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1.
Sci Rep ; 14(1): 3635, 2024 02 13.
Article in English | MEDLINE | ID: mdl-38351134

ABSTRACT

Highly pathogenic avian Influenza virus (HPAIV) has spread in an unprecedented extent globally in recent years. Despite the large reports of cases in Asia, Europe, and North America, little is known about its circulation in South America. Here, we describe the isolation, and whole genome characterization of HPAIV obtained from sampling 26 wild bird species in Peru, representing one of the largest studies in our region following the latest HPAIV introduction in South America. Out of 147 samples analyzed, 22 were positive for detection of avian influenza virus using a qRT-PCR-based assay. Following inoculation into embryonated chicken eggs, fourteen viral isolates were obtained from which nine isolates were selected for genome characterization, based on their host relevance. Our results identified the presence of HPAIV H5N1 subtype in a highly diverse wild bird species. Phylogenetic analysis revealed that these isolates correspond to the clade 2.3.4.4b, sharing a common ancestor with North American isolates and forming a monophyletic group along with isolates from Chile. Altogether, changes at the amino acid levels compared to their closest relatives indicates the virus is evolving locally, highlighting the need for constant genomic surveillance. This data evidence the chances for spillover events increases as the virus spreads into large populations of immunologically naïve avian species and adding conditions for cross species transmission.


Subject(s)
Influenza A Virus, H5N1 Subtype , Influenza A virus , Influenza in Birds , Animals , Chile , Peru/epidemiology , Phylogeny , Influenza A virus/genetics , Animals, Wild , Chickens
2.
Signal Transduct Target Ther ; 8(1): 405, 2023 10 25.
Article in English | MEDLINE | ID: mdl-37875500

ABSTRACT

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors demonstrated activity in terms of progression-free survival (PFS) in advanced dedifferentiated liposarcoma (DD-LPS), a sarcoma with CDK4 amplification. CDK4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK inhibitors. Preclinical investigators of this study found that CDK4 overexpression, while not of CDKN2A, was the most consistent predictive factor for palbociclib efficacy in sarcomas. Advanced adult-type soft-tissue sarcoma, excluding DD-LPS, or bone sarcoma patients, progressing after at least one systemic line, whose tumors overexpressed CDK4, but not CDKN2A at baseline biopsy, were accrued in this single-arm phase II trial (EudraCT number: 2016-004039-19). With the main endpoint of a 6-month PFS rate, 40% was considered promising in this population. Palbociclib was administered orally at 125 mg/day for 21 days in 28-day cycles. A total of 214 patients with 236 CDK4/CDKN2A determinations were assessed for prescreening, archival material (141), and screening, baseline biopsy (95). There were 28 (29%) with favorable mRNA profiles from 95 screened patients at baseline. From 23 enrolled patients, 21 evaluable, the 6-month PFS rate was 29% (95% CI 9-48), and there were 6 patients out of 21 with a PFS longer than 6 months. The median PFS and overall survival were 4.2 (95% CI 3.6-4.8) and 12 (95% CI 8.7-15.4) months, respectively. Translational research showed a significant correlation between CDK4 mRNA and protein expression. Palbociclib was active in a variety of sarcoma subtypes, selected by CDK4/CDKN2A, and deserves further investigation in the sarcoma context.


Subject(s)
Lipopolysaccharides , Sarcoma , Adult , Humans , Sarcoma/genetics , Piperazines/therapeutic use , Piperazines/pharmacology , RNA, Messenger , Cyclin-Dependent Kinase 4/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p16/metabolism
3.
Nat Commun ; 14(1): 5489, 2023 09 07.
Article in English | MEDLINE | ID: mdl-37679333

ABSTRACT

Highly pathogenic avian influenza (HPAI) A/H5N1 viruses (lineage 2.3.4.4b) are rapidly invading the Americas, threatening wildlife, poultry, and potentially evolving into the next global pandemic. In November 2022 HPAI arrived in Peru, triggering massive pelican and sea lion die-offs. We report genomic characterization of HPAI/H5N1 in five species of marine mammals and seabirds (dolphins, sea lions, sanderlings, pelicans and cormorants). Peruvian viruses belong to lineage 2.3.4.4b, but they are 4:4 reassortants where 4 genomic segments (PA, HA, NA and MP) position within the Eurasian lineage that initially entered North America from Eurasia, while the other 4 genomic segments (PB2, PB1, NP and NS) position within the American lineage (clade C) that circulated in North America. These viruses are rapidly accruing mutations, including mutations of concern, that warrant further examination and highlight an urgent need for active local surveillance to manage outbreaks and limit spillover into other species, including humans.


Subject(s)
Caniformia , Influenza A Virus, H5N1 Subtype , Influenza A virus , Influenza in Birds , Influenza, Human , Animals , Humans , Influenza in Birds/epidemiology , Influenza A Virus, H5N1 Subtype/genetics , Peru/epidemiology , Birds , Cetacea
4.
Cureus ; 15(6): e40329, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37448424

ABSTRACT

Pubis osteomyelitis is an uncommon disease, accounting for less than 1% of all bone infections. It occurs secondarily to hematogenous bacterial planting or direct inoculation. Clinically, it presents with intense acute pubic pain, limited mobility, and high fever, so it is rarely suspected initially. Its diagnosis can be easily confused with pubalgia, that do not respond to treatment. We present the case of a 17-year-old patient who sought consultation for three weeks of coxalgia associated with general discomfort and fever. Following a laboratory and imageological study, the diagnosis of acute pubis osteomyelitis was determined, which required surgical intervention and a subsequent pharmacological therapy for six weeks.

5.
Chemosphere ; 332: 138896, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37169092

ABSTRACT

Full-scale thermal hydrolysis processes (THP) showed an increase in nutrients release and formation of melanoidins, which are considered to negatively impact methanogenesis during mesophilic anaerobic digestion (AD). In this research, fractionation of THP-sludge was performed to elucidate the distribution of nutrients and the formed melanoidins over the liquid and solid sludge matrix. Degradation of the different fractions in subsequent AD was assessed, and the results were compared with non-pre-treated waste activated sludge (WAS). Results showed that the THP-formed soluble melanoidins were partially biodegradable under AD, especially the fraction with molecular weight under 1.1 kDa, which was related to protein-like substances. The use of THP in WAS increased the non-biodegradable soluble chemical oxygen demand (sCOD) after AD, from 1.1% to 4.9% of the total COD. The total ammoniacal nitrogen (TAN) concentration only slightly increased during THP without AD. However, after AD, TAN released was 34% higher in the THP-treated WAS compared to non-treated WAS, i.e., 36.7 ± 0.7 compared to 27.4 ± 0.4 mgTANreleased/gCODsubstrate, respectively. Results from modified specific methanogenic activities (mSMAs) tests showed that the organics solubilised during THP, were not inhibitory for acetotrophic methanogens. However, after AD of THP-treated sludge and WAS, the mSMA showed that all analysed samples presented strong inhibition on methanogenesis due to the presence of TAN and associated free ammonia nitrogen (FAN). In specific methanogenic activities (SMAs) tests with incremental concentration of TAN/FAN and melanoidins, TAN/FAN induced strong inhibition on methanogens, halving the SMA at around 2.5 gTAN/L and 100 mgFAN/L. Conversely, melanoidins did not show inhibition on the methanogens. Our present results revealed that when applying THP-AD in full-scale, the increase in TAN/FAN remarkably had a greater impact on AD than the formation of melanoidins.


Subject(s)
Sewage , Waste Disposal, Fluid , Sewage/chemistry , Anaerobiosis , Waste Disposal, Fluid/methods , Ammonia , Hydrolysis , Nitrogen , Methane , Bioreactors
6.
Rev. med. Urug ; 39(1): e203, 2023.
Article in Spanish | LILACS, BNUY | ID: biblio-1424193

ABSTRACT

Introducción: los adultos mayores son una población de riesgo para el desarrollo de reacciones adversas a los medicamentos. Los medicamentos potencialmente inapropiados son aquellos que representan mayores riesgos que beneficios en este grupo etario. Se cuenta con herramientas de apoyo a la prescripción en geriatría que permiten identificar a estos medicamentos y mediante la aplicación de estudios de utilización de medicamentos, podemos describir o analizar el uso de los mismos en una población. Objetivos: reconocer disponibilidad de medicamentos potencialmente inapropiados para adultos mayores en la RAP metropolitana de ASSE durante 2019 y establecer un diagnóstico de situación de consumo de los mismos durante ese año. Método: se realizó un análisis del vademécum institucional mediante la aplicación de los Criterios de Beers 2019 y dos escalas de riesgo anticolinérgico para identificar medicamentos potencialmente inapropiados. Posteriormente se realizó un estudio de utilización de los medicamentos identificados, mediante datos de dispensación de farmacia entre el 1 de enero y 31 de diciembre de 2019. El consumo se expresó en Dosis Diarias Definidas por cada 1000 adultos mayores-año (DHD). Resultados: se identificaron 16 medicamentos potencialmente inapropiados, de los cuales los más usados fueron clonazepam (DHD 69), quetiapina (65,6), alprazolam (DHD 43,7), flunitrazepam (DHD 42,7) y zolpidem (DHD 36,4). Conclusiones: la aplicación de herramientas explícitas facilita la identificación de medicamentos potencialmente inapropiados para adultos mayores y se evidenció un consumo elevado de los mismos durante el año 2019 a expensas de derivados benzodiazepínicos y quetiapina.


Introduction: older adults are at higher risk for developing adverse drug reactions. Potentially inappropriate medications are drugs that have more risks than benefits in this age group. There are a number of tools to support the prescription of medication in geriatrics that allow the identification of these medications, and by applying studies developed on the use of medications we may describe or analyze their impact on a given population. Objectives: to recognize availability of potentially inappropriate medications in older adults in ASSE's Metropolitan RAP during 2019 and to draw conclusions about the current situation in terms of the consumption of this kind of medications. Method: an institutional analysis of medications available in each healthcare provided was conducted through the application of Beers Criteria 2019, and two anticholinergic risk scales were used to identify potentially inappropriate medications. Subsequently, the use of the medications identified was studied by applying pharmacy dispensing data between January 1 and December 31, 2019. Consumption was expressed in defined daily doses every 1000 adults per year (DHD). Results: 16 potentially inappropriate medications were identified, the most widely used of which were clonazepam (DHD 69), quetiapine (65.6), alprazolam (DHD 43.7), flunitrazepam (DHD 42.7) and zolpidem (DHD 36.4). Conclusions: Applying explicit tools makes it easier to identify potentially inappropriate medications for older adults. An increased consumption of these kinds of drugs was noticed during 2019, as a result of benzodiazepine derivatives and quetiapine.


Introdução: os idosos são uma população de risco para o desenvolvimento de reações adversas a medicamentos. Medicamentos potencialmente inapropriados são aqueles que apresentam maiores riscos do que benefícios nessa faixa etária. Existem ferramentas de apoio à prescrição em geriatria que permitem identificar esses medicamentos e, por meio da aplicação de estudos de utilização de medicamentos, descrever ou analisar seu uso em uma população. Objetivos: reconhecer a disponibilidade de medicamentos potencialmente inapropriados para idosos na RAP metropolitana da ASSE durante o ano de 2019 e estabelecer um diagnóstico de consumo durante esse ano. Método: o formulário institucional foi analisado utilizando os Critérios de Beers 2019 e duas escalas de risco anticolinérgico para identificar medicamentos potencialmente inapropriados. Posteriormente, foi realizado um estudo de consumo dos medicamentos identificados, através dos dados de dispensação da farmácia entre 1 de janeiro e 31 de dezembro de 2019. O consumo foi expresso em Doses Diárias Definidas por 1000 idosos-ano (DHD). Resultados: foram identificados 16 medicamentos potencialmente inapropriados, sendo clonazepam (DHD 69), quetiapina (65,6), alprazolam (DHD 43,7), flunitrazepam (DHD 42,7) e zolpidem (DHD 36,4) os mais utilizados Conclusões: a aplicação de ferramentas explícitas facilita a identificação de medicamentos potencialmente inapropriados para idosos; foi observado um alto consumo dos mesmos em detrimento dos derivados benzodiazepínicos e da quetiapina durante o período do estudo.


Subject(s)
Humans , Aged , Aged, 80 and over , Drug Utilization , Prescription Drug Misuse/prevention & control , Aged , Inappropriate Prescribing/adverse effects
7.
Cureus ; 14(7): e26762, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35967175

ABSTRACT

Ingestion of corrosive agents is a well-known factor in extensive GI tract injury. Either acids or alkalis can lead to significant immediate and long-term complications throughout the GI system. The ingestion of these substances in children is often accidental, however, it is typical that in adults is due to suicidal attempts. A 25-year-old male with a history of suicidal attempt one month ago comes to the GI clinic due to unintentional weight loss of 19%, dysphagia of solids, emesis, and regurgitation. Evaluation with an upper gastrointestinal endoscopy was done which showed severe esophageal stenosis (90%), esophagitis Zargar 3a, and total pyloric stenosis. A dilation procedure was attempted, but complicated by severe bleeding; thus, the patient was hospitalized for a new attempt. During the second endoscopy, an esophageal dilation was successfully performed, but the pyloric dilation could not be completed. For that reason, a hepato-pancreato-biliary surgeon was consulted and a jejunostomy was performed for enteral nutrition. Caustic agent ingestion can cause different types of injuries including laryngospasms, perforations, necrosis, and mediastinitis in the short term. On the other hand, esophageal stenosis (ES), gastric outlet obstruction (GOO), and esophageal cancer can appear in the long term. In this case, we highlighted the importance of prompt recognition, identification, and grading of the lesions to determine a better outcome and prognosis for the patient.

8.
Gene Ther ; 29(3-4): 178-192, 2022 04.
Article in English | MEDLINE | ID: mdl-34853443

ABSTRACT

There are no effective cures for upper motor neuron (UMN) diseases, such as amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, and hereditary spastic paraplegia. Here, we show UMN loss occurs independent of spinal motor neuron degeneration and that UMNs are indeed effective cellular targets for gene therapy, which offers a potential solution especially for UMN disease patients. UCHL1 (ubiquitin C-terminal hydrolase-L1) is a deubiquitinating enzyme crucial for maintaining free ubiquitin levels. Corticospinal motor neurons (CSMN, a.k.a UMNs in mice) show early, selective, and profound degeneration in Uchl1nm3419 (UCHL1-/-) mice, which lack all UCHL1 function. When UCHL1 activity is ablated only from spinal motor neurons, CSMN remained intact. However, restoring UCHL1 specifically in CSMN of UCHL1-/- mice via directed gene delivery was sufficient to improve CSMN integrity to the healthy control levels. In addition, when UCHL1 gene was delivered selectively to CSMN that are diseased due to misfolded SOD1 toxicity and TDP-43 pathology via AAV-mediated retrograde transduction, the disease causing misfolded SOD1 and mutant human TDP-43 were reduced in hSOD1G93A and prpTDP-43A315T models, respectively. Diseased CSMN retained their neuronal integrity and cytoarchitectural stability in two different mouse models that represent two distinct causes of neurodegeneration in ALS.


Subject(s)
Amyotrophic Lateral Sclerosis , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/therapy , Animals , DNA-Binding Proteins/genetics , Disease Models, Animal , Genetic Therapy , Humans , Mice , Mice, Transgenic , Motor Neurons/pathology , Superoxide Dismutase/genetics , Superoxide Dismutase-1/genetics , Ubiquitin Thiolesterase/genetics
9.
Rev. colomb. reumatol ; 28(3): 218-220, jul.-set. 2021. graf
Article in Spanish | LILACS | ID: biblio-1357274

ABSTRACT

RESUMEN La tendinopatía calcificada del hombro se caracteriza por el depósito de cristales de hidroxiapatita en uno o varios tendones del hombro. Dentro de los procesos que ocurren en esta entidad está la fase de reabsorción, en la que los depósitos podrían migrar hacia estructuras adyacentes. Una muy rara complicación es la migración hacia la unión miotendinosa del tendón correspondiente, la cual provoca una importante reacción inflamatoria muscular que puede objetivarse en pruebas complementarias específicas. Presentamos un caso clínico de una tendinopatía calcificante del subescapular, con pos terior migración hacia la unión miotendinosa causando una miositis del mismo.


ABSTRACT Calcific tendinopathy of the shoulder is characterised by the deposit of hydroxy apatite crys tals in one or more tendons of the shoulder. Within the processes that occur within this disorder, there is the resorption phase, in which the deposits could migrate towards adjacent structures. A very rare complication is the migration towards the myotendinous junction of the corresponding tendon, which causes a significant muscular inflammatory reaction that can be seen in specific complementary tests. A clinical case is presented of a subscapular calcific tendinopathy, with subsequent migra tion to the myotendinous junction, causing myositis of the same.


Subject(s)
Humans , Female , Middle Aged , Pathological Conditions, Signs and Symptoms , Musculoskeletal Diseases , Aging, Premature , Edema , Tendinopathy , Muscular Diseases
10.
J Ultrason ; 21(85): e177-e181, 2021 Jun 07.
Article in English | MEDLINE | ID: mdl-34258044

ABSTRACT

We report the case of a 19-year-old professional volleyball player who presented with right shoulder pain exacerbated during sports activity. On physical examination, infraspinatus atrophy was evident. As the clinical setting suggested suprascapular nerve entrapment syndrome, shoulder MR and later CT were performed. The results showed radiological signs of subacute-chronic infraspinatus muscle denervation and a Bennett lesion of the shoulder, presumably due to chronic repetitive trauma during the classical overhead swing in volleyball. The patient agreed to surgical treatment, and arthroscopic decompression was achieved. After months of rehabilitation, the pain gradually subsided, the infraspinatus muscle recovered its trophism, and the patient progressively returned to her regular sports activity.

11.
Rev. Urug. med. Interna ; 6(2): 87-95, jul. 2021. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1288127

ABSTRACT

Resumen: Introducción: La resistencia antimicrobiana es uno de los principales problemas de salud pública mundial. Representa una causa importante de morbilidad en la población general y un elevado costo para los sistemas sanitarios. La Neumonía Aguda Comunitaria (NAC) representa una de las principales infecciones bacterianas en nuestro medio. Objetivo general: Evaluar la adecuación al flujograma del Programa de Optimización de Antimicrobianos (PROA) para el manejo de NAC en Departamento de Emergencia del Hospital de Clínicas (HC) entre julio y agosto de 2019. Materiales y métodos: Se realizó un estudio observacional, transversal, en el período de julio-agosto de 2019, en Departamento de Emergencia del Hospital de Clínicas. Se incluyeron pacientes mayores de 18 años, que firmaron el consentimiento informado, diagnosticados con NAC, cumpliendo criterios clínicos e imagenológicos establecidos en el flujograma del PROA del Hospital de Clínicas. Se elaboró una base de datos diseñada a partir del flujograma. Resultados: Se incluyeron 51 pacientes para el análisis. La edad promedio fue 54 años, 28 eran mujeres. Las comorbilidades más prevalentes fueron: tabaquismo, consumo de pasta base de cocaína y alcoholismo, presentes en 51% de la muestra. Treinta y cinco pacientes presentaron criterios de severidad, predominando insuficiencia respiratoria en 71%. Un 43 % presentaron factores de riesgo para microorganismos multirresistentes. Se observó una adecuación al PROA de 41%. Discusión: La adecuación al tratamiento recomendado fue inferior a la descrita en otros trabajos. El principal problema fue una errónea clasificación en los grupos de riesgo propuestos en el flujograma, ocasionando la hospitalización de pacientes que debieron recibir tratamiento ambulatorio, recibiendo antibioticoterapia de mayor espectro. Conclusiones: La existencia de PROA hospitalarios permite realizar monitoreo de prácticas diagnósticas y prescripción de antimicrobianos. Se observó una inadecuada aplicación del flujograma, lo que determinó el uso de antibióticos de mayor espectro con riesgo potencial del desarrollo de resistencia.


Abstract: Introduction: Antimicrobial resistance is one of the main world public health problems. It represents an important cause of morbidity in general population and a high cost for health systems. Community Acquired Pneumonia (CAP) represents one of the main bacterial infections in our midst. Objective: To evaluate the adequacy of the Antimicrobial Stewardship (AMS) in the management of CAP in the Emergency Department of Hospital de Clínicas (HC) between July and August 2019. Materials and methods: An observational, cross-sectional study was conducted from July-August 2019, in the Emergency Department of Hospital de Clínicas. Patients older than 18 years old were included, who signed the informed consent, diagnosed with CAP, fulfilling clinical and imaging criteria established in the flowchart. A database designed from the AMS flow chart of the Hospital de Clínicas was developed. Results: 51 patients were included for the analysis. The average age was 54 years, 28 were women. The most prevalent comorbidities were smoking, consumption of cocaine paste or alcoholism, present in 51% of the sample. Thirty-five patients presented severity criteria, prevailing respiratory failure in 71%. Risk factors for multiresistant microorganisms was 43%. PROA adequacy of 41.2% was observed. Discussion: The adequacy to the recommended treatment was lower than that described in other papers. The main problem was an erroneous classification in the risk groups proposed in the flowchart, causing hospitalization of patients who had to receive treatment at home, receiving broader spectrum antibiotic therapy. Conclusions: The existence of hospital stewardships allows monitoring of diagnostic practices and antimicrobial prescription. Inadequate application of the flow chart was observed, which determined the use of broader spectrum antibiotics with potential risk of developing resistance.


Resumo: Introdução: A resistência antimicrobiana é um dos principais problemas de saúde pública global. Representa uma das principais causas de morbidade na população em geral e um alto custo para os sistemas de saúde. A Pneumonia Aguda Comunitária (PAC) representa uma das principais infecções bacterianas em nosso meio. Objetivo: Avaliar a adequação do fluxograma do Programa de Otimização de Antimicrobianos (PROA) para o gerenciamento do PAC no Pronto Atendimento do Hospital de Clínicas (HC) entre julho e agosto de 2019. Materiais e métodos: Foi realizado um estudo observacional, transversal, no período de julho a agosto de 2019, no Pronto-Socorro do Hospital de Clínicas. Foram incluídos pacientes maiores de 18 anos, que assinaram o termo de consentimento livre e esclarecido, com diagnóstico de PAC, que preenchessem os critérios clínicos e de imagem estabelecidos no fluxograma do PROA do Hospital de Clínicas. Um banco de dados projetado a partir do fluxograma foi desenvolvido. Resultados: 51 pacientes foram incluídos para análise. A idade média era de 54 anos, 28 eram mulheres. As comorbidades mais prevalentes foram: tabagismo, consumo de pasta base de cocaína e etilismo, presentes em 51% da amostra. Trinta e cinco pacientes apresentaram critérios de gravidade, predominando insuficiência respiratória em 71%. 43% apresentaram fatores de risco para microrganismos multirresistentes. Observou-se adequação ao PROA de 41%. Discussão: A adequação ao tratamento recomendado foi inferior ao descrito em outros estudos. O principal problema era uma classificação errônea nos grupos de risco propostos no fluxograma, ocasionando a internação de pacientes que precisavam receber tratamento ambulatorial, recebendo antibioticoterapia de maior espectro. Conclusões: A existência de PROAs hospitalares permite o monitoramento das práticas diagnósticas e prescrição de antimicrobianos. Observou-se uma aplicação inadequada do fluxograma, que determinou o uso de antibióticos de maior espectro e com potencial risco de desenvolvimento de resistência.

12.
Entropy (Basel) ; 22(11)2020 Nov 13.
Article in English | MEDLINE | ID: mdl-33287059

ABSTRACT

In tonal music, musical tension is strongly associated with musical expression, particularly with expectations and emotions. Most listeners are able to perceive musical tension subjectively, yet musical tension is difficult to be measured objectively, as it is connected with musical parameters such as rhythm, dynamics, melody, harmony, and timbre. Musical tension specifically associated with melodic and harmonic motion is called tonal tension. In this article, we are interested in perceived changes of tonal tension over time for chord progressions, dubbed tonal tension profiles. We propose an objective measure capable of capturing tension profile according to different tonal music parameters, namely, tonal distance, dissonance, voice leading, and hierarchical tension. We performed two experiments to validate the proposed model of tonal tension profile and compared against Lerdahl's model and MorpheuS across 12 chord progressions. Our results show that the considered four tonal parameters contribute differently to the perception of tonal tension. In our model, their relative importance adopts the following weights, summing to unity: dissonance (0.402), hierarchical tension (0.246), tonal distance (0.202), and voice leading (0.193). The assumption that listeners perceive global changes in tonal tension as prototypical profiles is strongly suggested in our results, which outperform the state-of-the-art models.

15.
Front Mol Neurosci ; 13: 73, 2020.
Article in English | MEDLINE | ID: mdl-32508590

ABSTRACT

The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability, we investigated the motor cortex of hSOD1G93A mice at P30 (postnatal day 30), a presymptomatic time point. Glutamate uncaging by laser scanning photostimulation (LSPS) revealed altered dynamics especially within the inhibitory circuitry and more specifically in L2/3 of the motor cortex, whereas the excitatory microcircuits were unchanged. Observed microcircuitry changes were specific to CSMN in the motor column. Electrophysiological evaluation of the intrinsic properties in response to the microcircuit changes, as well as the exon microarray expression profiles of CSMN isolated from hSOD1G93A and healthy mice at P30, revealed the presence of a very dynamic set of events, ultimately directed to establish, maintain and retain the balance at this early stage. Also, the expression profile of key voltage-gated potassium and sodium channel subunits as well as of the inhibitory GABA receptor subunits and modulatory proteins began to suggest the challenges CSMN face at this early age. Since neurodegeneration is initiated when neurons can no longer maintain balance, the complex cellular events that occur at this critical time point help reveal how CSMN try to cope with the challenges of disease manifestation. This information is critically important for the proper modulation of UMNs and for developing effective treatment strategies.

16.
J Shoulder Elbow Surg ; 29(1): 104-112, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31409562

ABSTRACT

BACKGROUND: Subscapularis function after arthroscopic Bankart repair has been widely studied. However, data regarding subscapularis performance after arthroscopic Latarjet procedures are lacking. This study aimed to evaluate subscapularis clinical and radiologic performance after arthroscopic Latarjet procedures. METHODS: We included 40 patients who underwent arthroscopic Latarjet procedure with a minimum 2-year follow-up. Clinical evaluation included Western Ontario Shoulder Instability Index and Rowe scores, specific subscapularis isokinetic study, and lift-off tests. Contralateral measurements were used for comparison. Computed tomographic evaluation included graft consolidation, muscle dimensions, and degree of fatty atrophy, calculated as the mean muscle attenuation (MMA). RESULTS: There was a decrease of 8.3% of maximum internal rotation peak torque in the operated arm (P = .02). However, there was no significant difference in the agonist-antagonist ratio: 76.9% in the operated arm and 76% in the contralateral (P = .82). Lift-off strength test demonstrated a decrease in the first year but not at final follow-up (P = .38). There was a significant decrease in lift-off distance of 23% compared to the contralateral side (P < .001). Subscapularis MMA was diminished when compared to the infraspinatus/teres minor (P < .001) at the expense of its upper part (P = .03). Hyperlaxity and number of dislocation episodes were correlated to a lower MMA (P = .046 and P = .005). CONCLUSION: Arthroscopic Latarjet procedures provide satisfactory clinical results. There seems to be a diminished subscapularis MMA depending on its superior half. Hyperlaxity and number of previous dislocations were correlated to a lower MMA. Although there was a decrease in the maximum internal rotation peak torque, we did not find any difference in the agonist-antagonist ratio or in the final lift-off strength between sides.


Subject(s)
Joint Instability/surgery , Rotator Cuff/physiopathology , Shoulder Dislocation/surgery , Shoulder Joint/physiopathology , Adolescent , Adult , Arthroplasty/methods , Arthroscopy , Female , Follow-Up Studies , Humans , Joint Instability/physiopathology , Male , Muscle Strength , Prospective Studies , Rotation , Rotator Cuff/diagnostic imaging , Shoulder Dislocation/physiopathology , Shoulder Joint/surgery , Tomography, X-Ray Computed , Young Adult
18.
Rev. ANACEM (Impresa) ; 14(1): 74-80, 2020.
Article in Spanish | LILACS | ID: biblio-1123589

ABSTRACT

INTRODUCCIÓN: La artrosis rodilla es una enfermedad crónica, degenerativa, inflamatoria y multifactorial que afecta el cartílago articular, provocando dolor y pérdida de funcionalidad. Actualmente, existen una variedad de nuevos fármacos y protocolos terapéuticos, generando dudas al momento del tratamiento. Por lo anterior, el objetivo de este trabajo es entregar una revisión de la literatura con información reciente, con el fin de brindar una recomendación actualizada para el manejo de la artrosis de rodilla. MATERIALES Y MÉTODOS: Se realizó una revisión no sistemática de estudios publicados entre enero del 2000 y agosto del 2020, utilizando los términos MeSH "knee", "osteoarthritis" y "therapeutics". Se usaron como motores de búsqueda PubMed, The Cochrane Library y Trip Data base, excluyendo estudios en animales y población pediátrica. DISCUSIÓN: Es importante destacar que independientemente de la modalidad de tratamiento, este debe ser escalonado e individualizado, pues cada paciente va a responder de forma diferente. Se recomienda en primer lugar los cambios de estilo de vida, autocuidado y educación. En segundo lugar, la kinesioterapia, seguido de la farmacología tópica y oral (AINES y paracetamol) y como última opción, el tratamiento intraarticular en base a corticoides. CONCLUSIÓN: El tratamiento de la artrosis de rodilla debe ser integral y centrado tanto en el manejo farmacológico como no farmacológico. Actualmente, no existe un único fármaco seguro, altamente útil y costo-efectivo para el tratamiento crónico


INTRODUCTION: Knee osteoarthritis is a chronic, degenerative, inflammatory, and multifactorial disease that affects joint cartilage, causing pain and loss of functionality. Currently, there are a variety of new drugs and therapeutic protocols, raising doubts at the time of treatment. Therefore, the objective of this work is to provide a review of the literature with recent information, to provide an updated recommendation for the management of knee osteoarthritis. MATERIALS AND METHODS: A non-systematic review of studies published between January 2000 and August 2020 were performed, using the MeSH terms "knee", "osteoarthritis" and "therapeutics". PubMed, The Cochrane Library, and Trip Database were used as search engines, excluding studies in animals and the pediatric population. ABSTRACT: It is important to highlight that regardless of the treatment modality, it must be stepped and individualized, since each patient will respond differently. Lifestyle changes, self-care, and education are recommended first. Secondly, kinesiotherapy, followed by topical and oral pharmacology (NSAIDs and paracetamol) and as a last option, intra-articular treatment based on corticosteroids. CONCLUSION: Treatment of osteoarthritis of the knee should be comprehensive and focused on both pharmacological and non-pharmacological management. Currently, there is no single safe, highly useful, and cost-effective drug for chronic treatment


Subject(s)
Humans , Male , Female , Osteoarthritis, Knee/therapy , Conservative Treatment/methods , Self Care , Osteoarthritis, Knee/drug therapy
19.
Rev. ANACEM (Impresa) ; 14(1): 88-92, 2020. graf
Article in Spanish | LILACS | ID: biblio-1123599

ABSTRACT

Introducción: El síndrome de dolor patelofemoral, se define como aquel dolor retro o peripatelar agravado por al menos 1 actividad que cargue la articulación en flexión. Su diagnóstico, se basa en una correcta anamnesis, examen físico y pruebas de evocación de dolor e inestabilidad. El tratamiento puede ser quirúrgico o conservador, este último, tiene como objetivo disminuir el dolor e inflamación. Sin embargo, a pesar de su alta prevalencia, existen escasos protocolos sobre su manejo, por lo que el objetivo de este trabajo es entregar una revisión de la literatura con información reciente, a modo de dar una recomendación actualizada para su tratamiento. Materiales Y Métodos: Se realizó una revisión no sistemática de estudios publicados entre enero del 2005 y agosto del 2020, utilizando los términos MeSH "Anterior knee pain", "Patellofemoral pain syndrome" y "Treatment". Se usaron como motores de búsqueda PubMed, The Cochrane Library y Trip Data base, excluyendo estudios en animales y población pediátrica. Desarrollo: El tratamiento conservador del síndrome de dolor anterior de rodilla, puede dividirse en intervenciones proximales, locales y distales, todas centradas en una correcta pauta de fortalecimientos y estiramientos de los elementos comprometidos. Se recomienda esquemas asociados de fortalecimientos de core, cadera y rodilla, sin embargo, la literatura no es consistente en pautas de tratamiento protocolizados. Conclusión: El tratamiento conservador del síndrome del dolor patelofemoral depende exclusivamente de los resultados de un correcto examen físico y de las pruebas terapéuticas correspondientes.


Introduction: Patellofemoral pain syndrome is defined as that retro or peripatellar pain aggravated by at least one activity that loads the joint in flexion. Its diagnostic is based on the correct anamnesis, physical exam, pain evocation tests and instability. The treatment can be surgical or conservative, and the last one aims to reduce pain and inflammation. However, despite its high prevalence, there are few protocols concerning its handling, so the main objective of this research is to offer a literature review with updated information, in order to give an updated recommendation for its treatment. Materials And Methods: A non-systematic review of studies published between January 2005 and August 2020 were performed, using the MeSH "Anterior knee pain", "Patellofemoral pain syndrome" and "Treatment". PubMed, The Cochrane Library, and Trip Database were used as search engines, excluding studies in animals and the pediatric population. Development: The conservative treatment of anterior knee pain syndrome, can be divided into proximal, local and distal interventions, all of them focused on a correct guide of strengthening and stretching of the elements involved. Associated schemes of core, hip and knee strengthening are recommended, nevertheless, the literature is not consistent in terms of protocolized treatment guidelines. Conclusion: The conservative treatment of patellofemoral pain syndrome depends exclusively on the results of a correct physical examination, and the corresponding therapeutic tests.


Subject(s)
Humans , Patellofemoral Pain Syndrome/therapy , Exercise Therapy/methods , Knee Injuries/therapy , Patellofemoral Pain Syndrome/physiopathology , Conservative Treatment/methods
20.
J Neuroinflammation ; 16(1): 196, 2019 Oct 30.
Article in English | MEDLINE | ID: mdl-31666087

ABSTRACT

BACKGROUND: The involvement of non-neuronal cells and the cells of innate immunity has been attributed to the initiation and progression of ALS. TDP-43 pathology is observed in a broad spectrum of ALS cases and is one of the most commonly shared pathologies. The potential involvement of the neuroimmune axis in the motor cortex of ALS patients with TDP-43 pathology needs to be revealed. This information is vital for building effective treatment strategies. METHODS: We investigated the presence of astrogliosis and microgliosis in the motor cortex of ALS patients with TDP-43 pathology. prpTDP-43A315T-UeGFP mice, corticospinal motor neuron (CSMN) reporter line with TDP-43 pathology, are utilized to reveal the timing and extent of neuroimmune interactions and the involvement of non-neuronal cells to neurodegeneration. Electron microscopy and immunolabeling techniques are used to mark and monitor cells of interest. RESULTS: We detected both activated astrocytes and microglia, especially rod-like microglia, in the motor cortex of patients and TDP-43 mouse model. Besides, CCR2+ TMEM119- infiltrating monocytes were detected as they penetrate the brain parenchyma. Interestingly, Betz cells, which normally do not express MCP1, were marked with high levels of MCP1 expression when diseased. CONCLUSIONS: There is an early contribution of a neuroinflammatory response for upper motor neuron (UMN) degeneration with respect to TDP-43 pathology, and MCP1-CCR2 signaling is important for the recognition of diseased upper motor neurons by infiltrating monocytes. The findings are conserved among species and are observed in both ALS and ALS-FTLD patients.


Subject(s)
Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/pathology , DNA-Binding Proteins/metabolism , Motor Cortex/metabolism , Motor Cortex/pathology , Receptors, CCR2/metabolism , Adult , Aged , Animals , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Middle Aged
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