The Curious Case of Elevated Tryptase: Workup and Differential in Family of Four.

Elevated basal serum tryptase (BST) levels are markers of both mast cell activation and overall mast cell burden. We present a family of four individuals with elevated tryptase levels greater than or equal to 20 mcg/L, all of whom exhibited signs and symptoms suggestive of mast cell activation. Differential diagnoses included hereditary alpha tryptasemia (HaT), systemic mastocytosis (SM), and mast cell activation syndrome (MCAS).

Discordance of the Urinary and Pleural Fluid Antigen Test and False Positive for Streptococcus pneumoniae in Empyema Secondary to Necrotizing Bacterial Pneumonia.

Empyema is a severe complication of pneumonia with high morbidity and mortality rates. Rapid diagnosis and tailoring of antibiotic therapy are crucial to treatment success for these severe bacterial lung infections. A Streptococcus pneumoniae ( antigen test drawn from the pleural fluid rather than a urine sample has been found to have equivalent diagnostic utility to the urinary antigen test.

A Case of Lyme Carditis With Variable Heart Block Successfully Treated With Oral Doxycycline.

A 39-year-old male without significant past medical history presented with three weeks of worsening fatigue, migratory arthralgia, rash, and unilateral facial weakness after spending three months in Vermont. Serology showed positive Lyme titers 1:64 for both IgM and IgG. EKG on presentation showed a P-R interval of 384 ms, and the patient was admitted for concern of Lyme carditis.

Beyond Messiaen's birds: the post-verbal world of dementia.

This paper investigates the use of verbatim musical transcription as a research method in dementia care. It reports on an art-based ethnographic study (Aesthetic Research in Everyday Life (Aeriel)) in which verbatim transcription was applied to everyday interactions in dementia care, making use of musical-instead of verbal-notation. Starting from the notion that medical and healthcare settings can be sites of 'found performance', the paper reviews literature relating to artistic methodologies within medical humanities, music, ethnography and dementia care.

Influenza-Like Illness in Travelers to the Developing World.

Travelers to developing regions are at risk for development of influenza-like illness (ILI). Little is known of traveler and trip characteristics associated with the development of ILI. TravMil is a prospective observational study, enrolling subjects presenting to six military travel clinics or predeployment-screening sites.

Low-Virulence Organisms and Periprosthetic Joint Infection-Biofilm Considerations of These Organisms.

Purpose Of Review: The purpose of this manuscript is to provide a critical review of peer-reviewed literature over the last 5 years related to low virulent organisms associated with periprosthetic joint infection (PJI). We evaluated the most common organisms, the diagnostic challenges, and the novel tools available in the perioperative workup of PJI as well as the current understanding of how biofilm potentiates the indolent clinical presentation and explore a possible shift in the surgical management of these patients.

Recent Findings: Biofilm actively prevents macrophage phagocytosis by suppressing proinflammatory activity through the recruitment of myeloid-derived suppressor cells.

"Found Performance": Towards a Musical Methodology for Exploring the Aesthetics of Care.

Concepts of performance in fine art reflect key processes in music therapy. Music therapy enables practitioners to reframe patients as performers, producing new meanings around the clinical knowledge attached to medical histories and constructs. In this paper, music therapy practices are considered in the wider context of art history, with reference to allied theories from social research.

Characterizing the mitochondrial DNA polymerase gamma interactome by BioID identifies Ruvbl2 localizes to the mitochondria.

Human mitochondrial DNA (mtDNA) is replicated by the mitochondrial DNA polymerase gamma (POLG). Using proximity dependent biotin labelling (BioID), we characterized the POLG interactome and identified new interaction partners involved in mtDNA maintenance, transcription, translation and protein quality control. We also identified interaction with the nuclear AAA+ ATPase Ruvbl2, suggesting mitochondrial localization for this protein.

Analysis of Replicating Mitochondrial DNA by In Organello Labeling and Two-Dimensional Agarose Gel Electrophoresis.

Our understanding of the mechanisms of DNA replication in a broad range of organisms and viruses has benefited from the application of two-dimensional agarose gel electrophoresis (2D-AGE). The method resolves DNA molecules on the basis of size and shape and is technically straightforward. 2D-AGE sparked controversy in the field of mitochondria when it revealed replicating molecules with lengthy tracts of RNA, a phenomenon never before reported in nature.

Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication.

Encoding ribonuclease H1 (RNase H1) degrades RNA hybridized to DNA, and its function is essential for mitochondrial DNA maintenance in the developing mouse. Here we define the role of RNase H1 in mitochondrial DNA replication. Analysis of replicating mitochondrial DNA in embryonic fibroblasts lacking RNase H1 reveals retention of three primers in the major noncoding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L.

Disposition, metabolism and mass balance of delafloxacin in healthy human volunteers following intravenous administration.

1. The pharmacokinetics and disposition of delafloxacin was investigated following a single intravenous (300 mg, 100 µCi) dose to healthy male subjects. 2.

Quantitative whole-body autoradiography, LC-MS/MS and MALDI for drug-distribution studies in biological samples: the ultimate matrix trilogy.

The drug-development process requires an understanding of the ADME properties of the novel therapeutic agent. Determination of drug concentrations and identity in excreta (urine and feces) examines the products of these processes. Similar measurements made on plasma, while accurately determining exposure, show only what is being transported around the body.

The 'ripple effect': Towards researching improvisational music therapy in dementia care homes.

Increased interest in, and demand for, music therapy provision for persons with dementia prompted this study's exploration of music therapists' strategies for creating musical communities in dementia care settings, considering the needs and resources of people affected by dementia. Focus group discussions and detailed iterative study of improvisational music therapy work by six experienced practitioners clarify the contextual immediacy and socio-musical complexities of music therapy in dementia care homes. Music therapy's 'ripple effect', with resonances from micro (person-to-person musicking), to meso (musicking beyond 'session time') and macro level (within the care home and beyond), implies that all who are part of the dementia care ecology need opportunities for flourishing, shared participation, and for expanded self-identities; beyond 'staff', 'residents', or 'being in distress'.

A cryptic targeting signal creates a mitochondrial FEN1 isoform with tailed R-Loop binding properties.

A growing number of DNA transacting proteins is found in the nucleus and in mitochondria, including the DNA repair and replication protein Flap endonuclease 1, FEN1. Here we show a truncated FEN1 isoform is generated by alternative translation initiation, exposing a mitochondrial targeting signal. The shortened form of FEN1, which we term FENMIT, localizes to mitochondria, based on import into isolated organelles, immunocytochemistry and subcellular fractionation.

Mitochondrial DNA replication proceeds via a 'bootlace' mechanism involving the incorporation of processed transcripts.

The observation that long tracts of RNA are associated with replicating molecules of mitochondrial DNA (mtDNA) suggests that the mitochondrial genome of mammals is copied by an unorthodox mechanism. Here we show that these RNA-containing species are present in living cells and tissue, based on interstrand cross-linking. Using DNA synthesis in organello, we demonstrate that isolated mitochondria incorporate radiolabeled RNA precursors, as well as DNA precursors, into replicating DNA molecules.

Alternative translation initiation augments the human mitochondrial proteome.

Alternative translation initiation (ATI) is a mechanism of producing multiple proteins from a single transcript, which in some cases regulates trafficking of proteins to different cellular compartments, including mitochondria. Application of a genome-wide computational screen predicts a cryptic mitochondrial targeting signal for 126 proteins in mouse and man that is revealed when an AUG codon located downstream from the canonical initiator methionine codon is used as a translation start site, which we term downstream ATI (dATI). Experimental evidence in support of dATI is provided by immunoblotting of endogenous truncated proteins enriched in mitochondrial cell fractions or of co-localization with mitochondria using immunocytochemistry.

A microarray analysis of the hypoxia-induced modulation of gene expression in human adipocytes.

The effect of hypoxia on global gene expression in human adipocytes has been examined using DNA microarrays. Adipocytes (Zen-Bio, day 12 post-differentiation) were exposed to hypoxia (1% O(2)) or 'normoxia' (21% O(2)) for 24 h and extracted RNA probed with Agilent arrays containing 41,152 probes. A total of 1346 probes were differentially expressed (>2.

Modulation of adipokine production, glucose uptake and lactate release in human adipocytes by small changes in oxygen tension.

Adipose tissue becomes hypoxic in obesity, and cell culture studies have demonstrated that hypoxia leads to major changes in adipocyte function. Studies on the response of adipocytes to low O₂ tension have employed marked hypoxia (1% O₂). Here, we have examined the effects of modest hypoxia, utilising differing concentrations of O₂ (1-21%), on adipokine production and glucose uptake by human adipocytes.

Adipokine expression and secretion by canine adipocytes: stimulation of inflammatory adipokine production by LPS and TNFalpha.

Adiposity and obesity are increasing in dogs. We have examined here the endocrine function of canine adipose tissue and the regulation of production of inflammation-related adipokines by dog adipocytes. Adiponectin, leptin, IL-6, MCP-1 and TNFalpha genes were expressed in the main adipose depots of dogs, but there were no major depot differences in mRNA levels.

Obesity, its associated disorders and the role of inflammatory adipokines in companion animals.

Obesity is characterised by an expansion of white adipose tissue mass that can lead to adverse health effects, such as decreased longevity, diabetes mellitus, orthopaedic and respiratory disease and neoplasia. Once thought a passive fuel depot, adipose tissue is now recognised as an active endocrine organ that communicates with the brain and peripheral tissues by secreting a wide range of hormones and protein factors, collectively termed adipokines. Examples include leptin, adiponectin, cytokines (tumour necrosis factor-alpha, interleukin-6), chemokines, acute phase proteins, haemostatic and haemodynamic factors and neurotrophins.

Mammalian mitochondrial DNA replication intermediates are essentially duplex but contain extensive tracts of RNA/DNA hybrid.

We demonstrate, using transmission electron microscopy and immunopurification with an antibody specific for RNA/DNA hybrid, that intact mitochondrial DNA replication intermediates are essentially duplex throughout their length but contain extensive RNA tracts on one strand. However, the extent of preservation of RNA in such molecules is highly dependent on the preparative method used. These findings strongly support the strand-coupled model of mitochondrial DNA replication involving RNA incorporation throughout the lagging strand.

Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes.

Hypoxia modulates white adipose tissue function, and this includes stimulating glucose uptake and the expression of facilitative glucose transporters (particularly GLUT1) in adipocytes. This study has examined the effect of hypoxia on lactate release from adipocytes and whether the monocarboxylate transporters that mediate lactate transport (MCTs1-4) are expressed in human adipocytes and are induced by low O(2) tension. Exposure of human Simpson-Golabi-Behmel syndrome adipocytes to 1% O(2) for 24 h resulted in increased lactate release (2.

A soluble RecN homologue provides means for biochemical and genetic analysis of DNA double-strand break repair in Escherichia coli.

RecN is a highly conserved, SMC-like protein in bacteria. It plays an important role in the repair of DNA double-strand breaks and is therefore a key factor in maintaining genome integrity. The insolubility of Escherichia coli RecN has limited efforts to unravel its function.

Cellular hypoxia and adipose tissue dysfunction in obesity.

Expansion of adipose tissue mass, the distinctive feature of obesity, is associated with low-grade inflammation. White adipose tissue secretes a diverse range of adipokines, a number of which are inflammatory mediators (such as TNFalpha, IL-1beta, IL-6, monocyte chemoattractant protein 1). The production of inflammatory adipokines is increased with obesity and these adipokines have been implicated in the development of insulin resistance and the metabolic syndrome.