Objective and automatic classification of Parkinson disease with Leap Motion controller.

BACKGROUND: The main objective of this paper is to develop and test the ability of the Leap Motion controller (LMC) to assess the motor dysfunction in patients with Parkinson disease (PwPD) based on the MDS-UPDRSIII exercises. Four exercises (thumb forefinger tapping, hand opening/closing, pronation/supination, postural tremor) were used to evaluate the characteristics described in MDS-UPDRSIII. Clinical ratings according to the MDS/UPDRS-section III items were used as target. For that purpose, 16 participants with PD and 12 healthy people were recruited in Ospedale Cisanello, Pisa, Italy. The participants performed standardized hand movements with camera-based marker. Time and frequency domain features related to velocity, angle, amplitude, and frequency were derived from the LMC data. RESULTS: Different machine learning techniques were used to classify the PD and healthy subjects by comparing the subjective scale given by neurologists against the predicted diagnosis from the machine learning classifiers. Feature selection methods were used to choose the most significant features. Logistic regression (LR), naive Bayes (NB), and support vector machine (SVM) were trained with tenfold cross validation with selected features. The maximum obtained classification accuracy with LR was 70.37%; the average area under the ROC curve (AUC) was 0.831. The obtained classification accuracy with NB was 81.4%, with AUC of 0.811. The obtained classification accuracy with SVM was 74.07%, with AUC of 0.675. CONCLUSIONS: Results revealed that the system did not return clinically meaningful data for measuring postural tremor in PwPD. In addition, it showed limited potential to measure the forearm pronation/supination. In contrast, for finger tapping and hand opening/closing, the derived parameters showed statistical and clinical significance. Future studies should continue to validate the LMC as updated versions of the software are developed. The obtained results support the fact that most of the set of selected features contributed significantly to classify the PwPD and healthy subjects.

Fulminant hepatitis due to human adenovirus.

PURPOSE: To describe the demographics, clinical manifestations, treatment and outcomes of patients with human adenovirus (HAdV) hepatitis. METHODS: A case of fulminant HAdV hepatitis in a patient with chronic lymphocytic leukemia receiving rituximab and fludarabine is described. We conducted a comprehensive review of the English-language literature through May, 2012 in search of definite cases of HAdV hepatitis. RESULTS: Eighty-nine cases were reviewed. Forty-three (48 %) were liver transplant recipients, 19 (21 %) were bone marrow transplant recipients, 11 (12 %) had received chemotherapy, five (6 %) had severe combined immunodeficiency, four (4 %) were HIV infected, two had heart transplantation, and two were kidney transplant recipients. Ninety percent (46/51) of patients presented within 6 months following transplantation. Fever was the most common initial symptom. Abdominal CT scan revealed hypodense lesions in eight of nine patients. Diagnosis was made by liver biopsy in 43 (48 %), and on autopsy in 46 (52 %). The HAdV was isolated at other sites in 54 cases. Only 24 of 89 patients (27 %) survived: 16 whose immunosuppression was reduced, six with liver re-transplantation, and two who received cidofovir and intravenous immunoglobulin. CONCLUSION: HAdV hepatitis can manifest as a fulminant illness in immunocompromised hosts. Definitive diagnosis requires liver biopsy. Early consideration of a viral etiology, reduction in immunosuppression, and liver transplantation can be potentially life-saving.

Prevalence of buried Barrett's metaplasia in patients before and after radiofrequency ablation.

BACKGROUND AND STUDY AIM: Radiofrequency ablation (RFA) to treat Barrett's esophagus is increasingly accepted. Description of the etiology, natural history, and prevalence of buried Barrett's metaplasia (BBM) following RFA is limited, although BBM continues to pose a clinical dilemma. We aimed to assess the prevalence, characteristics, and eradication rate of BBM in patients with both dysplastic and nondysplastic Barrett's esophagus, treated with RFA and followed over time. PATIENTS AND METHODS: The presence of Barrett's esophagus, dysplasia, and BBM, before and after RFA, was assessed by two gastrointestinal pathologists in a retrospective chart review of patients who had undergone RFA at our center and had completed appropriate follow-up. RESULTS: We identified 112 patients with completed treatment and no further planned RFA. In 108, no residual Barrett's esophagus was seen after RFA; 4 patients with persistent Barrett's tissue underwent surgery. Regarding BBM, 17/112 patients (15.2%) had evidence of BBM during evaluation. In 12/17 (70.5%) BBM was found during the RFA treatment, with 8 having previously undergone non-RFA therapy and RFA for Barrett's esophagus and 4 having no previous intervention. In 5/17 (29.4%), BBM was seen only after RFA monotherapy. All 17 showed no evidence of BBM at final evaluation and were classified in the complete remission group (108/112). CONCLUSION: Both Barrett's esophagus and BBM were completely eradicated in all patients with long-term follow-up after RFA. Almost half of the patients with BBM had a prior history of non-RFA therapy for Barrett's esophagus compared with 26% the non-BBM cohort. All patients with previously identified Barrett's esophagus and BBM were completely cleared of disease at final follow-up.

[Plasmacytoid urothelial carcinoma of the urinary bladder. A study of 7 cases]. / Carcinoma urotelial plasmocitoide de vejiga urinaria. Estudio de 7 casos.

OBJECTIVE: Plasmacytoid urothelial carcinoma is a rare and aggressive variant of bladder cancer that mimics plasmacytoma histologically and that can be confused with hemolymphoid neoplasms secondarily affecting the urinary bladder. Only single cases and short series have been described so far. PATIENTS AND METHODS: Seven cases of plasmacytoid urothelial carcinoma have been found among 720 high grade urothelial carcinomas of the urinary bladder. RESULTS: In our series, 0.97% of high grade urothelial carcinomas of the urinary bladder show plasmacytoid phenotype. All the cases were smoking males between 58 and 75 years old. Histologically, two cases showed pure plasmacytoid features, while in the other five cases the plasmacytoid phenotype was mixed with conventional transitional cell or glandular histologies. By immunohistochemistry, all the plasmacytoid areas showed fair epithelial differentiation. The clinical behaviour was aggressive in all the cases, with distant metastases at diagnosis in three cases and early tumor recurrence after chemotherapy in four of them. CONCLUSIONS: In our experience, the plasmacytoid urothelial carcinoma of the urinary bladder is a rare tumor that can also be detected in association with areas of conventional urothelial carcinoma. It is mandatory to recognize this histological subtype due to the clinical and prognostic implications of this diagnosis.

Discovering intratumor heterogeneity: the next frontier for pathologists.

Discovering intratumor heterogeneity is a crucial issue in modern oncologic medicine. Highly sophisticated technology such as high-throughput DNA sequencing has demonstrated the real dimension of the problem. The overwhelming majority of malignant tumors show high levels of intratumor heterogeneity when thoroughly studied. Intratumor heterogeneity develops both in temporal and spatial domains and its distribution is not deterministic making each case truly unique and unrepeatable. Pathologists are main actors in intratumor heterogeneity detection since they are the medical specialists who sample the tumors. Recent evidences have shown that currently applied sampling protocols are insufficient for a reliable intratumor heterogeneity detection. Pathologists must adapt classic sampling to the new times thus continuing being key pieces in the multidisciplinary approach to neoplasia that modern medicine demands.

Drug-induced gastrointestinal injury (DIGI). Updates, reflections and key points.

The goals of this short narrative review are 1) to provide an update in recent developments in the field of drug-induced gastrointestinal injury (DIGI), and 2) to distill few key points to approach with confidence a difficult and vast area of gastrointestinal pathology. DIGI is a challenging diagnosis as it can produce almost any pattern of the injury of the gastrointestinal tract. The recognition of a pattern and the knowledge of which drugs can produce that pattern, are the first step of the diagnostic process; communication with the clinical team and a high level of suspicion are then paramount. The pathologist can be the leading clinicians of the care team in few situations in which she/he can recognize the drug at the microscope. Knowledge of the most relevant differential diagnoses of DIGI is essential to avoid significant pitfalls. Finally, several DIGIs due to recently developed immunomodulators used in oncology have shown relevance given their sometimes fatal outcome and the accumulating evidence of a common morphological appearance among them.

Leap motion evaluation for assessment of upper limb motor skills in Parkinson's disease.

The main goal of this study is to investigate the potential of the Leap Motion Controller (LMC) for the objective assessment of motor dysfunctioning in patients with Parkinson's disease (PwPD). The most relevant clinical signs in Parkinson's Disease (PD), such as slowness of movements, frequency variation, amplitude variation, and speed, were extracted from the recorded LMC data. Data were clinically quantified using the LMC software development kit (SDK). In this study, 16 PwPD subjects and 12 control healthy subjects were involved. A neurologist assessed the subjects during the task execution, assigning them a score according to the MDS/UPDRS-Section III items. Features of motor performance from both subject groups (patients and healthy controls) were extracted with dedicated algorithms. Furthermore, to find out the significance of such features from the clinical point of view, machine learning based methods were used. Overall, our findings showed the moderate potential of LMC to extract the motor performance of PwPD.

Peritumoral and nodal muciphages.

Three patients who underwent surgery for cancer showed Alcian blue positive cells in the sinusoids of the regional lymph nodes and, in one case, extensive infiltration in the soft tissues around the tumor. The cells contained variably sized vacuoles that occasionally indented the nuclei, imparting a signet-ringlike appearance. They were interpreted as muciphages based on morphology, reactivity with mucin stains, positive immunohistochemical staining for KP-1 and Mac-387, and negative staining for cytokeratin, S-100, and leukocyte common antigen (LCA). The material contained in these cells was Alcian blue positive at pH 2.5 and pH 1, and was strongly periodic acid-Schiff positive after diastase digestion. Hyaluronidase only slightly reduced the intensity of the Alcian blue stain. These results indicate that the bulk of the material was epithelial-type mucin. To our knowledge, this is the first report of muciphages in lymph nodes. Careful attention to morphology and immunohistochemical findings is necessary to avoid confusion with metastatic or infiltrating signet ring or mucinous adenocarcinoma.

The role of GABAA receptor function in peristaltic activity of the guinea-pig ileum: a comparative study with bicuculline, SR 95531 and picrotoxinin.

1. The peristaltic activity of the guinea-pig ileum was studied in the absence and in the presence of the blockade of GABAA receptors. 2. Bicuculline (1-30 microM), improved at the highest concentrations the efficiency of peristalsis by enhancing the frequency of propulsive contractions and the amount of fluid ejected per unit of time. 3. Neither SR 95531 (0.3-10 microM), a novel GABAA receptor antagonist, which competitively antagonized 3-aminopropane sulphonic acid induced contractions in myenteric plexus-longitudinal muscle preparations (pA2 value: 6.47), nor picrotoxinin (1-30 microM) modified peristaltic parameters or influenced the potentiating effect of bicuculline on peristaltic activity. 4. In myenteric plexus-longitudinal muscle preparations, bicuculline (1-30 microM) enhanced the amplitude of electrically-induced cholinergic contractions without modifying submaximal contractions to applied acetylcholine. SR 95531 and picrotoxinin had no effect on twitch amplitude. In the presence of each of these compounds, bicuculline retained its potentiating effect. 5. The results obtained with SR 95531 and picrotoxinin question the view that GABAA receptors may exert a critical role in intestinal propulsion by modulating the activity of nerve pathways subserving peristalsis. Bicuculline potentiates the peristaltic activity of the ileum probably via a facilitatory effect on enteric cholinergic transmission that is independent of GABAA receptor blockade.

Ionization of ozone/chlorofluorocarbon mixtures in atmospheric gases: formation and remarkable dissociation of

The reactions occurring upon ionization of mixtures containing ozone and CHX2Y (X = H, Cl, F; Y = Cl, F) halocarbons diluted in atmospheric gases (O2, N2) have been investigated in detail by mass spectrometric and theoretical methods. In all systems investigated the reactivity pattern is characterized by the preliminary formation of [CHXY x O3+] adducts which undergo unimolecular dissociation into HXYO2+ and CO. This remarkable dissociation which requires extensive molecular reorganization is exceptional for hydrogenated halocarbons. The work represents the first systematic study of the ionic chemistry in systems containing both ozone and halocarbons diluted in atmospheric gases.

Gas-phase reactions of nitronium ions with acetylene and ethylene: an experimental and theoretical study

A comparative study of the gas-phase reactions of NO2+ with acetylene and ethylene was performed by using FT-ICR, MIKE, CAD, and NfR/ CA mass spectrometric techniques, in conjunction with ab initio calculations at the MP2/6-31+G* level of theory. Both reactions proceed according to the same mechanism, that is, 1,3-dipolar cycloaddition, but yield products of different stability. The C2H2NO2+ adduct from acetylene has an aromatic character and hence is highly stabilized with respect to the C2H4NO2+ adduct from ethylene. Both cycloadducts tend to isomerize into O-nitroso derivatives, that is, nitrosated ketene and nitrosated acetaldehyde, which represent the thermodynamically most stable products from the addition of NO2+ to acetylene and ethylene, respectively. As prototypal examples of the reactivity of free nitronium ions with most simple pi systems, the reactions investigated are useful starting points to model the mechanism of aromatic nitration.

Occult papillary carcinoma of the thyroid presenting as a cervical cyst.

BACKGROUND: A cystic neck mass representing metastatic papillary thyroid cancer to a cervical lymph node may be the presenting symptom in patients with an occult papillary cancer of the thyroid. This cystic change can cause diagnostic problems and not infrequently delay identification of the primary thyroid tumor. This study investigates the frequency, treatment, and pathologic features of this entity. METHODS: All clinical charts and microscopic slides of 136 consecutive patients who underwent thyroid operation for papillary carcinoma (PC) from 1990 to 1995 were reviewed. Hematoxylin-and-eosin and immunohistochemical stains (IMHS) for thyroglobulin also were reviewed. RESULTS: Eight patients (5.8%) presented with a cystic neck mass and no palpable thyroid lesion. In all 8 patients, the diagnosis was made by an excision of the cystic neck mass. In 3 patients, the cyst demonstrated classical features of PC, such as papillae and psammoma bodies. In the remaining 5 (62%), only focal papillae or nuclear features of papillary carcinoma were present. A careful review of the histology and IMHS were necessary to arrive at the correct diagnosis in these 5 patients. CONCLUSIONS: Occult papillary cancer of the thyroid presenting as a cystic neck mass is not uncommon and must be considered in the differential diagnosis. Excision and careful review of the histology and IMHS is necessary to prevent delay of the proper diagnosis. Although the thyroid tumor was less than 1 cm and sometimes only microscopic, the extensive nodal metastasis has led us to favor near total or total thyroidectomy and modified neck dissection in this entity.

S3O, a new sulfur oxide identified in the gas phase.

S3O, a novel, linear sulfur oxide has been detected in the gas phase by means of neutralization reionization mass spectrometry; the upper limit of stability of acyclic forms of SnO oxides has been set by theoretical calculations.

Does open biopsy before mastectomy affect the prevalence of so-called axillary lymph node micrometastases detected immunohistochemically.

OBJECTIVE: To determine the effect of a previous open biopsy on the presence of immunohistochemically detected micrometastases, particularly single cells, in axillary lymph nodes in patients with "node-negative" invasive breast carcinoma. METHODS: Node-negative breast cancer patients were divided into group 1 (diagnostic frozen-section biopsy with immediate mastectomy and axillary dissection) and group 2 (open surgical biopsy with temporally delayed mastectomy and axillary dissection). Archival slides of lymph nodes were examined and new sections stained with hematoxylin-eosin and immunohistochemically with a cytokeratin cocktail to detect micrometastases. RESULTS: Four (12%) of 33 patients had unequivocal lymph node metastases on additional hematoxylin-eosin sections (3 cases) or review of original material (1 case). Immunohistochemical analysis contributed additional data in only 1 group 2 patient. In this case a single strongly keratin-positive sinus-based cell was detected in 1 lymph node. CONCLUSION: The study suggests that previous surgical biopsy of the breast does not increase the incidence of immunohistochemically detected keratin positive cells in axillary lymph nodes.

Collagenous gastritis associated with lymphocytic gastritis and celiac disease.

Collagenous gastritis is a rare disorder, with only 8 cases reported in the literature, 2 in children and 6 in adults. We report an additional case of collagenous gastritis in a 42-year-old man with celiac disease. A thickened (>10 microm) subepithelial collagen band with entrapped capillaries, fibroblasts, and inflammatory cells was seen in the stomach, associated with lymphocytic gastritis. The duodenal mucosa showed severe villous atrophy but no subepithelial collagen deposition. No evidence of lymphocytic or collagenous colitis was found in the colon. The patient became symptom-free on a gluten exclusion diet and showed partial improvement of histopathologic findings after 3 months. Collagenous gastritis is a rare disease, but a wider recognition of its histopathologic features and clinical associations may bring more cases to light and provide additional clues in determining its etiology and pathogenesis.

Lymphoepithelioma-like carcinoma of the colon in a patient with hereditary nonpolyposis colorectal cancer.

Tumors with features similar to those of nasopharyngeal carcinoma, so-called lymphoepithelioma-like carcinomas, have been described in several organs but are extremely rare in the colon. We describe a patient with a family history consistent with hereditary nonpolyposis colorectal cancer who had 3 malignant lesions in the right colon, namely, a mucinous cancer, a lymphoepithelioma-like carcinoma, and a well-differentiated adenocarcinoma with prominent lymphoid stroma. To the best of our knowledge, lymphoepithelioma-like carcinoma has not been described previously in hereditary nonpolyposis colorectal cancer.

Direct Experimental Evidence for the H(2)O(+)O(2)(-) Charge Transfer Complex: Crucial Support to Atmospheric Photonucleation Theory.

Where does rain come from? The first experimental evidence for the existence of the (H(2)O(+)O(2)(-)) charge transfer complex, predicted to play a key role as a nucleation center for atmospheric vapor photonucleation (see picture), is provided by the powerful neutralization - reionization mass spectrometric technique.

Ionization of Ozone/Chlorofluorocarbon Mixtures in Atmospheric Gases: Formation and Dissociation of

Complexes that undergo extensive molecular reorganization upon unimolecular metastable dissociation are obtained after ionization of atmospheric gases containing ozone and chlorofluorocarbons [Eq. (1)]. These unusual processes, which require fission of all bonds initially present in the CHX(2) unit (X=Cl, F) and combination of C with one of the O atoms of ozone, were demonstrated and their mechanism rationalized by the joint application of mass spectrometric and theoretical methods.

European consensus on the histopathology of inflammatory bowel disease.

The histologic examination of endoscopic biopsies or resection specimens remains a key step in the work-up of affected inflammatory bowel disease (IBD) patients and can be used for diagnosis and differential diagnosis, particularly in the differentiation of UC from CD and other non-IBD related colitides. The introduction of new treatment strategies in inflammatory bowel disease (IBD) interfering with the patients' immune system may result in mucosal healing, making the pathologists aware of the impact of treatment upon diagnostic features. The European Crohn's and Colitis Organisation (ECCO) and the European Society of Pathology (ESP) jointly elaborated a consensus to establish standards for histopathology diagnosis in IBD. The consensus endeavors to address: (i) procedures required for a proper diagnosis, (ii) features which can be used for the analysis of endoscopic biopsies, (iii) features which can be used for the analysis of surgical samples, (iv) criteria for diagnosis and differential diagnosis, and (v) special situations including those inherent to therapy. Questions that were addressed include: how many features should be present for a firm diagnosis? What is the role of histology in patient management, including search for dysplasia? Which features if any, can be used for assessment of disease activity? The statements and general recommendations of this consensus are based on the highest level of evidence available, but significant gaps remain in certain areas.