RESUMO
Parkinson's disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their applicability to humans. Although a single animal model cannot replicate all pathological features of the human disease, neuroinflammation is present in most animal models of PD and plays a critical role in understanding the involvement of the immune system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture models do not fully reflect the complexity of disease progression, they are limited in their ability to mimic long-term effects and need validation through in vivo studies. They are an indispensable tool for understanding the interplay between the IS and the pathogenesis of this disease. Understanding the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD. We believe that the development of methodological guidelines for experiments with animal models and PD patients is crucial to ensure the validity and consistency of the results.
Assuntos
Modelos Animais de Doenças , Doença de Parkinson , Doença de Parkinson/imunologia , Doença de Parkinson/patologia , Doença de Parkinson/etiologia , Animais , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/patologiaRESUMO
The occurrence of the pseudoaneurysm of visceral arteries in the field of chronic pancreatitis is a very rare complication that represents a life-threatening condition. The higher frequency of this complication is in the necrotic form of pancreatic inflammation, especially in patients with formed peripancreatic necrotic collections. The degradation of the arterial wall leads to bleeding and transforms these necrotic collections into a pseudoaneurysm. Urgent endovascular angioembolization is the first choice in the therapeutic approach as a valid minimally invasive solution with very satisfactory immediate and long-term outcomes. This successfully avoids open surgery, which is associated with a high mortality rate in these patients, especially in acute-on-chronic pancreatitis.
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Falso Aneurisma , Pancreatite Crônica , Humanos , Falso Aneurisma/terapia , Falso Aneurisma/etiologia , Pancreatite Crônica/complicações , Pancreatite Crônica/terapia , Masculino , Diagnóstico Precoce , Embolização Terapêutica/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodosRESUMO
In hospitals, many different professions work together with the same goal: optimal patient care. This challenge requires effective coordination and communication as well as good knowledge of each other's work. Due to an ever-increasing administrative workload and a large patient flow, time dedicated to this interprofessional collaboration is dwindling. Some hospitals, particularly in North America, have been using lean management concepts for some years, as an organizational aid and aiming at continuous improvement. A cockpit is a tool that aims at dedicating a space and a period of time to interprofessional communication and collaboration.
Au sein d'un hôpital, de nombreux corps de métiers travaillent ensemble dans un même but : la prise en charge optimale des patients. Ce défi nécessite une coordination et une communication performantes ainsi qu'une bonne connaissance du travail de chacun. En raison d'un travail administratif en constante augmentation et d'un flux de patients important, le temps dédié à cette collaboration interprofessionnelle s'amenuise. Certains hôpitaux, notamment en Amérique du Nord, utilisent depuis quelques années des concepts issus du « lean management ¼, comme aide organisationnelle et dans une perspective d'amélioration continue. Un « cockpit ¼ ou « salle de pilotage ¼ est un outil qui a pour but de consacrer un espace et une période de temps à la communication et à la collaboration interprofessionnelle.
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Comportamento Cooperativo , Relações Interprofissionais , Humanos , ComunicaçãoRESUMO
Periodontal disease is one of the most common conditions resulting from poor oral hygiene and is characterized by a destructive process in the periodontium that essentially includes gingiva, alveolar mucosa, cementum, periodontal ligament, and alveolar bone. Notably, the destructive event in the alveolar bone has been linked to homocysteine (Hcy) metabolism; however, it has not been fully investigated. Therefore; the implication of Hcy towards initiation, progression, and maintenance of the periodontal disease remains incompletely understood. Higher levels of Hcy (also known as hyperhomocysteinemia (HHcy)) exerts deleterious effects on gum health and teeth in distinct ways. Firstly, increased production of proinflammatory cytokines such as TNF-α, IL-1ß, IL-6, and IL-8 leads to an inflammatory cascade of events that affect methionine (Met) and Hcy metabolism (i.e., 1-carbon metabolism) leading to HHcy. Secondly, metabolic dysregulation during chronic medical conditions increases systemic inflammation leading to a decrease in vitamins, more specifically B6, B12, and folic acid, that play important roles as cofactors in Hcy metabolism. Also, given the folate level in the HHcy state that is important during dysbiosis, these two conditions appear to be intimately related, and in this context, HHcy-induced dysbiosis may be one of the potential causes of periodontal disease. This paper sums up the link between periodontitis and HHcy, with a special emphasis on the "oral-gut microbiome axis" and the potential probiotic intervention towards warding off some of the serious periodontal disease conditions.
Assuntos
Disbiose/complicações , Microbioma Gastrointestinal/fisiologia , Homocisteína/metabolismo , Hiper-Homocisteinemia/imunologia , Periodontite/imunologia , Disbiose/sangue , Disbiose/imunologia , Disbiose/microbiologia , Ácido Fólico/sangue , Ácido Fólico/metabolismo , Homocisteína/sangue , Homocisteína/imunologia , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/metabolismo , Metionina/metabolismo , Periodontite/sangue , Periodontite/metabolismo , ProbióticosRESUMO
The rapid progression of COVID-19 is an organizational challenge for all hospitals. To secure the patient overflow, the Department internal medicine of the University Hospital of Lausanne increased nurse and medical workforces as well as bed capacity by 65â %, with extraordinary help from other departments. The implemented crisis management stood upon three pillarsâ : a crisis management team, steering documents and internal communication. In this new form, the Department had already taken care of 442 COVID-19 admissions by April 16, 2020. Alongside organizational challenges, clinical issues such as rapid respiratory distress, clinical suspicions with negative PCR and treatment uncertainties in the absence of sufficient evidence were overcome. Despite the peak of the pandemic appearing to have passed, the next phase could be just as complicated.
La progression rapide du COVID-19 constitue un défi organisationnel pour tous les hôpitaux. Pour anticiper un afflux important de patients, le service de médecine interne du CHUV a ainsi augmenté ses forces de travail médico-soignantes et son nombre de lits de 65â % avec un soutien extraordinaire de toute l'institution. Pour opérer ces changements majeurs, l'organisation de crise mise en place s'est appuyée sur trois piliersâ : une cellule de conduite, des documents de pilotage et une communication interne. Sous cette nouvelle forme, le service a pris en charge 442 hospitalisations COVID-19 jusqu'au 16 avril 2020. Si les enjeux organisationnels ont été majeurs, la gestion des situations complexes, comme les manifestations respiratoires et les multiples incertitudes cliniques diagnostiques et thérapeutiques, ont été également une gageure. Le pic de la pandémie semble passé, mais la prochaine phase pourrait constituer un nouveau défi organisationnel.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Gestão de Recursos da Equipe de Assistência à Saúde , Pandemias , Pneumonia Viral , Centros de Atenção Terciária/organização & administração , COVID-19 , Infecções por Coronavirus/epidemiologia , França , Humanos , Pneumonia Viral/epidemiologia , SARS-CoV-2RESUMO
Clostridium (Clostridioides) difficile infections (CDIs) are among the most frequent healthcare-associated infections in Serbia. In 2013, Serbia participated in the European Clostridium difficile Infection Surveillance Network (ECDIS-Net) who launched a pilot study to enhance laboratory capacity and standardize surveillance for CDI. Two clinics of Clinical Center of Serbia [Clinic for Infectious and Tropical Diseases (CITD) and Clinic of Orthopedic Surgery and Traumatology (COT)] from Belgrade and one general hospital from another metropolitan area of Serbia, Uzice, participated. During a period of 3 months in 2013, all patients with diagnosed CDI were included. The CDI incidence rates in CITD, COT, and General Hospital Uzice were 19.0, 12.2, and 3.9 per 10,000 patient-days, respectively. In total, 49 patients were enrolled in the study with average age of 72 years. A complicated course of CDI was found in 14.3% of all patients. Six (12.2%) of 49 patients died, but not attributable to CDI. Of 39 C. difficile isolates, available for ribotyping, 78.9% belonged to ribotype 027; other PCR ribotypes were 001, 015, 002, 005, 010, 014, and 276. Antimicrobial susceptibility testing revealed low levels of MIC50 and MIC90 for metronidazole (0.5 µg/ml both) and vancomycin (0.25 and 0.5 µg/ml), while 28 strains of ribotype 027 were resistant to moxifloxacin with MIC ≥4 µg/ml. National surveillance is important to obtain more insight in the epidemiology of CDI and to compare the results with other European countries. This study by ECDIS-Net gives bases for a national surveillance of CDI in Serbia.
Assuntos
Clostridioides difficile/patogenicidade , Infecções por Clostridium/epidemiologia , Infecção Hospitalar/epidemiologia , Monitoramento Epidemiológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Clostridioides difficile/classificação , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/tratamento farmacológico , Infecção Hospitalar/microbiologia , Feminino , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Projetos Piloto , Ribotipagem , Sérvia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The incidence of Clostridium difficile infections (CDI) in the Clinical Center of Serbia (CCS) and the entire Serbia has been constantly rising in the previous 5 years. We aimed to study C. difficile PCR-ribotypes isolated from patients hospitalized at two healthcare institutions: CCS and Specialized Hospital for Cerebrovascular Diseases "Sveti Sava" (SS), both of them from Belgrade, and to investigate the incidence rates of CDI in hospital settings in Serbia, from 2009 to 2013. METHODS: The Bacteriology laboratory database at Clinic for Infectious and Tropical Diseases of CCS was queried from January 1, 2009 to December 31, 2013 for all patients who underwent immunochromatographic toxin A and/or toxin B stool testing and C. difficile stool culture for suspected infection caused by this bacterium. Toxigenic culture was not performed. Ninety- six C. difficile isolates were then selected and characterized by PCR-ribotyping. These were obtained from 94 patients hospitalized in different clinics of CCS and SS from November 2011 to December 2013. RESULTS: Among 6164 stool samples sent to Bacteriology laboratory for culture of C. difficile and toxin detection during the study period, 1775 (28.8%) were positive, displaying linear trend of growth. From 96 isolates, typed by PCR-ribotyping, majority (85; 88.54%) belonged to PCR-ribotype 027. The remaining 11 isolates belonged to PCR-ribotypes 014/020 (3 isolates), 015, SLO 191 (two isolates each), 017, 018, 070 and 001/072 (one isolate each). CONCLUSION: Our results demonstrated that C. difficile PCR-ribotype 027 is by far predominant in two hospital settings in Belgrade, at least since 2011.
Assuntos
Clostridioides difficile/classificação , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Variação Genética , Ribotipagem , Clostridioides difficile/genética , Fezes/microbiologia , Hospitais , Humanos , Incidência , Epidemiologia Molecular , Reação em Cadeia da Polimerase , Sérvia/epidemiologiaRESUMO
The hospital activity of physicians in training mainly consists in direct contacts with patients, tasks indirectly linked to patients such as administration, as well as clinical and theoretical training. In our era of digitalization, an important administrative work load without any added medical value fills their daily chores. In parallel activities of medical secretaries are getting more partitioned, with their desks situated far from physicians' and tasks often limited to finalizing discharge letters. Added to multiple overtime, this reduces physicians' and secretaries' work satisfaction. This article describes the context and development of delegating medico-administrative tasks to secretaries in our department of internal medicine.
L'activité hospitalière des médecins en formation se compose principalement de contacts directs avec les patients, de tâches indirectement liées au patient, essentiellement administratives, et de formations pratique et théorique. A l'heure de la numérisation, une importante activité administrative sans valeur médicale ajoutée remplit encore leur quotidien. Parallèlement, l'activité des secrétaires médicales se cloisonne, avec des bureaux éloignés des médecins et des tâches se limitant souvent à la finalisation de lettres de sortie. Ajoutés au cumul d'heures supplémentaires, ces éléments diminuent la satisfaction des médecins et des secrétaires dans leur travail. Cet article décrit le contexte et la mise en Åuvre d'une délégation de tâches médico-administratives à des secrétaires de médecins dans notre service de médecine interne hospitalière.
Assuntos
Internato e Residência , Satisfação no Emprego , Secretárias de Consultório Médico , Médicos , Humanos , Carga de TrabalhoRESUMO
Clostridium difficile infection (CDI) remains poorly controlled in many European countries, of which several have not yet implemented national CDI surveillance. In 2013, experts from the European CDI Surveillance Network project and from the European Centre for Disease Prevention and Control developed a protocol with three options of CDI surveillance for acute care hospitals: a 'minimal' option (aggregated hospital data), a 'light' option (including patient data for CDI cases) and an 'enhanced' option (including microbiological data on the first 10 CDI episodes per hospital). A total of 37 hospitals in 14 European countries tested these options for a three-month period (between 13 May and 1 November 2013). All 37 hospitals successfully completed the minimal surveillance option (for 1,152 patients). Clinical data were submitted for 94% (1,078/1,152) of the patients in the light option; information on CDI origin and outcome was complete for 94% (1,016/1,078) and 98% (294/300) of the patients in the light and enhanced options, respectively. The workload of the options was 1.1, 2.0 and 3.0 person-days per 10,000 hospital discharges, respectively. Enhanced surveillance was tested and was successful in 32 of the hospitals, showing that C. difficile PCR ribotype 027 was predominant (30% (79/267)). This study showed that standardised multicountry surveillance, with the option of integrating clinical and molecular data, is a feasible strategy for monitoring CDI in Europe.
Assuntos
Técnicas de Laboratório Clínico/normas , Clostridioides difficile/genética , Infecções por Clostridium/diagnóstico , Reação em Cadeia da Polimerase/normas , Vigilância da População/métodos , Ribotipagem/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Laboratório Clínico/métodos , Clostridioides difficile/isolamento & purificação , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reação em Cadeia da Polimerase/métodos , Adulto JovemAssuntos
Falso Aneurisma/etiologia , Pâncreas/patologia , Pancreatite Crônica/complicações , Artéria Esplênica , Falso Aneurisma/diagnóstico , Falso Aneurisma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico , Necrose/etiologia , Pancreatectomia/métodos , Pancreatite Crônica/diagnóstico , Esplenectomia/métodos , Tomografia Computadorizada por Raios X , Ultrassonografia DopplerRESUMO
While Clostridium difficile epidemiology is well documented in many European countries, data are largely missing for South Eastern European region. Here we report the PCR ribotype distribution of 249 C. difficile isolates received for typing from six hospital settings from Croatia, Bosnia and Herzegovina, Republic of Macedonia and Serbia in time period from 2008 to 2015. Twenty-four PCR ribotypes were detected. The majority of strains from Bosnia and Herzegovina and Serbia belonged to PCR ribotype 027 (65.8%). Other three dominating PCR ribotypes were 176 (18 strains; Croatia), 001/072 (15 strains; all countries) and 014/020 (15 strains; all countries).
Assuntos
Clostridioides difficile/classificação , Clostridioides difficile/isolamento & purificação , Surtos de Doenças , Enterocolite Pseudomembranosa/epidemiologia , Clostridioides difficile/genética , Enterocolite Pseudomembranosa/diagnóstico , Enterocolite Pseudomembranosa/microbiologia , Europa Oriental/epidemiologia , Hospitais , Humanos , Reação em Cadeia da Polimerase , RibotipagemRESUMO
Per- and polyfluoroalkyl substances (PFAS) analysis has become crucial due to their presence in the environment, their persistence and potential health risks. These compounds are commonly used in food contact materials (FCM) as a coating to provide water and grease-repellent properties. One of the pathways for PFAS to enter the human body is either through direct consumption of contaminated food or indirectly through migration from FCM into food. The purpose of this study was to investigate where the initial contamination of paper FCM occurs. We analysed paper material consisting of fresh fibre and secondary materials, intended to produce food packaging for the presence of PFAS. The samples were extracted and analysed for 23 different PFAS substances using the targeted approach with LC tandem mass spectrometry (LC-MS/MS). This analytical technique detects specific, easily ionisable PFAS with high sensitivity. However, one drawback of this approach is that it allows the identification of less than 1% of the PFAS known today. For this reason, we used combustion ion chromatography (CIC) to determine the content of extractable organic fluorine compounds (EOF) and compare it to the total fluorine content. The targeted analysis using LC-MS/MS measured an average sum concentration of PFAS of 0.17 ng g-1 sample. Our research shows that the primary PFAS contamination happens during the recycling process since all of the samples in which the targeted PFAS were measured belonged to the secondary material. The most frequently detected analytes were PFOA and PFOS, detected in 90% and 62% of the samples, respectively, followed by PFBS (in 29% of the samples). CIC showed that measured PFAS via LC-MS/MS amount to an average of 2.7 × 10-4% of total fluorine content, whereas the EOF was under the LOD in all of the measured samples. This result highlights the complexity of the accurate determination of PFAS compounds, displaying what kind of information the chosen methods provide.
Assuntos
Flúor , Fluorocarbonos , Contaminação de Alimentos , Embalagem de Alimentos , Papel , Flúor/análise , Fluorocarbonos/análise , Contaminação de Alimentos/análise , Espectrometria de Massa com Cromatografia Líquida , Espectrometria de Massas em TandemRESUMO
Background/purpose: Decubital lesions or traumatic ulcers caused by dentures usually appear one or two day(s) after new dentures placement due to mismatch of the microrelief of the tissue and the microrelief of the gingival surface of the prosthesis. The study aimed to analyze factors that could influence the healing of ulcers during a one-week period after the placement of new partial and complete dentures. Materials and methods: The prospective cohort study included 60 patients with new denture-induced traumatic ulcers. Traumatic ulcers were treated with denture adjustment, or combination of adjustment with 0.2% or 0.3% hyaluronic acid gels respectively for seven days. Healing of ulcers were observed through measurement of perimeter, area, maximum and minimum diameters on digital photographs. Multivariate logistic regression was used to predict other factors that could affect healing process. Results: Perimeter, area, maximum and minimum diameters of denture-related ulcers were significant decreased after application of gels on the fifth and seventh day. The fifth day ulcers were not healed if dentures were only adjusted, while healed lesion was 40% for the other two groups. On the seventh day, the percent of healed lesion in the group with dentures adjustment was 20%, while it was increased to 75% healed lesions for combination of denture adjustment and hyaluronic acid gels. Anticoagulant/anti-aggregation drugs also had positive impact on ulcer healing; antihypertensives that included diuretics slowed ulcer healing, other monitored factors in the study did not show a significant impact. Conclusion: Hyaluronic acid in combination with the dentures adjustment for seven days leads to higher healing rate, and reduction in size of ulcers that did not heal until this time point.
RESUMO
This study aimed to assess the effects of dental bleaching on the immediate shear bond strength (SBS) of composite to enamel. Different bleaching methods and time intervals between bleaching and composite restoration were examined. A total of 45 enamel specimens were divided into three groups (n = 15) based on the applied bleaching protocol: in-office (A), at-home (B), and unbleached control (C). Groups A and B were then subdivided into three time intervals until bonding: 1, 3, and 7 days. The composite was bonded to enamel using self-etch adhesive technique and submitted to SBS testing. The enamel surface and adhesive interface were observed under scanning electron microscope (SEM). The highest average SBS was measured in the control (unbleached) group (31.1 ± 3.4). A significant difference in SBS was found between the control and in-office bleaching (p < .001), as well as between control and at-home bleaching (p = .034), while the difference between in-office and at-home bleaching methods was insignificant. In relation to the waiting period, a significant reduction in SBS (p < .001) was found 1 day post-bleaching. The weakest marginal sealing to enamel under SEM was observed also 1 day after bleaching. Both bleaching methods significantly reduced the SBS of composite to enamel, especially immediately after the bleaching procedure. Reduction in SBS is temporary and 3-day waiting period seems to be sufficient to reverse the adverse effects of bleaching. RESEARCH HIGHLIGHTS: SBS of composite to enamel is significantly reduced by bleaching procedures, especially immediately after bleaching. The reduction in SBS is temporary and reversible by delaying the restoration for a minimum of 3 days.
Assuntos
Resinas Compostas , Colagem Dentária , Esmalte Dentário , Microscopia Eletrônica de Varredura , Resistência ao Cisalhamento , Clareamento Dental , Esmalte Dentário/efeitos dos fármacos , Esmalte Dentário/química , Clareamento Dental/métodos , Humanos , Resinas Compostas/química , Colagem Dentária/métodos , Clareadores Dentários/química , Propriedades de SuperfícieRESUMO
PURPOSE: When carrying out prosthetic rehabilitation of edentulous and partially edentulous patients, great attention is paid to the personal attitude of the patients, their satisfaction with oral health and psychosocial interaction due to tooth loss, as well as the treatment of the resulting disorders. This attention has led to the development of various instruments for examining the quality of life related to oral health. The aim of this study was to develop and validate a reliable instrument in the Serbian language suitable for measuring oral health-related quality of life in patients who have been rehabilitated with complete or partial dentures. Ðaterials and Methods: The study was unicentric and cross-sectional, and assessed the reliability and validity of a newly developed instrument for measuring the oral health-related quality of life in denture wearers (OHRQoL-DW). It was conducted on a sample of 200 adults from Serbia, wearers of various types of dentures, with a mean age 66.9 ± 10.3 years and male/female ratio of 86/114 (43%/57%). RESULTS: The definitive version of the OHRQoL-DW scale with 28 items showed very good reliability, with Cronbach's alpha = 0.938. Good temporal stability of the questionnaire was demonstrated, and satisfactory results were obtained for divergent and convergent validity tests. Exploratory factorial analysis revealed four domains of oral health-related quality of life in denture wearers: physical, psychosocial, environmental and aesthetic. CONCLUSIONS: The OHRQoL-DW scale is a reliable and valid generic instrument for measuring the oral health-related quality of life in patients wearing dentures, which is one of the most important outcomes of oral health in prosthetic treatment.
Assuntos
Saúde Bucal , Qualidade de Vida , Adulto , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Reprodutibilidade dos Testes , DentadurasRESUMO
Parkinson's disease (PD) is manifested by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and caudoputamen (Cp), leading to the development of motor and non-motor symptoms. The contribution of oxidative stress to the development and progression of PD is increasingly recognized. Experimental models show that strengthening antioxidant defenses and reducing pro-oxidant status may have beneficial effects on disease progression. In this study, the neuroprotective potential of intermittent theta burst stimulation (iTBS) is investigated in a 6-hydroxydopamine (6-OHDA)-induced PD model in rats seven days after intoxication which corresponds to the occurrence of first motor symptoms. Two-month-old male Wistar rats were unilaterally injected with 6-OHDA to mimic PD pathology and were subsequently divided into two groups to receive either iTBS or sham stimulation for 21 days. The main oxidative parameters were analyzed in the caudoputamen, substantia nigra pars compacta, and serum. iTBS treatment notably mitigated oxidative stress indicators, simultaneously increasing antioxidative parameters in the caudoputamen and substantia nigra pars compacta well after 6-OHDA-induced neurodegeneration process was over. Serum analysis confirmed the systemic effect of iTBS with a decrease in oxidative markers and an increase in antioxidants. Prolonged iTBS exerts a modulatory effect on oxidative/antioxidant parameters in the 6-OHDA-induced PD model, suggesting a potential neuroprotective benefit, even though at this specific time point 6-OHDA-induced oxidative status was unaltered. These results emphasize the need to further explore the mechanisms of iTBS and argue in favor of considering it as a therapeutic intervention in PD and related neurodegenerative diseases.
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Experimental autoimmune encephalomyelitis (EAE) is widely used animal model of multiple sclerosis (MS). The disease is characterized by demyelination and neurodegeneration triggered by infiltrated autoimmune cells and their interaction with astrocytes and microglia. While neuroinflammation is most common in the spinal cord and brainstem, it is less prevalent in the cerebellum, where it predisposes to rapid disease progression. Because the induction and progression of EAE are tightly regulated by adenosinergic signaling, in the present study we compared the adenosine-producing and -degrading enzymes, ecto-5'-nucleotidase (eN/CD73) and adenosine deaminase (ADA), as well as the expression levels of adenosine receptors A1R and A2AR subtypes in nearby areas around the fourth cerebral ventricle-the pontine tegmentum, the choroid plexus (CP), and the cerebellum. Significant differences in histopathological findings were observed between pontine tegmentum and cerebellum on the same horizontal section level. Reactive astrogliosis and massive infiltration of CD4 + cells and macrophages in CP and pontine tegmentum resulted in local demyelination. In cerebellum, there was no evidence of infiltrates, microgliosis and neuroinflammation at the same sectional level. In addition, Bergman glia showed no signs of reactive gliosis. As for adenosinergic signaling, significant upregulation of eN/CD73 was observed in all areas studied, but in association with different adenosine receptor subtypes. In CP and pons, overexpression of eN/CD73 was coupled with induction of A2AR, whereas in cerebellum, a modest increase in eN/CD73 in resident Bergman glia was accompanied by a strong induction of A1R in the same type of astrocytes. Thus, the presence of specialized astroglia and intrinsic differences in adenosinergic signaling may play a critical role in the differential regional susceptibility to EAE inflammation.
Assuntos
5'-Nucleotidase , Cerebelo , Encefalomielite Autoimune Experimental , Neuroproteção , Receptor A1 de Adenosina , Animais , Feminino , Camundongos , 5'-Nucleotidase/metabolismo , Adenosina Desaminase/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Cerebelo/patologia , Cerebelo/metabolismo , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/metabolismo , Gliose/patologia , Gliose/metabolismo , Camundongos Endogâmicos C57BL , Receptor A1 de Adenosina/metabolismo , Receptor A2A de Adenosina/metabolismoRESUMO
The present study shows that animals with experimental autoimmune encephalomyelitis (EAE) exhibit olfactory dysfunction and impaired general cognitive abilities, as well as anxiety-like behavior. Olfactory dysfunction occurs on average at 2 dpi, well before the onset of the first motor signs of EAE (8-10 dpi). After the initial olfactory dysfunction, the EAE animals show a fluctuation in olfactory performance that resembles the relapsing-remitting course of human MS. The study also shows severe neuroinflammation in the olfactory bulb (OB), with numerous infiltrated CD4+ T cells and peripheral macrophages in the superficial OB layers, marked microgliosis, and massive induction of TNF-α, IL-1ß, and IL-6. Reduced tyrosine hydroxylase activity in the glomerular layer, pronounced granule cell atrophy, and reduced numbers of type B neuroblasts in the rostral migratory stream also indicate altered plasticity of the neuronal network in the OB. Considering the exceptionally high purinome expression in the OB, the possible involvement of purinergic signaling was also investigated. The study shows that macrophages infiltrating the OB overexpress A3R, while highly reactive microglia overexpress the adenosine-producing enzyme eN/CD73 as well as A2BR, A3R, and P2X4R. Given the simultaneous induction of complement component C3, the results suggest that the microglial cells develop a functional phenotype of phagocytizing microglia. The study also demonstrates transcriptional and translational upregulation of A1R in mitral and tufted cells, which likely influence resting network activity in OB and likely contribute to olfactory dysfunction in EAE. Overall, our study shows that olfactory dysfunction and altered social and cognitive behavior in EAE are associated with increased adenosine signaling via A1R, A2BR, and A3R.
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Food contact materials (FCMs) from three countries were analysed for all extractable organofluorines (EOFs) from the materials and subsequently by target and non-target analysis for per- and polyfluoroalkyl substances (PFAS). The EOF varied by two orders of magnitude for FCM from UK and Saudi Arabia ranging between 2.14 and 483 ng cm-2 (0.2-48 ng g-1) showing that one quarter of all samples were above the Danish regulation for PFAS in FCM. Target PFAS showed high variability in composition and accounted for less than 1% of the EOF. Non-target PFAS screening using HPLC-ICP-MS and coupled simultaneously to HRMS showed the occurrence of organofluorines which were identified by neither LC-MS/MS nor LC-HRMS. This illustrates that the current target PFAS approaches fail to identify EOFs from FCM, which would be a problem with the new EU proposal to ban all PFAS.
Assuntos
Fluorocarbonos , Contaminação de Alimentos , Embalagem de Alimentos , Espectrometria de Massas em Tandem , Fluorocarbonos/análise , Contaminação de Alimentos/análise , Arábia Saudita , Cromatografia Líquida , Espectrometria de Massas , Cromatografia Líquida de Alta Pressão , Análise de Alimentos , Espectrometria de Massa com Cromatografia LíquidaRESUMO
This study presents the first results of DNA barcoding of water mites from Portugal. DNA barcodes were recovered from 19 water mite specimens morphologically assigned to eight species, seven of them newly reported from Portugal. Two species, Torrenticolahispanica (Lundblad, 1941) and A.cultellatus (K. Viets, 1930) were discovered more than 80 years after they were first described, and Atractidesmarizaesp. nov. is described as new for science.