Citations

AbstractThe neurotransmitter dopamine (DA) is known to be involved in a multitude of physiological processes. We investigated sexually dimorphic effects of disruptions in DA homeostasis and its relationship to senescence using three different Drosophila melanogaster mutants namely Catsup (Catsup26) with elevated DA levels, and pale (ple2), Punch (PuZ22) with depleted DA levels. In all genotypes including controls, DA levels were significantly lower in old (45–50‐day‐old) flies compared with young (3–5‐day‐old) in both sexes. Interestingly, females had lower DA content than males at young age whereas this difference was not observed in old age, suggesting that males had a larger decline in DA levels with age. Females, in general, were longer lived compared with males in all genotypes except ple2 mutants with depleted DA levels. This phenotype was abolished in the ple2 rescue flies. Interestingly, females also demonstrated marked age‐related decline in circadian locomotor activity compared with males. Old Catsup26 males with elevated DA levels accumulated significantly lower levels of lipid peroxidation product 4‐hydroxy 2‐nonenal (4‐HNE) compared with age‐matched wild type, ple2 and PuZ22 mutant males. In Catsup26 revertant lines this phenomenon was absent. We also observed a sexually dimorphic response in the expression levels of key stress and aging associated and/or related transcription factor genes across genotypes with elevated or depleted DA levels which was reverted to wild type levels in specific rescue lines. Taken together, our results reveal a novel sexually dimorphic involvement of DA in senescence characteristics of D. melanogaster.

Biologics have changed expectation and outcomes for rheumatoid arthritis (RA). However, the optimal duration and sequence of therapy for this disease has yet to be determined. Also, a significant number of patients do not satisfactorily respond to currently available therapies. The Janus kinase (JAK) inhibitors represent a new class of therapies for RA. These drugs work uniquely by inhibiting intracellular pathways thought to be important in the pathogenesis of RA. They are available as oral agents, which is also different from the currently available biologics. Baricitinib has now been evaluated in four phase III clinical trials, and although safety concerns cannot fully be answered until the drug is studied over longer periods of time, the data to date suggest that this drug with its once daily dosing, rapid onset of action and efficacy as monotherapy represents an important addition to the RA therapeutic armamentarium. Further study and experience will better define how baricitinib will be used and by which patients.

BackgroundThe new proposed classification for pancreaticobiliary cytology has advocated the use of carcinoembryonic antigen (CEA) analysis of cyst fluid as an ancillary diagnostic tool for the determination of mucinous neoplasms in pancreatic cyst aspirates. We aimed to investigate the effect of CEA cyst fluid analysis on cases primarily called negative or nondiagnostic and on the sensitivity and specificity of the method.MethodsWe retrospectively identified and collected all pancreatic cyst aspirates from 2010 to 2014 at Mayo Clinic, Jacksonville, Florida, along with available corresponding surgical diagnoses. Cases primarily classified as nondiagnostic or negative but that had a cyst CEA level of 192 ng mL−1 or higher were reclassified as mucinous neoplasms. Cytohistologic correlation was assessed whenever possible.ResultsWe retrieved pancreatic cyst aspirates from 255 patients who had a corresponding CEA level measurement. Median patient age was 70 years (range, 25–100 years). Among all samples, 129 (50.6%) had been classified as negative and 42 (16.4%) as nondiagnostic. Applying the new criteria, the number of samples previously classified as negative and nondiagnostic decreased considerably, with a statistically significant difference among negative cases. Fifty‐four cases (21.2%) had an available corresponding surgical diagnosis, and complete agreement was achieved in 95.4% of the cases. Use of the new cutoff for CEA levels increased the sensitivity and negative predictive value, compared with the original diagnoses.ConclusionsThe incorporation of the new proposed terminology and CEA fluid analysis has significantly decreased the number of samples primarily classified as negative and nondiagnostic, along with improved test characteristics. Diagn. Cytopathol. 2017;45:101–106. © 2016 Wiley Periodicals, Inc.