Automated particle recognition for engine soot nanoparticles.

A pre-trained convolution neural network based on residual error functions (ResNet) was applied to the classification of soot and non-soot carbon nanoparticles in TEM images. Two depths of ResNet, one 18 layers deep and the other 50 layers deep, were trained using training-validation sets of increasing size (containing 100, 400 and 1400 images) and were assessed using an independent test set of 200 images. Network training was optimised in terms of mini-batch size, learning rate and training length. In all tests, ResNet18 and ResNet50 had statistically similar performances, though ResNet18 required only 25-35% of the training time of ResNet50. Training using the 100-, 400- and 1400-image training-validation sets led to classification accuracies of 84%, 88% and 95%, respectively. ResNet18 and ResNet50 were also compared for their ability to categorise soot and non-soot nanoparticles via a fivefold cross-validation experiment using the entire set of 800 images of soot and 800 images of non-soot. Cross-validation was repeated 3 times with different training durations. For all cross-validation experiments, classification accuracy exceeded 91%, with no statistical differences between any of the network trainings. The most efficient network was ResNet18 trained for 5 epochs, which reached 91.2% classification after only 84 s of training on 1600 images. Use of ResNet for classification of 1000 images, the amount suggested for reliable characterisation of soot sample, requires <4 s, compared with >30 min for a skilled operator classifying images manually. Use of convolution neural networks for classification of soot and non-soot nanoparticles in TEM images is highly promising, particularly when manually classified data sets have already been established.

Acute rapamycin rescues the hyperexcitable phenotype of accumbal medium spiny neurons in the valproic acid rat model of autism spectrum disorder.

We previously demonstrated that prenatal exposure to valproic acid (VPA), an environmental model of autism spectrum disorder (ASD), leads to a hyperexcitable phenotype associated with downregulation of inward-rectifying potassium currents in nucleus accumbens (NAc) medium spiny neurons (MSNs) of adolescent rats. Aberrant mTOR pathway function has been associated with autistic-like phenotypes in multiple animal models, including gestational exposure to VPA. The purpose of this work was to probe the involvement of the mTOR pathway in VPA-induced alterations of striatal excitability. Adolescent male Wistar rats prenatally exposed to VPA were treated acutely with the mTOR inhibitor rapamycin and used for behavioral tests, ex vivo brain slice electrophysiology, single-neuron morphometric analysis, synaptic protein quantification and gene expression analysis in the NAc. We report that postnatal rapamycin ameliorates the social deficit and reverts the abnormal excitability, but not the inward-rectifying potassium current defect, of accumbal MSNs. Synaptic transmission and neuronal morphology were largely unaffected by prenatal VPA exposure or postnatal rapamycin treatment. Transcriptome analysis revealed extensive deregulation of genes implied in neurodevelopmental disorders and ionic mechanisms exerted by prenatal VPA, which was partially reverted by postnatal rapamycin. The results of this work support the existence of antagonistic interaction between mTOR and VPA-induced pathways on social behavior, neurophysiological phenotype and gene expression profile, thus prompting further investigation of the mTOR pathway in the quest for specific therapeutic targets in ASD.

Moderate ethanol drinking is sufficient to alter Ventral Tegmental Area dopamine neurons activity via functional and structural remodeling of GABAergic transmission.

Earlier studies have shown a major involvement of Ventral Tegmental Area (VTA) dopamine (DA) neurons in mediating the rewarding effects of ethanol (EtOH). Much less is known on the role of this system in mediating the transition from moderate to excessive drinking and abuse. Here we sought to explore the hypothesis that early stage drinking in rodents, resembling recreational EtOH use in humans, is sufficient to dysregulate VTA DA transmission thus increasing the propensity to use over time. To this purpose, midbrain slice recordings in mice previously exposed to an escalating (3, 6 and 12%) 18-day voluntary EtOH drinking paradigm was used. By recording from DA and γ-aminobutyric acid (GABA) VTA neurons in midbrain slices, we found that moderate EtOH drinking leads to a significant suppression of the spontaneous activity of VTA DA neurons, while increasing their response to acute EtOH application. We also found that chronic EtOH leads to the enhancement of GABA input frequency onto a subset of DA neurons. Structurally, chronic EtOH induced a significant increase in the number of GABA axonal boutons contacting DA neurons, suggesting deep rewiring of the GABA network. This scenario is consistent with a downmodulation of the reward DA system induced by moderate EtOH drinking, a neurochemical state defined as "hypodopaminergic" and previously associated with advanced stages of drug use in humans. In this context, increased sensitivity of DA neurons towards acute EtOH may represent the neurophysiological correlate of increased unitary rewarding value, possibly driving progression to addiction.

Progress towards a methodology for high throughput 3D reconstruction of soot nanoparticles via electron tomography.

The aim of this work is to make progress towards the development of 3D reconstruction as a legitimate alternative to traditional 2D characterization of soot. Time constraints are the greatest opposition to its implementation, as currently reconstruction of a single soot particle takes around 5-6 h to complete. As such, the accuracy and detail gains are currently insufficient to challenge 2D characterization of a representative sample (e.g. 200 particles). This work is a consideration of the optimization of the steps included within the computational reconstruction and manual segmentation of soot particles. Our optimal process reduced the time required by over 70% in comparison to a typical procedure, whilst producing models with no appreciable decrease in quality.

Circulation of a Simbu Serogroup Virus, Causing Schmallenberg Virus-Like Clinical Signs in Northern Jordan.

Schmallenberg virus (SBV)-like clinical cases of abortions in northern Jordan in early 2013, together with the emergence of SBV in Europe in 2011, its rapid spread within the following years and the detection of this virus in Turkey, raised questions about the distribution of SBV or related orthobunyaviruses. To evaluate the occurrence of SBV or related members of the Simbu serogroup of orthobunyaviruses in Jordan, bulk milk (cattle) and serum samples (cattle, sheep and goat) collected in northern Jordan in 2013 were first tested by commercially available SBV antibody ELISAs. Indeed, 3 of 47 bulk milk samples and 57 of 115 serum samples provided positive results, but SBV specificity of the ELISA results could not be confirmed by virus neutralization assays. Instead, subsequent cross-neutralization tests were able to further investigate the specificity of these antibodies. Here, a significant inhibition of Aino virus was observed. Thus, the causative agent was most likely a Simbu serogroup virus closely related to Aino virus. Consequently, these results confirm that members of this group of virus are not only present in Europe, Africa or Australia, but also in the Middle East.

Prognostic value of cancer stem cells, epithelial-mesenchymal transition and circulating tumor cells in lung cancer.

The epithelial-mesenchymal transition (EMT) is a program involved in embryonic development that is often activated during cancer invasion and metastasis. CD133 is the main marker identifying cancer stem cells (CSCs) in lung cancer. Circulating tumor cells (CTCs) are demonstrated to be useful as a biomarker for the diagnosis and treatment of cancer. The aim of this study was to correlate EMT, CSCs and CTCs with patient prognosis to verify whether they can contribute to better stratification of lung cancer patients at risk for recurrent and metastatic disease. Pulmonary venous blood was drawn after major pulmonary surgery in 45 patients with resectable non-small cell lung cancer (NSCLC) in order to identify CTCs. For the same patients, we also constructed prognostic lung tissue microarrays (TMA) for CD133 and c-kit and evaluated CSC and EMT markers using flow cytometry. Cytokeratin-positive cells were detectable in 11 (23.9%) cases. c-kit expression was heterogeneous in prognostic TMAs while CD133 expression was low or absent which was also confirmed by flow cytometry and RT-PCR. Flow cytometric analysis showed that the mean percentage of cells with CD133 expression was 1.6%. CD90 and CD326 markers were co-expressed with a mean percentage of 10.41%. When CD133 and CD90/CD326 expression was correlated with follow-up, CD133 showed a higher correlation with deceased patients when compared with CD90/CD326 co-expression (32.5 vs. 9.5%). CD133 expression demonstrated a strong significant association with patients exhibiting progressive disease when compared to CD90/CD326 expression (15 vs. 7.1%). CD133 may be significantly associated with invasion and metastatic spread of NSCLC. The co-expression of CD90, CD326 and CD133 has definite prognostic value in patients with NSCLC.

[Lung cancer with bronchial stenosis due to foreign body and Entoameba gingivalis infection]. / Carcinoma con stenosi bronchiale da corpo estraneo e infezione da Entoameba gingivalis. Case report.

Oral cavity infection by protozoarian agents may lead to pathologies such as stomatitis and gengivitis. An higher incidence has been reported in immunocompromised patients and in patients with dental disorders. Entoameba gingivalis localizes into oral cavity and in particular into interstitial and interdental spaces. Infection propagation to bronchial or lung parenchyma represents a complication. In this report the Authors, starting from a recently treated case, discuss on the incidence, complications and surgical management of lung infection by Entoameba gingivalis.

Vandetanib: An overview of its clinical development in NSCLC and other tumors.

Vandetanib is an oral inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), epidermal growth factor receptor (EGFR) and Ret tyrosine kinases involved in tumor growth, progression and angiogenesis. Phase I studies indicated that the recommended dose of vandetanib as a single agent is 300 mg/day. Rash, diarrhea, hypertension and asymptomatic Q-Tc prolongation were the most common adverse events. Four randomized phase III clinical trials evaluated the efficacy of vandetanib in non-small cell lung cancer (NSCLC) in combination with docetaxel (ZODIAC), pemetrexed (ZEAL) or as a single agent (ZEST and ZEPHYR). Only the ZODIAC trial met its primary endpoint (progression-free survival [PFS]), while no study showed an advantage in overall survival with vandetanib. No significant antitumor activity has been observed in small cell lung cancer, advanced ovarian, colorectal, breast, prostate cancer and multiple myeloma. In advanced metastatic medullary thyroid cancer, one randomized phase III clinical trial has demonstrated that vandetanib can significantly improve response rate, PFS and time to worsening of pain. Several key questions remain to be addressed regarding the identification of clinical or molecular biomarkers predictive of response, the choice of the optimal dose or schedule of vandetanib and the safety of long-term administration. The results of ongoing trials in untreated patients with advanced NSCLC and other tumors should better define the optimal clinical application of vandetanib.

[Bilateral and multiple traumatic pulmonary pseudo-cysts: a case report]. / Pneumatocele post-traumatico: a proposito di un caso a localizzazione multipla bilaterale.

Traumatic pulmonary pseudocyst is a very rare consequence of blunt chest trauma characterized by formation of cystic like parenchymal lesions. Generally multiple and bilateral distribution is more rare than a single localization. The computed tomography (CT) scan has an higher diagnostic value compared with conventional chest X-ray. Prognosis of traumatic pseudocysts is generally good with benign clinical course and spontaneous resolution within several months. However initial strictly patient follow-up is necessary to early discover and treat potentially severe complications. Utility of chest magnetic resonance imaging (MRI) to exclude potentially severe infectious complications is described. Any complications required percutaneous drainage or surgical resection.

Traditional uses of plants in the Eastern Riviera (Liguria, Italy).

AIM OF THE STUDY: The aim of the present study was to explore the traditional plant knowledge of a zone of the Ligurian coast, known as Riviera spezzina (RS), Eastern Liguria, Italy. MATERIALS AND METHODS: Ethnobotanical information was obtained through open informal interviews. The informants were residents, belonging to families living in the study area since generations, and involved, at least partially, in agriculture. RESULTS AND CONCLUSIONS: A total of 120 botanical taxa were recorded. Ethnobotanical data included medicinal (40.4%), alimentary (46.5%), veterinary (4.6%), domestic and cosmetic (4.3%), magic and ritual (1.8%) and other uses (2.4%). Medicinal plants are used to treat a wide range of diseases, mainly disorders of digestive system, skin, and genital-urinary and respiratory traits. The key role played by undomesticated edible herbs, locally known as "erbette", in traditional cooking recipes of RS was shown. These botanicals are rich in bioactive compounds, such as polyphenols, vitamins, complex sugars, essential fatty acids and fibers, and therefore might offer a valid protection against pathological conditions. Plant uses by RS people were compared with previous ethnobotanical literature, concerning the neighbouring areas of Liguria. Our results highlight the role of the traditional use of plants in the maintenance of health and the prevention of chronic and age-related diseases.

[Thoracic trauma: incidence, social and economic costs, educational opportunities. Experience on the last eight years of Thoracic Surgical Unit of Messina University]. / Il trauma toracico: incidenza, costi socio-economici, ricaduta didattico-formativa. Esperienza della Cattedra di Chirurgia Toracica dell'Università di Messina negli ultimi otto anni.

The Authors, after extensive introduction on the incidence, etiology, classification, pathophysiology, possible complications, diagnosis and treatment of thoracic trauma, relate their experience on the last eight years, stressing the diagnostic and therapeutic strategy in management of trauma simple and complicated and assessing finally serious social impact of these pathologies and the educational opportunities provided.

Effect of a symbiotic preparation on the clinical manifestations of irritable bowel syndrome, constipation-variant. Results of an open, uncontrolled multicenter study.

AIM: Irritable bowel syndrome (IBS) is frequently associated with an imbalance in intestinal bacteria. To date, few studies have evaluated the efficacy and safety of probiotic administration in patients with constipation-variant IBS. A new agent recently available in clinical practice is a symbiotic consisting of a probiotic, Bifidobacterium longum W11, and the short chain oligosaccharide prebiotic Fos Actilight. The aim of this study was to evaluate the efficacy and safety of this symbiotic in patients with constipation-variant IBS. METHODS: A total of 636 patients (250 men, 386 women) diagnosed with constipation-type IBS according to the Roma II criteria were enrolled in 43 centers and received the symbiotic at a dose of 3 g/die for at least 36 days. A validated questionnaire investigating symptoms and stool frequency was administered before and after treatment. RESULTS: Based on patient responses to visual scale items, frequency increased significantly after treatment in the ''no symptom'' class from 3% to 26.7% for bloating and from 8.4% to 44.1% for abdominal pain (P<0.0001). In the more severe symptoms classes (moderate-severe), symptom frequency dropped significantly from 62.9% to 9.6% and from 38.8% to 4.1% for bloating and abdominal pain, respectively. Stool frequency significantly increased from 2.9+/-1.6 times/week to 4.1+/-1.6 times/ week. CONCLUSIONS: The study product can increase stool frequency in patients with constipation-variant IBS and reduce abdominal pain and bloating in those with moderate-severe symptoms.

[Percutaneous radio frequency thermal ablation of non-resectable lung cancer: state of the art]. / Termoablazione percutanea con radiofrequenza dei tumori polmonari inoperabili: stato dell'arte.

BACKGROUND: Unfortunately, as of yet, most lung cancers are not operable as soon as diagnosis is available; in these situations chemo- and radio-therapy still play a key role, albeit palliative, improving survival rate moderately, but are not lacking in toxic effects, especially in case of concurrent pathology, reduced cardio-respiratory functionality or being advanced in years. Therefore thermal ablation mini-invasive techniques, already employed as ancillary treatments of hepatic cancer or in place of surgery, have been performed for these pathologies. AIM: Aim of this work is to define the current state of the art for Radio-Frequency Ablation (RFA) to be performed on non-resectable lung cancer, also by means of a thorough review of international literature, from which to infer purposes, suggestions, methodologies, effectiveness, safety, complications and achievements, also in terms of the possible improvement of life quality and/or survival expectancy. PATIENTS AND METHODS: Patients have been carefully selected. Pulmonary nodules have been treated with TC or echo-guided percutaneous thermal ablation and, afterwards, evaluated by radiological and clinical (sometimes histopathological) follow-up. RESULTS: The size of the RFA-treated nodules is necessary in order to evaluate full or partial necrosis extent and, therefore, average survival rate. CONCLUSIONS: Availability of more extensive and homogeneous case histories, as well as standard follow-up (TC and/or histopathological sampling) methodologies, is required. Nevertheless several authors agree that RFA is a safe and effective technique within the framework of a substitutive or complementary treatment of non-operable lung cancer. The best results can be achieved for cancers less than 3 cm wide; RFA, performed before chemo- and/or radio-therapy, plays a neoadjuvant role for larger cancers, decreasing cancer volume and weakening the symptoms.

[Role of thymectomy in the treatment of myasthenia gravis: considerations and personal cases]. / Ruolo della timectomia nel trattamento della miastenia gravis: considerazioni e casistica personale.

The therapeutic impact of thymectomy on the clinical course of myasthenia gravis is still very controversial. In fact, while nowadays the surgical approach is widely adopted for thymomas, its role is still debatable in patients suffering from myasthenia gravis. The surgical approach of choice for total thymectomy is represented by median sternotomy. Other surgical methodologies include cervical access and partial sternotomy. All these approaches have shown excellent results in the exeresis of the thymus. More recently video-assisted thoracoscopic thymectomy has been proposed as a less invasive and similarly effective technique for the removal of this organ and the treatment of myasthenia gravis. Aim of the present study is to report Author's experience with thymectomy, emphasizing the data available in the international literature on the surgical mortality, complications and aesthetical results of the different surgical accesses.

Plamsa leptin response to acute fasting and refeeding in untreated women with bulimia nervosa.

Leptin is known to regulate body weight, energy balance, and reproduction. Therefore, investigation of its physiology is of obvious interest in bulimia nervosa (BN), an eating disorder characterized by body weight-related psychopathology, acute changes in the energy balance, and reproductive alterations. To date, the few studies that have assessed leptin production in BN have had several limitations, including the measurement of blood leptin levels in treated patients and the lack of normal weight healthy controls, so that the information they provide is not conclusive. As the investigation of leptin dynamics is likely to be more informative, we decided to assess leptin response to acute fasting and refeeding in both untreated patients with BN and healthy controls. Twelve women meeting the diagnostic criteria for BN of the Diagnostic and Statistical Manual of Mental Disorders, and 10 healthy women of the same age range participated in a 3-day study. At 1800 h on day 1, they received a meal of 1088 Cal, with 53% carbohydrates, 17% protein, and 30% fat. Then, they fasted until 1800 h on day 2, when they received the same meal. On day 3, they received a standard hospital diet of 2600 Cal, divided into 3 meals, with the same percentages of nutrients as described above. Blood samples were collected at different time points for plasma leptin, glucose, and insulin measurements. In bulimic patients, plasma leptin values were significantly lower than in healthy women (P < 0.0001) and were positively related to body weight, expressed as body mass index (r = 0.86; P < 0.0001). The leptin response to the fasting/refeeding paradigm significantly differed between patients and controls (time x group interaction, P < 0.0001). In fact, in healthy subjects, acute fasting induced a 58% decline in the plasma leptin concentration, whereas such a decrease was only 7% in bulimic women (P < 0.001). After acute refeeding, plasma leptin increased in both groups, although in the patients it did not reach the absolute values observed in normal controls. No significant difference was observed between bulimics and controls in plasma insulin response to the fasting/refeeding paradigm, whereas an abnormal increase in blood glucose levels was observed in the patients after the first meal following acute fasting. We conclude that in untreated women with BN, leptin, despite its very low plasma values, still holds its function as a sensor of body weight changes, but loses its role of signaling acute changes in energy balance.

Seasonal variation in plasma prolactin response to D-fenfluramine in healthy subjects.

To assess dynamically a seasonal variation in the functioning of the central serotonin (5-HT) system, we investigated the prolactin (PRL) response to the specific serotonergic agent D-fenfluramine (D-FEN) in the different seasons of the year. Thirteen healthy women and 11 healthy men (six for each season), aged 20-50 years, received PO 30 mg D-FEN and placebo, according to a randomized double-blind design. As compared to placebo, D-FEN induced a clear-cut increase in plasma PRL levels in all the seasons; this response was higher in fall than in spring and summer (p < .01 and < .05, respectively). In all the subjects, as a group, the hormone response to the 5-HT probe was inversely correlated with the body weight and age. These results document a seasonal variability in the PRL response to D-FEN, which suggests a seasonal fluctuation in central 5-HT transmission in healthy humans.

Prolactin response to d-fenfluramine is blunted in people with anorexia nervosa.

BACKGROUND: Several studies have explored serotonin (5-HT) transmission in people with anorexia nervosa, but their results have been inconsistent. METHOD: According to a double-blind placebo-controlled design, plasma prolactin response to the specific serotonergic probed d-fenfluramine was investigated in 10 under weight and two normal-weight women with anorexia, and in 12 age-matched healthy females. Eating-related psychopathology, depressive and obsessive--compulsive symptoms, and aggressiveness were measured by appropriate rating scales. RESULTS: Compared with healthy control subjects, the women with anorexia showed reduced baseline prolactin and oestrogen levels and increased basal cortisol concentrations. The prolactin response to d-fenfluramine was blunted and did not correlate with psychopathological measures. CONCLUSIONS: These results support a dysfunction of 5-HT transmission in anorexia nervosa. This dysfunction does not seem to be related to concomitant depressive or obsessive--compulsive symptoms or to the level of aggressiveness of the patients.

Transforming growth factor-beta expression in mucosal biopsies in asthma and chronic bronchitis.

We assessed whether transforming growth factor-beta (TGF-beta), a fibrogenic growth factor, may be involved in remodeling of asthma and chronic bronchitis; its expression was compared with that of epidermal growth factor (EGF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in bronchial mucosal biopsies from 13 normal subjects, 24 asthmatics, and 19 patients with chronic bronchitis. TGF-beta immunoreactivity was highly increased in epithelium and submucosa of those with bronchitis and to a lesser extent in asthmatics. By comparison, with normal subjects, EGF immunoreactivity was significantly increased in the epithelium of bronchitic subjects and submucosa of asthmatics, and, GM-CSF immunoreactivity was increased in both epithelial and submucosal cells of asthmatics and to a lesser extent in submucosa of bronchitics. A significant correlation was found between the number of epithelial or submucosal cells expressing TGF-beta in both asthma and chronic bronchitis and basement membrane thickness and fibroblast number. No such correlation was found for EGF or GM-CSF. in situ hybridization for TGF-beta 1 mRNA confirmed the results obtained by immunohistochemistry. By combining in situ hybridization and immunohistochemistry, it was found that eosinophils and fibroblasts were synthetizing TGF-beta in asthma and bronchitis. These data suggest that TGF-beta, but not EGF or GM-CSF, is involved in airways remodeling in asthma and chronic bronchitis.

Decreased nocturnal secretion of melatonin in drug-free schizophrenics: no change after subchronic treatment with antipsychotics.

To evaluate the biosynthetic activity of the pineal gland in schizophrenia, the circadian rhythm of plasma melatonin was investigated in 9 drug-free chronic schizophrenics and in matched healthy subjects. In 7 of the patients, the 24-hour secretory pattern of the pineal hormone was reassessed after 10 weeks of treatment with antipsychotic drugs. In drug-free schizophrenics, the nocturnal increase in plasma melatonin levels was significantly blunted as compared to healthy subjects (p < 0.0001). Chronic treatment with antipsychotic drugs significantly improved psychotic symptomatology, but did not change the secretory pattern of melatonin. These data show that the biosynthetic activity of the pineal gland is impaired in chronic schizophrenia and that successful treatment with antipsychotic drugs does not go parallel with changes in the production of melatonin.