Ventral tegmental area dopamine projections to the hippocampus trigger long-term potentiation and contextual learning.

In most models of neuronal plasticity and memory, dopamine is thought to promote the long-term maintenance of Long-Term Potentiation (LTP) underlying memory processes, but not the initiation of plasticity or new information storage. Here, we used optogenetic manipulation of midbrain dopamine neurons in male DAT::Cre mice, and discovered that stimulating the Schaffer collaterals - the glutamatergic axons connecting CA3 and CA1 regions - of the dorsal hippocampus concomitantly with midbrain dopamine terminals within a 200 millisecond time-window triggers LTP at glutamatergic synapses. Moreover, we showed that the stimulation of this dopaminergic pathway facilitates contextual learning in awake behaving mice, while its inhibition hinders it. Thus, activation of midbrain dopamine can operate as a teaching signal that triggers NeoHebbian LTP and promotes supervised learning.

Passive Exercise Adaptation for Ankle Rehabilitation Based on Learning Control Framework.

Ankle injuries are among the most common injuries in sport and daily life. However, for their recovery, it is important for patients to perform rehabilitation exercises. These exercises are usually done with a therapist's guidance to help strengthen the patient's ankle joint and restore its range of motion. However, in order to share the load with therapists so that they can offer assistance to more patients, and to provide an efficient and safe way for patients to perform ankle rehabilitation exercises, we propose a framework that integrates learning techniques with a 3-PRS parallel robot, acting together as an ankle rehabilitation device. In this paper, we propose to use passive rehabilitation exercises for dorsiflexion/plantar flexion and inversion/eversion ankle movements. The therapist is needed in the first stage to design the exercise with the patient by teaching the robot intuitively through learning from demonstration. We then propose a learning control scheme based on dynamic movement primitives and iterative learning control, which takes the designed exercise trajectory as a demonstration (an input) together with the recorded forces in order to reproduce the exercise with the patient for a number of repetitions defined by the therapist. During the execution, our approach monitors the sensed forces and adapts the trajectory by adding the necessary offsets to the original trajectory to reduce its range without modifying the original trajectory and subsequently reducing the measured forces. After a predefined number of repetitions, the algorithm restores the range gradually, until the patient is able to perform the originally designed exercise. We validate the proposed framework with both real experiments and simulation using a Simulink model of the rehabilitation parallel robot that has been developed in our lab.

Variable Impedance Control and Learning-A Review.

Robots that physically interact with their surroundings, in order to accomplish some tasks or assist humans in their activities, require to exploit contact forces in a safe and proficient manner. Impedance control is considered as a prominent approach in robotics to avoid large impact forces while operating in unstructured environments. In such environments, the conditions under which the interaction occurs may significantly vary during the task execution. This demands robots to be endowed with online adaptation capabilities to cope with sudden and unexpected changes in the environment. In this context, variable impedance control arises as a powerful tool to modulate the robot's behavior in response to variations in its surroundings. In this survey, we present the state-of-the-art of approaches devoted to variable impedance control from control and learning perspectives (separately and jointly). Moreover, we propose a new taxonomy for mechanical impedance based on variability, learning, and control. The objective of this survey is to put together the concepts and efforts that have been done so far in this field, and to describe advantages and disadvantages of each approach. The survey concludes with open issues in the field and an envisioned framework that may potentially solve them.

Invasive pulmonary aspergillosis: comparative analysis in cancer patients with underlying haematologic malignancies versus solid tumours.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is commonly associated with haematologic malignancies but also occurs with solid tumours. AIM: To compare the diagnostic approaches and therapeutic outcomes for IPA between patients with haematologic malignancies and solid cancers. METHODS: A retrospective study was conducted evaluating consecutive cases of proven and probable IPA from 2004 to 2016. Patients >18 years of age with an underlying solid tumour, haematologic malignancy, or haematopoietic cell transplantation (HCT) within one year of IPA diagnosis were included. FINDINGS: Of the 311 patients analysed, 225 had haematologic malignancies and 86 had solid tumours. Patients with solid tumours were more likely to have had chronic obstructive pulmonary disease (COPD) or other pulmonary diseases, have Aspergillus fumigatus infections, and have received radiotherapy before IPA occurrence than were those with haematologic malignancies (all P<0.01). Antifungal monotherapy and voriconazole-based therapy were more often prescribed in the solid group (87% vs 56%, P<0.0001, and 77% vs 53%, P=0.0002, respectively). The median duration of primary antifungal therapy was longer in the solid group (64 days vs 20 days, P<0.0001). Complete or partial response to antifungal therapy was recorded in 66% of the solid group and 40% of the haematologic group (P=0.0001). At 12 weeks, overall mortality was similar in both groups, but IPA-attributable mortality was higher in the haematologic group (30% vs 18%, P=0.04). CONCLUSIONS: Monotherapy was more often prescribed in patients with solid tumours than in patients with haematologic malignancies. Patients with solid tumours had better antifungal therapy response and lower 12-week IPA-attributable mortality than did those with haematologic malignancies.

Practical Use of Robot Manipulators as Intelligent Manufacturing Systems.

This paper presents features and advanced settings for a robot manipulator controller in a fully interconnected intelligent manufacturing system. Every system is made up of different agents. As also occurs in the Internet of Things and smart cities, the big issue here is to ensure not only that implementation is key, but also that there is better common understanding among the main players. The commitment of all agents is still required to translate that understanding into practice in Industry 4.0. Mutual interactions such as machine-to-machine and man-to-machine are solved in real time with cyber physical capabilities. This paper explores intelligent manufacturing through the context of industrial robot manipulators within a Smart Factory. An online communication algorithm with proven intelligent manufacturing abilities is proposed to solve real-time interactions. The algorithm is developed to manage and control all robot parameters in real-time. The proposed tool in conjunction with the intelligent manufacturing core incorporates data from the robot manipulators into the industrial big data to manage the factory. The novelty is a communication tool that implements the Industry 4.0 standards to allow communications among the required entities in the complete system. It is achieved by the developed tool and implemented in a real robot and simulation.

The role of tumor suppressor p15Ink4b in the regulation of hematopoietic progenitor cell fate.

Epigenetic silencing of the tumor suppressor gene p15Ink4b (CDKN2B) is a frequent event in blood disorders like acute myeloid leukemia and myelodysplastic syndromes. The molecular function of p15Ink4b in hematopoietic differentiation still remains to be elucidated. Our previous study demonstrated that loss of p15Ink4b in mice results in skewing of the differentiation pattern of the common myeloid progenitor towards the myeloid lineage. Here, we investigated a function of p15Ink4b tumor suppressor gene in driving erythroid lineage commitment in hematopoietic progenitors. It was found that p15Ink4b is expressed more highly in committed megakaryocyte-erythroid progenitors than granulocyte-macrophage progenitors. More importantly, mice lacking p15Ink4b have lower numbers of primitive red cell progenitors and a severely impaired response to 5-fluorouracil- and phenylhydrazine-induced hematopoietic stress. Introduction of p15Ink4b into multipotential progenitors produced changes at the molecular level, including activation of mitogen-activated protein kinase\extracellular signal-regulated kinase (MEK/ERK) signaling, increase GATA-1, erythropoietin receptor (EpoR) and decrease Pu1, GATA-2 expression. These changes rendered cells more permissive to erythroid commitment and less permissive to myeloid commitment, as demonstrated by an increase in early burst-forming unit-erythroid formation with concomitant decrease in myeloid colonies. Our results indicate that p15Ink4b functions in hematopoiesis, by maintaining proper lineage commitment of progenitors and assisting in rapid red blood cells replenishment following stress.

The association of tooth wear, diet and dietary habits in adults aged 18-30 years old.

OBJECTIVE: The association of acidic foods and drinks to the development of erosive tooth wear was investigated in a single cohort of adults aged 18-30 years. METHOD: A tooth wear index was recorded on 1010 participant's who had a mean age of 21.9 years (SD 0.1) and of which 70% were female and 30% males. Participant's completed a previously validated questionnaire containing 50 questions about current and historical dietary habits. Data were analysed at the tooth level using odds ratio. RESULTS: Tooth wear was statistically significantly associated to acidic foods and drinks with high titratable acidity and dietary habits, including drinking from a glass and holding drinks, (OR 5 and 6.5 respectively). A history of heartburn was statistically significantly associated to palatal dentine exposure (p≤0.05 and OR 7.6). CONCLUSION: In this sample of adults, tooth wear was associated to a number of acidic dietary products and drinking habits.

[Chronic constrictive pericarditis: MR imaging features]. / Comment je fais une IRM pour péricardite chronique constrictive?

Chronic constrictive pericarditis is defined by an increase in the rigidity of the pericardium resulting in impairment of the ventricular filling conditions. Cardiac MR is both a morphological and functional study always complemented by multi-detector CT. Morphological analysis is based on axial, longitudinal long axis and short axis views on Turbo (fast) SE Dark Blood and CINE sequences. Functional analysis is based on real-time acquisitions in the short axis at the base of the ventricles by comparing spontaneous breathing and deep breathing. The excursion of the interventricular septum is a reliable sign of constriction. The study is supplemented by phase contrast acquisitions. In the setting of persistent inflammation or free pericardial fluid, delayed enhancement 3D and 2D sequences including Phase Sensitive Inversion Recovery (PSIR) are useful.

[Usefulness of magnetic resonance imaging in Churg-Strauss syndrome related cardiac involvement. A case series of three patients and literature review]. / Intérêt de l'imagerie par résonance magnétique nucléaire au cours de l'atteinte cardiaque du syndrome de Churg-Strauss. Trois observations et revue de la littérature.

PURPOSE: The reported prevalence of cardiac complications is variable in patients with Churg-Strauss syndrome (15-92%) and depends on diagnostic tools. Diagnosis at early stage of heart involvement is crucial, resulting in appropriate management. METHODS: We report three patients who developed cardiac manifestations, revealing Churg-Strauss syndrome. The diagnosis of cardiac involvement was obtained using cardiac magnetic resonance imaging (MRI). RESULTS: Two patients were males and the remaining one was a female. Presenting clinical manifestations were: cardiac failure (n=1) and retrosternal pain (n=2). Laboratory findings disclosed: high blood count of eosinophils (range: 6000-11,000/mm(3)); antineutrophil cytoplasmic antibodies were positive in a single patient. Cardiac MRI demonstrated: (1) late gadolinium enhancement (n=3), involving mainly the apical and mid-cavity left ventricular segments; (2) impaired left ventricular function (n=2), mean left ventricular ejection fraction being: 51%; and (3) pericardial effusion (n=3). Outcome was favourable after institution of combined therapy with prednisone and cyclophosphamide (n=2); one patient also underwent plasma exchanges. CONCLUSION: Our case series underlines that MRI is a helpful tool in the diagnosis of Churg-Strauss syndrome-related cardiac complications. We further suggest that clinical assessment of patients with Churg-Strauss syndrome should include cardiac MRI, in order to detect cardiac involvement at an early stage; indeed, because cardiac manifestations are predictive factors of poor prognosis, diagnosis at early stages of cardiac involvement may result in improvement of patients management.

A new index of tooth wear. Reproducibility and application to a sample of 18- to 30-year-old university students.

A modified wear index, in which the wear of enamel and dentine are recorded separately, is described. The index was applied to estimating the prevalence and extent of tooth wear in a single convenience sample of 18- to 30-year-old students attending a university in London. The subjects were examined under good lighting in a dental chair away from a dental school. A total of 707 females and 303 males were recruited with a mean age of 21.9 years (standard deviation = 0.1, range = 18-30) and examined by 3 trained and calibrated examiners. Intra-examiner intra-class correlation coefficients showed a range of 0.44-0.88. The unweighted kappa scores were above 0.88 for enamel and dentine. The presence of enamel wear was common to all subjects, but 6.1% of the participants had more than one third of the tooth surface affected. Dentine was exposed on 5.3% of all surfaces, with the largest proportion accounting for less than 10% of the tooth surface (grade 1). The proportion of subjects with at least 1 surface with dentine exposed was 76.9% of the total population. The males had significantly more wear in dentine than the females (p = 0.001). The inter-examiner intra-class correlation coefficients for enamel and dentine were 0.87 and 0.92, respectively. The reproducibility of the index was comparable to other analyses and provides an opportunity to assess the prevalence of enamel wear in large population-based studies.

Prosthetic joint infection by Mycobacterium tuberculosis: an unusual case report with literature review.

Prosthetic joint infection with Mycobacterium tuberculosis usually involves the hips or knees and can result from either local reactivation, or less often from hematogenous spread. Predisposing conditions include rheumatoid arthritis, chronic steroid use and pulmonary diseases. The most common symptom at presentation is pain, and the most common physical finding is joint swelling and/or a draining sinus tract. The sedimentation rate is helpful when elevated but is nonspecific, and initial skin testing is only helpful when positive. The diagnosis depends on culture and histologic examination of tissue. Removal of the joint combined with oral antituberculous treatment is necessary when the infection is discovered greater than six weeks post joint replacement. Early diagnosis leads to decreased morbidity. Tuberculous infection of prosthetic joints is a rare disease and its diagnosis depends on a high degree of clinical suspicion.

Genotypes of hepatitis C virus (HCV) among positive Lebanese patients: comparison of data with that from other Middle Eastern countries.

Recently we identified hepatitis C virus (HCV) genotype 4 as the principle genotype among Lebanese thalassaemics. In an attempt to confirm the predominance of genotype 4 in Lebanon and perhaps in the Middle East, genotyping was attempted on 142 HCV-infected Lebanese patients from five different hospitals in the country. These included 38 HCV-positive patients with symptomatic liver disease who were referred to gastroenterologists and 104 HCV-positive patients with no symptoms of liver disease: 27 patients with thalassaemia, 30 patients on haemodialysis, 32 multi-transfused and 15 intravenous drug users. HCV genotyping was performed on PCR HCV RNA-positive samples using a commercial line probe assay (LiPA; Innogenetics, Ghent, Belgium). HCV genotype 4 is found to be the predominant genotype among HCV-infected Lebanese patients (ranging from 34.2% to 53.3%) followed by 1a (ranging from 12.5% to 43.3%) and 1b (ranging from 8.0% to 34.4%). In patients with symptomatic liver disease, however, genotype 4 (34.2%) was preceded by genotype 1a (39.5%). The predominance of HCV genotype 4 in our population (45.7%) confirms the predominance of HCV genotype 4 in Lebanon and most of the Arab countries in the Middle East but contrasts with data reported from non-Arab Middle Eastern Countries as can be seen from the literature review. Implications of genotyping for clinical outcome of HCV infection, response to treatment as well as for vaccine development are discussed.

Distribution of hepatitis C virus genotypes in the Middle East.

It is well established that hepatitis C develops into cirrhosis of the liver and hepatocellular carcinoma (HCC) both of which are fatal diseases. The World Health Organization estimates that there are at least 21.3 million hepatitis C virus (HCV) carriers in the Eastern Mediterranean countries, which is close to the number of carriers estimated in the Americas and Europe combined. With such a high disease burden of HCV infection in this part of the world, and in light of the new evidence that genotypes may influence the outcome of antiviral therapy, the focus of this review is on the epidemiology and distribution of HCV genotypes in the Eastern Mediterranean countries. Accumulated data show that there are two main patterns for the distribution of HCV genotypes in the Middle East: in the first pattern, genotype 4 is prevalent in most of the Arab countries, and in the second pattern, genotype 1a or 1b predominates in the non-Arab countries. Results from the limited number of clinical trials on the treatment of chronic HCV genotype 4 using peginterferon alfa-2b in combination with ribavirin are encouraging. However, efforts to develop more effective antiviral therapies and the establishment of an effective HCV vaccine remain the largest challenges for the near future.

Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome.

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by parathyroid tumours, which are frequently carcinomas, and ossifying jaw fibromas. In addition, some patients may develop renal tumours and cysts. The gene causing HPT-JT, which is referred to as HRPT2 and is located on chromosome 1q31.2, encodes a 531 amino acid protein called PARAFIBROMIN. To date 42 mutations, of which 22 are germline, have been reported and 97% of these are inactivating and consistent with a tumour suppressor role for HRPT2. We have investigated another four HPT-JT families for germline mutations, searched for additional clinical phenotypes, and examined for a genotype-phenotype correlation. Mutations were found in two families. One family had a novel deletional-insertion at codon 669, and the other had a 2 bp insertion at codon 679, which has been reported in four other unrelated patients. These five unrelated patients and their families with the same mutation were not found to develop the same tumours, thereby indicating an absence of a genotype-phenotype correlation. An analysis of 33 HPT-JT kindreds revealed that affected women in 13 HPT-JT families suffered from menorrhagia in their second to fourth decades. This often required hysterectomy, which revealed the presence of uterine tumours. This resulted in a significantly reduced maternal transmission of the disease. Thus, the results of our analysis expand the spectrum of HPT-JT-associated tumours to include uterine tumours, and these may account for the decreased reproductive fitness in females from HPT-JT families.

Bronchiolitis obliterans organizing pneumonia as a manifestation of AIDS: case report and literature review.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a disease of the small airways characterized by intraluminal polyps of myxoid connective tissue. Although various infectious and non-infectious agents have been implicated as possible precipitants of BOOP, the concomitant occurrence of BOOP with human immunodeficiency virus (HIV) infection has rarely been described. We describe a unique case in which BOOP was a presenting feature in a patient with newly diagnosed AIDS, and we review the literature of BOOP occurring in the setting of HIV infection.