Dynamic Contrast-Enhanced MR Imaging Evaluation of Perfusional Changes and Ablation Zone Size after Combination Embolization and Ablation Therapy.

PURPOSE: The objectives of this study were to assess the utility of dynamic contrast-enhanced magnetic resonance (MR) imaging in quantifying parenchymal perfusional changes after embolization and to characterize the association between pharmacokinetic (PK) parameters and final microwave ablation volume. MATERIALS AND METHODS: PK parameters from dynamic contrast-enhanced MR imaging were used to quantify perfusional changes in the liver after transarterial embolization of the right or left lobe in a swine liver model (n = 5). Each animal subject subsequently underwent microwave ablation (60 W for 5 minutes) of the embolized and nonembolized liver lobes. Changes in PK parameters from dynamic contrast-enhanced MR imaging were correlated with their respective final microwave ablation volumes in each liver lobe. RESULTS: Microwave ablation volumes of embolized liver lobes were significantly larger than those of nonembolized liver lobes (28.0 mL ± 6.2 vs 15.1 mL ± 5.2, P < .001). PK perfusion parameters were significantly lower in embolized liver lobes than in nonembolized liver lobes (Ktrans = 0.69 min-1 ± 0.15 vs 1.52 min-1 ± 0.37, P < .001; kep = 0.69 min-1 ± 0.19 vs 1.54 min-1 ± 0.42, P < .001). There was a moderate but significant correlation between normalized kep and ablation volume, with each unit increase in normalized kep corresponding to a 9.8-mL decrease in ablation volume (P = .035). CONCLUSIONS: PK-derived parameters from dynamic contrast-enhanced MR imaging can be used to quantify perfusional changes after transarterial embolization and are directly inversely correlated with final ablation volume.

Reduced failure rates associated with playing a new online game developed to support learning of core content in human systems physiology.

A digital mobile card-matching game called eFlip was developed to assist second-year undergraduate medical science students to learn core content and understand key associations in physiology. Our team developed customized content of core physiological associations, of increasing difficulty, for upload on a generic card-matching platform. The generic game was extended with add-ons coded to allow identification and access of student usage data for students who consented to have their game usage linked to academic performance such as final course marks and grades. Here, we describe the development of the eFlip game content, the student usage profile, and the game's impact on learning. Students were invited to use eFlip prior to and during the final examination period. Of those who used eFlip, 152 students consented to participate in a study of game use on learning performance outcomes. Within the students who consented, 74 played the game and 78 did not play the game (nonplayers). The mean course mark of the students who played the game [69.57%; 95% confidence level (CI) (67.22, 71.92)] was higher than that of the nonplayers [65.33%; 95% CI (62.67, 67.99)] (P = 0.02). Playing eFlip was also associated with reduced failure rates in students who played the game (1% failure rate) compared with the students who did not play the game (10% failure rate; P = 0.02). The number of games played by students peaked just prior to the course final examination. Overall, students who chose to play eFlip demonstrated improved grades that were associated with a higher probability of passing the physiology course.

Efficacy and safety of 5-hydroxytryptophan on depression and apathy in Parkinson's disease: a preliminary finding.

BACKGROUND AND PURPOSE: Several studies have indicated that altered serotonergic neurotransmission may contribute to non-motor features commonly associated with Parkinson's disease (PD) such as apathy and depression. 5-hydroxytryptophan (5-HTP) is the intermediate metabolite of L-tryptophan in the production of serotonin. To date, there has been inconsistent research on the use of 5-HTP in PD. The purpose of this study was to compare the effects of 5-HTP with those of placebo on apathy and depressive symptoms in patients with PD. METHODS: A single-center, randomized, double-blind placebo-controlled cross-over trial was employed; 25 individuals were subsequently enrolled into the study. Patients received placebo and 50 mg of 5-HTP daily over a period of 4 weeks. For the assessment of efficacy on depressive and apathy symptoms the Beck Depression Inventory-II (BDI-II), Hamilton Depression Rating Scale (HDRS) and Apathy Scale (AS) were respectively administered at screening, baseline and weeks 4, 8, 12 and 16. Primary efficacy outcomes were the comparison of 5-HTP to placebo in mean change from baseline to weeks 4, 8, 12 and 16 in total score on the AS, BDI-II and HDRS. RESULTS: Repeated-measures analysis revealed a significant improvement of depressive symptoms during the 50-mg 5-HTP treatment compared with placebo as assessed by the HDRS. No effect of 5-HTP was seen on apathy symptoms assessed by the AS. CONCLUSIONS: This study provides preliminary evidence of clinical benefit of 5-HTP for treating depressive symptoms in PD. Larger studies with a longer treatment duration are needed to corroborate these early findings.

4D Flow MR Imaging to Improve Microwave Ablation Prediction Models: A Feasibility Study in an In Vivo Porcine Liver.

PURPOSE: To characterize the effect of hepatic vessel flow using 4-dimensional (4D) flow magnetic resonance (MR) imaging and correlate their effect on microwave ablation volumes in an in vivo non-cirrhotic porcine liver model. MATERIALS AND METHODS: Microwave ablation antennas were placed under ultrasound guidance in each liver lobe of swine (n = 3 in each animal) for a total of 9 ablations. Pre- and post-ablation 4D flow MR imaging was acquired to quantify flow changes in the hepatic vasculature. Flow measurements, along with encompassed vessel size and vessel-antenna spacing, were then correlated with final ablation volume from segmented MR images. RESULTS: The linear regression model demonstrated that the preablation measurement of encompassed hepatic vein size (ß = -0.80 ± 0.25, 95% confidence interval [CI] -1.15 to -0.22; P = .02) was significantly correlated to final ablation zone volume. The addition of hepatic vein flow rate found via 4D flow MRI (ß = -0.83 ± 0.65, 95% CI -2.50 to 0.84; P = .26), and distance from antenna to hepatic vein (ß = 0.26 ± 0.26, 95% CI -0.40 to 0.92; P = .36) improved the model accuracy but not significantly so (multivariate adjusted R2 = 0.70 vs univariate (vessel size) adjusted R2 = 0.63, P = .24). CONCLUSIONS: Hepatic vein size in an encompassed ablation zone was found to be significantly correlated with final ablation zone volume. Although the univariate 4D flow MR imaging-acquired measurements alone were not found to be statistically significant, its addition to hepatic vein size improved the accuracy of the ablation volume regression model. Pre-ablation 4D flow MR imaging of the liver may assist in prospectively optimizing thermal ablation treatment.

Physician experts in diabetes are natural team leaders for managing diabetic patients with foot complications. A position statement from the Italian diabetic foot study group.

Diabetic foot syndrome (DFS) is a complex disease. The best outcomes are reported with the multi-disciplinary team (MDT) approach, where each member works collaboratively according to his/her expertise. However, which health provider should act as the team leader (TL) has not been determined. The TL should be familiar with the management of diabetes, related complications and comorbidities. He/she should be able to diagnose and manage foot infections, including prompt surgical treatment of local lesions, such as abscesses or phlegmons, in an emergent way in the first meeting with the patient. According to the Organization for Economic Co-operation and Development (OECD) reports, Italy is one of countries with a low amputation rate in diabetic patients. Many factors might have contributed to this result, including 1)the special attention directed to diabetes by the public health system, which has defined diabetes as a "protected disease", and accordingly, offers diabetic patients, at no charge, the best specialist care, including specific devices, and 2)the presence of a network of diabetic foot (DF) clinics managed by diabetologists with medical and surgical expertise. The health care providers all share a "patient centred model" of care, for which they use their internal medicine background and skills in podiatric surgery to manage acute or chronic needs in a timely manner. Therefore, according to Italian experiences, which are fully reported in this document, we believe that only a skilled diabetologist/endocrinologist should act as a TL. Courses and university master's degree programmes focused on DF should guarantee specific training for physicians to become a TL.

Species diversity and molecular insights into phlebotomine sand flies in Sardinia (Italy)-an endemic region for leishmaniasis.

This study provides updated information on the distribution of the phlebotomine sand fly species and their genetic characterization in Sardinia, a Mediterranean island where leishmaniasis is endemic. From April to November 2017, sand flies were trapped in five different capture sites using sticky traps and light traps as collection methods, operated nearby sheep, poultry, cat, and dog shelters. Phlebotomine specimens (n = 513) collected were morphologically and molecularly identified as Phlebotomus perniciosus (249/513, 48.5%), Phlebotomus perfiliewi (236/513; 46%), and Sergentomyia minuta (28/513, 5.5%). Sand flies were collected from the second half of May to October confirming the well-defined seasonal activity, which peaks in August in Sardinia. Overall, correlation analyses indicated a significant positive association between the monthly number of sand flies collected and the mean temperature (r = 0.88, rho = 0.87, and tau = 0.69, P < 0.05), while there was non-significant, moderately negative correlation between the monthly number of sand flies collected and the monthly mean relative humidity and wind (r = - 0.22, rho = 0.02, and tau = 0.04, P > 0.05). This study provides the first data on the molecular characterization of phlebotomine sand flies in this region and confirms the presence of three sand fly species. Molecular results suggest that the morphological features used for analysis represent synapomorphic-derived characters which are shared among descendant taxa and the common ancestor.

Amino acid and hyaluronic acid mixtures differentially regulate extra cellular matrix genes in cultured human fibroblasts.

The aim of this screening study was to evaluate the efficacy of different proprietary mixtures of amino acid and hyaluronic acid (HA) in stimulating the production of extracellular matrix (ECM) components, particularly the neo-synthesis of elastin, and in promoting a more efficient deposition of elastic fibres (elastogenesis), while at the same time maintaining the stimulation of collagen. The study has allowed identification of the optimal ratios between the amino acids (AA) for the production of collagen and elastin. Human primary dermal fibroblasts from a 44-year-old female donor were used as a test system in an experimental design based on the evaluation of the expression of relevant ECM genes using a transcriptomic dynamic approach. The expression of ECM genes was evaluated by RTqPCR from 24 to 120 hours in the presence of the test items. Moreover, the production of ECM proteins was verified by Western blot analysis after a 120 h treatment period. In addition to elastin, collagen IV, a fundamental structural component of the basal lamina responsible for epithelial and connective tissue anchoring, was analysed as potential target for the modulation of ECM protein production by human fibroblast. The first phase of the study demonstrated that alanine and valine are essential to promote production of elastin, of which they are important constituents. The second phase of the study, which was conducted to clarify the interactions between the different clusters of AA, demonstrated that it is necessary to choose a mixture that contains specific amounts of amino acids of both proteins, collagen and elastin, to give a significant response and a significant production of both. This also proves the existence of a ratio between the 2 clusters (AA elastin/AA collagen) that guarantees an adequate and balanced response to gene expression and production by fibroblasts, collagen and elastin. The study has allowed identification of the optimal ratios between the AA for the production of collagen and elastin.

Microwave ablation of hepatic tumors with a third generation system: loco­regional efficacy in a prospective cohort study with intermediate term follow-up.

PURPOSE: To evaluate the safety and intermediate-term efficacy of percutaneous microwave ablation (MWA) in primary and secondary liver tumors using a third generation MWA device, under ultrasound guidance. PATIENTS AND METHODS: Sixty-two patients (median age 74 years, 73 % males) with 69 liver tumors were enrolled in this prospective observational study. Forty-seven patients (76 %) had hepatocellular carcinoma (HCC) and 15 (24 %) metastases. Median follow-up was 3.6 years. RESULTS: Median tumor diameter at contrast enhanced computed tomography was 23 mm (I-III quartiles, 18 - 31 mm). All procedures were performed percutaneously using a 2.45 GHz generator. Median ablation time was 10 minutes (I-III quartiles, 10 - 14 minutes). A single percutaneous antenna insertion was performed for 56/69 (81 %) of the tumors. Technical success was obtained in all tumors. Primary efficacy at 24 hours was achieved in 68/69 (99 %) tumors. The overall one-year cumulative local tumor progression rate was 15.1 % (95 % CI, 7.7 - 24.8 %) with no significant difference between HCC and metastases (p = 0.26). There was one procedure-related mortality (1.6 %) and one major bleeding (1.6 %). CONCLUSION: Microwave ablation is a valid option for thermal ablation of HCC and liver metastases with comparable complication rate to other local ablative procedures.

Dose-Response Effects on LBP, Sleep, and Depression of Online Pre-Partum and Post-Partum Pilates-Based Programs.

Purpose: Pilates-based programs can help pregnant women deal with the physical and psychological burden derived by major changes in their body. This study was designed to primarily test, in pregnant women, the dose-response and health effects of both pre-partum and post-partum, online Pilates-based program on weight control, low back pain (LBP) severity, sleep disturbances, mood and depression levels. Methods: A total of 136 pregnant women were screened for eligibility (low-risk pregnancy; aged 18-45 years; single pregnancy; 20-28-week gestational age, normal BMI). Participants completed an online Pilates-based program during pregnancy and after delivery, through an online platform guided by a Pilates, Yoga and Lagree certified instructor. Main outcomes (weight control, LBP disability, sleep quality, mood, and mental health) were assessed at baseline and at the completion of pre- and post-partum programs. Results: Regarding pre-partum, significant gains in weight were observed only in low- and intermediate-amount exercisers. Only high-amount exercisers did not display significant increase in LBP-related disability (+42.7%; p = .21) unlike low (+12.2%; p < .0001) and intermediate exercisers (+9.6%; p < .0001). Sleep disturbances increased significantly in low- (+24.3%; p = .005) but not in intermediate- (+4.6%; p = .50) and high-amount exercisers (-0.1%; p = .91). Regardless of the amount of exercise, depression scores improved in all groups. Following post-partum intervention (n = 40), only intermediate-amount exercisers showed significant reductions in sleep disturbances (-24.1%; p = .003) and depression (15.9%; p = .04). Conclusions: Approximately 270 min/week of an online Pilates-based program were needed to prevent LBP worsening, and sleep deterioration in pregnant women. A different pattern was outlined for those women resuming the Pilates-based intervention at post-partum, with 150 min/week emerging as the "dose" of exercise capable of inducing the largest improvements in LBP, sleep, and mood disturbances.

[Cancer risk among shift workers: a review]. / Rischio oncogeno nei lavoratori a turni: analisi della letteratura.

INTRODUCTION: According to IARC, shift work resulting in disruption of circadian rhythm is a probable human carcinogen (Group 2A). METHODS: We examined the scientific literature on the carcinogenic risk among shift workers for risk assessment purposes. RESULTS: Clock genes polymorphisms might contribute with suppression of melatonin synthesis, immuno-suppression from sleep deprivation, individual habits associated with shift work, and low vitamin D levels, in increasing risk of breast cancer, prostate cancer and lymphoma among shift workers. CONCLUSION: Although the epidemiological evidence seems scanty, the hypothesis that shift work-related sleep deprivation would contribute to increasing cancer risk seems based on solid ground.

Biological monitoring of low-level exposure to benzene.

INTRODUCTION: Conflicting opinions exist about the reliability of biomarkers of low-level exposure to benzene. We compared the ability of the urinary excretion of trans,trans-muconic acid (t,t-MA), s-phenilmercapturic acid (s-PAMA) and urinary benzene (U-Benz) to detect low level occupational and environmental exposure to benzene. METHODS: We monitored airborne benzene by personal air sampling, and U-Benz, s-PMAI, t,t-MA and cotinine (U-Cotinine) in spot urine samples, collected at 8 am and 8 pm, in 32 oil refinery workers and 65 subjects, randomly selected among the general population of urban and suburban Cagliari, Italy. Information on personal characteristics, diet and events during the sampling day was acquired through in person interviews. RESULTS: The median concentration of airborne benzene was 25.2 microg/m3 in oil refinery workers, and 8.5 microg/m3 in the general population subgroup. U-Benz in morning and evening samples was significantly more elevated among oil refinery workers than the general population subgroup (p = 0.012, and p = 7.4 x 10(-7), respectively) and among current smokers compared to non-smokers (p = 5.2 x 10(-8), and p = 5.2 x 10(-5) respectively). Benzene biomarkers and their readings in the two sampling phases were well correlated to each other. The Spearman's correlation coefficient with airborne benzene was significant for U-Benz in the evening sample, while no correlation was seen with t,t-MA and s-PMA readings in either samplings. The two benzene metabolites were frequently below limit of detection (LOD), particularly among the general population study subjects (17-9% and 39%, for t,t-MA and s-PMA respectively). Morning U-Cotinine excretion showed a good correlation with U-Benz in the morning and in the evening sampling (p < 0.001), and with s-PMA in the evening sample (p < 0.001), but not with t,t-MA in either samplings. t,t-MA in the evening sample was the only biomarker showing a moderate inverse correlation with BMI (p < 0.05). The multiple regression analysis adjusting by BMI and number of cigarettes smoked during the day confirmed the results of the univariate analysis. DISCUSSION: Our results suggest that unmetabolized U-Benz would allow a more reliable biomonitoring of low-level exposure to benzene than s-PMA and t,t-MA.

Validation of the SkinEthic HCE Time-to-Toxicity test method for eye hazard classification of chemicals according to UN GHS.

This study describes the within- and between-laboratory reproducibility (WLR and BLR) of a Time-to-Toxicity (TTT) approach for chemicals based on the SkinEthic™ HCE tissue construct, capable to distinguish chemicals that do not require classification for serious eye damage/eye irritation (No Cat.) from chemicals that require classification for eye irritation (Cat. 2), and serious eye damage (Cat. 1). The WLR and BLR was assessed with three participating laboratories. Each laboratory tested 40 coded chemicals in three independent runs. The predictive capacity of the method was assessed on a larger set of 150 chemicals (70 liquids and 80 solids) by combining the results of this study with the results of the test method developer. The WLR for the 20 liquids ranged from 85% to 95% with a BLR of 90%. For the 20 solids, a WLR and BLR of 100% was obtained. The test method developer obtained a WLR of 80% and 95%, based on 50 liquids and 48 solids tested in three independent runs, respectively. Regarding the predictive capacity, the SkinEthic™ HCE TTT test method identified 80.8% Cat. 1, 69.2% Cat. 2, and 74.9% No Cat. correctly. An independent peer review panel concluded that based on all available data, the relevance and reliability of the SkinEthic™ HCE TTT has been demonstrated for discriminating the three UN GHS eye hazard categories.

[Results of a health surveillance program for health care workers exposed to a patient affected by tuberculosis]. / Risultati di un programma di sorveglianza sanitaria post-esposizione in operatori sanitari esposti a mycobacterium tuberculosis.

A health surveillance program was implemented in 71 health care workers (HCW) exposed to a patient with active TB infection. A two-step tuberculin skin test (TST) was performed in all the exposed, and a QuantiFERON-TB Gold (QTF) test was scheduled for positive TST subjects. Clinical-radiological surveillance (CRS) was scheduled for subjects positive to TST and QTF or symptomatic. Thirty eight percent HCW were TST positive; 19% of them were also QTF positive and were referred to CRS. No clinical TB was observed among the exposed HCW. Comprehensive health surveillance allows to increase risk perception, compliance to HS and to reduce cost in respect to less cost-effective practices.

Microwaves create larger ablations than radiofrequency when controlled for power in ex vivo tissue.

PURPOSE: To compare ablation zones created with equal amounts of 2.45 GHz microwave and 480 kHz radiofrequency (RF) energy in ex vivo liver and lung. METHODS: A total of 38 ablations were performed in ex vivo liver and lung for 10 min each. Nineteen RF ablations (nine liver, ten lung) were performed with a 480 kHz system (200 W max, impedance-based pulsing) and cooled electrode while measuring the average RF power applied. Nineteen microwave ablations (nine liver, ten lung) were then created using a cooled triaxial antenna to deliver 2.45 GHz at the same power level as in RF experiments. Ablation zones were then sectioned and measured for minimum, maximum and mean diameters, and circularity. Measurements were compared using t-tests, with P < 0.05 indicating statistical significance. RESULTS: Mean diameters of microwave ablations were greater than RF ablations in both liver and lung (4.4 +/- 0.3 vs 3.3 +/- 0.2 cm in liver; 2.45 +/- 0.3 vs 1.6 +/- 0.5 cm in lungs; P < 0.0005 all comparisons). There was no significant difference in the mean power applied during microwave or RF ablations in either organ (54.44 +/- 1.71 W vs 56.4 +/- 6.7 W in liver, P > 0.05; 40 +/- 0.95 W vs 44.9 +/- 7.1 W in lung, P > 0.05). CONCLUSIONS: Using a single cooled applicator, microwave energy at 2.45 GHz produces larger ablations than an equivalent amount of 480 kHz RF energy in normal liver and lung. This was more apparent in lung, likely due to the high baseline impedance which limits RF, but not microwave power delivery.

A sensitive FRET probe assay for the selective detection of Mycobacterium marinum in fish.

Mycobacterium marinum is the causative agent of mycobacteriosis in wild and cultured fish and of atypical infection in humans. For the diagnosis of M. marinum, cultural and traditional polymerase chain reaction (PCR) methods are currently used. However, these protocols, although able to discriminate within Mycobacterium spp., have proved to be time-consuming or difficult to carry out. For this reason, the aim of this study was to obtain a rapid and specific diagnostic tool to quantify fish Mycobacterium spp. or to discriminate M. marinum from other mycobacteria. A primary PCR amplification with SYBR Green had a detection limit (dl) of 10(2)Mycobacterium DNA copies with a log-linear quantification range up to 10(4) (R(2) = 0.99). The second PCR using FRET probes, flanking a region containing species specific nucleotide variations, was designed and validated with synthetic erp gene fragments corresponding to different mycobacterial species, different whole mycobacteria suspensions, experimentally infected fish tissues, tissues from experimentally infected fish, and samples of cultured fish. The results show that the FRET probes demonstrate a high specificity as the melting curve analysis allowed efficient discrimination of M. marinum from Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium pseudoshottsii, Mycobacterium shottsii and Mycobacterium ulcerans. The kidney is the organ with the strongest detection signal and using fish tissues the method has a mean sensitivity of 50 DNA copies/PCR.

[Electrocardiogram changes in shift workers]. / Morfologia dell'elettrocardiogramma in lavoratori turnisti.

BACKGROUND: Besides a significant deterioration in their family and personal life, shift workers also suffer health problems ranging from chronic fatigue to gastro-intestinal disorders, changes in sleep rhythm and cardiovascular disease, including arrhythmia and ischaemic heart disease. OBJECTIVES: The aim of the study was to assess the prevalence of electrocardiographic changes, such as conduction disorders, alterations in the repolarization phase and frequency-adjusted QT interval (QTc) in relation to shift work. METHODS: We conducted a cross sectional survey of 125 male subjects, 60 of whom worked fixed hours, and 65 were shift workers on two different schedules: 32 were on duty for 24 hours followed by 96 hours rest, and 33 worked 8-hour shifts (3 x 8). During periodical health assessment we examined their electrocardiograms (ECG), classified the morphology and measured the QTc interval. RESULTS: The QTc interval did not differ by type of work shift or by the presence of morphological changes in the ECG, including concurrent conduction disorders, or alterations in the repolarization phase. However, unlike day workers and 24-h shift workers, the QTc interval tended to increase with age among 8-h shift workers (r = 0.338; p = 0.05). Also, risk of conduction disorders was moderately, but not significantly, elevated among 8-h shift workers compared with subjects working fixed hours (OR = 1.9; I.E 95% 0.6, 5.7). CONCLUSIONS: Our study did not reveal significant changes in the ECG morphology in relation to the type of work shift.

Dry eye disease treatment: the role of tear substitutes, their future, and an updated classification.

OBJECTIVE: The aim of this review is to summarize the results of a consensus meeting held by a group of experts in dry eye disease (DED) to discuss the importance of tear substitutes in the treatment of DED. The meeting focused especially on the main characteristics of lacrimal substitutes, the development of in vitro models to investigate DED pathophysiology and treatment, the importance of conducting rigorous clinical trials, the requirements of the upcoming European Legislation on medical devices, the advances in the formulation of safer preservatives, the peculiarities of treatment in younger subjects, and the importance of an updated terminology for lacrimal substitutes. MATERIALS AND METHODS: A literature search was conducted using MEDLINE, with different combinations of pertinent keywords, depending on the subject under discussion, such as "dry eye disease"; "tear substitutes"; "in vitro models"; "ocular surface"; "clinical trials"; "European Regulation"; "preservatives" "younger patients". Also, each author included in the discussion selected articles from their personal library. Using a consensus-based method called nominal group technique to reach a conclusion and proposal for a new classification of eye drops used to improve the tear film and ocular surface epithelia, the experts also conducted a round table meeting. RESULTS: The new terms proposed by the authors are "wetting agents", "multiple-action tear substitutes" or "ocular surface modulators". The new classification is needed to distinguish eye drops used to improve the tear film and ocular surface epithelia, in line with the new definition of DED, which recognizes the loss of ocular homeostasis, and the creation of a vicious circle of chronic inflammation and ocular damage as fundamental aspects of DED pathophysiology. CONCLUSIONS: Although tear substitutes have been historically used to provide eye lubrication to the ocular surface, recent advances in the pathophysiology of dry eye disease (DED) clarified that treatment should not just focus on tear film quality or quantity, but address the loss of homeostasis of the ocular surface, blocking the vicious circle of chronic inflammation and ocular damage. Given the scant comparative evidence on tear substitutes currently on the market, further studies should focus on developing new agents, considering the advantages provided by in vitro models, importance of conducting rigorous clinical trials, availability of less harmful preservatives and obligations related to the new European legislation on medical devices. Based on the discussion of these topics, a group of experts held a consensus meeting to identify new and more appropriate terms for different tear substitutes. The proposed terms are wetting agents, multiple-action tear substitutes and ocular surface modulators. Regardless of the agent used, it is important to note that tear substitutes represent one of many options for DED treatment, which should not overlook the psychological aspects of the disease and the peculiarities of younger subjects, who seem to have a higher risk for DED, possibly related to digital devices excessive use.

Human salivary Raman fingerprint as biomarker for the diagnosis of Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease leading to progressive and irreversible muscle atrophy. The diagnosis of ALS is time-consuming and complex, with the clinical and neurophysiological evaluation accompanied by monitoring of progression and a long procedure for the discrimination of similar neurodegenerative diseases. The delayed diagnosis strongly slows the potential development of adequate therapies and the time frame for a prompt intervention. The discovery of new biomarkers could improve the disease diagnosis, as well as the therapeutic and rehabilitative effectiveness and monitoring of the pathological progression. In this work saliva collected from 19 patients with ALS, 10 affected by Parkinson's disease, 10 affected by Alzheimer's disease and 10 healthy subjects, was analysed using Raman spectroscopy, optimizing the parameters for detailed and reproducible spectra. The statistical multivariate analysis of the data revealed a significant difference between the groups, allowing the discrimination of the disease onset. Correlation of Raman data revealed a direct relationship with paraclinical scores, identifying multifactorial biochemical modifications related to the pathology. The proposed approach showed a promising accuracy in ALS onset discrimination, using a fast and sensitive procedure that can make more efficient the diagnostic procedure and the monitoring of therapeutic and rehabilitative processes in ALS.

Does REM sleep behavior disorder change in the progression of Parkinson's disease?

OBJECTIVES/BACKGROUND: Rapid eye movement (REM) Sleep Behavior Disorder (RBD) in Parkinson's disease (PD) may be associated with a malignant phenotype. Despite its prognostic value, little is known about the time course of RBD in PD. In this study, we aimed to ascertain whether or not RBD is a stable feature in PD. In this study, we prospectively evaluated clinical and neurophysiological features of RBD, including REM Sleep Without Atonia (RSWA), in PD patients with RBD at baseline and after three years then assessed whether the changes in measures of RSWA parallel the progression of PD. PATIENTS/METHODS: In sum, 22 (17M, mean age 64.0 ± 6.9 years) moderate-to-advanced PD patients (mean PD duration at baseline:7.6±4.8 years) with RBD, underwent a video-polysomnography (vPSG) recording and clinical and neuropsychological assessment at baseline and after three years. RESULTS: At follow-up, the self-assessed frequency of RBD symptoms increased in six patients, decreased in six and remained stable in 10, while RSWA measures significantly increased in all subjects. At follow-up, patients showed worse H&Y stage (p = 0.02), higher dopaminergic doses (p = 0.05) and they performed significantly worse in phonetic and semantic fluency tests (p = 0.02; p = 0.04). Changes in RSWA correlated significantly with the severity in levodopa-induced dyskinesia (r = 0.61,p = 0.05) and motor fluctuation (r = 0.54,p = 0.03) scores, and with the worsening of executive functions (r = 0.78,p = 0.001) and visuo-spatial perception (r = -0.57,p = 0.04). CONCLUSION: Despite the subjective improvement of RBD symptoms in one-fourth of PD patients, all RSWA measures increased significantly at follow-up, and their changes correlated with the clinical evolution of motor and non-motor symptoms. RBD is a long-lasting feature in PD and RSWA is a marker of the disease's progression.

Identification of the prosurvival activity of nerve growth factor on cardiac myocytes.

Neurotrophins (NTs) control neuron survival and regeneration. Recent research showed that NTs possess cardiovascular actions. In this study, we investigated the hypothesis that the NT nerve growth factor (NGF) prevents cardiomyocyte apoptosis. We demonstrated that cultured rat neonatal cardiomyocytes (RNCMs) produce NGF and express its trkA (tropomyosin-related receptor A (NGF high-affinity receptor)) receptor. RNCMs given a neutralizing antibody for NGF or the trkA inhibitor K252a underwent apoptosis, thus suggesting that NGF is an endogenous prosurvival factor for cardiomyocytes. Adenovirus (Ad)-mediated NGF overexpression protected RNCMs from apoptosis induced by either hypoxia/reoxygenation or angiotensin II (AngII). Similarly, recombinant NGF inhibited AngII-induced apoptosis in isolated rat adult cardiomyocytes. Finally, in a rat model of myocardial infarction, NGF gene transfer promoted cardiomyocyte survival. In RNCMs, recombinant NGF induced trkA phosphorylation, followed by Ser473 phosphorylation and nuclear translocation of phospho-protein kinase B (Akt). In response to Akt activation, Forkhead transcription factors Foxo-3a and Foxo-1 were phosphorylated and excluded from the nucleus. The prosurvival effect of adenoviral vector carrying the human NGF gene was inhibited in vitro by K252a, LY294002 (a pan-phosphatidyl inositol 3-kinase - PI3K - inhibitor), an Akt small interfering RNA, and adenoviruses carrying a dominant negative mutant form of Akt (Ad.DN.Akt) or an Akt-resistant Foxo-3a (Ad.AAA-Foxo-3a). These results newly demonstrate the cardiac prosurvival action of NGF and provide mechanistic information on the signaling pathway, which encompasses trkA, PI3K-Akt, and Foxo.