Mathematical generation of data-driven hippocampal CA1 pyramidal neurons and interneurons copies via A-GLIF models for large-scale networks covering the experimental variability range.

Efficient and accurate large-scale networks are a fundamental tool in modeling brain areas, to advance our understanding of neuronal dynamics. However, their implementation faces two key issues: computational efficiency and heterogeneity. Computational efficiency is achieved using simplified neurons, whereas there are no practical solutions available to solve the problem of reproducing in a large-scale network the experimentally observed heterogeneity of the intrinsic properties of neurons. This is important, because the use of identical nodes in a network can generate artifacts which can hinder an adequate representation of the properties of a real network. To this aim, we introduce a mathematical procedure to generate an arbitrary large number of copies of simplified hippocampal CA1 pyramidal neurons and interneurons models, which exhibit the full range of firing dynamics observed in these cells - including adapting, non-adapting and bursting. For this purpose, we rely on a recently published adaptive generalized leaky integrate-and-fire (A-GLIF) modeling approach, leveraging on its ability to reproduce the rich set of electrophysiological behaviors of these types of neurons under a variety of different stimulation currents. The generation procedure is based on a perturbation of model's parameters related to the initial data, firing block, and internal dynamics, and suitably validated against experimental data to ensure that the firing dynamics of any given cell copy remains within the experimental range. A classification procedure confirmed that the firing behavior of most of the pyramidal/interneuron copies was consistent with the experimental data. This approach allows to obtain heterogeneous copies with mathematically controlled firing properties. A full set of heterogeneous neurons composing the CA1 region of a rat hippocampus (approximately 1.2 million neurons), are provided in a database freely available in the live paper section of the EBRAINS platform. By adapting the underlying A-GLIF framework, it will be possible to extend the numerical approach presented here to create, in a mathematically controlled manner, an arbitrarily large number of non-identical copies of cell populations with firing properties related to other brain areas.

Modeling realistic synaptic inputs of CA1 hippocampal pyramidal neurons and interneurons via Adaptive Generalized Leaky Integrate-and-Fire models.

Computational models of brain regions are crucial for understanding neuronal network dynamics and the emergence of cognitive functions. However, current supercomputing limitations hinder the implementation of large networks with millions of morphological and biophysical accurate neurons. Consequently, research has focused on simplified spiking neuron models, ranging from the computationally fast Leaky Integrate and Fire (LIF) linear models to more sophisticated non-linear implementations like Adaptive Exponential (AdEX) and Izhikevic models, through Generalized Leaky Integrate and Fire (GLIF) approaches. However, in almost all cases, these models are tuned (and can be validated) only under constant current injections and they may not, in general, also reproduce experimental findings under variable currents. This study introduces an Adaptive GLIF (A-GLIF) approach that addresses this limitation by incorporating a new set of update rules. The extended A-GLIF model successfully reproduces both constant and variable current inputs, and it was validated against the results obtained using a biophysical accurate model neuron. This enhancement provides researchers with a tool to optimize spiking neuron models using classic experimental traces under constant current injections, reliably predicting responses to synaptic inputs, which can be confidently used for large-scale network implementations.

Association of CTLA-4 polymorphisms with improved overall survival in melanoma patients treated with CTLA-4 blockade: a pilot study.

CTLA-4 blockade with monoclonal antibodies can lead to cancer regression in patients with metastatic melanoma (MM). CTLA-4 gene polymorphisms may influence the response to anti-CTLA-4 antibodies although few data are available regarding this issue. We analyzed six CTLA-4 single nucleotide polymorphisms (-1661A > G, -1577G > A, -658C > T, -319C > T, +49A > G, and CT60G > A) in 14 Italian MM patients and 45 healthy subjects. We found a significant association between the -1577G/A and CT60G/A genotypes and improved overall survival (Pc < 0.006, Bonferroni corrected), further confirmed by the diplotype analysis (-1577 & CT60 GG-AA diplotype, p < 0.001). A positive trend toward an association between these genotypes and response to therapy was also observed.

Clinical and biological features of an intranodal palisaded myofibroblastoma.

Intranodal palisaded myofibroblastoma (IPM) is a rare benign tumor of the lymph nodes probably arising from smooth muscle-like cells. The tumor is characterized by intranodal proliferation of spindle cells. Neoplastic spindle-cell proliferation is most often of metastatic repetition which is very important in the recognition of IPM, because it may be mistaken for metastasis or other tumors such as Kaposi's sarcoma. We report a novel case of IPM that confirms the myofibroblastic differentiation of the tumor. The onset of IPM has been associated with Epstein-Barr virus (EBV). In addition, recently reported cases of IPM have been seen with cyclin 1 overexpression and also with human herpes virus (HHV)-8 and EBV DNA sequences. In our case, there was no evidence of HHV-8 and EBV DNA sequences and we were not able to find cyclin 1 overexpression.

Determining firms׳ utility functions and competitive roles from data on market shares using Lotka-Volterra models.

In this article, we include data on historical and estimated market shares of two markets. In particular, we include annual data on the market shares of the Japanese beer market (1963-2000) and biannual data on the market shares of the mobile phones market in Greece (1998-2007). In addition, we estimate monthly data on market shares for both markets. We show how this data can be used to derive firms' utility functions and their competitive roles.

Predictive factors of outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Studies to define the optimal upper limits of tumor size and number as predictors of outcome after orthotopic liver transplantation (OLT) have yielded conflicting results. We analyzed 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 12-year period in a single center. Predictive factors for survival and tumor recurrence, according to the Milan criteria, were also examined. Our cohort included 60 men and 12 women of mean age 54 +/- 8 years and mean follow-up of 40 +/- 39 months. Origin of cirrhosis was postviral in 70% and Child class B or C in two thirds of patients. HCC was multifocal in 61%; about one fifth of patients had micro- or macrovascular involvement or positive nodes upon histologic examination. The cumulative size of the lesions was <3 cm in 17 patients; >3 to < or =5 cm in 28 patients; >5 to < or =8 cm in 14 patients; and >8 cm in 13 patients. According to the number and size of tumor nodules, 49 patients met the Milan criteria. During follow-up 25 patients died, 13 due to tumor recurrence. The 1- and 2-year survivals were 90% and 85% for patients who met the Milan criteria versus 57% and 51% for patients exceeding those limits (P = .006). A cumulative tumor size >8 cm was predictive of survival and tumor recurrence upon multivariate analysis. The adoption of Milan criteria for selection of cirrhotic patients has improved survival and reduced the rate of tumor recurrence. The evaluation of cumulative tumor size might further improve patient selection.

Orbital osteoclastoma of apparent extraskeletal origin in a pagetic patient: a case report.

A large mass in the right orbit, causing proptosis, ptosis of the right upper eyelid, and limitation to eye movements, was surgically removed from a 51-year-old woman suffering from Paget's bone disease (PBD). Histologically, a giant cell tumor of the bone (osteoclastoma) was diagnosed. No bony involvement was apparent either operatively, microscopically, or on preoperative computed tomographic scans. The neoplasm has not recurred in a 3-year follow-up. In addition to the fact that osteoclastoma complicating PBD is rare, the extraskeletal origin of the tumor is a matter of interest and can be tentatively explained by an unusually powerful systemic stimulus acting on circulating osteoclast precursors. HUM PATHOL 31:1527-1531.

Evaluation of a commercial serological kit for detection of salivary immunoglobulin G to Helicobacter pylori: a multicentre study.

OBJECTIVE: To evaluate the usefulness of a commercial serological enzyme immunoassay (EIA) for detecting salivary immunoglobulin (Ig) G to Helicobacter pylori. DESIGN: Prospective, multicentre study. SETTING: The study was conducted at 11 gastroenterology hospital centres throughout Italy. PARTICIPANTS AND INTERVENTIONS: Two hundred and thirteen dyspeptic patients underwent gastroscopy with antral biopsies. At each centre, two of the following three tests for H. pylori diagnosis were performed: urease quick test, histology, and 13C-urea breath test. Samples of unstimulated saliva and venous blood were collected from each patient. Salivary and serum H. pylori IgG were determined with the EIA Helori-test IgG (Eurospital, Trieste, Italy). MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and accuracy of the salivary and serum EIAs. RESULTS: By using a receiver operating characteristic curve, salivary EIA yielded 81% (95% confidence interval 73-87%) sensitivity, 73% (62-83%) specificity, 84% (76-90%) positive predictive value, 69% (58-79%) negative predictive value, and 78% (72-84%) accuracy. At the cut-off suggested by the manufacturer, serum EIA had 90% (84-95%) sensitivity, 78% (67-86%) specificity, 88% (81-93%) positive predictive value, 82% (71-90%) negative predictive value, and 86% (81-91%) accuracy. CONCLUSION: In this large multicentre study, detection of salivary H. pylori IgG with a commercial serological EIA was a fairly accurate diagnostic method. Data confirm that saliva testing does not compare favourably with serology in the assessment of H. pylori status.

Double-blind study of a multivitamin complex supplemented with ginseng extract.

To remedy the deterioration in quality of life in large cities, the addition of ginseng root extract to a multivitamin base appears to produce a promising dietary supplement. The aim of the present study was to compare the quality-of-life parameters in subjects receiving multivitamins plus ginseng with those found in subjects receiving multivitamins alone. The study was comparative, randomized and double-blind, and it involved 625 patients of both sexes divided into two groups taking one capsule per day for 12 weeks. Group A received vitamins, minerals, trace elements and ginseng extract G115 (Pharmaton Capsules) while group B received vitamins, minerals and trace elements (multivitamin capsules) only. The resulting quality-of-life was assessed by a standardized 11-item questionnaire, validated by the Medical School of the National Autonomous University of Mexico (UNAM). Of the 625 patients recruited, 124 were excluded from the study due to lack of compliance with the treatment, so that 338 patients in group A and 163 patients in group B completed the study. By the end of the study, the 4th of the monthly assessments showed that both the group-A and the group-B treatments had induced a significant increase in the quality-of-life index, the change being 11.9 points for Pharmaton Capsules in group A which was significantly superior to the 6.4 average increase with the group-B capsules containing multivitamins alone. Group A showed significant improvement in every one of the 11 questionnaire items, whereas group B did not show significant improvement in any of these items. Significant increases in body weight and in diastolic blood pressure were recorded in the group B treated with the multivitamin alone. Adverse effects of the capsules were minimal in both groups. This study has demonstrated that Pharmaton Capsules were more effective than the multivitamin capsules alone in improving the quality-of-life in a population subjected to the stress of high physical and mental activity.

[Duhring and Brocq dermatitis herpetiformis. Recent immunologic findings. Personal observations in a patient]. / Dermatite erpetiforme di Duhring e Brocq. Recenti acquisizioni immunologiche. Osservazioni personali su un paziente.

The clinical, anatomopathological and therapeutic aspects of herpetiform dermatitis are nowadays almost completely clarified; for this reason in this study we limit ourselves to evaluating only its essential characteristics. The above study is mainly intended to present an exhaustive documentation of the immunological pattern of Duhring-Brocq dermatitis.

[Cryptogenetic ulcerative colitis. Our clinical experience with new therapeutic approaches]. / Colite ulcerosa criptogenetica. Nostra esperienza clinica sulle nuove vedute terapeutiche.

Sixteen patients with flare-ups of ulcerative colitis were studied. Before and after treatment, patients were submitted to the customary laboratory tests and to x-ray (contrast enema) and endoscopic examination, biopsy material being harvested during the latter. Treatment consisted in the oral administration of 2-4 g 5-ASA daily for 30 days. Only one patient did not tolerate 5-ASA which was withdrawn. All other patients had good or very good results with remission of symptoms.

[Hyperlipidemia: physiopathology and our experience in the ambulatory care of 3 groups of patients undergoing blood lipid normalization treatment]. / Le iperlipidemie. Fisiopatologia e nostre esperienze ambulatoriali su tre gruppi di pazienti sottoposti a trattamento normolipemizzante.

The authors tested the efficacy of three different lipid-lowering drugs in subjects with more or less severe alterations of the lipoprotein pattern. All subjects were submitted to blood tests prior to and at the end of treatment with special attention to the trend of the lipid pattern, assaying cholesterol, HDL, LDL, triglyceride, total lipid blood levels and lipid electrophoresis. The drugs employed were: pantothenic acid, sulodexide, and DEAE-dextran.

[Simvastatin in the treatment of hypercholesterolemia]. / La simvastatina nel trattamento delle ipercolesterolemie.

We have treated twelve patients with simvastatin: six had type IIA hypercholesterolaemia and the other six had type IIB. These patients have been examined before and after therapy, by an ophthalmologist. After therapy, the levels of the total cholesterol and triglycerides were decreased while HDL cholesterol was increased. Untoward side effects of ophthalmologic alterations were not observed.