Hybrid cooperative complexes to decrease VAS score and enhance sexual function in women with vulvar lichen sclerosus.

OBJECTIVE: Lichen sclerosus is a chronic, inflammatory, progressive skin disease predominantly affecting anogenital areas. Vulvar lichen sclerosus (VLS) is one of the most common conditions treated in vulvar clinics; most patients report distressing symptoms of itching, burning, stinging, and pain (particularly during or after sexual intercourse). A preliminary, prospective, single-center study was performed to investigate the efficacy of hyaluronan hybrid cooperative complex (HCC) comprising high and low molecular weight hyaluronic acid to treat menopausal women with VLS. PATIENTS AND METHODS: Patients (N = 30) received two HCC injections at 32 mg/ml (one month apart). At baseline and one and six months after treatment, patients completed validated psychometric questionnaires to assess their self-reported pain, itching, and dryness using the Visual Analogue Scale (VAS) and sexual function by the Female Sexual Function Index (FSFI). RESULTS: After treatment with HCC, no side effects or complications were reported. VAS scores showed a trend towards reduced pain and itching intensity, and there was a statistically significant reduction in median VAS score for dryness at follow-up vs. baseline (p=0.038). For sexual function, there was a statistically significant improvement in lubrication (p=0.001) and orgasm (p=0.001) FSFI domains. CONCLUSIONS: Overall, this preliminary study demonstrated the promising efficacy of HCC in menopausal women with VLS without side effects.

Platelet-rich plasma for genital lichen sclerosus: analysis and results of 94 patients. Are there gender-related differences in symptoms and therapeutic response to PRP?

BACKGROUND: Lichen sclerosus is a chronic relapsing inflammatory dermatosis with a predilection for anogenital skin in 85%-98% of cases and is more prevalent in women (3%) than in men (> 0.07%). OBJECTIVES: The purpose of this study was to investigate gender differences in clinical presentation and therapeutic response to treatment with platelet-rich plasma (PRP), an emerging innovative strategy for LS. METHODS: Forty-three male and 51 female patients affected by LS were evaluated. Each patient was subjected to PRP treatment (1 infiltration every 15 days, for 3 times). RESULTS: The PRP procedure was well tolerated by all patients and an overall significant decrease in symptoms was reported 6 months after PRP infiltration. Reduction in pain and burning sensation was significant in both gender but more accentuated in women than in men, whereas reduction of itching was similar. On the contrary, dyspareunia evidenced sex-related difference since a significant diminution was observed only in male. CONCLUSIONS: This study demonstrates that PRP based therapy may exert a relevant role in LS patient management due to its effect on Quality of Life (QoL) and sexual function in both gender. In addition, the study underlined gender-related differences in severity of symptoms and disease age onset.

Cardiovascular outcome in asymptomatic hemodialysis patients submitted to aggressive medical therapy: results of a four-year follow-up.

AIM: Cardiovascular disease is a leading cause of morbidity and mortality in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Neither traditional nor emerging risk factors for cardiovascular disease can explain completely this excess of morbidity and mortality and the role and timing of primary prevention strategies in this population has not been clarified. The aim of this study was to assess if an aggressive pharmacological preventive treatment may reduce the myocardial ischemic burden and then improve the cardiovascular outcome In ESRD patients. METHODS: Forty-three asymptomatic ESRD patients on maintenance HD were evaluated. Asymptomatic patients with neither history nor clinical evidence of cardiovascular disease were considered. A total of 31 ESRD patients were enrolled into the study and were submitted to Tc-99m SESTAMIBI myocardial gated- single-photon emission computed tomography (SPECT) stress test. All patients then received an aggressive medical regimen with statins, antiplatelet drugs, ACE inhibitors (ACE-I) and/or Angiotensin II Receptor Blockers (ARB) and other hypotensive, glucose-lowering medications, sevelamer, calcium carbonate and calcitriol if required. RESULTS: A significant reduction of coronary functional reserve was found in more than 50% of otherwise asymptomatic HD patients and may often be reverted by prolonged aggressive medical therapy. After a four-year follow-up under aggressive medical therapy no significant difference was observed neither in the incidence of conventional and emerging cardiovascular risk factors nor in cardiovascular outcome of patients with or without silent myocardial ischemia (SMI). CONCLUSION: As cardiovascular disease (CVD) is by far the first cause of death in ESRD, an aggressive medical management may be highly advisable for the primary prevention of major adverse cardiac events in all HD patients despite the stress test evidence of inducible myocardial ischemia .

Usefulness of video thermography in the evaluation of platelet-rich plasma effectiveness in vulvar lichen sclerosus: preliminary study.

BACKGROUND: Lichen sclerosus (LS) is a chronic-relapsing and potentially serious skin disease that has a preference for genital skin. Currently, there is no standardized method for assessing the effects of therapies. OBJECTIVE: The objective of this preliminary study is to use video thermography (VTG) in the evaluation of vulvar lichen sclerosus (VLS) before and after platelet-rich plasma (PRP) therapy. METHODS: A sample of six female patients was enrolled. Patients were subjected to PRP treatment. Patients selected for the study had been assessed at baseline (T0) and after 7 and 30 d from PRP treatment (T1 and T2, respectively). Clinical and VTG evaluation was executed in every visit. RESULTS: The VTG examination showed at least one hypothermic area (HA) in all our patients. The average temperature measured in the vulvar and perineal region taken as a reference for each patient was found to be between 33.7 °C and 36.3 °C, with a fair difference between the patients. HAs showed thermal differences which varied between 2.2 °C and 1.2 °C. CONCLUSIONS: It is demonstrated here that PRP offers satisfactory effectiveness in treating VLS and that video thermograpy could represent a useful paraclinic method in the identification and follow-up of LS.

Role of ion exchange membranes and capacitive electrodes in membrane capacitive deionization (MCDI) for CO2 capture.

Recently we showed that membrane capacitive deionization (MCDI) can be used to capture CO2, but we found that the performance decreases with decreasing current density. In the present study, we investigate the effect of electrodes and ion exchange membranes by performing experiments with two membranes (CO2-MCDI), with one membrane (cation or anion exchange membrane), and without membranes (CO2-CDI). We find that the anion exchange membrane is essential to keep high CO2 absorption efficiencies ( [Formula: see text] /ncharge), while the absorption efficiency of the CO2-CDI cell was lower than expected (Λa≈0.5 for CO2-MCDI against Λa≈0.18 for CO2-CDI). Moreover, we theoretically investigate ion adsorption mechanisms in the electrodes by comparing experimental data of a CO2-CDI cell with theoretical results of the classic amphoteric-Donnan model developed for conventional CDI. By comparing the experimental results with the amph-D model, we find that the model overestimates the absorption efficiency in CO2-CDI experiments. To understand this discrepancy, we investigate the effects of other phenomena, i.e., (i) low ion concentration, (ii) passive CO2 absorption, and (iii) the effect of acid-base reactions on the chemical surface charge.

Extracellular recordings from locally dense microelectrode arrays coupled to dissociated cortical cultures.

High-density microelectrode arrays (MEAs) enabled by recent developments of microelectronic circuits (CMOS-MEA) and providing spatial resolutions down to the cellular level open the perspective to access simultaneously local and overall neuronal network activities expressed by in vitro preparations. The short inter-electrode separation results in a gain of information on the micro-circuit neuronal dynamics and signal propagation, but requires the careful evaluation of the time resolution as well as the assessment of possible cross-talk artifacts. In this respect, we have realized and tested Pt high-density (HD)-MEAs featuring four local areas with 10microm inter-electrode spacing and providing a suitable noise level for the assessment of the high-density approach. First, simulated results show how possible artifacts (duplicated spikes) can be theoretically observed on nearby microelectrodes only for very high-shunt resistance values (e.g. R(sh)=50 kOmega generates up to 60% of false positives). This limiting condition is not compatible with typical experimental conditions (i.e. dense but not confluent cultures). Experiments performed on spontaneously active cortical neuronal networks show that spike synchronicity decreases by increasing the time resolution and analysis results show that the detected synchronous spikes on nearby electrodes are likely to be unresolved (in time) fast local propagations. Finally, functional connectivity analysis results show stronger local connections than long connections spread homogeneously over the whole network demonstrating the expected gain in detail provided by the spatial resolution.

[Cytomegalovirus and BK polyomavirus infection after renal transplantation]. / Infezione da citomegalovirus (CMV) e da polioma BK virus (BKV) dopo trapianto di rene.

Cytomegalovirus (CMV) and BK polyomavirus (BKV) infections have been described in a high percentage of renal transplant patients and are known to cause various complications in renal transplantation. They are closely related to immunosuppressive therapy and implicated in the progression of graft failure. This review focuses on the clinical aspects of CMV and BKV infection after renal transplantation, optimal monitoring, and recent preventive measures and interventions to improve graft function and recipient survival.

[Merkel cell carcinoma and sentinel lymph node dissection: nine cases report]. / Carcinoma a cellule di Merkel e linfonodo sentinella: osservazioni su nove casi clinici.

Merkel cell carcinoma (MCC) is an aggressive cutaneous-neuroendocrine neoplasia with poor prognosis and high propensity for locoregional and distant metastasis. Lack of knowledge about its biological behavior, pathogenesis, and prognostic factors, complicates the prospective evaluation. Sentinel node dissection, concomitant with radical excision of the lesion, has increased in the last few years. The suitability of this technique is linked to the MCC high tendency to spread "in primis" at locoregional nodes such as other malignancies such as cutaneous melanoma. Aim of the study is the prospective evaluation of the sentinel node dissection and of the adjuvant therapies in 9 patients MCC affected. All patients, underwent evaluation and staging of the neoplasia. Diagnosis was made by excisional biopsy and histological examination. Sentinel node dissection was performed in patients without clinical locoregional metastases (8 cases). Patients with sentinel node positive for metastasis underwent radical lymphadenectomy (3 cases). One patient affected by clinically locoregional metastases had, at once, radical lymphadenectomy. Radiotherapy and/or chemotherapy as adjuvant therapy were implemented (4 cases).

[A case of vulvar melanoma: surgical strategy and five years follow-up]. / Un caso di melanoma vulvare: strategia chirurgica e follow-up a 5 anni.

We report a case of a woman with vulvar melanoma, arisen from a plane melanocytic lesion, extended from clitoris to the left minor labium. After diagnostic biopsy, a preoperative lymphoscintigraphy with 99m-Tc nanocolloid was performed. Surgery consisted in a radical vulvectomy, radio-controlled lymphadenectomy and vulvar reconstruction by two bilateral subgluteus soft-tissue flaps, anastomosing the urethral and vaginal stumps. Five years follow-up was negative for neoplastic recurrence.

An organic neurophysiological tool for neuronal metabolic activity monitoring.

Monitoring cell metabolism in vitro is considered a relevant methodology in several scientific fields ranging from fundamental biology research to neuro-toxicology. In the last 20 years, several in vitro neuro-pharmacological and neuro-toxicological approaches have been developed, with the intent of addressing the increasing demand for real-time, non-invasive in vitro systems capable of continuously and reliably monitoring cellular activity. In this paper, an Organic Charge Modulated Field Effect Transistor-based device is proposed as a promising tool for neuro-pharmacological applications, thanks to its ultra-high pH sensitivity and a simple fabrication technology. The preliminary characterization of this versatile organic device with primary neuronal cultures shows how these remarkable properties can be exploited for the realization of ultra-sensitive metabolic probes, which are both reference-less and low cost. These features, together with the already assessed capability of this sensor to also monitor the electrical activity of electrogenic cells, could provide important advances in the fabrication of multi-sensing lab-on-chip devices, thus opening up interesting perspectives in the neuro-pharmacological field.

Renal resistive index and cardiovascular organ damage in a large population of hypertensive patients.

We evaluated the relationship between renal resistive index (RRI) of the intrarenal vasculature and cardiovascular (CV) organ damage such as left ventricular hypertrophy (LVH), diastolic dysfunction and carotid atherosclerosis in a large sample of hypertensive patients. 566 hypertensive patients underwent echocardiography with conventional Doppler and Doppler tissue imaging (DTI), carotid and renal ultrasonography. In addition, lipids profile, creatinine in serum, and urinary albumin concentrations were determined. The patients were divided according to their RRI values in 2 groups: <70 and >or=70. Subjects with high RRI were older, had higher systolic and pulse pressure (PP) and more years of hypertension, compared to those with low RRI (P<0.0001). Patients with the higher RRI showed an increased left ventricular mass index (LVMI) and carotid intima-media thickness (IMT) with a higher prevalence of LVH, carotid plaques and microalbuminuria (P<0.001). There were differences in overall diastolic parameters, in particular when evaluated by DTI (P<0.001). A positive correlation was found between RRI and age, PP, carotid IMT, LVMI, SBP and a negative correlation was found with DTI diastolic parameters (P<0.001). Age, PP, carotid IMT and LVMI were independently related to RRI. While, RRI was independently related to IMT and IVRT. RRI, especially the higher values, are positively correlated with target organ damage in hypertensive patients, indicating that renal vascular resistance is related to morphologic and hemodynamic alteration of the CV system. The evaluation of RRI could predict the presence of early CV damage and provide an accurate estimate of overall risk.

Vulvar primitive melanoma and sentinel lymph node: case report.

The case of a 54-year-old woman who developed vulvar melanoma arising from a melanocytic lesion, extending from the clitoris to the left labium minor, without clinical involvement of the groin node station bilaterally is presented. The patient first underwent an incisional diagnostic biopsy that revealed a melanoma 4 mm in thickness; subsequently preoperative lymphoscintigraphy with 99m Tc Nanocoll was executed. Surgery consisted of a radio-controlled lymphadenectomy and radical vulvectomy. Two bilateral subgluteus soft-tissue flaps were made to reconstruct the surgical defect, anastomosing the urethral and vaginal stump. At 36 months follow-up the patient was negative for neoplastic recurrence.

Work capacity and oxygen uptake abnormalities in hyperthyroidism.

AIM: The aim of our study was to evaluate the haemodynamic and the respiratory response to exercise in patients with hyperthyroidism before and 30 days after normalized thyroid hormones levels. These findings were compared with those of 10 control patients. METHODS: Thirty patients (23 women, aged 34.3 +/- 12 years) with untreated hyperthyroidism were studied. Twenty-four patients were treated with methimazole, 13 of which were also treated with propranolol. Six patients underwent surgery. A symptom-limited cardiopulmonary exercise test and an echocardiography were performed in all patients. RESULTS: At rest patients with hyperthyroidism showed at echocardiography an increased cardiac index (P = 0.006 vs euthyroid, P = 0.007 vs normal) and a higher ejection fraction (P = 0.008 vs euthyroid, P = 0.007 vs normal). The duration of the exercise was lower in hyperthyroid patients (P = 0.006 vs euthyroid; P = 0.0068 vs normal). Anaerobic threshold was reached at 49.6% of peak VO2 during hyperthyroidism, at 60.8% during euthyroidism (P = 0.01) and at 62% in normal (P = 0.01). Work rate was lower in patients with hyperthyroidism at anaerobic threshold (P = 0.01 vs euthyroid, P = 0.03 vs normal) and at maximal work (P = 0.001 vs euthyroid, P = 0.01 vs normal). Patients in hyperthyroidism showed a lower increment of heart rate between rest and anaerobic threshold (P = 0.021 vs euthyroid, P < 0.0001 vs normal) and a lower VO2 at anaerobic threshold (P = 0.03 vs euthyroid; P = 0.04 vs normal). Oxygen pulse at anaerobic threshold was significantly reduced in hyperthyroidism (P = 0.04 vs euthyroid, P = 0.005 vs normal). CONCLUSIONS: The mean result is that after only 30 days of appropriate antithyroid treatment there was an appreciable improvement of exertion capacity.

Correlation between tumor-associated glycoprotein 72 mucin levels in tumor and serum of colorectal patients as measured by the quantitative CA 72-4 immunoassay.

Colorectal tissue biopsies were obtained from 110 patients diagnosed with primary colorectal carcinoma (tumor and normal colonic mucosa samples), 20 patients diagnosed with benign colorectal disease, and 31 healthy donors. The level of expression of tumor-associated glycoprotein 72 (TAG-72) was quantitatively measured in each sample using a double-determinant RIA with monoclonal antibodies B72.3 and CC49 and detecting the sialyl-Tn epitope; this assay was termed CA 72-4. Statistical analysis revealed a significant (approximately 10-fold) increase of TAG-72 expression in the colon tumor biopsies when compared with the expression in normal colonic mucosa from the same patients. A regression analysis revealed a significant correlation (r = 0.459; P < 0.001) between TAG-72 levels measured in biopsies from the tumor lesions and those found in the corresponding normal colonic mucosa. Furthermore, regression analysis showed a significant positive correlation between TAG-72 levels in the tumors and sera of the same patients (r = 0.491; P < 0.001). TAG-72 levels in normal colonic mucosa from healthy donors and patients diagnosed with colorectal cancer were compared. TAG-72 expression was 5-fold higher in the normal mucosa from the colorectal carcinoma patients. No relationship between TAG-72 tumor tissue content and stage of disease was found. Moreover, the correlation between TAG-72 distribution and degree of tumor differentiation observed (P < 0.05) was not any more evident when mucinous carcinomas were excluded. Finally, the results provide further evidence that TAG-72 may be considered an important early marker for colorectal cancer and/or other dysplastic colonic diseases. The statistical correlation between TAG-72 levels in tumors and circulating TAG-72 indicates that patients with elevated levels of serum TAG-72, as measured by the CA 72-4 assay, would be most suited for diagnostic and/or therapeutic intervention with the anti-TAG-72 monoclonal antibodies B72.3 or CC49 or vaccine trials using the sialyl-Tn epitope.

Arctic cut-off high drives the poleward shift of a new Greenland melting record.

Large-scale atmospheric circulation controls the mass and energy balance of the Greenland ice sheet through its impact on radiative budget, runoff and accumulation. Here, using reanalysis data and the outputs of a regional climate model, we show that the persistence of an exceptional atmospheric ridge, centred over the Arctic Ocean, was responsible for a poleward shift of runoff, albedo and surface temperature records over the Greenland during the summer of 2015. New records of monthly mean zonal winds at 500 hPa and of the maximum latitude of ridge peaks of the 5,700±50 m isohypse over the Arctic were associated with the formation and persistency of a cutoff high. The unprecedented (1948-2015) and sustained atmospheric conditions promoted enhanced runoff, increased the surface temperatures and decreased the albedo in northern Greenland, while inhibiting melting in the south, where new melting records were set over the past decade.

Diagnostic and prognostic value of peritoneal immunocytology in gastric cancer.

PURPOSE: Among the clinical factors with a pivotal role in the prediction of outcome for patients with gastric cancer, intraperitoneal (i.p.) microscopic dissemination may represent an important cause of recurrences, even in the early stages of the disease. In this context, the cytologic examination of intraoperative peritoneal washings may be essential to identify metastatic free cells, although a number of false-negative cases may be encountered. PATIENTS AND METHODS: To determine whether immunocytochemical (ICC) methods that used a panel of three monoclonal antibodies (MoAbs), B72.3, AR3, and BD5, directed to gastric cancer-associated antigens can improve peritoneal cytology by providing more accurate prognostic indications, we immunocytochemically and morphologically evaluated 144 peritoneal washings sampled from patients surgically treated for gastric cancer. RESULTS: The ICC analysis allowed the identification of metastatic free peritoneal cells in 35% of the patients, with a 14% improvement over routine cytopathology (P < .0001). Furthermore, a 54-month survival analysis by Kaplan-Meier curves showed a statistically significant decrease in overall survival (OS) in patients with stages I through III disease with peritoneal microscopic disease detected morphologically and/or by ICC at the time of the primary surgery. CONCLUSION: Our data indicate that the use of a combination of selected MoAbs may allow the identification of cytologically false-negative cases that provide valuable prognostic information. This may be useful to stratify patients on more adequate therapeutic trials.

In vitro cortical neuronal networks as a new high-sensitive system for biosensing applications.

By taking advantages of the main features of the microelectrode array (MEA) technology (i.e. multisite recordings, stable and long-term coupling with the biological preparation), we analyzed the changes in activity patterns induced by applying specific substances to dissociated cortical neurons from rat-embryos (E18). Data were recorded simultaneously from 60 electrodes, and the electrophysiological behavior was investigated during the third week in vitro, both at the spike and burst level. The analysis of the electrophysiological activity modulation, by applying agonists of the ionotropic glutamate receptors at low (i.e. 0.2-1-5 microM) and high (i.e. 50-100 microM) concentrations, is presented. Preliminary results show that the dynamics of the in vitro cortical neurons is very sensitive to pharmacological manipulation of the glutamatergic transmission and the effects on the network behavior are strictly dependent from the drug concentration. In particular, the addition of a high-dose of agonist determined a global and irreversible depression of the network activity, while, in the low-concentration case, the electrophysiological behavior showed different results, depending on the type of receptor involved. From these observations, we are encouraged to think of a more engineered system, based on in vitro cortical neurons, as a novel sensitive system for drug (pre)-screening and neuropharmacological evaluations.

An organic transistor-based system for reference-less electrophysiological monitoring of excitable cells.

In the last four decades, substantial advances have been done in the understanding of the electrical behavior of excitable cells. From the introduction in the early 70's of the Ion Sensitive Field Effect Transistor (ISFET), a lot of effort has been put in the development of more and more performing transistor-based devices to reliably interface electrogenic cells such as, for example, cardiac myocytes and neurons. However, depending on the type of application, the electronic devices used to this aim face several problems like the intrinsic rigidity of the materials (associated with foreign body rejection reactions), lack of transparency and the presence of a reference electrode. Here, an innovative system based on a novel kind of organic thin film transistor (OTFT), called organic charge modulated FET (OCMFET), is proposed as a flexible, transparent, reference-less transducer of the electrical activity of electrogenic cells. The exploitation of organic electronics in interfacing the living matters will open up new perspectives in the electrophysiological field allowing us to head toward a modern era of flexible, reference-less, and low cost probes with high-spatial and high-temporal resolution for a new generation of in-vitro and in-vivo monitoring platforms.