Estrogens and progesterone promote persistent CCND1 gene activation during G1 by inducing transcriptional derepression via c-Jun/c-Fos/estrogen receptor (progesterone receptor) complex assembly to a distal regulatory element and recruitment of cyclin D1 to its own gene promoter.

Transcriptional activation of the cyclin D1 gene (CCND1) plays a pivotal role in G(1)-phase progression, which is thereby controlled by multiple regulatory factors, including nuclear receptors (NRs). Appropriate CCND1 gene activity is essential for normal development and physiology of the mammary gland, where it is regulated by ovarian steroids through a mechanism(s) that is not fully elucidated. We report here that CCND1 promoter activation by estrogens in human breast cancer cells is mediated by recruitment of a c-Jun/c-Fos/estrogen receptor alpha complex to the tetradecanoyl phorbol acetate-responsive element of the gene, together with Oct-1 to a site immediately adjacent. This process coincides with the release from the same DNA region of a transcriptional repressor complex including Yin-Yang 1 (YY1) and histone deacetylase 1 and is sufficient to induce the assembly of the basal transcription machinery on the promoter and to lead to initial cyclin D1 accumulation in the cell. Later on in estrogen stimulation, the cyclin D1/Cdk4 holoenzyme associates with the CCND1 promoter, where E2F and pRb can also be found, contributing to the long-lasting gene enhancement required to drive G(1)-phase completion. Interestingly, progesterone triggers similar regulatory events through its own NRs, suggesting that the gene regulation cascade described here represents a crossroad for the transcriptional control of G(1)-phase progression by different classes of NRs.

Varicocele repair in severe oligozoospermia: A case report of post-operative azoospermia.

Varicocele has been implicated as a cause in 35%-50% of patients with primary infertility and up to 81% of men with secondary infertility. Although a large number of reports have shown improvement in the semen parameters after correction of varicocele, other studies have suggested no benefit. We report the first case of azoospermia after surgery in a young infertile male patient with left-sided varicocele and severe oligozoospermia undergoing laparoscopic varicocelectomy. A pregnancy was only achieved with assisted reproductive technology because semen cryopreservation was performed before surgery. In the light of the above, the deterioration of sperm count after varicocele repair in patients with severe oligozoospermia could be due to irreversible impairment of spermatogenesis of such patients, together with the possible temporary damage of the surgical repair. This possible complication could therefore turn the severe oligozoospermia into an indication to perform cryopreservation before surgery, on both clinical and medico-legal grounds. Further research is needed before drawing definitive conclusions regarding the management of varicocele-related severe oligozoospermia.

DNA oxidation as triggered by H3K9me2 demethylation drives estrogen-induced gene expression.

Modifications at the N-terminal tails of nucleosomal histones are required for efficient transcription in vivo. We analyzed how H3 histone methylation and demethylation control expression of estrogen-responsive genes and show that a DNA-bound estrogen receptor directs transcription by participating in bending chromatin to contact the RNA polymerase II recruited to the promoter. This process is driven by receptor-targeted demethylation of H3 lysine 9 at both enhancer and promoter sites and is achieved by activation of resident LSD1 demethylase. Localized demethylation produces hydrogen peroxide, which modifies the surrounding DNA and recruits 8-oxoguanine-DNA glycosylase 1 and topoisomeraseIIbeta, triggering chromatin and DNA conformational changes that are essential for estrogen-induced transcription. Our data show a strategy that uses controlled DNA damage and repair to guide productive transcription.

[Family psychoeducational interventions for schizophrenia in routine settings: impact on patients' clinical status and social functioning and on relatives' burden and resources]. / Interventi psicoeducativi familiari per la schizofrenia nella pratica clinica: effetto sullo stato clinico e la disabilità dei pazienti e sul carico e le risorse familiari.

OBJECTIVE: This study explored the effectiveness of a psychoeducational family intervention for schizophrenia on patients' clinical status and disability and relatives' burden and perceived support. METHODS: The study has been carried out in 17 mental health centres. In each of them, 2 professionals were trained in a psychoeducational intervention and applied it for six months with families of users with schizophrenia. At baseline and six months later, patients' clinical status and disability, and relatives' burden, social network and professional support were assessed by validated tools. RESULTS: Of the seventy-one recruited families, 48 (68%) completed the intervention. At six months, a significant improvement was found in patients' clinical status and social functioning, as well as in relatives' burden and social and professional support. In particular, the percentage of patients with poor or very poor global social functioning dropped from 50% to 27% at six months. Forty percent of patients and 45% of relatives reported a significant improvement in their social contacts over the intervention period. CONCLUSIONS: The results of this study confirm the hypothesis that psychoeducational family interventions may have a significant effect on social outcome and family burden in schizophrenia when provided in routine conditions.

[Benefits and difficulties in implementing family psychoeducational interventions for schizophrenia in mental health services: results from a multicentre Italian study]. / Aspetti positivi e difficoltà nella diffusione degli interventi psicoeducativi familiari nella pratica clinica: uno studio multicentrico in 23 CSM italiani.

AIMS: This study aims to explore: a) the feasibility of psycho-educational interventions for families of users with schizophrenia in clinical practice by trained staff; b) the benefits and problems encountered by professionals in the use of these interventions. METHODS: 46 professionals from 23 Italian Mental Health Services (MHS) attended at a three-module training course in psycho-educational interventions and four supervisions in the subsequent year. Following the course, participants provided the intervention to families of users with schizophrenia. The difficulties and benefits encountered by trainees to use the intervention were registered on the Famnily Intervention Schedule. RESULTS: 83% of the participants completed the training course. Following the course, the intervention started in 71 families from 17 MHS. 76% of trainees provided the intervention to 2-5 families, while 13% of them only held informative sessions on schizophrenia. During the supervision period, the organisational difficulties experienced by the professionals were stable, while the benefits increased. Differences in benefits and difficulties were detected in relation to the trainees' experience and professional roles. CONCLUSIONS: It is possible to introduce psycho-educational interventions in MHS after a relatively brief period of training and supervision of the staff. Organisational difficulties need to be addressed to increase the dissemination of these interventions on a large scale.