Trèlat's beads as oral manifestations in patients with HIV/TB

Tuberculosis (TB) is a contagious infectious disease caused by Mycobacterium tuberculosis (Koch's bacillus). Co-infection with human immunodeficiency virus (HIV) and TB has reached a significant importance as a public health problem and this association has been recognized as the most significant event that changed "the balance between man and Koch's bacillus" in the last century, and has a large contribution to the risk for disease spreading. Tuberculosis has two main standard categories of clinical manifestations: primary and secondary. Primary TB is responsible for the initial infection with lungs being the involved organ. Oral lesions are observed as a secondary TB clinical manifestation with most frequent sites being hard and soft palate, tongue, lips, gums, tonsils, and salivary glands. A case of classical TB lesions in the oral cavity is reported, and the importance of a correct diagnosis through careful history taking is emphasized. Treatment selection needs to be done assertively, with great determination and building a link between patient and treatment protocol, in order to promote patient's adherence.

Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease

The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.

Different Kinds of Paraneoplastic Syndromes in Childhood Neuroblastoma

Background: Clinical presentations of paraneoplastic syndromes in neuroblastoma may multiply. Review of the clinical data and the literature on this syndrome may help in the diagnosis of neuroblastoma. Objectives: In order to make more accurate diagnosis, we reviewed the clinical data and the literature on this syndrome. Patients and Methods: Between April 2007 and April 2012, 68 children were diagnosed with neuroblastoma or ganglioneuroblastoma in our institution, 9 of which presented exclusively with paraneoplastic syndromes and were not treated with chemotherapy prior to diagnosis. After the diagnosis, all patients received chemotherapy and operation on NB97 protocol. Results: Among 68 pediatric patients with neuroblastoma or ganglioneuroblastoma, 4 (5.9%) patients suffered from neurological complications at diagnosis, 2 (2.9%) patients had digestive tract disorders, 2 (2.9%) patients had immune diseases, and 1 (1.5%) suffered from hematological disorder (without bone marrow involvement). All paraneoplastic syndrome patients achieved complete remission on paraneoplastic syndrome before completion of chemotherapy. Conclusions: Neuroblastoma may present with a range of non-specific neurologic symptoms in addition to the well-known opsoclonus-myoclonus syndrome and cerebellar ataxia. In any case, the presence of unexplained neurologic manifestations and other common clinical presentations such as rash, constipation, diarrhea, and especially immune disorders in an otherwise healthy child had raised the possibility of paraneoplastic syndrome due to the presence of an undiagnosed tumor.

The effect of chaperone compounds on glucocerebrosidase stability and activity in fibroblasts from Gaucher Disease patients with different genotypes

Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014

Atopic Manifestations: Dermatitis, Allergic Rhinitis and Asthma in Patients With Hypogammaglobulinemia

Background: Most of the hypogammaglobulinemic patients have a clinical history in favor of allergic respiratory disease. Nevertheless, in these patients the importance and prevalence of atopic disorders have not been completely explained. Objectives: This study was aimed to evaluate atopic manifestations (dermatitis, allergic rhinitis and asthma) and pulmonary function in patients with hypogammaglobulinemia. Patients and Methods: We used the international study of asthma and allergies in childhood (ISAAC) questionnaire in forty-five patients diagnosed with hypogammaglobulinemia and spirometry was done in 41 patients older than 5 years. Results: Spirometry results were normal in 21 (51%), and showed obstructive in 15 (37%) and restrictive pattern in 5 (12%) of the 41 patients who were evaluated. By the end of the study, asthma was diagnosed in nine (20%) patients and other atopies (rhinitis and dermatitis) identified in 10 (22%), and four (9%), respectively. Conclusions: Atopic conditions should be investigated in the hypogammaglobulinemic patients and the prevalence in these patients may be higher than in normal population. Also, it is recommended to perform a pulmonary function test as a routine procedure in patients with hypogammaglobulinemia and atopy should be assessed in these patients.

Programme d'intervention visant la diminution des manifestations d'opposition et de provocation chez les enfants de 3 ans par l'apprentissage des habiletés sociales et d'autocontrôle, en intégrant un volet soutien à l'éducatrice au programme Brindami

Rapport d'analyse d'intervention présenté à la Faculté des arts et sciences en vue de l'obtention du grade de Maîtrise ès sciences (M. Sc.) en psychoéducation.

Programme d'intervention visant la diminution des manifestations d'opposition et de provocation chez les enfants de 3 ans par l'apprentissage des habiletés sociales et d'autocontrôle, en intégrant un volet soutien à l'éducatrice au programme Brindami

Rapport d'analyse d'intervention présenté à la Faculté des arts et sciences en vue de l'obtention du grade de Maîtrise ès sciences (M. Sc.) en psychoéducation.

Investigating the Roles and Requirements, Manifestations and Management of Metadata in the Creation of Reliable and Preservation of Authentic Electronic Entities Created by Dynamic, Interactive and Experiential Systems: Report on the Work and Findings of the Interpares 2 Description Cross Domain Group

Metadata that is associated with either an information system or an information object for purposes of description, administration, legal requirements, technical functionality, use and usage, and preservation, plays a critical role in ensuring the creation, management, preservation and use and re-use of trustworthymaterials, including records. Recordkeeping1 metadata, of which one key type is archival description, plays a particularly important role in documenting the reliability and authenticity of records and recordkeeping systemsas well as the various contexts (legal-administrative, provenancial, procedural, documentary, and technical) within which records are created and kept as they move across space and time. In the digital environment, metadata is also the means by which it is possible to identify how record components – those constituent aspects of a digital record that may be managed, stored and used separately by the creator or the preserver – can be reassembled to generate an authentic copy of a record or reformulated per a user’s request as a customized output package.Issues relating to the creation, capture, management and preservation of adequate metadata are, therefore, integral to any research study addressing the reliability and authenticity of digital entities, regardless of the community, sector or institution within which they are being created. The InterPARES 2 Description Cross-Domain Group (DCD) examined the conceptualization, definitions, roles, and current functionality of metadata and archival description in terms of requirements generated by InterPARES 12. Because of the needs to communicate the work of InterPARES in a meaningful way across not only other disciplines, but also different archival traditions; to interface with, evaluate and inform existing standards, practices and other research projects; and to ensure interoperability across the three focus areas of InterPARES2, the Description Cross-Domain also addressed its research goals with reference to wider thinking about and developments in recordkeeping and metadata. InterPARES2 addressed not only records, however, but a range of digital information objects (referred to as “entities” by InterPARES 2, but not to be confused with the term “entities” as used in metadata and database applications) that are the products and by-products of government, scientific and artistic activities that are carried out using dynamic, interactive or experiential digital systems. The nature of these entities was determined through a diplomatic analysis undertaken as part of extensive case studies of digital systems that were conducted by the InterPARES 2 Focus Groups. This diplomatic analysis established whether the entities identified during the case studies were records, non-records that nevertheless raised important concerns relating to reliability and authenticity, or “potential records.” To be determined to be records, the entities had to meet the criteria outlined by archival theory – they had to have a fixed documentary format and stable content. It was not sufficient that they be considered to be or treated as records by the creator. “Potential records” is a new construct that indicates that a digital system has the potential to create records upon demand, but does not actually fix and set aside records in the normal course of business. The work of the Description Cross-Domain Group, therefore, addresses the metadata needs for all three categories of entities.Finally, since “metadata” as a term is used today so ubiquitously and in so many different ways by different communities, that it is in peril of losing any specificity, part of the work of the DCD sought to name and type categories of metadata. It also addressed incentives for creators to generate appropriate metadata, as well as issues associated with the retention, maintenance and eventual disposition of the metadata that aggregates around digital entities over time.

Les manifestations d’autodétermination par les élèves ayant participé à la TÉVA sur les plans scolaire, professionnel et personnel

Cet essai s’intéresse à l’autonomie des jeunes adultes ayant un handicap moteur, physique, sensoriel ou intellectuel et qui ont participé à la démarche de la transition de l’école à la vie active (TÉVA). L’objectif de l’essai est de répertorier les manifestations d’autodétermination dans leur vie professionnelle, scolaire et personnelle. Le contenu des 23 entrevues conduites auprès d’élèves ayant participé à la TÉVA ou de leurs proches dans le cadre d’une étude de Bourdon et Lessard (2015) portant sur la modélisation de la démarche TÉVA en Estrie a été analysé afin d’en extraire les manifestations d’autodétermination. L’analyse thématique des entrevues a permis d’identifier des manifestations d’autodétermination issues d’une régulation externe, d’une régulation introjectée et d’une régulation identifiée. Les résultats obtenus révèlent que les jeunes adultes ayant participé à la TÉVA semblent avoir une bonne connaissance d’eux-mêmes, de leurs intérêts scolaires et professionnels. En contrepartie, le sentiment de compétence, la fierté personnelle et la connaissance des actions à poser pour atteindre leurs objectifs semblent se présenter moins fréquemment en termes de manifestation d’autodétermination chez les jeunes adultes de l’échantillon. Dans peu de cas, les élèves ont rapporté avoir entamé de leur propre chef des démarches pour obtenir un milieu de stage pour lequel ils entretenaient de l’intérêt. L'analyse des entrevues a également révélé que la conseillère ou le conseiller d'orientation ne semble pas être une professionnelle ou un professionnel particulièrement sollicité pour soutenir les élèves en difficulté dans l'élaboration d'un projet professionnel. Bien que l’implication de la famille et du milieu scolaire des jeunes à propos de la transition à la vie adulte et de l’élaboration de projets soit sans aucun doute essentielle, les compétences du conseiller d’orientation en matière d’accompagnement des élèves dans l’élaboration et la mise en œuvre d’un projet scolaire ou professionnel pourraient être également mises à profit pour mieux préparer et accompagner les jeunes adultes dans leur transition. Ainsi, les données analysées dans le cadre de cet essai indiquent qu’il y a une place à prendre pour les conseillers d’orientation dans le soutien des élèves vivant avec un handicap.

Manifestations of Stigma and Prejudice Informed by Treated Lepers

Introduction: The segregation of people affected by leprosy in lepercolonies as well as presenting itself ineffective, caused irreversible and irreparable consequences in the lives of individuals who came to carry the marks of stigma and prejudice surrounding the disease. Objective: To identify traits related to the stigma and prejudice in the content of lepers' 12 speeches, separated compulsorily in Saint Francis of Assisi Colony in the city of Natal, located in the state of Rio Grande do Norte. Method: Descriptive study focusing on the oral history of life. The narratives were collected in April 2010 through a recorded interview and analyzed by means of the technique of Thematic Content Analyses. Results: The stigma and the prejudice crystallized in our culture had caused and still cause huge suffering and pain in the participants, who grew up and several aged in biological terms, living with a stigmatizing disease and its complications, sometimes disabling ones. In social and psychological terms, they were discriminated, rejected and even expelled from the familiar conviviality and the original social nucleus. Conclusion: In this manner, one notices the need of these people recover their attachments, values and self-esteem, share feelings and build relationships so as to be integrated in the real world.

"Portuguese Observatory of Taeniasis and Cysticercosis": A "One Health" example for epidemiological surveillance of one neglected disease in a European country

Cysticercosis results from the ingestion Taenia solium eggs directly by faecal-oral route or contaminated food or water. Human tapeworm carriers who have become infected after ingesting pork meat contaminated with cysticerci release these eggs. Cysticercosis occurs after tapeworm eggs are ingested by an intermediate host (pig or human) and then hatch, migrate, and lodge in the host's tissues, where they develop onto larval cysticerci. When they lodged in the central nervous system of humans, results in the disease condition called Neurocysticercosis (NCC), with a heterogeneous manifestations depending of the locations of cysts, number, size and their stage of evolution (1). Consequently the prognostic ranges from asymptomatic to situations leading to death in 2% to 9.8%. of cases (7) In swine’s there are few studies, but recent works have proved that animals, for the same reasons, also have neurological abnormalities, expressed by seizures, stereotypic walk in circles, chewing motions with foamy salivation included tonic muscle contractions followed by a sudden diminution in all muscle tone leading to collapse (2). Conventional domestic wastewater treatment processes may not be totally effective in inactivating parasites eggs from Taenia solium, allowing some contamination of soils and agricultural products (11). In Portugal there are some evidence of aggregation of human cysticercosis cases in specific regions, bases in ecological design studies (6). There are few information about human tapeworm carriers and social and economic factors associated with them. Success in knowledge and consequently in lowering transmission is limited by the complex network of biological and social factors that maintain the spread. Effective control of mostly zoonosis require One Health approach, after a real knowledge and transparency in the information provided by the institutions responsible for both animal and human health, allowing sustained interventions targeted at the transmission cycle's crucial nodes. In general, the model used to control, reflects a rural reality, where pigs are raised freely, poor sanitation conditions and incipient sanitary inspection. In cysticercosis, pigs are obligate intermediate hosts and so considered as first targets for control and used as sentinels to monitor environmental T. solium contamination (3). Usually environmental contamination with Taenia spp. eggs is a key issue in most of studies with landscape factors influencing presence of Taenia spp. antigens in both pigs and humans (5). Soil-related factors as well as socio-economic and behavioural factors are associated with the emergence of significant clustering human cysticercosis (4,5). However scarce studies has been produced in urban environmental and in developed countries with the finality to characterize the spatial pattern. There are still few data available regarding its prevalence and spatial distribution; Transmission patterns are likely to exhibit correlations as housing conditions, water supply, basic sanitation, schooling and birthplace of the individual or relatives, more than pigs rearing free, soil conditions (9). As a matter of fact, tapeworm carriers from endemic zones can auto-infect or transmit infection to other people or arrive already suffering NCC (as a result of travelling to or being a citizen from an endemic cysticercosis country) to a free cysticercosis country. Transmission is fecal-oral; this includes transmission through person-to-person contact, through autoinfection, or through contaminated food This has been happening in different continents as North America (5.4–18% been autochthonous), Europe and Australia (7). Recently, case reports of NCC have also emerged from Muslim countries. (10). Actually, different papers relate an epidemic situation in Spain and Portugal (7, 8). However the kind of study done does not authorize such conclusion. There are no evidence that infections were acquired in Portugal and there are not characterized the mode of transmission. Papers with these kind of information will be allow to have economic consequences resulted from artificial trade barriers with serious consequences for pig producers and pig meat trade. We need transparency in information’s that allow provide the basis to support the development and targeting of future effective control programmes (and prove we need that). So, to have a real picture of the disease, it is necessary integrate data from human, animal and environmental factors surrounding human and pig cases to characterize the pattern of the transmission. The design needs to be able to capture unexpected, and not common outcomes (routine data). We need to think “One Health” to get a genuine image of the situation.

Network analysis and machine learning assist drug repurposing and safety assessment in neurological diseases

In recent decades, two prominent trends have influenced the data modeling field, namely network analysis and machine learning. This thesis explores the practical applications of these techniques within the domain of drug research, unveiling their multifaceted potential for advancing our comprehension of complex biological systems. The research undertaken during this PhD program is situated at the intersection of network theory, computational methods, and drug research. Across six projects presented herein, there is a gradual increase in model complexity. These projects traverse a diverse range of topics, with a specific emphasis on drug repurposing and safety in the context of neurological diseases. The aim of these projects is to leverage existing biomedical knowledge to develop innovative approaches that bolster drug research. The investigations have produced practical solutions, not only providing insights into the intricacies of biological systems, but also allowing the creation of valuable tools for their analysis. In short, the achievements are: • A novel computational algorithm to identify adverse events specific to fixed-dose drug combinations. • A web application that tracks the clinical drug research response to SARS-CoV-2. • A Python package for differential gene expression analysis and the identification of key regulatory "switch genes". • The identification of pivotal events causing drug-induced impulse control disorders linked to specific medications. • An automated pipeline for discovering potential drug repurposing opportunities. • The creation of a comprehensive knowledge graph and development of a graph machine learning model for predictions. Collectively, these projects illustrate diverse applications of data science and network-based methodologies, highlighting the profound impact they can have in supporting drug research activities.

Characterization and natural history of different phenotypes in hereditary transthyretin amyloidosis: 40-year experience at a single Italian referral center

- Aims: Hereditary Transthyretin Amyloidosis (ATTRv) is one of the leading etiologies of systemic amyloidosis with more than 135 mutations described and a broad spectrum of clinical manifestations. We aimed to provide a systematic description of a population of individuals carrying pathogenic mutations of transthyretin (TTR) gene and to investigate the major clinical events during follow up. - Methods: Observational, retrospective, cohort study including consecutive patients with mutations of TTR gene, admitted to a tertiary referral center in Bologna, Italy, between 1984 and 2022. - Results: Three hundred twenty-five patients were included: 106 asymptomatic carriers, 49 cardiac phenotype, 49 neurological phenotype and 121 mixed phenotype. Twenty-three different mutations were found, with Ile68Leu (41.8%), Val30Met (19%), and Glu89Gln (10%) being the most common. After a median follow-up of 51 months data from 290 subjects were analyzed; among them 111 (38.3%) died and 123 (42.4%) had a major clinical event (death or hospitalization for heart failure). Nine (11.5%) of the 78 asymptomatic carriers showed signs and symptoms of the disease. Carriers had a prognosis comparable to healthy population, while no significant differences were seen among the three phenotypes adjusted by age. Age at diagnosis, NYHA functional class, left ventricular ejection fraction, mPND score and disease-modifying therapy were independently associated with survival. - Conclusions: This study offers a wide and comprehensive overview of ATTRv from the point of view of a tertiary referral center in Italy. Three main phenotypes can be identified (cardiac, neurological and mixed) with specific clinical and instrumental features. Family screening programs are essential to identify paucisymptomatic affected patients or unaffected carriers of the mutation, to be followed through the years. Lastly, disease-modifying therapy represents an evolving cornerstone of the management of ATTRv, with a great impact on mortality.

[the Sociology Of Health In Brazil - The Creation Of An Identity].

This article analyzes the historical, social and cognitive dimensions of the sociology of medicine in the construction of its identity, from Wolf Lepenies' perspective. It is understood that the construction of an identity does not end with the first historical manifestations, but is consolidated when it is institutionalized and structured as a field of knowledge by creating its own forms of cognitive expression. The text is divided into three parts: in the first the precursors are presented, highlighting the role played by some travelers, naturalists and folklore scholars, followed by social physicians-scientists and the first social scientists (1940-1969). In the second part, aspects of the consolidation of the social sciences in health are presented at two significant moments, namely the 1970s and 1980s. In the third part, the issues raised by the field are addressed in general terms. It is considered that once the main structural stages are in place there is still a need for the formation of new generations of social scientists in health. It is also essential to disseminate scientific production and to ensure that the relations are studied in depth and institutionalized with the sociological matrices on the one hand and with the field of health on the other.

Cardiac Magnetic Resonance Assessment Of Interstitial Myocardial Fibrosis And Cardiomyocyte Hypertrophy In Hypertensive Mice Treated With Spironolactone.

Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR). Mice were randomized to l-nitro-ω-methyl ester (l-NAME, 3 mg/mL in water; n=22), or l-NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (τic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of l-NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and τic compared with placebo-treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and l-NAME (l-NAME+S) showed less concentric remodeling, and a lower myocardial ECV and τic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43 ± 0.09 for l-NAME versus 0.25 ± 0.03 for l-NAME+S, P<0.001; τic: 0.42 ± 0.11 for l-NAME groups versus 0.12 ± 0.05 for l-NAME+S group). Mice treated with a combination of l-NAME and spironolactone were similar to placebo-treated controls at 7 weeks. Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure-overload, furthering our understanding of HF progression.