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1.
Curr Biol ; 33(24): 5456-5466.e5, 2023 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-38070504

RESUMO

Insects and mammals have independently evolved odorant receptor genes that are arranged in large genomic tandem arrays. In mammals, each olfactory sensory neuron chooses to express a single receptor in a stochastic process that includes substantial chromatin rearrangements. Here, we show that ants, which have the largest odorant receptor repertoires among insects, employ a different mechanism to regulate gene expression from tandem arrays. Using single-nucleus RNA sequencing, we found that ant olfactory sensory neurons choose different transcription start sites along an array but then produce mRNA from many downstream genes. This can result in transcripts from dozens of receptors being present in a single nucleus. Such rampant receptor co-expression at first seems difficult to reconcile with the narrow tuning of the ant olfactory system. However, RNA fluorescence in situ hybridization showed that only mRNA from the most upstream transcribed odorant receptor seems to reach the cytoplasm where it can be translated into protein, whereas mRNA from downstream receptors gets sequestered in the nucleus. This implies that, despite the extensive co-expression of odorant receptor genes, each olfactory sensory neuron ultimately only produces one or very few functional receptors. Evolution has thus found different molecular solutions in insects and mammals to the convergent challenge of selecting small subsets of receptors from large odorant receptor repertoires.


Assuntos
Formigas , Neurônios Receptores Olfatórios , Receptores Odorantes , Animais , Receptores Odorantes/metabolismo , Formigas/genética , Formigas/metabolismo , Hibridização in Situ Fluorescente , Neurônios Receptores Olfatórios/fisiologia , Mamíferos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
2.
Hernia ; 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37432512

RESUMO

OBJECTIVE: Progressive pneumoperitoneum (PPP) is useful tool in the preparation of patients with loss of domain hernias (LODH). The purpose of this observational retrospective study was to report our experience in the management of complications associated with the PPP procedure after treating 180 patients with LODH and to report preventive measures to avoid them. METHODS: Of the 971 patients with a ventral incisional hernia operated on between June 2012 and July 2022, 180 consecutive patients with LODH were retrospectively analysed. Diameters of abdominal cavity, and volumes of incisional hernia and abdominal cavity were calculated from CT scan, based on the modified index of Tanaka. Complications related to the PPP procedure (catheter placement and following insufflations of air) were recorded by Clavien-Dindo classification. RESULTS: Complications associated to PPP were 26.6%. No complications occurred during the administration of botulinum toxin (BT). Eighteen patients (10% of 180 patients) developed subcutaneous emphysema during the last days of the insufflations; there were 2 accidental perforations of the small bowel and four punctures with liver and splenic hematomas, detected during catheter placement; a laparotomy, however, was not needed because it was solved with conservative treatment. We diagnosed it as a peritoneum-cutaneous fistula due to the cutaneous atrophy secondary to chronic eventration. CONCLUSION: PPP is a safe technique well tolerated by patients, although at the cost of some specific complications. Hernia surgeons must understand these complications to prevent them and to inform the LODH patient about their existence.

3.
Neurologia (Engl Ed) ; 38(5): 326-333, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37263727

RESUMO

BACKGROUND: STAT-ON™ is an objective tool that registers ON-OFF fluctuations making possible to know the state of the patient at every moment of the day in normal life. Our aim was to analyze the opinion of different Parkinson's disease experts about the STAT-ON™ tool after using the device in a real clinical practice setting (RCPS). METHODS: STAT-ON™ was provided by the Company Sense4Care to Spanish neurologists for using it in a RCPS. Each neurologist had the device for at least three months and could use it in PD patients at his/her own discretion. In February 2020, a survey with 30 questions was sent to all participants. RESULTS: Two thirds of neurologists (53.8% females; mean age 44.9±9 years old) worked in a Movement Disorders Unit, the average experience in PD was 16±6.9 years, and 40.7% of them had previously used other devices. A total of 119 evaluations were performed in 114 patients (range 2-9 by neurologist; mean 4.5±2.3). STAT-ON™ was considered "quite" to "very useful" by 74% of the neurologists with an overall opinion of 6.9±1.7 (0, worst; 10, best). STAT-ON™ was considered better than diaries by 70.3% of neurologists and a useful tool for the identification of patients with advanced PD by 81.5%. Proper identification of freezing of gait episodes and falls were frequent limitations reported. CONCLUSION: STAT-ON™ could be a useful device for using in PD patients in clinical practice.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Prova Pericial , Inquéritos e Questionários , Neurologistas
4.
Rev Clin Esp (Barc) ; 222(7): 393-400, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35637092

RESUMO

INTRODUCTION: In July 2020, a draft bill was introduced in Spain's Congress which proposed that continuing medical education be funded exclusively by the Spanish government, barring involvement from private entities. AIMS: This work aims to gather physicians' and pharmacists' opinions on this draft bill, learn what they think about the funding of continuing medical education and possible conflicts of interest. METHODS: This work is a descriptive cross-sectional study conducted via voluntary anonymous surveys aimed at physicians and hospital pharmacists. RESULTS: Four hundred thirty-five surveys were analyzed, 59.8% of which were from women. Of the respondents, 87.6% were specialist physicians and 77.2% were part of a specialist department. A total of 55.2% did not agree with the draft bill while 92.4% agreed that the government and private institutes should subsidize training for their workers. Furthermore, 52.4% disagreed that each professional should pay for his or her own training while 14% agreed they should. A total of 19.8% have felt uncomfortable when a course or conference has been paid for by another entity and 74.5% believe that the involvement of private entities in funding does not influence prescribing. CONCLUSIONS: The majority of those surveyed did not agree with a draft bill aimed at prohibiting the pharmaceutical industry from funding continuing medical education. Nearly all agreed that the government and private institutions should fund training for their workers. In general, those surveyed did not find conflicts of interest in their relationship with the industry.


Assuntos
Educação Médica Continuada , Medicina , Atitude do Pessoal de Saúde , Estudos Transversais , Indústria Farmacêutica , Feminino , Humanos , Masculino
5.
Rev Esp Quimioter ; 35(4): 307-332, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35277084

RESUMO

Ambient air quality, pollution and its implication on health is a topic of enormous importance that is normally dealt with by major specialists in their particular areas of interest. In general, it is not discussed from multidisciplinary approaches or with a language that can reach everyone. For this reason, the Health Sciences Foundation, from its prevention area, has formulated a series of questions to people with very varied competences in the area of ambient air quality in order to obtain a global panorama of the problem and its elements of measurement and control. The answers have been produced by specialists in each subject and have been subjected to a general discussion that has allowed conclusions to be reached on each point. The subject was divided into three main blocks: external ambient air, internal ambient air, mainly in the workplace, and hospital ambient air and the consequences of its poor control. Along with the definitions of each area and the indicators of good and bad quality, some necessary solutions have been pointed out. We have tried to know the current legislation on this problem and the competences of the different administrations on it. Despite its enormous importance, ambient air quality and health is not usually a topic of frequent presence in the general media and we have asked about the causes of this. Finally, the paper addresses a series of reflections from the perspective of ethics and very particularly in the light of the events that the present pandemic raises. This work aims to provide objective data and opinions that will enable non-specialists in the field to gain a better understanding of this worrying reality.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , Causalidade , Exposição Ambiental/análise , Humanos , Pandemias
6.
Rev Esp Cir Ortop Traumatol ; 66(4): 281-289, 2022.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34344618

RESUMO

INTRODUCTION: Anterior glenohumeral bone loss reconstruction reduces failure rates after soft tissue surgery in patients with large glenoid bone defects. Multiple bone block techniques have been described, most with metal hardware fixation. The objective of this study is to evaluate the safety, as well as the short-term functional and radiological results of an arthroscopic bone block metal-free fixation or bone block cerclage. MATERIAL AND METHODS: Retrospective study of patients with glenohumeral instability and>15% glenoid bone loss operated during 2019 with follow-up of at least 12 months. Radiography and computerized tomography studies were performed. Functional outcomes were evaluated before and after surgery with the Western Ontario Shoulder Instability Index and Rowe score. RESULTS: A total of 21 patients with a median age of 30.6 (SD 7.1) were included. All showed radiographic consolidation at 3 months follow-up. A percentage of 90.4 of bone grafts presented osteolysis at peripherical areas and 95.2% revealed consolidation in the areas with contact to the glenoid. The median glenoid estimated surface went from 79.3% before surgery to 98.4% at 12 months. Functional scores were statically significant (P<.001) for Western Ontario Shoulder Instability Index (35.6-86.9) and Rowe score (25.2 to 96.4). No serious complications were reported. CONCLUSION: The bone block cerclage is a safe, metal-free technique that achieves total consolidation of the bone graft and favorable functional and radiological outcomes at 12 months follow-up.

7.
Parkinsons Dis ; 2021: 8871549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094501

RESUMO

INTRODUCTION: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. MATERIALS AND METHODS: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. RESULTS: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). CONCLUSION: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

8.
Rev Neurol ; 72(1): 1-8, 2021 01 01.
Artigo em Espanhol | MEDLINE | ID: mdl-33378073

RESUMO

INTRODUCTION: The treatment of Parkinson's disease (PD) is complex, and the establishment of second-line therapies in advanced PD remains controversial. AIM: To analyze the assistance of patients with PD in Catalonia, with special attention to the use of second-line therapies in advanced PD. SUBJECTS AND METHODS: Online self-administered survey to neurologists in Catalonia who treated patients with PD, through the Catalan Society of Neurology. RESULTS: 72 neurologists who visited a monthly average of 38 PD patients (37.3% motor complications) participated. 86% routinely asked about motor. The main reasons for indicating second-line therapies were disability in off (83.1%), impact of dyskinesias (76.9%), impact of time in off (75.4%) and time in off (73.8%). 70% of neurologists declared limitations to establish second-line therapies: lack of resources in their hospital, lack of time to visit the patient or to perform administrative tasks and lack nursing support. Second-line therapies is not used in 72% of patients who could potentially be candidates, especially due to patient rejection (37.9%). CONCLUSIONS: The majority of neurologists in Catalonia who visit patients with PD routinely ask about motor complications without using specific tools. Although neurologists are well aware of the indications for the establishment of second-line therapies, the refusal of the patient, the lack of time and the lack of defined care protocols to refer patients, they can contribute to a lower use of second-line therapies in advanced PD.


TITLE: Estudio DISCREPA: tratamiento de la enfermedad de Parkinson avanzada y utilización de terapias de segunda línea en Cataluña.Introducción. El tratamiento de la enfermedad de Parkinson (EP) es complejo y la instauración de terapias de segunda línea en la EP avanzada sigue siendo controvertida. Objetivo. Analizar la asistencia de pacientes con EP en Cataluña, con especial atención a la utilización de las terapias de segunda línea en la EP avanzada. Sujetos y métodos. Encuesta en línea autoadministrada a través de la Societat Catalana de Neurologia a neurólogos de Cataluña que atendían a pacientes con EP. Resultados. Participaron 72 neurólogos que visitaban una media mensual de 38 pacientes con EP (el 37,3% con complicaciones motoras). El 86% preguntaba rutinariamente por complicaciones motoras. Los principales motivos para indicar terapias de segunda línea fueron la discapacidad en off (83,1%), el impacto de las discinesias (76,9%), el impacto del tiempo en off (75,4%) y el tiempo en off (73,8%). El 70% de los neurólogos declaró limitaciones para instaurar terapias de segunda línea: escasez de recursos en su hospital, falta de tiempo para visitar al paciente o para realizar tareas administrativas y falta de soporte de enfermería (33,3%). No se utilizan terapias de segunda línea en el 72% de los pacientes que podrían ser potencialmente candidatos, sobre todo por rechazo del paciente (37,9%). Conclusiones. La mayoría de los neurólogos en Cataluña que visitan pacientes con EP pregunta rutinariamente por complicaciones motoras sin utilizar herramientas específicas. Aunque los neurólogos conocen bien las indicaciones de instauración de terapias de segunda línea, la negativa del paciente, la falta de tiempo y la falta de protocolos asistenciales definidos para derivar a pacientes pueden contribuir a una menor utilización de terapias de segunda línea en la EP avanzada.


Assuntos
Doença de Parkinson/terapia , Pesquisas sobre Atenção à Saúde , Humanos , Neurologia , Padrões de Prática Médica , Autorrelato , Índice de Gravidade de Doença , Espanha
9.
Neurologia (Engl Ed) ; 2020 Dec 24.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33358530

RESUMO

BACKGROUND: STAT-ON™ is an objective tool that registers ON-OFF fluctuations making possible to know the state of the patient at every moment of the day in normal life. Our aim was to analyze the opinion of different Parkinson's disease experts about the STAT-ON™ tool after using the device in a real clinical practice setting (RCPS). METHODS: STAT-ON™ was provided by the Company Sense4Care to Spanish neurologists for using it in a RCPS. Each neurologist had the device for at least three months and could use it in PD patients at his/her own discretion. In February 2020, a survey with 30 questions was sent to all participants. RESULTS: Two thirds of neurologists (53.8% females; mean age 44.9±9 years old) worked in a Movement Disorders Unit, the average experience in PD was 16±6.9 years, and 40.7% of them had previously used other devices. A total of 119 evaluations were performed in 114 patients (range 2-9 by neurologist; mean 4.5±2.3). STAT-ON™ was considered "quite" to "very useful" by 74% of the neurologists with an overall opinion of 6.9±1.7 (0, worst; 10, best). STAT-ON™ was considered better than diaries by 70.3% of neurologists and a useful tool for the identification of patients with advanced PD by 81.5%. Proper identification of freezing of gait episodes and falls were frequent limitations reported. CONCLUSION: STAT-ON™ could be a useful device for using in PD patients in clinical practice.

11.
Eur J Neurol ; 27(7): 1210-1223, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32181979

RESUMO

BACKGROUND AND PURPOSE: The objective of this study was to analyze the relationship between motor complications and non-motor symptom (NMS) burden in a population of patients with Parkinson's disease (PD) and also in a subgroup of patients with early PD. METHODS: Patients with PD from the COPPADIS cohort were included in this cross-sectional study. NMS burden was defined according to the Non-Motor Symptoms Scale (NMSS) total score. Unified Parkinson's Disease Rating Scale (UPDRS) part IV was used to establish motor complication types and their severity. Patients with ≤5 years of symptoms from onset were included as patients with early PD. RESULTS: Of 690 patients with PD (62.6 ± 8.9 years old, 60.1% males), 33.9% and 18.1% presented motor fluctuations and dyskinesia, respectively. The NMS total score was higher in patients with motor fluctuations (59.2 ± 43.1 vs. 38.3 ± 33.1; P < 0.0001) and dyskinesia (63.5 ± 40.7 vs. 41.4 ± 36.3; P < 0.0001). In a multiple linear regression model and after adjustment for age, sex, disease duration, Hoehn & Yahr stage, UPDRS-III score and levodopa equivalent daily dose, UPDRS-IV score was significantly related to a higher NMSS total score (ß = 0.27; 95% confidence intervals, 2.81-5.61; P < 0.0001), as it was in a logistic regression model on dichotomous NMSS total score (≤40, mild or moderate vs. >40, severe or very severe) (odds ratio, 1.31; 95% confidence intervals, 1.17-1.47; P < 0.0001). In the subgroup of patients with early PD (n = 396; mean disease duration 2.7 ± 1.5 years), motor fluctuations were frequent (18.1%) and similar results were obtained. CONCLUSIONS: Motor complications were frequent and were associated with a greater NMS burden in patients with PD even during the first 5 years of disease duration.


Assuntos
Doença de Parkinson , Idoso , Estudos Transversais , Feminino , Humanos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Índice de Gravidade de Doença
14.
Rev Clin Esp (Barc) ; 220(4): 215-227, 2020 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31540666

RESUMO

BACKGROUND: The medical certificate of cause of death is a dual-purpose document: an official registration of an individual's death and a statistical analysis of the populational causes of death. However, the completion of this document in clinical practice creates significant conflicts. OBJECTIVES: To analyse the completion and detect the main errors that occur when filling in these documents. We then compared the most important variables between the various types of documents analysed. MATERIAL AND METHODS: We conducted a descriptive cross-sectional study that analysed 513 certificates in the municipality of Madrid, Spain. The analysis included official documents (new and old versions) and hospital documents. RESULTS: The study's main finding was that 316 documents employed the term "cardiopulmonary arrest" as the immediate cause of death. In 98 other cases, other poorly defined immediate causes were listed. We were able to conclude that the hospital documents do not always have the required sections for the certificate to be legally functional. In the Professional Medical Association certificates, there is poorer completion of the current document because the document itself hinders its appropriate completion and requires better physician training to complete. CONCLUSIONS: We propose possible improvements to the official document so that it meets the legal requirements, facilitates its completion and fulfils its function. We also offer recommendations for hospitals that have their own document and suggestions for improving its completion.

15.
Hernia ; 24(6): 1263-1273, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31773546

RESUMO

PURPOSE: The use of cyanoacrylate (CA)-based tissue adhesives for mesh fixation in abdominal hernia repair is increasing due to the fast action and bond strength of these glues. The aim of the present study was to assess tissue changes induced by different CA glues used for mesh fixation in an animal model. METHODS: Parietal defects were induced in the abdominal wall of 60 rats and repaired by polyvinylidene fluoride (PVDF) mesh fixation using different CA glues. At 1, 7, 15, and 30 days post-surgery, macroscopic and histopathological studies were performed to evaluate mesh adhesion, the presence of complications and the tissue response. RESULTS: All meshes were successfully fixed without signs of inflammatory reaction, displacement or detachment. In areas where CA adhesives were applied, the acute tissue response was limited and transient. At 7 days post-surgery, collagen fibril production around prosthetic materials was observed, and collagen maturation was achieved at 30 days post-surgery. Good mesh incorporation was detected with all three glues, but the application of Glubran-2 was associated with an early macrophagic response and the early production and maturation of collagen fibrils. CONCLUSIONS: Our study confirmed that CA tissue adhesives induced the good incorporation of prosthetic mesh within host tissue with a low incidence of complications and reduced acute tissue reaction. At 30 days post-surgery no signs of mesh disinsertion or migration were observed, the prosthetic mesh adhesion was due to the presence of a dense mature connective tissue rich in type I collagen fibres.


Assuntos
Imuno-Histoquímica/métodos , Polivinil/uso terapêutico , Adesivos Teciduais/uso terapêutico , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
16.
J Neural Transm (Vienna) ; 126(12): 1599-1608, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31673927

RESUMO

C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/análise , Transtornos Neurológicos da Marcha/sangue , Doença de Parkinson/sangue , Idoso , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações
17.
Med Oral Patol Oral Cir Bucal ; 24(5): e659-e672, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31433392

RESUMO

BACKGROUND: Despite decades of research, our knowledge of several important aspects of periodontal pathogenesis remains incomplete. Epigenetics allows to perform dynamic analysis of different variations in gene expression, providing this great advantage to the static measurement provided by genetic markers. The aim of this systematic review is to analyze the possible relationships between different epigenetic mechanisms and periodontal diseases, and to assess their potential use as biomarkers of periodontitis. MATERIAL AND METHODS: A systematic search was conducted in six databases using MeSH and non-MeSH terms. The review fulfilled PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-analysis). RESULTS: 36 studies met the inclusion criteria. Due to the heterogeneity of the articles, it was not possible to conduct quantitative analysis. Regarding qualitative synthesis, however, it was found that epigenetic mechanisms may be used as biological markers of periodontal disease, as their dynamism and molecular stability makes them a valuable diagnostic tool. CONCLUSIONS: Epigenetic markers alter gene expression, producing either silencing or over-expression of molecular transcription that respond to the demands of the cellular surroundings. Gingival crevicular fluid collection is a non-invasive and simple procedure, which makes it an ideal diagnostic medium for detection of both oral and systemic issues. Although further research is needed, this seems to be a promising field of research in the years to come.


Assuntos
Doenças Periodontais , Periodontite , Epigênese Genética , Líquido do Sulco Gengival , Humanos , Periodontia
18.
J Neurol ; 266(10): 2396-2405, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31190169

RESUMO

OBJECTIVE: To describe the clinical, biochemical, and neuropathological findings of an autosomal dominant globular glial tauopathy caused by the P301T mutation at the MAPT gene. METHODS: Five patients from two unrelated pedigrees underwent clinical evaluation. Genetic analysis, brain pathological examination, and biochemical analysis of tau were performed. RESULTS: The patients studied were 3 men and 2 women with a mean age at onset of 52.2 years and mean disease duration of 5.2 years. Three patients presented a corticobasal syndrome, one patient an asymmetric pyramidal syndrome compatible with primary lateral sclerosis, and one patient a frontotemporal dementia. In both pedigrees (4 patients) Sanger sequencing showed the p.P301T mutation in exon 10 of the MAPT gene. Neuropathological findings consisted of atrophy of frontal and temporal lobes with marked spongiosis and astrogliosis, and abundant phosphorylated tau protein deposits in the frontal and temporal cortex, limbic area, basal ganglia, and brain stem. The most striking finding was the presence of oligodendroglial 4R phospho-tau globular positive inclusions in the white matter and cortex. Globose-type neurofibrillary neuronal tangles, and in particular astrocytic globular inclusions and coarse tufts, were present in the grey matter. Biochemical analysis of sarkosyl-insoluble fractions revealed two tau bands of 64 and 68 kDa and case-dependent bands of lower molecular weight. CONCLUSION: This is the first pathological and biochemical study of the MAPT p.P301T mutation showing variable clinical manifestation and neuropathological phenotype of globular glial tauopathy not only among different families but also within families.


Assuntos
Substância Cinzenta , Neuroglia , Tauopatias , Substância Branca , Proteínas tau/metabolismo , Idoso , Feminino , Substância Cinzenta/metabolismo , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroglia/metabolismo , Neuroglia/patologia , Linhagem , Espanha , Tauopatias/genética , Tauopatias/metabolismo , Tauopatias/patologia , Tauopatias/fisiopatologia , Substância Branca/metabolismo , Substância Branca/patologia , Proteínas tau/genética
19.
Transplant Proc ; 51(2): 369-371, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879543

RESUMO

OBJECTIVES: To evaluate whether the levels of some molecules implicated in nucleocytoplasmic transport in human cardiomyocytes are related to the severity of heart failure (HF) in patients on the heart transplantation (HT) waiting list, and to determine whether there is a differential pattern of molecular alteration between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (DCM). METHODS: Sixty-three blood samples collected before HT were analyzed to identify the levels of IMPORTIN5 (IMP5); IMPORTINalpha2; ATPaseCaTransp (ATPCa); NUCLEOPORIN153kDa (Nup153); NUCLEOPORIN160kDa (Nup160); RANGTPaseAP1 (RanGAP1) and EXPORTIN4 (EXP4). These data were then compared between patients with advanced HF with or without the need for ventricular support with extracorporeal membrane oxygenation (ECMO) as a bridge for HT, as well as between patients with non-ischemic DCM and patients with ICM. RESULTS: Thirty-three patients had ICM, 26 had non-ischemic DCM, and 4 had heart disease. Seventeen patients required ventricular assistance as a bridge to HT. The levels of ATPCa, RanGAP1, and IMP5 were significantly higher in patients with ECMO, while EXP4 was significantly higher in patients without ECMO. Patients with DCM showed higher levels of IMP5, RanGAP1, and Nup153 than those with ICM. CONCLUSION: Patients with advanced HF in critical condition (with ECMO as a bridge for HT) presented with significantly higher levels of ATPCa, RanGAP1, and IMP5, while patients with DCM had significantly higher levels of RanGAP1, IMP5, and Nup153. It remains to be clarified whether the determination of these molecules would facilitate the early identification of this group or if their alteration occurs as consequence of circulatory support with ECMO.


Assuntos
Transporte Ativo do Núcleo Celular/fisiologia , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/metabolismo , Adulto , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Medição de Risco , Listas de Espera
20.
Med Oral Patol Oral Cir Bucal ; 23(3): e308-e314, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29680855

RESUMO

BACKGROUND: The study and identification of new biomarkers for periodontal disease, such as microRNAs (miRNAs), may give us more information about the location and severity of the disease and will serve as a basis for treatment planning and disease-monitoring. miRNAs are a group of small RNAs which are involved in gene regulation by binding to their messenger RNA target (mRNA). In this pilot study, the procedure for purifying miRNAs from gingival crevicular fluid (GCF) was, for the first time, described. In addition, the concentration of miRNAs in GCF was analyzed and compared between patients with moderate or severe chronic periodontitis (CP) and healthy controls. MATERIAL AND METHODS: GCF samples were collected from single-rooted teeth of patients with moderate or severe CP (n=9) and of healthy individuals (n=9). miRNAs were isolated from GCF using miRNeasy Serum/Plasma kit (Qiagen, CA. USA). Reverse transcription polymerase chain reaction (qRT-PCR) was used to determine the expression of a series of miRNAs candidates that are related to bone metabolism. The significance of differences in miRNA levels between both groups was determined using Mann-Whitney U test. RESULTS: The results from this pilot study indicate that miRNAs can be isolated from GCF. Six different miRNAs were analyzed (miR-671, miR-122, miR-1306, miR-27a, miR-223, miR-1226), but only miR-1226 showed statically significant differences between the CP group and healthy controls (p<0.05). This miRNA was downregulated in patients with CP. CONCLUSIONS: Within the limitations of the present study, it may be concluded that miR-1226 can be a promising biomarker for periodontal disease, adding relevant information to common clinical parameters used for diagnosis and prognosis of periodontitis.


Assuntos
Periodontite Crônica/diagnóstico , Líquido do Sulco Gengival/química , MicroRNAs/análise , Adulto , Biomarcadores/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto
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