Heart rate analysis during very deep dives in flooded caves: single case study

The purpose of this study is to investigate the heart rate adaptations during deep dave diving with MCCR (mechanical closed circuit rebreather). Previous studies on this matter have not been conducted to the depths reached in this study and most of them have been conducted inside hyperbaric chambers trying to recreate the immersion conditions. The data collection took place during the exploration of two hydrogeological sites by a professional cave diver. The recordings were made using a SCUBAPRO GALILEO SOL® dive computer capable of monitoring the heart rate, with a sampling interval of 0,25 Hz. The data collected confirm a direct relationship between the increase in diving depth and the increase in the detected heart rate

Molecular epidemiology and pathogenic potential of underdiagnosed human papillomavirus types

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) tests are crucial diagnostic tools for the prevention of neoplastic lesions of the uterine cervix. However most commercial methods are designed to detect high-risk (HR) HPV types and a limited selection of low-risk ones, thus missing a fair number of intermediate/low-risk types. As a result, many HPV infections remain undiagnosed, generating distrust in virological diagnosis among gynaecologists, who continue to rely preferentially on cytological and colposcopic findings.</p> <p>Results</p> <p>In this study, we tested 6,335 consecutive clinical samples, most of them from Italian patients with cytological abnormalities. The samples, collected in 2000–2007, were analyzed using PCR amplification of a 173–206 bp (depending on HPV type) conserved region in the L1 open reading frame, restriction endonuclease analysis and, where required, sequence analysis for type determination. Analysis of a smaller male sample and long term follow-up of a few female subjects was also performed. A total of 2,161 samples tested positive for HPV DNA (32.1%); 21.3% of them were mixed infections. Overall, 59 known and 2 unknown HPV types were detected. Their relative prevalence was calculated; notably, types not clearly identifiable using the most common commercial method accounted for 36% of infections. Clinical findings associated with the underdiagnosed types ranged from H-SIL to low-grade abnormalities, although none of these infections resulted in invasive cancer.</p> <p>Conclusion</p> <p>Given the high prevalence of some underdiagnosed HPV types in the population (principally HPV53, HPV66, HPV84, and HPV87) and their frequent association with cytological abnormalities, techniques capable of detecting and typing them would prove extremely useful.</p

Surgical Treatment of Paget Disease of the Vulva

ObjectiveThe aim of the study was to evaluate the risk of recurrence according to the surgical margin status and the presence of invasion or of superficially invasive carcinoma in patients with extramammary Paget disease (EMPD) of the vulva, who underwent elective surgical treatment.Materials and MethodsWe performed a retrospective analysis of 27 patients with first diagnosis of extramammary Paget disease of the vulva, who underwent primary and elective surgical treatment from January 1989 to December 2014. A p value of less than .05 was considered statistically significant. Multivariable logistic regression was performed to adjust for confounding factors.ResultsWe observed invasive disease in 11 cases, with microinvasion in 8 of them. A positive surgical margin was found in 10 patients. During a median follow-up period of 79.5 months, 8 patients (29.6%) showed a first recurrence after a median (range) time of 4.9 (2.3-7.1) years. No significant differences were observed between patients with recurrence and patients without recurrence with respect to age, number of vulvar sectors involved, bilaterality and multifocality, presence of invasion or microinvasion, and surgical margin status. However, during the follow-up period, the presence of invasion was higher (67% vs 41%) in patients with recurrence compared with patients without recurrence.ConclusionsThe rate of recurrence of the disease after therapy is high. Patients should be subjected to a close and long-term follow-up to identify those who must undergo further treatment, especially if they presented with an invasive or even microinvasive disease. A free margin of no greater than 1 to 2 cm might be the most appropriate surgical choice

Number of Nodes Removed With Inguinofemoral Lymphadenectomy and Risk of Isolated Groin Recurrence in Women With FIGO Stage IB-II Squamous Cell Vulvar Cancer

Aim: The aim of this study was to evaluate if the lymph node count from inguinofemoral lymphadenectomy impacted the risk of isolated groin recurrence in patients with nodenegative squamous cell vulvar cancer.Materials and Methods: This is a retrospective cohort study of women with squamous cell vulvar cancer (stage IBYII according to the 2009 Revised International Federation of Gynecology and Obstetrics staging system) who underwent primary radical vulvar surgery and groin lymphadenectomy between January 2005 and December 2014. Patients' sociodemographic characteristics, the disease characteristics, the number of nodes removed from each groin, and the oncologic outcomewere evaluated. A cutoff value of at least 6 nodes removed from each groin was used to define the adequacy of inguinofemoral dissection.Results: Seventy-six patients, fulfilling the study inclusion criteria, were considered. The mean number of nodes removed (bilaterally) was 14.5 (T5.3, SD), with a range of 2 to 29 nodes. Thirty-three women (43.4%) had less than 6 nodes removed from each groin. In the whole study cohort, 4 cases of isolated groin recurrence (5.3%) were detected, and all these recurrences developed in patients with less than 6 nodes removed. Considering the demographic, clinical, and histopathological characteristics potentially related to the risk of groin recurrence, only the number of nodes removed showed a significant correlation.Conclusions: Women treated for vulvar cancer in which less than 6 nodes are removed from each groin are at higher risk of groin recurrence

Vaginal Intraepithelial Neoplasia: Histopathological Upgrading of Lesions and Evidence of Occult Vaginal Cancer

Objective The aim of this study was to analyze women treated with excisional procedures for vaginal high-grade squamous intraepithelial lesions (HSILs). The histopathological upgrading of the lesions previously detected on vaginal biopsy and the presence of occult invasive vaginal cancer in the specimens excised were investigated, to identify a higher risk subset of women.Materials and Methods A retrospective analysis of the medical records of 86 women with a biopsy histopathologic diagnosis of vaginal HSIL (vaginal intraepithelial neoplasias [VaINs]: VaIN2 and VaIN3) and subsequent excisional therapy, consecutively referred to the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014, was performed.Results Of the 86 patients, 4 cases (4.6%) of occult vaginal cancer were detected, all of them in women previously diagnosed with VaIN3 on biopsy (4/39 cases, 10.3%). Women with diagnosis of VaIN2 on biopsy showed an upgrading of lesions, with diagnosis of VaIN3 on the final specimen in 5 (10.6%) of 47 cases, with no cases of VAIN2 upgraded to invasive cancer. In 33.3% of the women initially diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related disease, a final histopathological upgrading of lesions emerged. Furthermore, tobacco use was significantly related to the histopathological upgrading of lesions previously detected on vaginal biopsy.Conclusions Women diagnosed with VaIN3 should be treated with excisional procedures as first-line surgical approach, given the risk of occult invasive disease in 10% of the cases. Women diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related cervical diseases should always be carefully evaluated and possibly excised, given the higher risk of histopathological upgrading of lesions and thus the potential risk of occult vaginal cancer. Tobacco users should be considered as high-risk group

Laser Excisional Treatment for Vaginal Intraepithelial Neoplasia to Exclude Invasion

Objective: We undertook a retrospective analysis of the incidence of complications of carbon dioxide (CO2) laser excision for high-grade vaginal intraepithelial neoplasia (HG-VaIN).Materials and Methods: Retrospective large case series on 128 CO2 laser excisions for HG-VaIN in 106 women treated at the Department of Gynecologic Oncology, Oncologic Referral Center, Aviano, Italy. These procedures were performed under local anesthesiawith a 20-Wcontinuous laser beam focused to a 0.2-mm spot size. Complications were defined as "minor" when limited to vagina, and "major" when surrounding organs were injured or the vaginal vault was opened. To identify possible factors associated with surgical complications, we performed a univariate analysis with the t test for continuous variables and x(2) or Fisher exact test for qualitative variables as appropriate.Results: The overall rate of complication was 7.8% (10/128); nine of themwere vaginal bleeding, and only one (0.8%) was amajor complication with vaginal vault perforation. A greater number of previous destructive treatments and of two or more previous laser vaginal excisional treatments was present in patients with complications compared with ones without complications (10% vs 3.9 %, p = .92, and 30% vs 15.2%, p = .44, respectively), although these differences were not statistically significant. A total of 10.5% (6/57) of occult vaginal cancer was detected in women with initial diagnosis of VaIN3 (HG-VaIN) on biopsy.Conclusions: Carbon dioxide laser excision for HG-VaIN seems to be a safe approach with low rate of complications, probably because of the better accuracy achieved by CO2 laser resections, and permits diagnosis of occult invasive disease

Raf Kinase Inhibitor Protein (RKIP) expression and function in human myometrium and leiomyoma

Many growth factors been identified in human myometrium and leiomyoma and activate multiple signaling pathways in order to regulate major cellular processes, including proliferation and fibrosis which are linked to uterine leiomyoma development and growth. The Raf kinase inhibitor protein (RKIP) has emerging roles as regulator of multiple signaling networks including mitogen activated protein (MAP) kinase cascade, as well as interaction with glycogen synthase kinase 3 (GSK3). In our study, we aimed to investigate the presence of RKIP in human myometrium and leiomyoma as well as to determine the effect of locostatin (RKIP inhibitor) on extracellular matrix (ECM) production, proliferation and migration in human myometrial and leiomyoma cells. Myometrial and leiomyoma tissues were used to investigate the localization and the expression level of RKIP through immunohistochemistry and western blotting. Myometrial and leiomyoma cells were treated with locostatin to measure ECM expression by real time PCR, GSK3b expression by western blotting, cell migration by wound-healing assay and cell proliferation by MTT assay. We found that RKIP is expressed in human myometrial and leiomyoma tissue. Locostatin treatment resulted in the activation of the MAPK signal pathway (ERK phosphorylation), providing a powerful validation of our targeting protocol. Further, RKIP inhibition by locostatin reduces ECM components. Moreover, the inhibition of RKIP by locostatin impaired cell proliferation and migration in both leiomyoma and myometrial cells. Finally, locostatin treatment reduced GSK3β expression. Therefore, even if the activation of MAPK pathway should increase proliferation and migration, the destabilization of GSK3β leads to the reduction of proliferation and migration of myometrial and leiomyoma cells

TGF beta family members function in uterine healthy and fibrotic smooth muscle cells

Uterine leiomyomas are the most common benign tumors of fertile women and the most common indication for hysterectomy. Despite the high prevalence, significant health problems, and huge economical impact on the healthcare system, relatively little is understood about the etiology and pathophysiology of uterine leiomyoma (1). Consequently, medical treatments are still limited (2). The role of the growth factors as ultimate mediators of the steroids hormone is evident in the modulation of the cell proliferation and the morphological cells appearance (3). Activin-A and myostatin are growth factors belonging to TGF-β super family expressed and acting in myometrial (4,5) and leiomyoma cells (6) We aimed to explore the functions of activin and myostatin in human myometrial and leiomyoma cells. First we tested both Smad and non-Smad signaling pathways by western blot. We found that activin-A and myostatin can activate only Smad signaling pathway in both myometrial and leiomyoma cells. Next we explored the effect on cell proliferation and on fibrotic phenotype. We found that activin-A and myostatin are able to suppress primary myometrial cell proliferation but they cannot alter the proliferation of leiomyoma cells. In the next step, we found that activin-A can significantly increase fibronectin expression in leiomyoma cells. Those above results suggest that activin-A and myostatin may express antiproliferative and/or fibrotic effects depending on the cell types by activating Smad signaling pathway