A Complex Case of Cholestasis in a Patient with ABCB4 and ABCB11 Mutations

The low-phospholipid-associated cholelithiasis (LPAC) syndrome is a form of symptomatic cholelithiasis occurring in young adults, characterized by recurrence of symptoms after cholecystectomy and presence of hepatolithiasis. The case refers to a healthy 39-year-old Caucasian male who presented with abdominal pain and jaundice. His blood tests showed conjugated hyperbilirubinemia and elevated liver enzymes (total bilirubin 6.65 mg/dL, γ-glutamyltransferase 699 IU/L) and abdominal computed tomography revealed dilation of common bile duct and left intrahepatic ducts. Magnetic resonance cholangiopancreatography identified choledocholithiasis, retrieved by endoscopic retrograde cholangiopancreatography, after which there was a worsening of jaundice (total bilirubin 23 mg/dL), which persisted for several weeks, possibly due to ciprofloxacin toxicity. After an extensive workup including liver biopsy, the identification of two foci of hepatolithiasis on reevaluation abdominal ultrasound raised the hypothesis of LPAC syndrome and the patient was started on ursodeoxycholic acid, with remarkable improvement. Genetic testing identified the mutation c.1954A>G (p.Arg652Gly) in ABCB4 gene (homozygous) and c.1331T>C (p.Val444Ala) in ABCB11 gene (heterozygous). In conclusion, we describe the unique case of an adult male with choledocholithiasis, hepatolithiasis, and persistent conjugated hyperbilirubinemia after retrieval of stones, fulfilling the criteria for LPAC syndrome and with possible superimposed drug-induced liver injury, in whom ABCB4 and ABCB11 mutations were found, both of which had not been previously described in association with LPAC.info:eu-repo/semantics/publishedVersio

Integration of touch attention mechanisms to improve the robotic haptic exploration of surfaces

This text presents the integration of touch attention mechanisms to improve the efficiency of the action-perception loop, typically involved in active haptic exploration tasks of surfaces by robotic hands. The progressive inference of regions of the workspace that should be probed by the robotic system uses information related with haptic saliency extracted from the perceived haptic stimulus map (exploitation) and a “curiosity”-inducing prioritisation based on the reconstruction's inherent uncertainty and inhibition-of-return mechanisms (exploration), modulated by top-down influences stemming from current task objectives, updated at each exploration iteration. This work also extends the scope of the top-down modulation of information presented in a previous work, by integrating in the decision process the influence of shape cues of the current exploration path. The Bayesian framework proposed in this work was tested in a simulation environment. A scenario made of three different materials was explored autonomously by a robotic system. The experimental results show that the system was able to perform three different haptic discontinuity following tasks with a good structural accuracy, demonstrating the selectivity and generalization capability of the attention mechanisms. These experiments confirmed the fundamental contribution of the haptic saliency cues to the success and accuracy of the execution of the tasks

The albumin-bilirubin score predicting the mortality of patients with decompensated cirrhosis.

info:eu-repo/semantics/publishedVersio

On the use of the cumulative strain energy density for fatigue life assessment in advanced high-strength steels

Publisher Copyright: © 2022 Elsevier LtdIn this paper, the applicability of the cumulative strain energy density is explored as a fatigue indicator parameter for advanced high-strength steels subjected to strain-controlled conditions. Firstly, the cyclic stress–strain responses of nine steels, selected from three multiphase families, encompassing different elemental compositions and different heat treatment routes, were studied. Then, the predictive capabilities of the proposed model were compared with those of other strain-based and energy-based approaches. It was found that the cumulative strain energy density decreases as the strain amplitude increaes. It was also found that the cumulative strain energy density and the fatigue life can be related via a power function. In addition, the relationship between the cumulative strain energy and the fatigue life was not significantly affected by the elemental composition or the heat treatment route. Finally, the fatigue lives computed through the cumulative strain energy density concept were close to those of the other models but were slightly more conservative.publishersversionpublishe

Morphometry and gyrification in bipolar disorder and schizophrenia: A comparative MRI study

Schizophrenia is believed to be a neurodevelopmental disease with high heritability. Differential diagnosis is often challenging, especially in early phases, namely with other psychotic disorders or even mood disorders. such as bipolar disorder with psychotic symptoms. Key pathophysiological changes separating these two classical psychoses remain poorly understood, and current evidence favors a more dimensional than categorical differentiation between schizophrenia and bipolar disorder. While established biomarkers like cortical thickness and grey matter volume are heavily influenced by post-onset changes and thus provide limited possibility of accessing early pathologies, gyrification is assumed to be more specifically determined by genetic and early developmental factors. The aim of our study was to compare both classical and novel morphometric features in these two archetypal psychiatric disorders. We included 20 schizophrenia patients, 20 bipolar disorder patients and 20 age- and gender-matched healthy controls. Data analyses were performed with CAT12/SPM12 applying general linear models for four morphometric measures: gyrification and cortical thickness (surface-based morphometry), and whole-brain grey matter/grey matter volume (voxel-based morphometry - VBM). Group effects were tested using age and gender as covariates (and total intracranial volume for VBM). Voxel-based morphometry analysis revealed a schizophrenia vs. control group effect on regional grey matter volume (p < 0.05, familywise error correction) in the right globus pallidus. There was no group effect on white matter volume when correcting for multiple comparisons neither on cortical thickness. Gyrification changes in clinical samples were found in the left supramarginal gyrus (BA40) - increased and reduced gyrification, respectively, in BPD and SCZ patients - and in the right inferior frontal gyrus (BA47), with a reduction in gyrification of the SCZ group when compared with controls. The joint analysis of different morphometric features, namely measures such as gyrification, provides a promising strategy for the elucidation of distinct phenotypes in psychiatric disorders. Different morphological change patterns, highlighting specific disease trajectories, could potentially generate neuroimaging-derived biomarkers, helping to discriminate schizophrenia from bipolar disorder in early phases, such as first-episode psychosis patients.info:eu-repo/semantics/publishedVersio

A fundamental distinction in early neural processing of implicit social interpretation in schizophrenia and bipolar disorder

Background: Social cognition impairment is a key phenomenon in serious mental disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). Although genetic and neurobiological studies have suggested common neural correlates, here we hypothesized that a fundamental dissociation of social processing occurs at an early level in these conditions. Methods: Based on the hypothesis that key structures in the social brain, namely the temporoparietal junction, should present distinctive features in SCZ and BPD during low-level social judgment, we conducted a case-control study in SCZ (n = 20) and BPD (n = 20) patients and controls (n = 20), using task-based fMRI during a Theory of Mind (ToM) visual paradigm leading to interpretation of social meaning based on simple geometric figures. Results: We found opposite neural responses in two core ToM regions: SCZ patients showed social content-related deactivation (relative to controls and BPD) of the right supramarginal gyrus, while the opposite pattern was found in BPD; reverse patterns, relative to controls and SCZ, were found in the left posterior superior temporal gyrus, a region involved in inferring other's intentions. Receiver-operating-characteristic curve analysis showed 88% accuracy in discriminating the two clinical groups based on these neural responses. Conclusions: These contrasting activation patterns of the temporoparietal junction in SCZ and BPD represent mechanistic differences of social cognitive dysfunction that may be explored as biomarkers or therapeutic targets.info:eu-repo/semantics/publishedVersio

Peptide Receptor Radionuclide Therapy with 177 Lu-DOTA-TATE As a Promising Treatment of Malignant Insulinoma: a Series of Case Reports and Literature Review

Introduction: Insulinomas are a rare type of pancreatic neuroendocrine tumours characterized by insulin hypersecretion. They are considered malignant when metastases are present. Traditional therapies often promote only temporarily symptomatic relief and may be associated with severe adverse effects. There is scarce experience in treating malignant insulinomas with peptide receptors radionuclide therapy (PRRNT). Patients and methods: We describe PRRNT results in four patients with inoperable malignant insulinomas with poorly controllable hypoglycaemia. All patients received therapy with 177Lu-DOTA-TATE after conventional therapies failed in controlling disease progression and symptoms. The activity administered per cycle was 4.8-7.4 GBq. The interval between cycles was 10-16 weeks. Haematology, liver and kidney function tests were performed before treatment initiation and 5 and 10 weeks after each cycle. Results: Patient 1 presented significant clinical benefit for 13 months after PRRNT, with imaging improvement. Patient 2 obtained reduction of the number and severity of hypoglycaemic episodes during 15 months after therapy. Patient 3 is asymptomatic since PRRNT first cycle performed 23 months ago and revealed significant imaging improvement. Patient 4 had resolution of hypoglycaemia only 3 days after PRRNT first cycle and today, 16 months after therapy, the disease seems to be in remission and the patient maintains euglycaemic state. PRRNT was well tolerated, with only hematologic grade 2 toxicity in patient 1 and mild kidney toxicity in patient 3. Conclusions: After the start of 177Lu-DOTA-TATE all patients achieved hypoglycaemia symptomatic control and had evident improvement of their quality of life. Three patients showed imagiological improvement suggesting reduced tumour load.info:eu-repo/semantics/publishedVersio

Agricultura apoiada pela comunidade: poderia a experiência dos agricultores americanos ser útil para os agricultores urbanos brasileiros?

O objetivo deste trabalho foi obter algumas informações sobre o projeto Agricultura Apoiada pela Comunidade (AAC) nos EUA e avaliar se consumidores e produtores urbanos pobres de uma cidade brasileira de baixa renda aceitariam se engaja neste tipo de projeto

Study of the middle ear behavior considering the presence of fluid

O objetivo deste trabalho foi estudar a influência de diferentes fluidos dentro e fora da cavidade timpânica no comportamento biomecânico do ouvido médio. O modelo computacional 3 D da cadeia tímpano‐ossicular foi construído através de imagens de tomografia axial computorizada (TAC). Após a construção do modelo da cadeia tímpano‐ossicular, para a parte interna da membrana timpânica foi criada a caixa timpânica, que inclui toda a cadeia ossicular, e para a parte externa da membrana foi criada uma passagem, simulando o canal auditivo externo. A discretização do modelo foi feita utilizando o método dos elementos finitos, com base no software ABAQUS. As propriedades mecânicas foram extraídas de trabalhos anteriores. Foram obtidos os deslocamentos do umbo e de um ponto central da platina do estribo, para um nível de pressão sonora de 105 dB aplicada na membrana timpânica, comparando a cadeia tímpano‐ossicular e os diferentes níveis de pressão externa e interna do ouvido médio (fluido líquido e fluido gasoso). Os resultados demonstram que o comportamento biomecânico do ouvido médio é diferente para os diferentes níveis de pressões testadas neste modelo. Quando utilizada uma pressão de fluido líquido, os deslocamentos são de amplitude inferior quando comparados com os resultados obtidos com pressão de ar.The objective of this work is to study the influence of different fluids of the tympanic cavity into the biomechanical behavior of the middle ear. The 3 D computer model of the tympanic ossicular chain was built using images from computed tomography (CT). After construction of the tympanic ossicular chain model, it was adapted the simulation by placing the passage to the external auditory canal and to the tympanic cavity. The discretization of the model was made using the finite element method based on ABAQUS software. The mechanical properties were extracted from previous works. The umbo and the stapes footplate displacements, for a sound pressure level of 105 dB applied in tympanic membrane were obtained, comparing the tympanic ossicular chain and the different levels of external and internal pressure in the middle ear (liquid and air). The results demonstrate that the biomechanical behavior of the middle ear is different for different levels of pressure tested in this model. When using liquid, displacements are of lower amplitude when compared with the results obtained with air.Peer Reviewe

ESMO Guidance for Reporting Oncology real-World evidence (GROW)

Clinical epidemiolog