß-Lactamase producers were grouped together based on por genotyping. Our results suggest that the ß-lactamase-producing strains likely originate from a single plasmid-bearing K. kingae isolate that traveled from Europe to the United States, or vice versa. This study highlights the prevalence of penicillin resistance among K. kingae strains in some regions and emphasizes the importance of surveillance for antibiotic resistance of the pathogen.

Medication for Gravid and Nursing Oral and Maxillofacial Surgery Patients.

The purpose of this article is to clarify clinically impactful features of the perioperative and postoperative pharmacologic management of pregnant and lactating patients in the maxillofacial or dental setting. Before prescribing any drug to a nursing mother or pregnant patient, the maxillofacial surgeon and other dental and medical providers should consider the available evidence, benefits, and risk for that particular drug. There are many complex factors to consider when prescribing in order to maintain the safety of the pregnant individual, fetus, and infant. This article aims to provide concise, memorable, and actionable information to use in your clinical practice.

Pharmacologic Management of Neuropathic Pain.

This article aims to provide the practitioner with therapeutic options to treat a broad spectrum of acute and chronic orofacial pain syndromes. The focus will be nonsurgical that the oral health care physician can implement to treat this population of patients. The World Health Organization estimated that more than 1 in every 3 people suffers from acute or chronic pain. This article is primarily devoted to medication management once the diagnosis of neuropathic pain, a true trigeminal neuralgia, or a variant of trigeminal neuralgia often referred to as traumatic neuropathic pain or traumatic trigeminal neuralgia.

All-on-4 Concept Update.

Over the past 17 years, the All-on-4 treatment concept has been a reliable and predictable modality to rehabilitate edentulous jaws with immediate function as full-arch prostheses. This article highlights clinically relevant data compiled by numerous All-on-4 investigators including complications and their remedies, occlusion and cantilever trends, implant size utilization, and controversial topics. We provide insights for navigating the complexities of medically diverse populations, faced by our daily practice, with a focus on patient avoidance, risk factors for implant and prosthetic failures, in hopes to minimize complications so clinicians would choose this treatment with confidence.

Oral Manifestation of Systemic Diseases.

The US Surgeon General's report Oral Health in America highlighted ways in which oral health and systemic conditions are associated with each other. An oral examination can reveal signs and symptoms associated with systemic diseases. In this article, multiple systemic diseases including but not limited to viral and immune modulated conditions and associated oral symptoms are discussed.