MicroRNAs in autoimmune rheumatic diseases.

The etiology of autoimmune diseases remains largely unknown. In recent years, besides genetic factors, several studies proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically epigenetic regulatory mechanisms comprise DNA methylation, a variety of histone modifications, and microRNA (miRNA) activity, all of which act upon gene and protein expression levels. In particular it is well known that epigenetic mechanisms are important for controlling the pattern of gene expression during development, the cell cycle, and the response to biological or environmental changes. In the present review a description of the most frequent epigenetic deregulations, in particular the role of miRNAs, in rheumatic autoimmune disorders will be investigated.

Inhibitory effect of synthetic cannabinoids on cytokine production in rheumatoid fibroblast-like synoviocytes.

OBJECTIVE: To verify whether synthetic cannabinoids (CP55,940 and WIN55,212-2) are able to exert an anti-inflammatory effect on rheumatoid fibroblast-like synoviocytes (FLS) by down-regulating cytokine production, and determine whether this effect could be mediated by CB1/CB2 cannabinoid receptors. METHODS: Interleukin-6 (IL-6) and interleukin-8 (IL-8) were assayed in the supernatant from cultured FLS by ELISA method before and after 3 hours of incubation with CP55,940 (10 microM) and WIN55,212-2 (10 microM). Co-stimulation of cells with the cannabinoid receptor antagonists was performed to evaluate receptor involvement in cytokine modulation. All the experiments were conducted in basal conditions and after 1 hour pre-incubation with 0.1 ng/ml IL-1beta. FLS expression of CB1 and CB2 receptor was studied by Western Blot analyses. RESULTS: Both CP55,940 and WIN55,212-2 induced a potent and significant reduction in IL-6 and IL-8 secretion from IL-1beta. stimulated FLS. Although FLS express CB1 and CB2 receptor, cannabinoid receptor antagonists did not significantly modify the inhibition of cytokines secretion induced by CP55,940 and WIN55,212-2. CONCLUSIONS: In vitro, CP55,940 and WIN55,212-2 exert a potent anti-inflammatory effect on rheumatoid FLS via a non-CB1/CB2 receptor mediated mechanism.

Cervical neoplasia risk in women provided hormonal contraception without a Pap smear.

The study was conducted to determine whether women using a demonstration program providing hormonal birth control without concurrent pelvic examination (First Stop) are at higher risk of cervical neoplasia compared to women using traditional family planning clinics. Using retrospective ion of medical charts, we compared risk factors for cervical neoplasia among 400 First Stop clients and 400 traditional site clients matched on age, race, and contraceptive method. We determined prevalence of these factors: previous abnormal cervical smear, <16 years at first intercourse, multiple sexual partners, high parity, history of sexually transmitted infections, and current cigarette smoking. First Stop clients were not at greater likelihood of having any risk factor for cervical neoplasia except high parity. First Stop clients who failed to follow through on a referral to a traditional clinic were not more likely to be of higher risk than those who did follow through. Of 13 First Stop clients with the highest risk profiles (previous abnormal cervical smear plus one other risk factor), one did not follow through with referral. First Stop clients choosing hormonal contraception without a pelvic examination do not appear to be at substantially higher risk of cervical neoplasia. Future research should quantify more precisely the risks and benefits of the general application of this strategy on a population level.

Provision of hormonal contraceptives without a mandatory pelvic examination: the first stop demonstration project.

CONTEXT: First Stop, an 18-month demonstration project that operated in 1996-1997, was designed to offer low-income adult women in California hormonal contraceptives without requiring a pelvic examination. METHODS: An evaluation was undertaken to assess the contraceptives adopted by First Stop clients, compare health risks of these women with risks among women using traditional family planning clinics and assess clients'satisfaction. Data on 2,065 First Stop clients and 1,507 women attending traditional clinics were collected through several self- and clinician-administered instruments, including questionnaires, a telephone survey and medical chart abstractions. RESULTS: After the initial First Stop visit, 38% of women adopted a more effective method than they had used at last sex, 4 7% remained with the same method, 12% switched to a less-effective method and 3% accepted no method. Of clients who were referred for additional medical care, 73% followed through on their referrals. Compared with clients at traditional clinics, First Stop clients were less likely to have a regular source of health care, but more likely to have made a health care visit in the past year. Most First Stop clients valued the project's services; 76% said it was important to be able to receive pills or injections without a pelvic examination. CONCLUSIONS: Programs that provide hormonal contraceptives without requiring a pelvic examination can expand low-income women's access to these methods and improve the chances that they will obtain other reproductive health services.

A randomized controlled trial of laminaria, oral misoprostol, and vaginal misoprostol before abortion.

OBJECTIVE: To compare the efficacy and acceptability of oral misoprostol, vaginal misoprostol, and laminaria tents for cervical dilation before surgical abortion. METHODS: We conducted a randomized, double-blind, placebo-controlled trial comparing oral misoprostol 400 microg, vaginal misoprostol 400 microg, and one medium laminaria for dilating the cervix over 4 hours before surgical abortion. The study sample consisted of 106 women at 7-14 weeks' gestation who presented to San Francisco General Hospital requesting abortion. The primary outcome was the amount of cervical dilation measured by Pratt dilators. Secondary outcomes were the proportion of subjects needing further manual dilation, difficulty of dilation, duration of the procedure, blood loss, and side effects. RESULTS: The vaginal-misoprostol group had a significantly greater mean dilation (28.0 mm) than the oral misoprostol group (24.2 mm; P < .05) and a greater mean dilation than the laminaria group (25.9 mm), although this difference did not reach significance. Women who received laminaria reported significantly more pain at the time of placement (85.7% reported at least "a little" pain) compared with women who received misoprostol by either route (28.9% of oral-misoprostol and 34.0% of vaginal-misoprostol subjects reported "a little" pain; P < .01). The proportion of subjects who required further manual dilation, ease of dilation, duration of the procedure, and blood loss were not significantly different among the groups. There was no difference in side effects during the 4-hour waiting period among the three groups, and gastrointestinal side effects were rare in all groups. CONCLUSION: Vaginal misoprostol is superior to oral misoprostol and is an acceptable alternative to laminaria tents for cervical dilation before surgical abortion in pregnancies of 7-14 weeks' gestation. It is inexpensive and easy to administer, and achieves equal or greater dilation with less pain on insertion and no increase in side effects compared with laminaria.

Modified therapeutic community for homeless mentally ill chemical abusers. Sociodemographic and psychological profiles.

This paper, the first in a series of reports from a field study on the efficacy of modified therapeutic community (TC) treatment for homeless mentally ill chemical abusers, presents sociodemographic profiles, psychiatric diagnosis, and psychological symptom data on 342 homeless mentally ill chemical abusing clients seeking treatment in mental health community residence settings. The findings reflect the multidimensional deficits, social dysfunctionality, and severity of psychopathology of the study sample. The paper discusses the implications of these findings for program design and program planning, with special reference to modified TC programs.

Field independence as a function of sex, sex-roles, and the sex-role appropriateness of the task.

Two experiments were conducted to explain the sex difference in field independence by reference to socialization factors. It was hypothesized that the sex-role appropriateness of the task as masculine or feminine-typed would influence the performance of masculine and feminine women in a manner congruent with their sex-role orientation. 28 pilot subjects and 100 subjects in Study 2 were equally divided between the sexes. Both studies used the Bem Sex-role Inventory, but different versions of the Embedded Figures Test. The over-all results suggested that feminine women varied their performance according to task appropriateness, although not always in a manner congruent with their sex-role orientation. Androgynous individuals and masculine men did not alter their performance.