It is well documented that estrogen can activate rapid signaling pathways in a variety of cell types. These non-classical effects of estrogen have been reported to be important for cell survival after exposure to a variety of neurotoxic insults. Since direct evidence of the ability of the estrogen receptors (ERs) a and/or b to mediate such responses is lacking, the hippocampal-derived cell line HT22 was stably transfected with either ERa (HTERa) or ERb (HTERb). In HTERa and HTERb cells, but not untransfected cells, an increase in ERK2 phosphorylation was measured within 15 min of 17b-estradiol treatment. The ER antagonist ICI 182, 780 (1 lM) and the MEK inhibitor, PD98059 (50 lM) blocked this increase in ERK2 phosphorylation. Treatment of HT22, HTERa and HTERb cells with the b-amyloid peptide (25-35) (10 lM) resulted in a significant decrease in cell viability. Pre-treatment for 15 min with 10 nM 17b-estradiol resulted in a 50% increase in the number of living cells in HTERa and HTERb cells, but not in HT22 cells. Finally, ICI 182, 780 and PD98059 prevented 17b-estradiol-mediated protection. This study demonstrates that both ERa and ERb can couple to rapid signaling events that mediate estrogen-elicited neuroprotection.

Background:Proximal biceps pathology is a significant factor in shoulder pain. Surgical treatment options include biceps tenotomy and subpectoral biceps tenodesis. Tenotomy is a simple procedure, but it may produce visible deformity, subjective cramping, or loss of supination strength. Tenodesis is a comparatively technical procedure involving a longer recovery, but it has been hypothesized to achieve better outcomes in younger active patients (<55 years).Hypothesis:This study investigated the outcomes of younger patients who underwent either a biceps tenotomy or tenodesis as part of treatment for shoulder pain. The hypothesis was that, apart from cosmetic deformity, there will be no difference in outcome between the 2 treatment options.Study Design:Cohort study; Level of evidence, 3.Methods:Isometric strength and endurance testing of operative and nonoperative shoulders for forearm supination (FS) and elbow flexion (EF) were tested utilizing an isometric dynamometer. Objective physical assessment was also performed. Subjective outcomes using the modified American Shoulder and Elbow Surgeons score (ASES); Disability of the Arm, Shoulder, and Hand (DASH); visual analog scale (VAS); and perceived biceps symptoms were collected.Results:A total of 42 patients (22 tenotomy, 20 tenodesis) with an average follow-up of 3.3 years were studied. The average age at follow-up was 49.9 years. Thirty-five percent (7/20) of tenotomy patients exhibited a “Popeye” deformity, compared with 18.2% (4/22) of tenodesis patients. Strength prior to fatiguing exercise was similar between tenodesis and tenotomy for FS (6.9 vs 7.3 lbs; P < .05), EF in neutral (35.4 vs 35.4 lbs), and EF in supination (33.8 vs 34.2 lbs). Strength was not significantly different between groups for isometric strength and endurance measures. Subjective functional outcome measured by the DASH, ASES, and VAS scores were similar between groups. Frequency of complaints of cramping was higher in the tenotomy group (4/20 vs 1/22), and complaints of pain were higher in the tenodesis group (11/22 vs 5/20).Conclusion:Despite increased demands and activity placed on biceps function in a younger population, this study showed no differences in functional and subjective outcome measurements. The choice between biceps tenotomy and tenodesis for pathology of the proximal biceps tendon can continue to be based on surgeon and patient preference.

The term "duty to recontact" refers to the possible ethical and/or legal obligation of genetics service providers (GSPs) to recontact former patients about advances in research that might be relevant to them. Although currently this practice is not part of standard care, some argue that such an obligation may be established in the future. Little information is available, however, on the implications of this requirement, from the point of view of GSPs. To explore the opinions of genetics professionals on this issue, we sent a self-administered questionnaire to 1,000 randomly selected U.S. and Canadian members of the American Society of Human Genetics. We received 252 completed questionnaires. The major categories of respondents were physician geneticist (41%), Ph.D. geneticist (30%), and genetic counselor (18%); 72% of the total stated that they see patients. Respondents indicated that responsibility for staying in contact should be shared between health professionals and patients. Respondents were divided about whether recontacting patients should be the standard of care: 46% answered yes, 43% answered no, and 11% did not know. Those answering yes included 44% of physician geneticists, 53% of Ph.D. geneticists, and 31% of genetic counselors; answers were statistically independent of position or country of practice but were dependent on whether the respondent sees patients (43% answered yes) or not (54% answered yes). There also was a lack of consensus about the possible benefits and burdens of recontacting patients and about various alternative methods of informing patients about research advances. Analysis of qualitative data suggested that most respondents consider recontacting patients an ethically desirable, but not feasible, goal. Points to consider in the future development of guidelines for practice are presented.

ABSTRACT:Dehydroepiandrosterone (DHEA) is a steroid produced by the human adrenal gland. Administration of pharmacological doses of DHEA to rats changes expression of many genes, including the cytochrome P450 family members CYP4A1 and CYP3A23. It is known that induction of CYP4A expression by DHEA requires the peroxisome proliferator-activated receptor ␣ (PPAR␣). In the current study, PPAR␣-null mice were used to examine the role of PPAR␣ in expression of CYP3A. In wild-type mice, 150 mg/kg DHEA-sulfate induced Cyp4a and Cyp3a11 mRNAs by 5-and 2-fold, respectively. Induction of Cyp4a expression by DHEA-sulfate was not observed in PPAR␣-null mice, whereas induction of Cyp3a11 expression by DHEA-sulfate was similar between genotypes. This suggests that PPAR␣ is not involved in induction of Administration of dehydroepiandrosterone (DHEA 2 ) to rodents results in several beneficial biological responses. DHEA acts as a chemopreventive agent in rodent cancer models (Schwartz, 1979;Schwartz and Tannen, 1981;Nyce et al., 1984;Pashko et al., 1984). Rodents with a predisposition toward obesity demonstrate decreased rates of weight gain without appetite suppression upon treatment with DHEA (Yen et al., 1977). Administration of DHEA ameliorated symptoms of diabetes and systemic lupus erythematosis in the appropriate rodent models (Coleman et al., 1982;Lucas et al., 1985). DHEA may act as a neurosteroid, and is thought to enhance memory function (Robel and Baulieu, 1995), as well as immune function (Morfin and Courchay, 1994).DHEA is the most abundant circulating steroid in humans. It is secreted by the adrenal gland as the 3␤-sulfate conjugate. DHEAsulfate (DHEA-S) is taken up by target tissues (e.g., testis and ovary), and hydrolyzed by sulfatases back to DHEA (Kroboth et al., 1999). DHEA can then be further metabolized to active androgens and estrogens in steroidogenic tissues, as well as to several hydroxylated metabolites in liver (Fitzpatrick et al., 2001).In rodents, DHEA is not produced by the adrenal, but limited amounts of DHEA are produced from progesterone in steroidogenic tissues (Pelletier et al., 1992;van Weerden et al., 1992). Although treatment of rodents with exogenous DHEA can produce the beneficial effects described above, high doses of DHEA induce peroxisome proliferation (Wu et al., 1989;Prough et al., 1994). Peroxisome proliferators, including DHEA, modulate expression of genes involved in fatty acid metabolism, including fatty acyl CoA oxidase, cytochrome P450 4A (CYP4A), and malic enzyme (Webb et al., 1996).3 DHEA and other peroxisome proliferators require the perox- drost-5-en-17-one); DHEA-S, dehydroepiandrosterone 3␤-sulfate; PPAR␣, peroxisome proliferator-activated receptor ␣; PXR, pregnane X receptor; ADIOL, androst-5-ene-3␤,17␤-diol; ADIONE, androst-4-ene-3,17-dione; 11␤-hydroxy-DHEA, 3␤,11␤-dihydroxy-androst-5-en-17-one; 16␣-hydroxy-DHEA, 3␤,16␣-dihydroxy-androst-5-en-17-one; 7-oxo-DHEA, 3␤-hydroxy-androst-5-ene-7,17-dione; 7␣-hydroxy-DHEA, 3␤,7␣-dihydroxy-androst-5-en-17-one; DMSO, dimethyl s...