Contemporary Trends in Oral Anticoagulant Prescription in Atrial Fibrillation Patients at Low to Moderate Risk of Stroke After Guideline-Recommended Change in Use of the CHADS to the CHADS-VASc Score for Thromboembolic Risk Assessment: Analysis From the National Cardiovascular Data Registry's Outpatient Practice Innovation and Clinical Excellence Atrial Fibrillation Registry.

Background: Use of the CHADS-VASc score instead of the CHADS score for thromboembolic risk stratification and initiation of oral anticoagulation (OAC) was recommended in the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society atrial fibrillation (AF) guidelines. We sought to define the proportion of patients with AF qualifying for and receiving OAC in contemporary practice by applying the CHADS-VASc score to patients with a low CHADS score.

Methods And Results: Among patients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registry's outpatient Practice Innovation and Clinical Excellence registry (2008-2014) CHADS score of 0 or 1, we calculated the impact of adoption of the CHADS-VASc score on the proportion of patients with an indication for OAC.

Improved Survival Among all Interferon-α-Treated Patients in HCV-002, a Veterans Affairs Hepatitis C Cohort of 2211 Patients, Despite Increased Cirrhosis Among Nonresponders.

Background: As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.

Aim: To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.

Methods: Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.

Keratins let liver live: Mutations predispose to liver disease and crosslinking generates Mallory-Denk bodies.

Keratin polypeptides 8 and 18 (K8/K18) are the cytoskeletal intermediate filament proteins of hepatocytes while K8/K18/K19 are the keratins of hepatobiliary ductal cells. Hepatocyte K8/K18 are highly abundant and behave as stress proteins with injury-inducible expression. Human association studies show that K8/K18 germline heterozygous mutations predispose to end-stage liver disease of multiple etiologies ( approximately 3 fold increased risk), and to liver disease progression in patients with chronic hepatitis C infection.

A disease- and phosphorylation-related nonmechanical function for keratin 8.

Keratin 8 (K8) variants predispose to human liver injury via poorly understood mechanisms. We generated transgenic mice that overexpress the human disease-associated K8 Gly61-to-Cys (G61C) variant and showed that G61C predisposes to liver injury and apoptosis and dramatically inhibits K8 phosphorylation at serine 73 (S73) via stress-activated kinases. This led us to generate mice that overexpress K8 S73-to-Ala (S73A), which mimicked the susceptibility of K8 G61C mice to injury, thereby providing a molecular link between K8 phosphorylation and disease-associated mutation.

"Heads and tails" of intermediate filament phosphorylation: multiple sites and functional insights.

Intermediate filaments (IFs) are major components of the mammalian cytoskeleton. They are among the most abundant cellular phosphoproteins; their phosphorylation typically involves multiple sites at repeat or unique motifs, preferentially within the "head" or "tail" domains. Phosphorylation and dephosphorylation are essential for the regulation of IF dynamics by modulating the intrinsic properties of IFs: solubility, conformation and filament organization, and, in addition, for the regulation of other IF post-translational modifications.

Bispecific and human disease-related anti-keratin rabbit monoclonal antibodies.

Rabbit antibodies may have favorable properties compared to mouse antibodies, including high affinities and better antigen recognition. We used a biochemical and reverse immunologic approach to generate and characterize rabbit anti-phospho-keratin and anti-keratin monoclonal antibodies (MAb). Human keratins 8 and 18 (K8/K18) were used as immunogens after isolation from cells pretreated with okadaic acid or pervanadate to promote Ser/Thr or Tyr hyperphosphorylation, respectively.

Caregiver self-efficacy, ethnicity, and kinship differences in dementia caregivers.

Objective: The authors sought to determine the effect of kinship status (daughters versus wives) and ethnicity (Hispanic/Latino versus Caucasian) on self-efficacy to perform tasks relevant to caregiving in a sample of family caregivers for people with memory problems.

Methods: Baseline data were collected from 238 female caregivers who participated in an intervention program. Ethnic and kin relationship groups were compared on measures of caregiver self-efficacy, acculturation within the Hispanic/Latino sample, and the relationship of self-efficacy to key outcome variables.

Phase II trial of the histone deacetylase inhibitor pivaloyloxymethyl butyrate (Pivanex, AN-9) in advanced non-small cell lung cancer.

This multicenter phase II trial evaluated the therapeutic activity and safety profile of pivaloyloxymethyl butyrate (Pivanex, AN-9) as a single agent in refractory non-small cell lung cancer (NSCLC). Pivanex (2.34 g/m2 per day) was administered as a 6-h continuous intravenous infusion, daily for 3 days, and repeated every 21 days until disease progression.

Keratin mutation in transgenic mice predisposes to Fas but not TNF-induced apoptosis and massive liver injury.

Hepatocytes express keratins 8 and 18 (K8/18) as their only cytoskeletal intermediate filament (IF) proteins, and K8/18 mutations predispose their carriers to liver cirrhosis. Transgenic mice that overexpress mutant human K18 (Arg89-->Cys [R89C]) develop mild chronic hepatitis, hepatocyte fragility, keratin filament disruption, and increased susceptibility to drug-induced liver injury. K18 is a major caspase substrate during apoptosis, and K8- or K18-null mice are significantly predisposed to Fas- and possibly tumor necrosis factor (TNF)-mediated apoptosis in the liver.

Axonal multifocal motor neuropathy without conduction block or other features of demyelination.

Background: Conduction block is considered an essential finding for the distinction between motor neuropathies and lower motor neuron disorders. Only a small number of reports describe patients with multifocal motor neuropathies who lack overt conduction block, although in these cases other features of demyelination still suggest the presence of a demyelinating disorder. In contrast, a purely axonal multifocal motor neuropathy has not been described.

Effect of mutation and phosphorylation of type I keratins on their caspase-mediated degradation.

Type I keratins K18 and K19 undergo caspase-mediated degradation during apoptosis. Two known K18 caspase cleavage sites are aspartates in the consensus sequences VEVDA and DALDS, located within the rod domain and tail domain, respectively. Several K14 (another type I keratin) mutations within the caspase cleavage motif have been described in patients with epidermolysis bullosa simplex.

Keratins turn over by ubiquitination in a phosphorylation-modulated fashion.

Keratin polypeptides 8 and 18 (K8/18) are intermediate filament (IF) proteins that are expressed in glandular epithelia. Although the mechanism of keratin turnover is poorly understood, caspase-mediated degradation of type I keratins occurs during apoptosis and the proteasome pathway has been indirectly implicated in keratin turnover based on colocalization of keratin-ubiquitin antibody staining. Here we show that K8 and K18 are ubiquitinated based on cotransfection of His-tagged ubiquitin and human K8 and/or K18 cDNAs, followed by purification of ubiquitinated proteins and immunoblotting with keratin antibodies.

Brachial amyotrophic diplegia: a slowly progressive motor neuron disorder.

Objective: To describe a sporadic motor neuron disorder that remains largely restricted to the upper limbs over time.

Background: Progressive amyotrophy that is isolated to the upper limbs in an adult often suggests ALS. The fact that weakness can remain largely confined to the arms for long periods of time in individuals presenting with this phenotype has not been emphasized.