Improved protection of outdoor workers from solar ultraviolet radiation: position statement.

The vast majority of non-melanoma skin cancer (NMSC) is attributable to excessive exposure to ultraviolet radiation (UVR). Outdoor workers are exposed to an UVR dose at least 2 to 3 times higher than indoor workers and often to daily UVR doses 5 times above internationally recommended limits. The risk of UVR workplace exposure is vastly neglected, and the evident future challenges presented in this statement are contrasted with the current situation regarding legal recognition, patient care and compensation. While prevention is crucial to reduce cancer risks for outdoor workers, it is as much of relevance to better protect them through legally binding rules and regulations. Specific actions are outlined in five recommendations based on a Call to Action (table 1). The role of health professionals, including dermatologists, in this context is crucial.

Computational study of the inhibitory mechanism of the kinase CDK5 hyperactivity by peptide p5 and derivation of a pharmacophore.

The hyperactivity of the cyclic dependent kinase 5 (CDK5) induced by the activator protein p25 has been linked to a number of pathologies of the brain. The CDK5-p25 complex has thus emerged as a major therapeutic target for Alzheimer's disease (AD) and other neurodegenerative conditions. Experiments have shown that the peptide p5 reduces the CDK5-p25 activity without affecting the endogenous CDK5-p35 activity, whereas the peptide TFP5, obtained from p5, elicits similar inhibition, crosses the blood-brain barrier, and exhibits behavioral rescue of AD mice models with no toxic side effects. The molecular basis of the kinase inhibition is not currently known, and is here investigated by computer simulations. It is shown that p5 binds the kinase at the same CDK5/p25 and CDK5/p35 interfaces, and is thus a non-selective competitor of both activators, in agreement with available experimental data in vitro. Binding of p5 is enthalpically driven with an affinity estimated in the low µM range. A quantitative description of the binding site and pharmacophore is presented, and options are discussed to increase the binding affinity and selectivity in the design of drug-like compounds against AD.

Segmenting time-lapse phase contrast images of adjacent NIH 3T3 cells.

We present a new method for segmenting phase contrast images of NIH 3T3 fibroblast cells that is accurate even when cells are physically in contact with each other. The problem of segmentation, when cells are in contact, poses a challenge to the accurate automation of cell counting, tracking and lineage modelling in cell biology. The segmentation method presented in this paper consists of (1) background reconstruction to obtain noise-free foreground pixels and (2) incorporation of biological insight about dividing and nondividing cells into the segmentation process to achieve reliable separation of foreground pixels defined as pixels associated with individual cells. The segmentation results for a time-lapse image stack were compared against 238 manually segmented images (8219 cells) provided by experts, which we consider as reference data. We chose two metrics to measure the accuracy of segmentation: the 'Adjusted Rand Index' which compares similarities at a pixel level between masks resulting from manual and automated segmentation, and the 'Number of Cells per Field' (NCF) which compares the number of cells identified in the field by manual versus automated analysis. Our results show that the automated segmentation compared to manual segmentation has an average adjusted rand index of 0.96 (1 being a perfect match), with a standard deviation of 0.03, and an average difference of the two numbers of cells per field equal to 5.39% with a standard deviation of 4.6%.

ITalian Observational Study of the management of mild-to-moderate Post-Operative Pain (ITOSPOP).

BACKGROUND: The multicenter observational ITalian Observational Study on the management of mild-to-moderate PostOperative Pain (ITOSPOP) was carried out in 24 hospitals to describe current postoperative pain management in Italy and the intensity of pain experienced by patients during the first 48 hours after surgery. METHODS: Adult patients, after surgery expected to result in mild-moderate postoperative pain, underwent six evaluations. The primary endpoint was the level of organization and standardization of postoperative pain management. Secondary objectives included the intensity of postoperative pain, and an assessment of incident pain, postoperative analgesic and concomitant treatment administration. RESULTS: Only 16.7% hospitals had an acute pain service and 41.7% hospitals applied a standardized protocol for postoperative pain management. The majority (>60%) of the 1952 patients monitored underwent all six assessments, >70% of which were performed by a physician. The proportion of patients with moderate pain decreased during the study period, but almost 10% of patients still experienced moderate pain at study end. Mild pain was reported by 50% of the patients for the entire study duration. At the final assessment, 5% of patients still presented with incident pain frequently interfering with daily activities. Most patients were treated with analgesics, but 20% of patients did not receive any pain medications despite experiencing pain. CONCLUSION: The level of organization and standardization of postoperative pain management in Italian hospitals remains low. Postoperative analgesic treatment remained suboptimal and almost two-thirds of patients continued to experience pain.

Structural and dynamic determinants of ligand binding and regulation of cyclin-dependent kinase 5 by pathological activator p25 and inhibitory peptide CIP.

The crystal structure of the cdk5/p25 complex has provided information on possible molecular mechanisms of the ligand binding, specificity, and regulation of the kinase. Comparative molecular dynamics simulations are reported here for physiological conditions. This study provides new insight on the mechanisms that modulate such processes, which may be exploited to control pathological activation by p25. The structural changes observed in the kinase are stabilized by a network of interactions involving highly conserved residues within the cyclin-dependent kinase (cdk) family. Collective motions of the proteins (cdk5, p25, and CIP) and their complexes are identified by principal component analysis, revealing two conformational states of the activation loop upon p25 complexation, which are absent in the uncomplexed kinase and not apparent from the crystal. Simulations of the uncomplexed inhibitor CIP show structural rearrangements and increased flexibility of the interfacial loop containing the critical residue E240, which becomes fully hydrated and available for interactions with one of several positively charged residues in the kinase. These changes provide a rationale for the observed high affinity and enhanced inhibitory action of CIP when compared to either p25 or the physiological activators of cdk5.

[Comparison of 100 of hysterectomy laparoscopic against 100 cases hysterectomy laparotomy]. / Confronto di 100 casi isterectomia laparoscopica vs 100 casi isterectomia laparotomica.

OBJECTIVE: The aim of our study is to obtain the parameters for assessment of patient, so that policy guidelines for surgical procedures to choose from (laparoscopy or laparotomy). This way you get a chance to prefer the choice of surgical approach over another. Moreover, the ultimate goal is to determine if there is any superiority of one surgical technique over another according to clinical parameters. METHODS: This was a randomized observational study, using the comparison between a first sample of 100 patients treated with hysterectomy by laparotomy and a second sample of 100 patients treated with hysterectomy laparoscopy (THL). A comparison of results obtained in the short term whereas the biennium 2007/2008, using as a method of patient selection, the system of systematic randomization. RESULTS: The results of this work reveals the superiority of laparoscopic hysterectomy over abdominal hysterectomy by taking into account the parameters of evaluation and risk factors. CONCLUSION: In conclusion it is important to a precise preoperative evaluation according to specific parameters that impinge on efficacy and safety of laparoscopic surgery. If you made a careful preoperative evaluation of the patient is able to make it even safer laparoscopic surgical technique with a clear superiority in terms of efficacy, safety and less invasiveness of laparoscopy compared to laparotomy.

Involvement of PGC-1, NRF-1, and NRF-2 in metabolic response by rat liver to hormonal and environmental signals.

We studied liver oxidative capacity and O2 consumption in hypothyroid rats treated for 10 days with T4, or T3, or treated for 10 days with T3 and exposed to cold for the last 2 days. The metabolic response of homogenates and mitochondria indicated that all treatments increased the synthesis of respiratory chain components, whereas only the cold-induced mitochondrial proliferation. Determination of mRNA and protein expression of transcription factor activators, such as NRF-1 and NRF-2, and coactivators, such as PGC-1, showed that mRNA levels, except PGC-1 ones, were not related to aerobic capacities. Conversely, a strong correlation was found between cytochrome oxidase activity and PGC-1 or NRF-2 protein levels. Such a correlation was not found for NRF-1. Our results strongly support the view that in rat liver PGC-1 and NRFs are responsible for the iodothyronine-induced increases in respiratory chain components, whereas their role in cold-induced mitochondrial proliferation needs to be further on clarified.

The global momentum for smokefree public places: best practice in current and forthcoming smokefree policies.

The Global Smokefree Partnership has recently prepared a map of smokefree campaigns and policies around the world. It focuses primarily on countries that are parties to the WHO Framework Convention on Tobacco Control, but other countries were included. The smokefree status of 172 countries was mapped. Of these countries, 31 (18.0%) have established comprehensive smokefree policies, either nationally or at state or city level - best practice; 25 (14.6%) are planning to implement smokefree policies in 2008 or 2009; and 51(29.6%) are making significant progress with smokefree policies. Only 65 countries (37.8%) have limited or no smokefree polices. A selection of countries representing best practices in smokefree policies or planning to implement smokefree policies in 2008 or 2009 is highlighted. They illustrate the significant global momentum for smokefree policies, the success of established policies, the importance of civil society and the sharing of experience between countries.

The global momentum for smokefree public places: best practice in current and forthcoming smokefree policies / El momento global para espacios públicos libres de tabaco: mejores prácticas en políticas actuales y futuras

The Global Smokefree Partnership has recently prepared a map of smokefree campaigns and policies around the world. It focuses primarily on countries that are parties to the WHO Framework Convention on Tobacco Control, but other countries were included. The smokefree status of 172 countries was mapped. Of these countries, 31 (18.0 percent) have established comprehensive smokefree policies, either nationally or at state or city level - best practice; 25 (14.6 percent) are planning to implement smokefree policies in 2008 or 2009; and 51(29.6 percent) are making significant progress with smokefree policies. Only 65 countries (37.8 percent) have limited or no smokefree polices. A selection of countries representing best practices in smokefree policies or planning to implement smokefree policies in 2008 or 2009 is highlighted. They illustrate the significant global momentum for smokefree policies, the success of established policies, the importance of civil society and the sharing of experience between countries.

El Global Smokefree Partnership recién completó un mapa de las campañas para promover políticas de ambientes libres de humo (ALH) a nivel mundial. El mapa se centra en los países Partes al Convenio Marco para el Control del Tabaco de la OMS, aunque otros países también se incluyen, y documenta el estatus de 172 países en el tema de los ALH. De estos países, 31 (18.0 por ciento) tienen políticas comprehensivas de ALH, a nivel nacional, provincial, y/o estatal - mejores prácticas; 25 (14.6 por ciento) prevén la implementación de políticas de ALH en 2008 o 2009; y 51 (29.6 por ciento) han progresado significativamente con estas políticas. Sólo 65 países (37.8 por ciento) no tienen políticas de ALH, o sólo políticas limitadas en este ámbito. Este ensayo destaca una selección de países que representan las mejores prácticas en las políticas de ALH o que prevén la implementación de estas políticas en 2008 o 2009, con tal de ilustrar el movimiento global hacia los ambientes libres de humo; el éxito de las políticas ya establecidas; la importancia de la sociedad civil en este proceso; y el intercambio de experiencias entre países.

A new uterine suture technique for postpartum hemorrhage.

At present, postpartum hemorrhage is still an important cause of maternal mortality and morbidity. When medical therapy has no success, conservative surgical procedures are applied before making a hysterectomy. Three transverse sutures are applied to the entire uterine wall both to the right and the left side of the uterus. Our technique has been applied to 4 women with postpartum hemorrhage secondary to uterine atony. Bleeding was stopped immediately by compressive sutures. The four patients had normal menstruation cycles after delivery and had new pregnancies. No woman had postoperative complications. Uterus compressive suture is an effective alternative to hysterectomy to treat postpartum hemorrhage secondary to atony. This is a simple and quick procedure that preserves fertility.

Double laparotomy wound recurrence of endometrial carcinoma.

INTRODUCTION: Abdominal scar recurrence of endometrial carcinoma after abdominal total hysterectomy is very rare. We report a case of a 65-year-old woman who had two recurrences in the abdominal incisional scar after total hysterectomy. CASE REPORT: A 65-year-old woman underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy because of well-differentiated endometrial adenocarcinoma (Stage IIB). Thus, the patient was treated by external beam radiotherapy. She developed two recurrences in the abdominal incisional scar two and three years after total hysterectomy, respectively. Surgery plus chemotherapy and surgery plus hormonal therapy were used for treatment of the first and second scar recurrence, respectively. CONCLUSIONS: It is a very intriguing and controversial biologic question how neoplastic cells can implant and grow in an abdominal scar without other concomitant metastases. We report a review of the literature and the possible mechanism of recurrences in laparotomy wounds.

Female adnexal tumor of probable wolffian origin: clinicopathological, immunohistochemical and cytofluorimetric analyses of a 22-year-old virgin. case report.

The term female adnexal tumor of probable Wolffian origin "FATWO" designs this tumor wich arises by the rare persisting remnants of the mesonephric duct (Wolffian duct). About 40 cases have been reported in literature. Few cases of recurrence have been reported, FATWO usually shows no signs of hormonal activity. We report a case of the youngest patient affected by FATWO in October 2002. At laparotomy the left adnexa were deformed by a well-capsulated mass, totally removed and sent to the pathologist with a specimen of peritoneal fluid and of the omentum. The histological examination showed a prevalent tubular structure with focal retiform area, without intraluminal mucines. Immunohistochemical findings of the case reported are similar to those described by other authors, except for inhibin which has not been detected by us. The cytofluorimetry showed the low presence of aneuploid cells, with a very low prolifing component (< 1%).

Comparative evaluation of standard criteria and CA-125 in ovarian cancers treated with platinum or paclitaxel.

PURPOSE: To assess CA-125 in defining tumor response in patients treated with paclitaxel. PATIENTS AND METHODS: We analyzed 150 women treated for epithelial ovarian carcinoma with platinum or paclitaxel. We compared the patients treated with two agents, using a precise definition of CA-125 response, determined by 50% and 75% reductions, like other authors have published. RESULTS: CA-125 criteria gave response rates very similar to the standard response rates, both for patients treated with platinum (75% vs 63%) and also for those treated with paclitaxel (40% vs 39%). Rates of false-positive prediction of response by CA-125 were also similar for patients treated with these two agents. CONCLUSION: Precise 50% or 75% CA-125 response criteria are as sensitive as standard criteria for assessing activity of therapy for the ovarian cancers treated with platinum or paclitaxel. We propose that they may be useful in defining response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer.

AGUS and ASCUS: different incidence in pre- and postmenopausal women.

PURPOSE OF INVESTIGATION: The aim of this study was to determine the incidence of AGUS (atypical glandular cells of undetermined significance), ASCUS (atypical squamous cells of undetermined significance) and SIL (squamous intraepithelial lesion) in the cytologic diagnosis in pre- and postmenopausal women. METHODS: We did a retrospective study selecting 183 patients who were screened for cervical pathology. Ninety-six patients were in postmenopausal age. We determined the incidence of cytologic abnormalities defined as ASCUS, SIL, and AGUS in pre- and postmenopausal women. RESULTS: We expected a marked incidence of low-grade SILs in the fertile population, while the postmenopausal group was thought to be affected more by AGUS and ASCUS. We obtained different results. In our population study, premenopausal women presented more AGUS and ASCUS; the two subgroups presented the same incidence of low-grade SILs; postmenopausal women were more affected by high-grade SILs. CONCLUSIONS: The significance of the new categories introduced by the Bethesda System is still uncertain for different authors. As we look to the future new markers that more specifically identify individuals at-risk can be expected.

Second-line therapy of advanced ovarian cancer with GnRH analogs.

Ovarian cancer is still the first cause of death among female malignancies. The standard treatment adopted in ovarian cancer is a radical surgical treatment or cytoreduction, followed by six courses of platinum-based chemotherapy; second-line regimens are associated with severe side effects. GnRH analogs could represent an alternative therapeutical approach. The aim of our study was to evaluate the role of GnRH analogs in the management of platinum-resistant ovarian cancers. We enrolled 12 patients affected by advanced ovarian cancer, previously treated with six courses of platinum-paclitaxel. In second-line therapy, we used leuprolide on 1, 8, and 28 days of treatment. CA 125 levels were recorded for each patient. One case of clinical partial response was obtained (8.3%). Stable disease was diagnosed in three patients (25%). Progression was recorded in eight cases (66.7%). Progression-free survival was 6 months. The treatment was well tolerated by patients. The high tolerability and the results obtained with leuprolide versus platinum in second-line therapy might permit a better use of the analogs for advanced ovarian cancer.

How to evaluate organ donation: the quality programme in Tuscany.

The shortage of cadaveric organ donors imposes a severe limit on the number of patients who can benefit from transplantation. This paper describes a programme for evaluation and improvement of the organ donation process, which has been implemented in the hospitals of the Tuscany region, Italy. After analysing the first results it was found that there was great potential for growth, especially in those hospitals with neurosurgery where the weakest points of the process were detected The development of a quality improvement programme in cadaveric organ donation is an adequate and scientific method to detect where the problems in the process of organ donation lie. Ideally, the comparison of these data with those of other Italian or European regions should be very useful to plan adequate strategies to improve cadaveric organ donation.

Utilisation of hydrogen peroxide in the treatment of recurrent bacterial vaginosis.

AIM: The authors have evaluated the real efficacy of using hydrogen peroxide for previously treated recurrent bacterial vaginosis that is resistant to other forms of treatment. METHODS: The study included 58 women aged between 18 and 42 years old. Vaginal irrigations with 30 ml of hydrogen peroxide (3%) were prescribed in the evening for a week. The follow-up was carried out 3 months after the end of treatment. RESULTS: The results clearly show that the use of hydrogen peroxide in vagina can eliminate the main symptoms of bacterial vaginosis, and in particular the malodorous leucoxanthorrhea in 89% of cases at 3 months after the end of treatment, a result that is comparable to that obtained using metronidazole or clindamycin as a vaginal cream. Moreover, hydrogen peroxide facilitates the restoration of normal vaginal bacterial flora (represented by H202-producing lactobacillus) in 100% of cases and normal acid pH (pH<4.5) in 98% of cases; it also fosters the disappearance of clue cells from vaginal smears and anaerobic pathogenic flora from vaginal secretions in 100% of cases. The amine test became negative in 97.8% of cases. All results underwent statistical analysis and were found to be statistically significant. CONCLUSION: Hydrogen peroxide represents a valid alternative to conventional treatments for recurrent bacterial vaginosis, and associates the absence of collateral effects with low costs, excellent tolerability and real therapeutic efficacy.

Second-line with paclitaxel and carboplatin for recurrent disease following first paclitaxel and platinum compounds in ovarian carcinoma.

OBJECTIVE: The combination of paclitaxel and platinum compounds is considered the best first-line regimen for advanced ovarian carcinoma. The purpose of this study was to evaluate a paclitaxel and carboplatin combination in pretreated patients who recurred within 24 months after a complete clinical response with the same regimen used as first-line chemotherapy. METHODS: 18 patients were included in this study. Second-line chemotherapy consisted of paclitaxel, 175 mg/m2 as a 3-hour infusion, and carboplatin AUC 6 every 21 days. RESULTS: Among 15 evaluable patients, eight (53%) complete and five (34%) partial responses were observed, while two (13%) patients had stable disease (SD). The response rate was 67% among patients with measurable disease and 52% for evaluable disease. The median progression-free interval after second-line chemotherapy was 8.3 months. The median progression-free interval for patients with measurable disease was 8.6 months and for evaluable disease it was 7.9 months. Seven (46%) of 15 patients have developed recurrence after second-line chemotherapy with paclitaxel and carboplatin with a median time to recurrence of 9.8 months. CONCLUSION: Paclitaxel 175 mg/m2 and carboplatin AUC 6 as second-line chemotherapy in this sensitive population is effective in terms of response rate and progression-free interval.

Regulation of androgen receptor mRNA expression in primary culture of Harderian gland cells: cross-talk between steroid hormones.

The androgen receptor (AR) must be considered a transcription factor belonging to the steroid-thyroid hormones receptor superfamily. Previous results gained from the Harderian gland, a tubulo-alveolar gland located in the orbital cavity of the golden hamster, indicate that Harderian gland cells express mRNAs encoding for androgen, glucocorticoid, thyroid hormone (T(3)), and estrogen receptors, respectively. Since in other systems, these receptors have been related to the expression of the androgen receptor, we have studied the regulation of AR expression in primary cultures of the male hamster Harderian gland. Our in vitro experiments show that androgen, and thyroid hormones increase the expression of AR. Retinoic acids also show a positive effect on AR expression, while exposure to glucocorticoid or estrogen blocks AR expression. Since these steroids differently modulate AR expression, our results must be considered in the context of multi-hormonal control of gene expression that could act through cross-talk between members of the steroid-thyroid hormones.

High third-order nonlinear optical susceptibility in new fluorinated poly(p-phenylenevinylene) copolymers measured with the Z-scan technique.

The third-order nonlinear optical properties of a series of copoly(2, 3, 5, 6-tetrafluoro-1, 4-phenylenevinylene-2, 5-dioctyloxy-1, 4-phenylenevinylene) that contain variable ratios of two differently substituted monomers have been studied in chloroform solutions at l=1064 nm by the picosecond Z-scan technique. Nonlinear refractive index n(2) of the samples investigated has been found to be negative, and a strong dependence of its magnitude on the copolymer's composition has been observed. The highest third-order nonlinear optical susceptibility, |x((3))|=(6 +/- 2)x 10(-10) esu, was measured for a copolymer obtained by reaction of equimolar quantitites of the parent monomers.