Quantifying peripheral sympathetic activations during sleep by means of an automatic method for pulse wave amplitude drop detection.

Sudden drops in pulse wave amplitude (PWA) measured by finger photoplethysmography (PPG) are known to reflect peripheral vasoconstriction resulting from sympathetic activation. Previous work demonstrated that sympathetic activations during sleep typically accompany the occurrence of pathological respiratory and motor events, and their alteration may be associated with the arising of metabolic and cardiovascular diseases. Importantly, PWA-drops often occur in the absence of visually identifiable cortical micro-arousals and may thus represent a more accurate marker of sleep disruption/fragmentation. In this light, an objective and reproducible quantification and characterization of sleep-related PWA-drops may offer a valuable, non-invasive approach for the diagnostic and prognostic evaluation of patients with sleep disorders. However, the manual identification of PWA-drops represents a time-consuming practice potentially associated with high intra/inter-scorer variability. Since validated algorithms are not readily available for research and clinical purposes, here we present a novel automated approach to detect and characterize significant drops in the PWA-signal. The algorithm was tested against expert human scorers who visually inspected corresponding PPG-recordings. Results demonstrated that the algorithm reliably detects PWA-drops and is able to characterize them in terms of parameters with a potential physiological and clinical relevance, including timing, amplitude, duration and slopes. The method is completely user-independent, processes all-night PSG-data, automatically dealing with potential artefacts, sensor loss/displacements, and stage-dependent variability in PWA-time-series. Such characteristics make this method a valuable candidate for the comparative investigation of large clinical datasets, to gain a better insight into the reciprocal links between sympathetic activity, sleep-related alterations, and metabolic and cardiovascular diseases.

Comparison between laparoscopy and laparotomy in the surgical re-staging of granulosa cell tumors of the ovary.

OBJECTIVE: To evaluate the role of laparoscopic (LPS) and laparotomic (LPT) re-staging in patients with incompletely surgically staged ovarian granulosa cell tumors (OGCT). METHODS: We conducted a medical chart retrospective analysis of all patients with sex cord stromal tumors (SCSTs) who were managed in our division between March 1994 and March 2017. After a complete review of surgical and pathological notes, patients with incomplete staging were restaged according to the FIGO guidelines. Statistical analysis was conducted using Statistical Package version 20.0 for Windows (SPSS, Inc., Chicago, Illinois). RESULTS: Out of a total of 170 patients SCSTs, 84 patients (49,5%) received primary surgery that included a hysterectomy; 86 patients (50,5%) underwent fertility-sparing surgery. Eighty-one patients (48%) with diagnosis of OGCT were incompletely surgically staged at another institution. We evaluated our results in terms of laparoscopic approach (56 patients) and open treatment (25 patients). Among the IA patient's group, 1 was upstaged to IIB stage and 2 to IIIB; among patients with IC stage, 1 was upstaged to IIA, 2 to IIB and 1 to IIIB stage. Adjuvant chemotherapy was given to the upstaged patients with final stage IIB-IIIC. No statistically significant difference between laparoscopy and open-surgery was detected in terms of upstaged patients after second surgery (p = 0,36). CONCLUSION: According to our series, laparoscopic restaging compared to the open approach seems to be a feasible and efficient technique to complete surgical staging in patients with GCTs incorrectly staged. Surgical restaging seems to upstage a considerable number of OGCT, mainly in the initial stage IC group of patients. However, the impact of restaging on final outcome and survival remains to be demonstrated.

A pilot study of soft gel technology: a new vaginal device to improve the symptomatology of vulvovaginal atrophy in post-partum, menopause and in patients with recurrent vulvovaginitis.

OBJECTIVE: This is a pilot study to evaluate the effectiveness of the treatment with Vaginal Soft gels technology in the improvement of common signs and symptoms in postmenopausal, postpartum and with recurrent vulvovaginitis patients. These conditions may cause the onset of Vulvovaginal Atrophy (VVA) with effects on sexual activity, self-confidence and daily activities. The main symptoms are itching, irritation and dryness. Many therapies have been evaluated and almost all those without hormonal component have shown poor results. PATIENTS AND METHODS: Women diagnosed with severe VVA from January to September 2018 were recruited. The study groups were composed of 25 postmenopausal women, 30 post-partum women and 30 women with recurrent vulvovaginitis. For each group, patients were randomized 1:1 among those who carried out the experimental treatment and those that did not perform it. The efficacy of treatment was evaluated with a clinical visit in which Vaginal Health Index (VHI) was estimated. The symptomatology was determined through the questionnaire Female Sexual Function Index (FSFI). RESULTS: A significant improvement has been shown with regard to the sexual function (orgasm, lubrification, pain) in patients who performed the treatment. A significant increase in VHI has been evaluated in postmenopausal patients (4 months p=0.054, 6 months p=0.005) and in recurrent vulvovaginitis but not in post-partum patients (4 months p=0.681, 6 months p=0.109). An improvement of lubrication, satisfaction, orgasm, pain, as well as dyspareunia, was observed in the three study groups. CONCLUSIONS: In this pilot study the treatment with soft gels seems to be effective in improving sexual health and atrophy being a treatment available for all types of patients thanks to the absence of systemic and local side effects. It is an excellent alternative especially for patients who cannot use hormones. These findings must be confirmed by larger and randomized further studies.

"Guidelines for the prevention and control of legionnaire's disease in Italy": guidelines or guidance?

The creation of guidelines is a methodologically complex activity that requires technical expertise, resources and time. Methods of guideline production must meet at least these three criteria: multidisciplinarity, systematic review, and ranked recommendations. In May 2015, the new "Guidelines for the prevention and control of Legionnaire's disease" were published on the website of the Italian Ministry of Health in order to "gather, update and integrate in a single document all the previous national recommendations published". The critical review of the document has led us to conclude that this document does not comply with these three criteria, and we emphasize that guidelines should make decision-making easier, considering the various scientific approaches to a health problem and choosing the one considered most effective. Therefore, the persons responsible for the development of guidelines should strive to widely adopt and use current standards for the development of guidelines as a means to improve patient care and health outcomes.

Analysis of Residual Dependencies of Independent Components Extracted from fMRI Data.

Independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data can be employed as an exploratory method. The lack in the ICA model of strong a priori assumptions about the signal or about the noise leads to difficult interpretations of the results. Moreover, the statistical independence of the components is only approximated. Residual dependencies among the components can reveal informative structure in the data. A major problem is related to model order selection, that is, the number of components to be extracted. Specifically, overestimation may lead to component splitting. In this work, a method based on hierarchical clustering of ICA applied to fMRI datasets is investigated. The clustering algorithm uses a metric based on the mutual information between the ICs. To estimate the similarity measure, a histogram-based technique and one based on kernel density estimation are tested on simulated datasets. Simulations results indicate that the method could be used to cluster components related to the same task and resulting from a splitting process occurring at different model orders. Different performances of the similarity measures were found and discussed. Preliminary results on real data are reported and show that the method can group task related and transiently task related components.

The direct, not V1-mediated, functional influence between the thalamus and middle temporal complex in the human brain is modulated by the speed of visual motion.

The main visual pathway that conveys motion information to the middle temporal complex (hMT+) originates from the primary visual cortex (V1), which, in turn, receives spatial and temporal features of the perceived stimuli from the lateral geniculate nucleus (LGN). In addition, visual motion information reaches hMT+ directly from the thalamus, bypassing the V1, through a direct pathway. We aimed at elucidating whether this direct route between LGN and hMT+ represents a 'fast lane' reserved to high-speed motion, as proposed previously, or it is merely involved in processing motion information irrespective of speeds. We evaluated functional magnetic resonance imaging (fMRI) responses elicited by moving visual stimuli and applied connectivity analyses to investigate the effect of motion speed on the causal influence between LGN and hMT+, independent of V1, using the Conditional Granger Causality (CGC) in the presence of slow and fast visual stimuli. Our results showed that at least part of the visual motion information from LGN reaches hMT+, bypassing V1, in response to both slow and fast motion speeds of the perceived stimuli. We also investigated whether motion speeds have different effects on the connections between LGN and functional subdivisions within hMT+: direct connections between LGN and MT-proper carry mainly slow motion information, while connections between LGN and MST carry mainly fast motion information. The existence of a parallel pathway that connects the LGN directly to hMT+ in response to both slow and fast speeds may explain why MT and MST can still respond in the presence of V1 lesions.

Imiquimod 5% cream versus cold knife excision for treatment of VIN 2/3: a five-year follow-up.

BACKGROUND: Vulvar intraepithelial neoplasia (VIN) is a premalingnant condition. For long time, surgery was considered the first-line therapy in the treatment of high grade VIN. Imiquimod was recently introduced as an alternative to surgery. AIM: To compare the overall complete response, the recurrence rate and the risk factors for relapse among patients with VIN 2/3 treated with Imiquimod or surgical excision. PATIENTS AND METHODS: Eighty women who had histological diagnosis of VIN 2 and VIN 3 were enrolled in this prospective study. Patients immunocompromised, with recurrent VIN, with well differentiated type VIN or VIN 1 and women treated more than once were excluded from the study. Patients were divided into two groups: group A was treated with Imiquimod, group B underwent surgical excision. Patients' characteristics analyzed were: age, smoking, degree of the primary lesion, state of margins, multifocal disease. We have evaluated the recurrence rate, the relapse rate, and the overall complete response, considering as recurrence the onset of a lesion after an initial complete response to Imiquimod and/or after the surgical treatment and as relapse all patients who had a recurrence plus those with medical treatment failure. RESULTS: Multifocal lesions (p = 0.03) and VIN 3 (p = 0.002) were associated with a higher risk of relapse. The recurrence rate was higher in the group B (p = 0.009), but the relapse rate was higher in the group A (p = 0.04). The overall complete response was better in the group B (p = 0.04). CONCLUSIONS: Although the advent of new medical options can decrease the morbidity associated with invasive surgical procedures, surgical treatments remain the best treatment modality for VIN with regard to relapse and overall complete response.

Gynecologic sarcoma: a clinico-pathological review.

Most of the cases showing good prognosis in literature are probably intermediate tumors between benign and malignant of undetermined malignant potential (UMP) and other tumors with intermediate features which are currently not considered among sarcomas. Misdiagnosis of a malignant lesion as a benign one has a tragic outcome for the patient. Best therapic choice for sarcomas remains surgery, while chemotherapy (CTX) and radiation therapy (RT) could be used in adjuvant settings. A major effort should be played in the understanding of biological features and behavior of the disease to address a better clinical practice. Uterine sarcomas are rare gynecological tumors; their incidence has been increasing during the last few years.

Fertility-sparing treatment of endometrial cancer precursors among young women: a reproductive point of view.

BACKGROUND: Early-stage endometrial cancer and complex atypical hyperplasia are treated with hysterectomy and bilateral salpingo-oophorectomy. An emerging issue among younger women affected is the possibility of a fertility-sparing treatment with progestative therapy and close follow-up. AIM: To assess the possibility of conceiving after a diagnosis of atypical endometrial hyperplasia among women younger than 40 years old, in term of delaying definitive treatment and achieving pregnancy. MATERIALS AND METHODS: 15 women younger than 40 years old with complex CAH or early carcinoma of the endometrium and a wish to preserve fertility. Progestins were administered orally for at least a 12 weeks period. Endometrial biopsies were used at follow-up. RESULTS: In 11 women, a complete pathological remission of the disease was observed. 4 pregnancies were attained in 4 women. 3 showed progression and underwent definitive surgery at 18 months. 1 showed no response at 24 months and 3 cycles and was counseled to receive a hysterectomy. CONCLUSIONS: A conservative approach in patients younger than 40 years appears a valid option, and a progestative therapy trial should be attempted whether a valid consensus is attained. Considering the risk to find AEH at biopsies and eventually a carcinoma at hysterectomy (25% of cases) a careful management is strictly required.

Spatiotemporal dynamics of single-letter reading: a combined ERP-FMRI study.

This work investigates the neural correlates of single-letter reading by combining event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI), thus exploiting their complementary spatiotemporal resolutions. Three externally-paced reading tasks were administered with an event-related design: passive observation of letters and symbols and active reading aloud of letters. ERP and fMRI data were separately recorded from 8 healthy adults during the same experimental conditions. Due to the presence of artifacts in the EEG signals, two subjects were discarded from further analysis. Independent Component Analysis was applied to ERPs, after dimensionality reduction by Principal Component Analysis: some independent components were clearly related to specific reading functions and the associated current density distributions in the brain were estimated with Low Resolution Electromagnetic Tomography Analysis method (LORETA). The impulse hemodynamic response function was modeled as a linear combination of linear B-spline functions and fMRI statistical analysis was performed by multiple linear regression. fMRI and LORETA maps were superimposed in order to identify the overlapping activations and the activated regions specifically revealed by each modality. The results showed the existence of neuronal networks functionally specific for letter processing and for explicit verbal-motor articulation, including the temporo-parietal and frontal regions. Overlap between fMRI and LORETA results was observed in the inferior temporal-middle occipital gyrus, suggesting that this area has a crucial and multifunctional role for linguistic and reading processes, likely because its spatial location and strong interconnection with the main visual and auditory sensory systems may have favored its specialization in grapheme-phoneme matching.

Tactile spatial working memory activates the dorsal extrastriate cortical pathway in congenitally blind individuals.

In sighted individuals, both the visual and tactile version of the same spatial working memory task elicited neural responses in the dorsal "where" cortical pathway (Ricciardi et al., 2006). Whether the neural response during the tactile working memory task is due to visually-based spatial imagery or rather reflects a more abstract, supramodal organization of the dorsal cortical pathway remains to be determined. To understand the role of visual experience on the functional organization of the dorsal cortical stream, using functional magnetic resonance imaging (fMRI) here we examined brain response in four individuals with congenital or early blindness and no visual recollection, while they performed the same tactile spatial working memory task, a one-back recognition of 2D and 3D matrices. The blind subjects showed a significant activation in bilateral posterior parietal cortex, dorsolateral and inferior prefrontal areas, precuneus, lateral occipital cortex, and cerebellum. Thus, dorsal occipito-parietal areas are involved in mental imagery dealing with spatial components in subjects without prior visual experience and in response to a non-visual task. These data indicate that recruitment of the dorsal cortical pathway in response to the tactile spatial working memory task is not mediated by visually-based imagery and that visual experience is not a prerequisite for the development of a more abstract functional organization of the dorsal stream. These findings, along with previous data indicating a similar supramodal functional organization within the ventral cortical pathway and the motion processing brain regions, may contribute to explain how individuals who are born deprived of sight are able to interact effectively with the surrounding world.

Neural correlates of spatial working memory in humans: a functional magnetic resonance imaging study comparing visual and tactile processes.

Recent studies of neural correlates of working memory components have identified both low-level perceptual processes and higher-order supramodal mechanisms through which sensory information can be integrated and manipulated. In addition to the primary sensory cortices, working memory relies on a widely distributed neural system of higher-order association areas that includes posterior parietal and occipital areas, and on prefrontal cortex for maintaining and manipulating information. The present study was designed to determine brain patterns of neural response to the same spatial working memory task presented either visually or in a tactile format, and to evaluate the relationship between spatial processing in the visual and tactile sensory modalities. Brain activity during visual and tactile spatial working memory tasks was measured in six young right-handed healthy male volunteers by using functional magnetic resonance imaging. Results indicated that similar fronto-parietal networks were recruited during spatial information processing across the two sensory modalities-specifically the posterior parietal cortex, the dorsolateral prefrontal cortex and the anterior cingulate cortex. These findings provide a neurobiological support to behavioral observations by indicating that common cerebral regions subserve generation of higher order mental representations involved in working memory independently from a specific sensory modality.

A compatible electrocutaneous display for functional magnetic resonance imaging application.

In this paper we propose an MR (magnetic resonance) compatible electrocutaneous stimulator able to inject an electric current, variable in amplitude and frequency, into the fingertips in order to elicit tactile skin receptors (mechanoreceptors). The desired goal is to evoke specific tactile sensations selectively stimulating skin receptors by means of an electric current in place of mechanical stimuli. The field of application ranges from functional magnetic resonance imaging (fMRI) tactile studies to augmented reality technology. The device here proposed is designed using safety criteria in order to comply with the threshold of voltage and current permitted by regulations. Moreover, MR safety and compatibility criteria were considered in order to perform experiments inside the MR scanner during an fMRI acquisition for functional brain activation analysis. Psychophysical laboratory tests are performed in order to define the different evoked tactile sensation. After verifying the device MR safety and compatibility on a phantom, a test on a human subject during fMRI acquisition is performed to visualize the brain areas activated by the simulated tactile sensation.

Occult ligamentous injury of the cervical spine.

Evaluating the cervical spine for injury is an essential part of the assessment of a traumatized patient. Clinical examination and radiographs are the traditional techniques used for this evaluation. Often, however, a reliable clinical examination is not possible because of head injury, altered mental status, or "distracting" injuries. In such cases, cervical spine injury that is not apparent on radiographs may be missed. This case report illustrates a purely ligamentous cervical spine injury resulting in cervical instability. We describe our method of screening for and evaluating these types of injuries using physician-controlled stretch, flexion, and extension examination under fluoroscopy.

Anti-HBs responses in children vaccinated with different schedules of either plasma-derived or HBV DNA recombinant vaccine.

This study evaluated the immunogenic and protective effects of plasma-derived and DNA recombinant anti-hepatitis B virus vaccines administered to infants at various ages and with different vaccination schedules: 3 monthly doses in the first 3 months of life, 3 doses (at 3, 5 and 11 months) or 2 doses (at 1 and 3 months) or 2 doses (at 3 and 5 months). Anti-HBs (hepatitis B surface) and anti-HBc (hepatitis B core) markers were investigated twice: one month and ten years after vaccination in 261 children immunized with plasma-derived vaccine, and one month and five years after vaccination in 449 children immunized with DNA recombinant vaccine. In all groups, the appearance of anti-HBs protective levels one month after vaccination and their persistence in the following years were found in a larger number of subjects when the vaccine doses had been administered after the third month of life rather than in the first three months. Moreover, our results show that the reappearance of surface antibodies a week after the booster, in vaccinated children who became anti-HBs- in the years following vaccination, occurred in a larger number of subjects when the primary vaccination with 3 doses had been performed in the first quarter or with 2 or 3 doses in the second quarter. In contrast, protective levels of anti-HBs were found in a small number of children belonging to the group vaccinated with 2 doses in the first three months, and among them the majority seroconverted only one month after the booster. Anti-HBc was found 10 years after vaccination in only one child immunized with 2 doses of plasma-derived vaccine, and 5 years after vaccination in two children immunized with 2 doses of DNA recombinant vaccine. All these children were found to lose anti-HBs, and none of them had signs of disease or became a carrier. Based on these results, the disappearance, in some children, of protective levels of anti-HBs in the years following vaccination does not mean the loss of anti-HBV protection. In fact, the trial showed that they reacted immediately to booster stimulation, demonstrating a solid immunologic memory. Therefore, there may be no reason for giving booster injections when the vaccination of infants is carried out correctly.