Alpha-v-beta3 integrin expression in melanocytic nevi and cutaneous melanoma

BACKGROUND: Alpha-v-beta3 integrin (alphavbeta3) is a vitronectin ligand and plays an important role in melanoma progression. OBJECTIVES: The purpose of the study was to evaluate the expression of alphavbeta3 in superficial spreading cutaneous melanoma, in both conventional and tissue microarray (TMA) paraffin-embedded-tissue specimens, and correlate with histopathological variables and patient survival. MATERIAL AND METHODS: A total of 159 tissue samples from compound nevi (n = 19), in situ melanoma (n = 5), thin melanoma (n = 34), thick melanoma (n = 72) and metastatic melanoma (n = 29) were studied. RESULTS: Compound nevus epithelioid cells had a mild expression of alphavbeta3. In situ melanoma cells had the highest expression among all specimens, when compared to nevi (p = 0.0000) and to invasive melanoma (p = 0.0003). Expression of alphavbeta3 did not differ according to depth of invasion or did it increase in metastatic cells. CONCLUSION: Our results suggested that alphavbeta3 integrin might have no impact on melanoma behavior. However, high levels of alphavbeta3-integrin expression for in situ melanoma may be related to pre-invasive phenotype with marked potential to invade.     

Biphasic Insulin Aspart 30/70: Pharmacokinetics and Pharmacodynamics Compared With Once-Daily Biphasic Human Insulin and Basal-Bolus Therapy

OBJECTIVE

Pharmacological profiles of biphasic insulin aspart 30/70 (BIAsp 30) once daily (OD), twice daily (b.i.d.), and three times daily (t.i.d.) were compared with other insulin regimens in two crossover glucose clamp studies of insulin-treated type 2 diabetic patients.

RESEARCH DESIGNS AND METHODS

Study 1 consisted of BIAsp 30 OD, b.i.d., and t.i.d. versus biphasic human insulin 30/70 (BHI 30), OD (n = 24). Study 2 examined BIAsp 30 t.i.d. versus basal-bolus therapy (insulin glargine OD plus insulin glulisine t.i.d.) (n = 24). Pharmacokinetics/pharmacodynamics (PK/PD) were investigated over 24 h.

RESULTS

Study 1: PK and PD were markedly different between BIAsp 30 OD and BHI 30 OD: the maximum insulin concentration and glucose infusion rate (GIR) were higher for BIAsp 30; time to maximum metabolism was 1.7 h sooner for BIAsp 30. Study 2: both regimens showed three distinct prandial-related GIR peaks. GIR 24-h area under the curve for BIAsp t.i.d. was higher than for basal-bolus therapy: 2,585.2 vs. 2,289.2 mg/kg.

CONCLUSIONS

BIAsp had pharmacological advantages over BHI. BIAsp t.i.d. had a similar PD profile to basal-bolus therapy.Premixed insulin analogs are a commonly prescribed first insulin therapy for type 2 diabetic patients and may be a simpler alternative to basal-bolus therapy (1,2). Compared with biphasic human insulin 30/70 (BHI 30), the modern premixed insulin analog, biphasic insulin aspart 30/70 (BIAsp 30) has pharmacokinetics (PK) that more closely match endogenous insulin secretion (3,4). Therefore, an initial once-daily (OD) BIAsp 30 regimen can be safely intensified to twice-daily (b.i.d.) or three-times-daily (t.i.d.) injections (5). To compare the PK and pharmacodynamic (PD) profiles of these different regimens, two crossover glucose clamp studies were carried out in insulin-treated patients with type 2 diabetes.     

Finasteride treatment of female pattern hair loss

OBJECTIVE: To evaluate the efficacy of oral finasteride therapy associated with an oral contraceptive containing drospirenone and ethinyl estradiol in premenopausal women with female pattern hair loss. SETTING: Outpatient consultation for hair disorders at the Department of Dermatology, University of Bologna. PATIENTS AND INTERVENTION: Thirty-seven women with female pattern hair loss were treated with oral finasteride, 2.5 mg/d, while taking an oral contraceptive containing drospirenone and ethinyl estradiol. Treatment efficacy was evaluated using global photography and the hair density score from videodermoscopy. A self-administered questionnaire was used to assess patient evaluation of treatment effectiveness. RESULTS: At 12-month follow-up, 23 of the 37 patients were rated as improved using global photography (12 were slightly improved, 8 were moderately improved, and 3 were greatly improved). No improvement was recorded in 13 patients. One patient experienced worsening of the condition. There was a statistically significant (P = .002) increase in the hair density score in 12 patients. No adverse reactions to the drug were reported. CONCLUSIONS: Sixty-two percent of the patients demonstrated some improvement of their hair loss with the use of finasteride, 2.5 mg/d, while taking the oral contraceptive. It is unclear whether the success was due to a higher dosage of finasteride (2.5 mg instead of 1 mg) or to its association with the oral contraceptive containing drospirenone, which has an antiandrogenic effect. Further studies are necessary to understand which patterns of female pattern hair loss respond better to this treatment.     

The nail in systemic diseases

Although abnormalities of the nails have been reported in different systemic disorders,most of these abnormalities are nonspecific. This article reports and discusses only those nail signs that provide the clinician with clues for the diagnosis of systemic disorders.     

Jury decision-making: the impact of engagement and perceived threat on verdict decisions

The present study examined the role of political orientation and task engagement in juror decision-making. The study was conducted as a 2 (mode: laboratory versus online) × 2 (role: juror, observer) × 3 (evidence: admissible, inadmissible, control) between-subjects experiment, with participants (N?=?157) recruited from a mid-sized Australian university. Findings supported our predictions that political conservatism is associated with convictions, and that university students endorse a wide range of political orientations. Participants who were more engaged in the study perceived more threat in the defendant, and threat, in turn, led to higher conviction rates; furthermore, the effect of participation mode on verdict decisions was completely mediated by perceptions of the threat posed by the defendant. Findings are discussed in terms of their implications for jury decision-making research and its relevance to actual juror decisions.     

The Drosophila CG1674 gene encodes a synaptopodin 2-like related protein that localizes to the Z-disc and is required for normal flight muscle development and function

Background

To identify novel myofibrillar components of the Drosophila flight muscles, we carried out a proteomic analysis of chemically demembranated flight muscle myofibrils, and characterized the knockdown phenotype of a novel gene identified in the screen, CG1674.

Results

The CG1674 protein has some similarity to vertebrate synaptopodin 2-like, and when expressed as a FLAG-tagged fusion protein, it was localized during development to the Z-disc and cytoplasm. Knockdown of CG1674 expression affected the function of multiple muscle types, and defective flight in adults was accompanied by large actin-rich structures in the flight muscles that resembled overgrown Z-discs. Localization of CG1674 to the Z-disc depended predominantly upon presence of the Z-disc component alpha-actinin, but also depended upon other Z-disc components, including Mask, Zasp52, and Sals. We also observed re-localization of FLAG-CG1674 to the nucleus in Alpha-actinin and sals knockdown animals.

Conclusions

These studies identify and characterize a previously unreported myofibrillar component of Drosophila muscle that is necessary for proper myofibril assembly during development.