Ulcerative Heliotrope Rash in Antimelanoma Differentiation-Associated Gene 5 Dermatomyositis.

Antimelanoma differentiation-associated gene 5 dermatomyositis (anti-MDA5 DM) is an amyopathic subtype of DM that presents with the classic cutaneous findings of DM, such as a heliotrope rash, Gottron papules, and the shawl sign, combined with mucocutaneous ulcerations. This subtype of DM also is highly associated with rapidly progressive interstitial lung disease (ILD). We report 2 cases of a heretofore novel presentation of the overlap of these cutaneous features in the form of an ulcerative heliotrope rash; furthermore, the rash was associated with progression of ILD in both cases. Finally, we review the current state of clinical care and research related to anti-MDA5 DM in terms of clinical presentations, diagnostic methods, and treatment options.

Effectiveness and tolerability of simeprevir and sofosbuvir in nontransplant and post-liver transplant patients with hepatitis C genotype 1.

BACKGROUND: Hepatitis C virus genotype 1a (HCV-1a), prior treatment, cirrhosis and post-transplant status are historically associated with poor treatment responses. The new oral direct-acting agents appear to be effective and safe in these patients. AIMS: To evaluate the effectiveness and tolerability of simeprevir and sofosbuvir in a diverse real-life cohort of patients, including difficult-to-treat patients. METHODS: We conducted a retrospective cohort study in 198 consecutive patients with hepatitis C genotype 1 (148 nontransplant, 50 post transplant), who were treated with simeprevir and sofosbuvir for 12 weeks between December 2013 and December 2014. Primary outcome was sustained virological response with undetectable HCV RNA 12 weeks after completion of therapy (SVR12). Risk factors evaluated for lack of SVR12 included HCV 1a (vs. 1b), prior treatment (vs. none), and cirrhosis (vs. no cirrhosis). RESULTS: SVR12 rates were similar in non- and post-transplant settings, 82% and 88%, respectively. There were no significant differences in adverse events in patients regardless of cirrhosis or transplant status. On multivariate analysis also inclusive of gender and liver transplant status, negative predictors of SVR12 were having at least 2 or 3 risk factors (OR 0.30, 95% CI 0.10-0.87, P = 0.027 or 0.29, 95% CI 0.09-0.85, P = 0.025, respectively). CONCLUSION: Simeprevir and sofosbuvir combination is a safe and effective regimen for the treatment of non- and post-transplant patients with traditional risk factors for poor treatment response, unless more than 2 difficult-to-treat risk factors are present.

Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis.

We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

Precore and basal core promoter mutations in Asian American patients with hepatitis B e antigen-positive chronic hepatitis B.

BACKGROUND: Prior studies have shown that precore mutations abolish and basal core promoter (BCP) mutations down-regulate hepatitis B e antigen (HBeAg) production. Thus, the presence of precore and BCP mutations in HBeAg-positive patients indicates an infection with a mixed viral population of wild-type and precore and/or BCP mutant hepatitis B virus (HBV). To date, there has been limited study of the prevalence and clinical significance of precore and BCP mutations in patients with HBeAg-positive chronic hepatitis B. AIM: To determine the prevalence, predictors and clinical characteristics of mixed wild-type and precore/BCP HBV infection, through a cross-sectional study, in a US cohort of patients with chronic hepatitis B. METHODS: We conducted a retrospective study of 828 chronic hepatitis B patients with HBV genotype and mutation panel testing seen at three US gastroenterology and liver clinics from June 2005 to September 2009. RESULTS: A majority of our patients (92.3%) were either Vietnamese or Chinese American. In the HBeAg-positive cohort, 17% of patients had precore mutations only, 28% had BCP mutations only and 5% had both BCP and precore mutations. On multivariate analyses, HBV genotype C, increasing age, lower HBV DNA level and an ALT quotient >2 were independent predictors for the presence of precore and/or BCP mutations. CONCLUSIONS: The current distinction and management recommendations for HBeAg-positive vs. HBeAg-negative patients with chronic hepatitis B should be reassessed. Additional biomarkers and treatment endpoints should be studied for their usefulness in predicting continued viral suppression after treatment discontinuation.

Prospective study of risk factors for hepatitis C virus acquisition by Caucasian, Hispanic, and Asian American patients.

Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos. We hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics, and our aim was to conduct a survey of risk factors in HCV-infected patients in these ethnic groups. In this prospective study, 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008. Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics. The laboratory profiles were similar, and genotype 1 was the most common infection in all groups (74-75%). The great majority of Caucasians (94%) and Hispanics (86%) identified with commonly known risk factors, which was in contrast to 67% of Asians (P < 0.0001). The most common risk factors in Asians were blood transfusions (50%) and acupuncture (50%). Furthermore, 74% of Caucasians and 66% of Hispanics identified more than one major risk factor, while only 20% of Asians reported having more than one risk factor (P < 0.0001). Survey for established risk factors for acquisition of HCV may be more appropriate for risk assessment of Caucasians and Hispanics, but not for Asian Americans. These findings may guide the development of HCV screening in our increasingly diverse population.

Nutrition and division of labor: Effects on foraging and brain gene expression in the paper wasp Polistes metricus.

Deeply conserved molecular mechanisms regulate food-searching behaviour in response to nutritional cues in a wide variety of vertebrates and invertebrates. Studies of the highly eusocial honey bee have shown that nutritional physiology and some conserved nutrient signalling pathways, especially the insulin pathway, also regulate the division of labour between foraging and non-foraging individuals. Typically, lean workers leave the nest to forage for food, and well-nourished workers perform tasks inside the nest. Here we provide the first direct test of whether similar mechanisms operate in a primitively eusocial insect in an independently evolved social lineage, the paper wasp Polistes metricus. We found that food deprivation caused reduced lipid stores and higher levels of colony and individual foraging. Individuals with greatly reduced lipid stores foraged at extremely elevated levels. In addition, brain expression of several foraging-related genes was influenced by food deprivation, including insulin-like peptide 2 (ilp2). Together with previous findings, our results demonstrate that nutrition regulates foraging division of labour in two independently evolved social insect lineages (bees and wasps), despite large differences in social organization. Our results also provide additional support for the idea that nutritional asymmetries among individuals, based on differences in nutritional physiology and expression of conserved nutrient signalling genes in the brain, are important in the division of labour in eusocial societies.

Congruence of counselor self-disclosure and perceived effectiveness.

Sixty-seven college students rated a counselor on expertness, trustworthiness, and attractiveness based on reading 1 of 2 randomly assigned session transcripts. The desire to choose the depicted counselor was also measured. In both transcripts, the counselor self-disclosed his or her use of prayer. A single-client statement varied across the 2 transcripts such that one contained a congruent counselor self-disclosure (counselor disclosure after client disclosure) and the other included an incongruent self-disclosure (counselor disclosure without client disclosure). A potential covariate, religiosity, was examined but did not draw significant variance. Participants in the congruent group reported a more favorable total perception, a higher attractiveness perception, and a greater desire to choose the counselor than did participants in the incongruent group. Limitations and implications for future research are discussed.

Childhood trauma and current anxiety among college men.

In an examination of the prevalence and effects of childhood trauma among college freshmen, as expected, the majority of 515 youth reported at least one traumatic experience in childhood. When fear of death or serious injury accompanies a traumatic event, posttraumatic symptoms may be more likely. As hypothesized, scores on the Reaction Index by Frederick were elevated for subjects who reported trauma with concurrent fear. The combination of trauma and fear was also associated with elevated scores on trait anxiety. While most adolescents do not develop mental illness following single traumatic events, many may be made more vulnerable to the psychogenic effects of future trauma.

Feedback on ability in counseling, self-efficacy, and persistence on task.

Self-efficacy in counseling varied with randomly manipulated feedback on ability, such that the 29 college students who received negative feedback on their ability reported lower self-efficacy than those 16 who received positive feedback. Persistence on task, however, was not related to the type of feedback received.

Are perceived professional qualities affected by knowledge of a counselor's sexual orientation?

The experimentally manipulated sexual orientation of a female counselor was not related to the perceptions of her Expertness, Attractiveness, or Trustworthiness rated by 8 male and 22 female, heterosexual college students.

Spontaneous hypoglycemia associated with congestive heart failure attributable to hyperinsulinism.

OBJECTIVE: To report a case of spontaneous hypoglycemia associated with congestive heart failure in an adult. METHODS: We describe a 72-year-old man in whom profound hypoglycemia (serum glucose level, 21 mg/dL) developed during an exacerbation of heart failure. Clinical and laboratory data are reviewed. RESULTS: An inverse relationship was found between both serum insulin and C peptide levels and serum glucose level. Serum glipizide and glyburide levels were undetectable, and no insulinoma was found on radiologic imaging. Hypoglycemia resolved after alleviation of the congestive heart failure. CONCLUSION: In this case, the hypoglycemia was attributed to hyperinsulinemia. Possible mechanisms include impaired insulin degradation and shunting of portal blood into the systemic circulation.

Short-term effects of research participation on college men.

College students in a social science core curriculum course were given an option of completing a packet of psychological inventories and demographic questions. The last inventory in the packet, the Lazarus Stress Questionnaire, evaluated the emotional impact of answering the questionnaires. Positive feelings were endorsed significantly more than negative feelings. Further analyses, using the Eysenck Personality Questionnaire and the Life Experiences Survey, revealed characteristics that may predispose participants to positive or negative emotional reactions to participation in research. Results are discussed in terms of self-focus mechanisms and ethical standards in the treatment of students who participate in research.

A comparison of children's behaviors following three types of stressors.

One purpose of this study was to examine the differences in behavior of children exposed to trauma versus no trauma. Another goal was to compare different types of traumatic events in terms of their effects on behaviors. Our analysis indicated significant differences between trauma and no trauma groups. Additional analyses indicated that those children who were allegedly sexually abused were rated as exhibiting higher levels of symptomatology on all three factors of the Pediatric Emotional Distress Scale (PEDS) as well as the Total PEDS score than the other three groups.

Response perseveration, inhibitory control, and central dopaminergic activity in childhood behavior disorders.

We screened students (N = 710) in grades four through six at two public elementary schools for behavior problems, using the Revised Behavior Problem Checklist. Five groups of children were identified: conduct disorder (n = 8), attention deficit disorder (n = 9), conduct disorder plus attention deficit disorder with hyperactivity (n = 11), anxiety-withdrawal (n = 12), and normal control (n = 15). A response perseveration task, inhibitory control task, and a noninvasive measure of dopaminergic activity were administered to selected students, and group differences were predicted based on Quay's hypotheses as derived from Gray's theory of brain function. Hypothesized group differences were not found, although analyses revealed dimensional relationships that were consistent with the hypotheses. Results are discussed in terms of Quay's hypotheses and potential modifications to tasks for future research.

Children's coping styles and report of depressive symptoms following a natural disaster.

The present study examined the relationship between children's coping styles (Spirito, Stark, & Williams, 1988) and self-reported levels of depressive symptoms (Kovacs, 1983) following a major stressor. 257 third- to fifth-grade children consented to participate in the study, 5 months following a hurricane. The number of coping strategies employed was positively related to depression scores, whereas coping efficacy was negatively related to depression scores. Social withdrawal, self-blaming, and emotional regulation were associated with more severe depressive symptoms. Lower levels of symptomatology were found among children who sought social support and engaged in cognitive restructuring. The overall symptom level in the sample did not exceed that of normative samples. Results are discussed in terms of competing theories of childhood depression.

Response perseveration and delayed responding in childhood behavior disorders.

Students (N = 814) in grades 3 through 6 at a public school were screened for behavior problems using the Revised Behavior Problem Checklist. Fifty-three selected students, representing Conduct Disorder, Attention Deficit Disorder with Hyperactivity, Conduct Disorder plus Attention Deficit Disorder with Hyperactivity, Anxiety-Withdrawal Disorder, and normal controls were administered a response perseveration task and delayed responding task (DRL). It was predicted that performance on the two tasks would vary as a function of group membership. While DRL performance did not vary between groups, findings on the response perseveration task provided support for the hypothesis of the perseverative responding for reward in Conduct Disorder.

Cytotoxic and hemolytic effects of Tritrichomonas foetus on mammalian cells.

Geographically distinct lines of Tritrichomonas foetus were assayed for their ability to cause cytotoxicity in nucleated mammalian cells and lysis of bovine erythrocytes. T. foetus was highly cytotoxic toward a human cervical cell line (HeLa) and early bovine lymphosarcoma (BL-3) but displayed low levels of cytotoxicity against African green monkey kidney (Vero) cells. In addition to variation in the extent of cytotoxicity toward different targets, differences in the levels of cytotoxicity in the same nucleated target occurred with different parasite lines. Whole T. foetus, unfractionated whole-cell extracts, and parasite-conditioned medium (RPMI 1640 without serum) all caused lysis of bovine erythrocytes. Lytic activity in the conditioned medium was substantially reduced by repeated freezing and thawing or heating to 90 degrees C for 30 min. Damage of mammalian target cells by live T. foetus could be reduced by the presence of protease inhibitors; however, such inhibitors did not diminish the lytic effects of conditioned medium. These results suggested that proteolytic enzymes were necessary for the lytic mechanism of the live parasites but were not required once lytic factors were released into the parasite-conditioned medium. They further suggested that the lytic molecules were either proteins or had proteinaceous components.