Characteristics of Interval Colorectal Cancer: A Canadian Retrospective Population-Level Analysis from Newfoundland and Labrador.

Interval colorectal cancers (I-CRCs) arise during the interval time period between scheduled colonoscopies. Predicting which patients are at risk of I-CRCs remains an elusive undertaking, but evidence would suggest that most I-CRCs arise from lesions missed on index endoscopy. The procedural factors that lead to missed lesions are numerous and lack consensus in the literature. In Canada, the province of Newfoundland and Labrador has the highest incidence of CRCs. In this study our aim was to examine I-CRCs (3-60 months after last colonoscopy) in NL through a population-level analysis covering 67% of the province from 2001-2018. We estimated the I-CRC rate to be up to 9.3%. Median age of I-CRC diagnosis was 67.1 years with an interval time of 2.9 years. About 57% of these tumors occurred proximal to the splenic flexure, with 53% presenting as local disease. No temporal differences were observed in interval time or tumor distribution. On univariate and multivariable logistical regression, risk of right-sided I-CRC did not correlate to the index colonoscopy indication, bowel preparation quality, size of largest polyp removed, colonoscopy completion rate, or stage at presentation. Improvements in synoptic reporting utilization and national registries are needed to identity risk factors and reduce I-CRC frequency.

Structure, amphipathy, and topology of the membrane-proximal helix 8 influence apelin receptor plasma membrane localization.

G-protein coupled receptors (GPCRs) typically have an amphipathic helix ("helix 8") immediately C-terminal to the transmembrane helical bundle. To date, a number of functional roles have been associated with GPCR helix 8 segments, but structure-function analysis for this region remains limited. Here, we examine helix 8 of the apelin receptor (AR or APJ), a class A GPCR with wide physiological and pathophysiological relevance. The 71 residue C-terminal tail of the AR is primarily intrinsically disordered, with a detergent micelle-induced increase in helical character. This helicity was localized to the helix 8 region, in good agreement with the recent AR crystal structure. A series of helix 8 mutants were made to reduce helicity, remove amphipathy, or flip the hydrophobic and hydrophilic faces. Each mutant AR was tested both biophysically, in the isolated C-terminal tail, and functionally in HEK 293 T cells, for full-length AR. In all instances, micelle interactions were maintained, and steady-state AR expression was efficient. However, removal of amphipathy or helical character led to a significant decrease in cell surface localization. Flipping of helix 8 amphipathic topology restored cell surface localization to some degree, but still was significantly reduced relative to wild-type. Structural integrity, amphipathy to drive membrane association, and correct topology of helix 8 membrane association all thus appear important for cell surface localization of the AR. This behavior correlates well to GPCR C-terminal tail sequence motifs, implying that these serve to specify key topological features of helix 8 and its proximity to the transmembrane domain.

Pulmonary and cutaneous O2gas exchange: a student laboratory exercise in the frog.

Gas exchange in animals is ultimately diffusion based, generally occurring across dedicated respiratory organs. In many aquatic amphibians, however, multiple modes of gas exchange exist, allowing for the partitioning of O2 uptake and CO2 excretion between respiratory organs with different efficiencies. For example, due to the physical properties of O2 being vastly different between air and water phases, the lung and skin play disproportionately important roles in O2 uptake. Many aquatic frogs are renowned for their cutaneous gas exchange capacity, where often the majority of CO2 is excreted across the skin. Furthermore, the roles of these gas exchange organs change with the animal's behavior. Under diving conditions, most of the frog's gas exchange needs must be met by the skin. In this article, we describe an interactive undergraduate laboratory that allows a class of students to share equipment while assessing pulmonary and cutaneous respiration in frogs provided with an air/water choice and under enforced dive conditions. Concepts explored in this laboratory exercise include animal energetics, diving reflex, pulmonary and cutaneous gas exchange processes, diffusion-based gas flux, and O2 debt.

A fish out of water: gill and skin remodeling promotes osmo- and ionoregulation in the mangrove killifish Kryptolebias marmoratus.

The euryhaline, amphibious mangrove killifish Kryptolebias marmoratus is known to survive weeks out of water in moist environments. We tested the hypothesis that the skin is a site of osmo- and ionoregulation in K. marmoratus. We predicted that under terrestrial conditions, gill and skin remodeling would result in an enhanced role for skin and a diminished role for the gills in osmo- and ionoregulation. Fish were exposed to water-either freshwater (FW, 1‰) or hypersaline water (saltwater [SW], 45‰)-or air over a moist surface of FW or SW for 9 d and then recovered in water. When fish were emersed for 9 d, (22)Na and (3)H-H(2)O were exchanged across the cutaneous surface. Homeostasis of whole-body Cl(-) and water levels but not of Na(+) levels was maintained over 9 d in air. In air-exposed fish, there was a significant increase in the size of skin ionocytes (in SW), a decrease in the number of skin mucous cells (in SW), and an increase in the gill interlamellar cell mass relative to those of fish in water. Gill ionocytes were mostly embedded away from the external surface in air-exposed fish, but the number and size of ionocytes increased (in FW). Interestingly, skin ionocytes formed distinct clusters of 20-30 cells. The estimated number of ionocytes over the whole skin surface was comparable to that in the gills. Overall, the findings support the hypothesis that the skin is a site of osmo- and ionoregulation in K. marmoratus in aquatic and terrestrial environments. Reversible cellular and morphological changes to the skin and gills during air exposure probably enhanced the cutaneous contribution to ion and water balance.

Increasing incidence of methicillin-resistant Staphylococcus aureus in hand infections: a 3-year county hospital experience.

BACKGROUND: Staphylococcus aureus is the most common cause of skin and soft-tissue infections. Methicillin-resistant S. aureus and community-acquired methicillin-resistant S. aureus have shown an increase in prevalence among soft-tissue infections over the past several years, with overall rates approaching 50 percent at the authors' institution in 2002. The object of this study was to determine the incidence of methicillin-resistant S. aureus with respect to hand infections, the antibiotic resistance pattern of methicillin-resistant S. aureus isolates, and implications for a change in antibiotic treatment algorithms for hand infections. METHODS: A retrospective chart review of 761 patients with hand infections tracked by International Classification of Diseases, 9th Revision codes for finger or hand abscesses from 2001 to 2003 was performed at Parkland Memorial Hospital, Dallas, Texas. Culture results were obtained from 436 patients and analyzed for type of organism, and sensitivity profiles were obtained for all methicillin-resistant S. aureus isolates. RESULTS: The median age of 761 patients was 40 years (range, 16 to 77 years); 71 percent were male and 28 percent were female. Of the 436 cultures reviewed, 371 (85 percent) had organisms identified. Methicillin-resistant S. aureus was the dominant single organism in hand infections cultured in all 3 years. The overall methicillin-resistant S. aureus rate was 61 percent of all hand infections in 2003. The percentage of S. aureus isolates identified as methicillin-resistant S. aureus increased from 55 percent to 78 percent over 3 years, up from 34 percent in 2001. Fortunately, 86 percent of these methicillin-resistant S. aureus isolates demonstrated sensitivity to conventional antibiotics, but a trend of resistance is developing. CONCLUSIONS: The incidence of community-acquired methicillin-resistant S. aureus increased from 34 percent to 61 percent over a 3-year period at the authors' county institution. An increasing trend of resistance patterns among conventional antibiotics was also demonstrated. As a result of this study, the treatment algorithm at Parkland Memorial Hospital has been modified to include abscess drainage accompanied by an antibiotic regimen targeted specifically at methicillin-resistant S. aureus. These data also have implications for broader application regarding simple skin infections and current antibiotic treatment algorithms.