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1.
Infection ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858325

RESUMO

This case reports a 14-month-old child with Staphylococcal Scalded Skin Syndrome (SSSS). The child presented generalized scaling erythema accompanied by skin pain, and perioral crusts and fissures and she required hospital admission for antibiotic treatment with intravenous cloxacillin and hidroelectrolyte replacement.SSSS is a blistering skin disorder, mainly affecting children, caused by specific Staphylococcus aureus strains producing exfoliative toxins. It shows erythema in skin folds progressing to blisters within 48 h, often with perioral crusts and fissures. Its diagnosis relies on clinical assessment and it often requires intravenous antibiotics for its treatment.

2.
Infection ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38668921

RESUMO

This case report highlights a case of a 65-year-old woman who presented to our clinic with suspicion of refractory scabies. She had undergone multiple treatments without improvement. However, the clinical condition was not scabies but rather Gianotti-Crosti Syndrome (GCS), leading to rapid clinical improvement and avoiding the need for further unnecessary tests and treatments. GCS is a postviral exanthem characterized by symmetrical, red papules on the extremities and buttocks, typically occurring in children but can also affect adults. It is crucial for every physician to distinguish it from other causes of rash, including scabies, to ensure an accurate diagnosis and appropriate management.

3.
Crit Care ; 28(1): 75, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486268

RESUMO

BACKGROUND: Flow starvation is a type of patient-ventilator asynchrony that occurs when gas delivery does not fully meet the patients' ventilatory demand due to an insufficient airflow and/or a high inspiratory effort, and it is usually identified by visual inspection of airway pressure waveform. Clinical diagnosis is cumbersome and prone to underdiagnosis, being an opportunity for artificial intelligence. Our objective is to develop a supervised artificial intelligence algorithm for identifying airway pressure deformation during square-flow assisted ventilation and patient-triggered breaths. METHODS: Multicenter, observational study. Adult critically ill patients under mechanical ventilation > 24 h on square-flow assisted ventilation were included. As the reference, 5 intensive care experts classified airway pressure deformation severity. Convolutional neural network and recurrent neural network models were trained and evaluated using accuracy, precision, recall and F1 score. In a subgroup of patients with esophageal pressure measurement (ΔPes), we analyzed the association between the intensity of the inspiratory effort and the airway pressure deformation. RESULTS: 6428 breaths from 28 patients were analyzed, 42% were classified as having normal-mild, 23% moderate, and 34% severe airway pressure deformation. The accuracy of recurrent neural network algorithm and convolutional neural network were 87.9% [87.6-88.3], and 86.8% [86.6-87.4], respectively. Double triggering appeared in 8.8% of breaths, always in the presence of severe airway pressure deformation. The subgroup analysis demonstrated that 74.4% of breaths classified as severe airway pressure deformation had a ΔPes > 10 cmH2O and 37.2% a ΔPes > 15 cmH2O. CONCLUSIONS: Recurrent neural network model appears excellent to identify airway pressure deformation due to flow starvation. It could be used as a real-time, 24-h bedside monitoring tool to minimize unrecognized periods of inappropriate patient-ventilator interaction.


Assuntos
Aprendizado Profundo , Respiração Artificial , Adulto , Humanos , Inteligência Artificial , Pulmão , Respiração Artificial/métodos , Ventiladores Mecânicos
4.
Dev Med Child Neurol ; 66(7): 902-909, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38111130

RESUMO

AIM: The aim of this observational study was to determine the immune status and function in young adults with cerebral palsy (CP) in comparison to typically developing individuals. METHOD: Blood samples from 12 individuals with CP (five males, seven females; mean age: 25 years 1 month (5 years 9 months); age range: 19-38 years) and 17 typically developing individuals (eight males, nine females; mean age: 31 years 4 months (6 years 2 months); age range: 20-40 years) were collected before, immediately after, and 1 hour after 45 minutes of frame running or running respectively. Independent t-tests were used to compare heart rate, level of exertion, and baseline cell proportions between groups. Mixed model analysis of variance was utilized to investigate immune cell responses to exercise across groups. RESULTS: Baseline levels of gamma delta (TCRγδ+) T-cells were significantly higher (absolute percentage: +2.65, p = 0.028) in the individuals with CP. Several cell populations showed similar significant changes after exercise in both CP and typically developing groups. Cytotoxic (CD8+) T-cells were only significantly elevated immediately after exercise in the typically developing participants (p < 0.01). Individuals with CP exhibited significantly lower heart rates (-11.1%, p < 0.01), despite similar ratings of perceived exertion. INTERPRETATION: Elevated baseline TCRγδ+ T-cells may indicate low-grade inflammation in adults with CP. Although most of the cell populations showed typical responses to endurance exercise, the absence of response in CD8+ T-cells in individuals with CP may indicate the need for higher intensity during exercise. WHAT THIS PAPER ADDS: TCRγδ+ T-cell baseline levels are elevated in adults with cerebral palsy (CP). The CD8+ T-cell response to exercise was blunted in adults with CP. Exercise intensity is decisive for CD8+ T-cell responses in individuals with CP.


Assuntos
Paralisia Cerebral , Humanos , Masculino , Paralisia Cerebral/imunologia , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/sangue , Feminino , Adulto , Adulto Jovem , Exercício Físico/fisiologia , Resistência Física/fisiologia , Frequência Cardíaca/fisiologia , Descanso , Linfócitos T CD8-Positivos/imunologia
5.
Arch Womens Ment Health ; 27(1): 1-9, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37923930

RESUMO

Prior studies have identified that mentally healthy people tend to share common characteristics and common ways of coping with stressful life events; they show similar patterns of behavior and more flexible and adaptive social roles. The objectives of the study are to assess the influence of personality factors on gender roles and mental health, to identify personality patterns along with gender roles, and to assess the influence of the patterns identified on mental health. Data collection from a sample of 795 university students was carried out during 2019. Multilevel analyses tested the associations between gender (BSRI) and personality (TIPI) and between personality and health -mental health (GHQ12) and wellbeing (MHC-SF). Cluster analysis explored tendencies of gender and personality, and each cluster showed different health patterns. Individuals with high scores in extraversion, conscientiousness, emotional stability, openness to experience, and very high agreeableness score, as well as high femininity and masculinity scores, presented a decreased psychological morbidity (ß= -3.62, 0.57 (SE), p<0.001) and an increased well-being (ß=7.68, 1.15 (SE), p<0.001). The most relevant indicators of mental health were identified in androgynous individuals, those individuals with high scores in masculinity and femininity, as well as high scores in extraversion, openness to experience, emotional stability, agreeableness, and conscientiousness.


Assuntos
Identidade de Gênero , Personalidade , Masculino , Feminino , Humanos , Transtornos da Personalidade , Inventário de Personalidade
6.
Ann Rheum Dis ; 82(6): 799-808, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36858822

RESUMO

OBJECTIVES: To identify the arthritogenic B cell epitopes of glucose-6-phosphate isomerase (GPI) and their association with rheumatoid arthritis (RA). METHODS: IgG response towards a library of GPI peptides in patients with early RA, pre-symptomatic individuals and population controls, as well as in mice, were tested by bead-based multiplex immunoassays and ELISA. Monoclonal IgG were generated, and the binding specificity and affinity were determined by ELISA, gel size exclusion chromatography, surface plasma resonance and X-ray crystallography. Arthritogenicity was investigated by passive transfer experiments. Antigen-specific B cells were identified by peptide tetramer staining. RESULTS: Peptide GPI293-307 was the dominant B cell epitope in K/BxN and GPI-immunised mice. We could detect B cells and low levels of IgM antibodies binding the GPI293-307 epitopes, and high affinity anti-GPI293-307 IgG antibodies already 7 days after GPI immunisation, immediately before arthritis onset. Transfer of anti-GPI293-307 IgG antibodies induced arthritis in mice. Moreover, anti-GPI293-307 IgG antibodies were more frequent in individuals prior to RA onset (19%) than in controls (7.5%). GPI293-307-specific antibodies were associated with radiographic joint damage. Crystal structures of the Fab-peptide complex revealed that this epitope is not exposed in native GPI but requires conformational change of the protein in inflamed joint for effective recognition by anti-GPI293-307 antibodies. CONCLUSIONS: We have identified the major pathogenic B cell epitope of the RA-associated autoantigen GPI, at position 293-307, exposed only on structurally modified GPI on the cartilage surface. B cells to this neo-epitope escape tolerance and could potentially play a role in the pathogenesis of RA.


Assuntos
Artrite Reumatoide , Epitopos de Linfócito B , Camundongos , Animais , Glucose-6-Fosfato Isomerase , Formação de Anticorpos , Autoanticorpos , Cartilagem/metabolismo , Imunoglobulina G
7.
Acta Psychiatr Scand ; 147(5): 460-474, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36744298

RESUMO

INTRODUCTION: Delirium is common among patients admitted to the intensive care unit (ICU) and its impact on the neurocognitive and psychiatric state of survivors is of great interest. These new-onset or worsening conditions, together with physical alterations, are called post-intensive care syndrome (PICS). Our aim is to update on the latest screening and follow-up options for psychological and cognitive sequelae of PICS. METHOD: This narrative review discusses the occurrence of delirium in ICU settings and the relatively new concept of PICS. Psychiatric and neurocognitive morbidities that may occur in survivors of critical illness following delirium are addressed. Future perspectives for practice and research are discussed. RESULTS: There is no "gold standard" for diagnosing delirium in the ICU, but two extensively validated tools, the confusion assessment method for the ICU and the intensive care delirium screening checklist, are often used. PICS complaints are frequent in ICU survivors who have suffered delirium and have been recognized as an important public health and socio-economic problem worldwide. Depression, anxiety, post-traumatic stress disorder, and long-term cognitive impairment are recurrently exhibited. Screening tools for these deficits are discussed, as well as the suggestion of early assessment after discharge and at 3 and 12 months. CONCLUSIONS: Delirium is a complex but common phenomenon in the ICU and a risk factor for PICS. Its diagnosis is challenging with potential long-term adverse outcomes, including psychiatric and cognitive difficulties. The implementation of screening and follow-up protocols for PICS sequelae is warranted to ensure early detection and appropriate management.


Assuntos
Estado Terminal , Delírio , Humanos , Estado Terminal/psicologia , Unidades de Terapia Intensiva , Cuidados Críticos/métodos , Cuidados Críticos/psicologia , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia
8.
Crit Care ; 27(1): 188, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37189173

RESUMO

BACKGROUND: Intensive Care Unit (ICU) COVID-19 survivors may present long-term cognitive and emotional difficulties after hospital discharge. This study aims to characterize the neuropsychological dysfunction of COVID-19 survivors 12 months after ICU discharge, and to study whether the use of a measure of perceived cognitive deficit allows the detection of objective cognitive impairment. We also explore the relationship between demographic, clinical and emotional factors, and both objective and subjective cognitive deficits. METHODS: Critically ill COVID-19 survivors from two medical ICUs underwent cognitive and emotional assessment one year after discharge. The perception of cognitive deficit and emotional state was screened through self-rated questionnaires (Perceived Deficits Questionnaire, Hospital Anxiety and Depression Scale and Davidson Trauma Scale), and a comprehensive neuropsychological evaluation was carried out. Demographic and clinical data from ICU admission were collected retrospectively. RESULTS: Out of eighty participants included in the final analysis, 31.3% were women, 61.3% received mechanical ventilation and the median age of patients was 60.73 years. Objective cognitive impairment was observed in 30% of COVID-19 survivors. The worst performance was detected in executive functions, processing speed and recognition memory. Almost one in three patients manifested cognitive complaints, and 22.5%, 26.3% and 27.5% reported anxiety, depression and post-traumatic stress disorder (PTSD) symptoms, respectively. No significant differences were found in the perception of cognitive deficit between patients with and without objective cognitive impairment. Gender and PTSD symptomatology were significantly associated with perceived cognitive deficit, and cognitive reserve with objective cognitive impairment. CONCLUSIONS: One-third of COVID-19 survivors suffered objective cognitive impairment with a frontal-subcortical dysfunction 12 months after ICU discharge. Emotional disturbances and perceived cognitive deficits were common. Female gender and PTSD symptoms emerged as predictive factors for perceiving worse cognitive performance. Cognitive reserve emerged as a protective factor for objective cognitive functioning. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04422444; June 9, 2021.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cognição , COVID-19/epidemiologia , Demografia , Unidades de Terapia Intensiva , Alta do Paciente , Estudos Retrospectivos , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Sobreviventes
9.
Br J Cancer ; 126(8): 1168-1177, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34969998

RESUMO

BACKGROUND: Improving cancer immunotherapy long-term clinical benefit is a major priority. It has become apparent that multiple axes of immune suppression restrain the capacity of T cells to provide anti-tumour activity including signalling through PD1/PD-L1 and LAG3/MHC-II. METHODS: CB213 has been developed as a fully human PD1/LAG3 co-targeting multi-specific Humabody composed of linked VH domains that avidly bind and block PD1 and LAG3 on dual-positive T cells. We present the preclinical primary pharmacology of CB213: biochemistry, cell-based function vs. immune-suppressive targets, induction of T cell proliferation ex vivo using blood obtained from NSCLC patients, and syngeneic mouse model anti-tumour activity. CB213 pharmacokinetics was assessed in cynomolgus macaques. RESULTS: CB213 shows picomolar avidity when simultaneously engaging PD1 and LAG3. Assessing LAG3/MHC-II or PD1/PD-L1 suppression individually, CB213 preferentially counters the LAG3 axis. CB213 showed superior activity vs. αPD1 antibody to induce ex vivo NSCLC patient T cell proliferation and to suppress tumour growth in a syngeneic mouse tumour model, for which both experimental systems possess PD1 and LAG3 suppressive components. Non-human primate PK of CB213 suggests weekly clinical administration. CONCLUSIONS: CB213 is poised to enter clinical development and, through intercepting both PD1 and LAG3 resistance mechanisms, may benefit patients with tumours escaping front-line immunological control.


Assuntos
Antígenos CD/imunologia , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Antígenos CD/metabolismo , Antígeno B7-H1 , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Receptor de Morte Celular Programada 1 , Linfócitos T , Proteína do Gene 3 de Ativação de Linfócitos
10.
Crit Care Med ; 50(7): e619-e629, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35120043

RESUMO

OBJECTIVES: To characterize clusters of double triggering and ineffective inspiratory efforts throughout mechanical ventilation and investigate their associations with mortality and duration of ICU stay and mechanical ventilation. DESIGN: Registry-based, real-world study. BACKGROUND: Asynchronies during invasive mechanical ventilation can occur as isolated events or in clusters and might be related to clinical outcomes. SUBJECTS: Adults requiring mechanical ventilation greater than 24 hours for whom greater than or equal to 70% of ventilator waveforms were available. INTERVENTIONS: We identified clusters of double triggering and ineffective inspiratory efforts and determined their power and duration. We used Fine-Gray's competing risk model to analyze their effects on mortality and generalized linear models to analyze their effects on duration of mechanical ventilation and ICU stay. MEASUREMENTS AND MAIN RESULTS: We analyzed 58,625,796 breaths from 180 patients. All patients had clusters (mean/d, 8.2 [5.4-10.6]; mean power, 54.5 [29.6-111.4]; mean duration, 20.3 min [12.2-34.9 min]). Clusters were less frequent during the first 48 hours (5.5 [2.5-10] vs 7.6 [4.4-9.9] in the remaining period [p = 0.027]). Total number of clusters/d was positively associated with the probability of being discharged alive considering the total period of mechanical ventilation (p = 0.001). Power and duration were similar in the two periods. Power was associated with the probability of being discharged dead (p = 0.03), longer mechanical ventilation (p < 0.001), and longer ICU stay (p = 0.035); cluster duration was associated with longer ICU stay (p = 0.027). CONCLUSIONS: Clusters of double triggering and ineffective inspiratory efforts are common. Although higher numbers of clusters might indicate better chances of survival, clusters with greater power and duration indicate a risk of worse clinical outcomes.


Assuntos
Estado Terminal , Ventiladores Mecânicos , Adulto , Estado Terminal/terapia , Humanos , Respiração Artificial
11.
Cephalalgia ; 42(7): 618-630, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34875903

RESUMO

BACKGROUND: Clinical presentation is the key to the diagnosis of patients with migraine and tension-type headache, but features may overlap when both become chronic. Psychophysical parameters may distinguish both conditions. We aimed to compare psychophysical aspects of patients with chronic migraine, chronic tension-type headache and headache-free controls, and to determine whether these can predict headache frequency. METHODS: An examiner blinded to the diagnosis assessed 100 participants (chronic migraine (n = 38), chronic tension-type headache (n = 31) and controls (n = 31)). Assessed variables included painful area, pressure pain thresholds, temporal summation, cervical range of motion, neck posture, headache and neck impact, quality of life, and kinesiophobia. Comparison between groups was performed with one-way ANOVA and multiple linear regression was used to assess the headache frequency predictors. RESULTS: We found differences of both headache groups compared to controls (p < 0.01), but not between headache groups. Neck disability was a significant predictor of headache frequency for chronic tension-type headache (adjusted R2 = 0.14; ß = 0.43; p = 0.03) and chronic migraine (adjusted R2 = 0.18; ß = 0.51; p < 0.01). CONCLUSIONS: Chronic tension-type headache and chronic migraine showed similar psychophysical results, but were significantly worse when compared to controls. The psychophysical examination did not discriminate between headache types. The variable best explaining headache frequency for both headache types was neck disability.


Assuntos
Transtornos de Enxaqueca , Cefaleia do Tipo Tensional , Cefaleia , Humanos , Transtornos de Enxaqueca/diagnóstico , Cervicalgia , Qualidade de Vida , Cefaleia do Tipo Tensional/diagnóstico
12.
Eur Arch Psychiatry Clin Neurosci ; 272(3): 497-507, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33948693

RESUMO

Some evidence suggests that patients with bipolar disorder (BD) have better Theory of Mind (ToM) skills than patients with schizophrenia/schizoaffective disorder (SCH). However, this difference is not consistently reported across studies, so rather than being global, it may be restricted to specific aspects of ToM. Our primary objective was to compare higher order ToM performance between BD and SCH patients using the Hinting Task (HT). Ninety-four remitted patients were recruited (BD = 47, SCH = 47). Intelligence quotient (IQ), attention, memory, executive functions, and processing speed were also assessed. Patients with BD performed better on the HT than patients with SCH, even when the analysis was adjusted for IQ and neurocognition (p < 0.001, [Formula: see text] = 0.144). Regression analysis in the total sample showed that a diagnosis of SCH and lower IQ were associated with lower HT scores (R2 = 0.316, p < 0.001). In the BD group, verbal memory and processing speed were the main predictors of HT performance (R2 = 0.344, p < 0.001). In the SCH group, no variable was significant in explaining HT performance. In the context of previous studies that found no significant differences in the most basic aspects of ToM (e.g., understand other people's thoughts/beliefs), our results suggest that differences between the two disorders might be limited to the more challenging aspects (e.g., understand the intended meaning of indirect requests). No causal inferences can be made in this cross-sectional study. However, regression analyses show that whereas in BD patients, ToM functioning would be partially modulated by neurocognitive performance, in SCH patients, it could be largely independent of the well-known neurocognitive impairment.


Assuntos
Transtorno Bipolar , Transtornos Psicóticos , Esquizofrenia , Teoria da Mente , Transtorno Bipolar/psicologia , Estudos Transversais , Humanos , Testes Neuropsicológicos , Transtornos Psicóticos/complicações , Esquizofrenia/complicações , Esquizofrenia/diagnóstico
13.
Pediatr Phys Ther ; 34(4): 529-534, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36067377

RESUMO

PURPOSE: To determine the physiological response and association to peak oxygen uptake of the 6-minute Frame Running test (6-MFRT) in persons with cerebral palsy (CP). METHODS: Twenty-four participants with CP, Gross Motor Function Classification System II/III/IV, performed the 6-MFRT. Distance, peak heart rate (HR peak ), peak respiratory exchange ratio (RER peak ), and peak oxygen uptake ( O 2peak ) were measured. RESULTS: HR peak ranged from 146 to 201 beats per minute, RER peak from 0.94 to 1.49, 6-MFRT distance from 179 to 1220 m and O 2peak from 0.62 to 2.18 L/min. HR peak was achieved in 63%, RER peak in 71%. A strong correlation was observed between 6-MFRT and O 2peak . CONCLUSIONS: The 6-MFRT represented a (near) maximum effort for 75% of the participants and the 6-MFRT can be used to estimate oxygen consumption on an individual basis.


Assuntos
Paralisia Cerebral , Corrida , Adulto , Paralisia Cerebral/reabilitação , Criança , Teste de Esforço , Frequência Cardíaca/fisiologia , Humanos , Oxigênio , Consumo de Oxigênio/fisiologia
14.
J Physiol ; 599(13): 3363-3384, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33913170

RESUMO

KEY POINTS: Ribosome biogenesis and MYC transcription are associated with acute resistance exercise (RE) and are distinct from endurance exercise in human skeletal muscle throughout a 24 h time course of recovery. A PCR-based method for relative ribosomal DNA (rDNA) copy number estimation was validated by whole genome sequencing and revealed that rDNA dosage is positively correlated with ribosome biogenesis in response to RE. Acute RE modifies rDNA methylation patterns in enhancer, intergenic spacer and non-canonical MYC-associated regions, but not the promoter. Myonuclear-specific rDNA methylation patterns with acute mechanical overload in mice corroborate and expand on rDNA findings with RE in humans. A genetic predisposition for hypertrophic responsiveness may exist based on rDNA gene dosage. ABSTRACT: Ribosomes are the macromolecular engines of protein synthesis. Skeletal muscle ribosome biogenesis is stimulated by exercise, although the contribution of ribosomal DNA (rDNA) copy number and methylation to exercise-induced rDNA transcription is unclear. To investigate the genetic and epigenetic regulation of ribosome biogenesis with exercise, a time course of skeletal muscle biopsies was obtained from 30 participants (18 men and 12 women; 31 ± 8 years, 25 ± 4 kg m-2 ) at rest and 30 min, 3 h, 8 h and 24 h after acute endurance (n = 10, 45 min cycling, 70% V̇O2max ) or resistance exercise (n = 10, 4 × 7 × 2 exercises); 10 control participants underwent biopsies without exercise. rDNA transcription and dosage were assessed using quantitative PCR and whole genome sequencing. rDNA promoter methylation was investigated using massARRAY EpiTYPER and global rDNA CpG methylation was assessed using reduced-representation bisulphite sequencing. Ribosome biogenesis and MYC transcription were associated primarily with resistance but not endurance exercise, indicating preferential up-regulation during hypertrophic processes. With resistance exercise, ribosome biogenesis was associated with rDNA gene dosage, as well as epigenetic changes in enhancer and non-canonical MYC-associated areas in rDNA, but not the promoter. A mouse model of in vivo metabolic RNA labelling and genetic myonuclear fluorescence labelling validated the effects of an acute hypertrophic stimulus on ribosome biogenesis and Myc transcription, and also corroborated rDNA enhancer and Myc-associated methylation alterations specifically in myonuclei. The present study provides the first information on skeletal muscle genetic and rDNA gene-wide epigenetic regulation of ribosome biogenesis in response to exercise, revealing novel roles for rDNA dosage and CpG methylation.


Assuntos
Epigênese Genética , Ribossomos , Animais , Humanos , Hipertrofia/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Biossíntese de Proteínas , Ribossomos/metabolismo
15.
J Gen Virol ; 102(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33830912

RESUMO

The alpaca is a very important social and economic resource for the production of fibre and meat for Andean communities. Peru is the main producer of alpacas. Group A rotavirus (RVA) has been sporadically detected in alpacas. In this study, a total of 1423 faecal samples from alpacas from different locations of the Puno department in Peru were collected and analysed by an antigen-capture ELISA in order to detect RVA. Four per cent of the samples were RVA-positive (57/1423). The genotype constellation of three selected alpaca RVA strains were G3/8 P[1/14]-I2-R2/5-C2/3-M2/3-A17-N2/3-T6-E3-H3. Two of the analysed strains presented a bovine-like genotype constellation, whereas the third strain presented six segments belonging to the AU-1-like genogroup (G3, M3, C3, N3, T3 and E3), suggesting reassorting events. Monitoring of the sanitary health of juvenile alpacas is essential to reduce the rates of neonatal mortality and for the development of preventive health strategies.


Assuntos
Camelídeos Americanos/virologia , Infecções por Rotavirus , Rotavirus/isolamento & purificação , Animais , Fezes/virologia , Genoma Viral , Genótipo , Peru/epidemiologia , Rotavirus/classificação , Infecções por Rotavirus/veterinária , Infecções por Rotavirus/virologia
16.
FASEB J ; 34(6): 7958-7969, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32293758

RESUMO

This study explored the muscle genome-wide response to long-term unloading (84-day bed rest) in 21 men. We hypothesized that a part of the bed rest-induced gene expression signature would be resilient to a concurrent flywheel resistance exercise (RE) countermeasure. Using DNA microarray technology analyzing 35 345 gene-level probe-sets, we identified 335 annotated probe-sets that were downregulated, and 315 that were upregulated after bed rest (P < .01). Besides a predictable differential expression of genes and pathways related to mitochondria (downregulation; false-discovery rates (FDR) <1E-04), ubiquitin system (upregulation; FDR = 3E-02), and skeletal muscle energy metabolism and structure (downregulation; FDR ≤ 3E-03), 84-day bed rest also altered circadian rhythm regulation (upregulation; FDR = 3E-02). While most of the bed rest-induced changes were counteracted by RE, 209 transcripts were resilient to the exercise countermeasure. Genes upregulated after bed rest were particularly resistant to training (P < .001 vs downregulated, non-reversed genes). Specifically, "Translation Factors," "Proteasome Degradation," "Cell Cycle," and "Nucleotide Metabolism" pathways were not normalized by RE. This study provides an unbiased high-throughput transcriptomic signature of one of the longest unloading periods in humans to date. Classical disuse-related changes in structural and metabolic genes/pathways were identified, together with a novel upregulation of circadian rhythm transcripts. In the context of previous bed rest campaigns, the latter seemed to be related to the duration of unloading, suggesting the transcriptomic machinery continues to adapt throughout extended disuse periods. Despite that the RE training offset most of the bed rest-induced muscle-phenotypic and transcriptomic alterations, we contend that the human skeletal muscle also displays a residual transcriptomic signature of unloading that is resistant to an established exercise countermeasure.


Assuntos
Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Transcriptoma/genética , Adaptação Fisiológica/genética , Adaptação Fisiológica/fisiologia , Adulto , Repouso em Cama , Regulação para Baixo/genética , Metabolismo Energético/genética , Metabolismo Energético/fisiologia , Humanos , Masculino , Atrofia Muscular/genética , Atrofia Muscular/fisiopatologia , Treinamento Resistido/métodos , Regulação para Cima/genética
17.
Dev Med Child Neurol ; 63(10): 1204-1212, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34176131

RESUMO

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP). METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were analyzed with a focused query investigating metabolism- and mitochondria-related gene networks. RESULTS: The mtDNA to genomic DNA ratio was lower in the children with CP compared to the typically developing group (-23%, p=0.002). Out of five investigated complexes in the mitochondrial respiratory chain, we observed lower protein levels of all complexes (I, III, IV, V, -20% to -37%; p<0.05) except complex II. Total peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) messenger RNA (p<0.004), isoforms PGC1α1 (p=0.05), and PGC1α4 (p<0.001) were reduced in CP. Transcriptional similarities were observed between CP, aging, and 90 days' bed rest. INTERPRETATION: Mitochondrial biogenesis, mtDNA, and oxidative phosphorylation protein content are reduced in CP muscle compared with typically developing muscle. Transcriptional pathways shared between aging and long-term unloading suggests metabolic dysregulation in CP, which may guide therapeutic strategies for combatting CP muscle pathology. What this paper adds Cerebral palsy (CP) muscle contains fewer energy-generating organelles than typically developing muscle. Gene expression in CP muscle is similar to aging and long-term bed rest.


Assuntos
Paralisia Cerebral/genética , DNA Mitocondrial/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Músculo Esquelético/metabolismo , Adolescente , Estudos de Casos e Controles , Paralisia Cerebral/metabolismo , Criança , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/genética , Complexo II de Transporte de Elétrons/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/genética , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Fosforilação Oxidativa , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
18.
Pain Med ; 22(9): 1905-1915, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-33538821

RESUMO

OBJECTIVE: Knee arthroplasty (KA) is an effective and cost-effective treatment for end-stage knee osteoarthritis. Despite high surgical success rates, as many as 25% of patients report compromised postoperative functioning, persistent pain, and reduced quality of life. The purpose of this study was to assess the predictive value of psychological factors in health functioning and quality of life, during a 6-month period after KA. DESIGN: A prospective observational study. SETTING: Surgery at two hospitals and follow-up was carried out through the domiciliary rehabilitation service. SUBJECTS: In total, 89 patients (age 70.27 ± 7.99 years) met the inclusion criteria. METHOD: A test battery composed of Health functioning associated with osteoarthritis (WOMAC), Health-related quality of life (EQ-5D-5L), Anxiety and Depression (HADS), Pain attitudes (SOPA-B), Pain catastrophizing (PCS), and Fear of Movement (TSK-11) was assessed at 1 week, and 1, 3, and 6 months after surgery. A mixed effects linear model was used to estimate the effect of time and covariates. An exploratory factor analysis was used to identify the number of dimensions underlying the group of psychological measurements. RESULTS: In WOMAC model, anxiety level (F = 120.8), PCS (F = 103.9), depression level (F = 93.6) and pain score (F = 72.8) were the most influential variables. Regarding EQ-5D-5L model, anxiety level (F = 98.5), PCS (F = 79.8), depression level (F = 78.3) and pain score (F = 45) were the most influential variables. Pain score and the psychosocial variables of PCS, TSK, HADS-A, HADS-D, SOPA-B Emotion, SOPA-B Harm and SOPA-B Disability loaded in one single dimension. CONCLUSIONS: Postoperative acute pain and psychosocial factors of pain catastrophizing, anxiety, depression, and pain attitudes might influence health functioning and quality of life during KA rehabilitation. Such factors could be gathered into one single dimension defined as pain-related psychologic distress.


Assuntos
Artroplastia do Joelho , Qualidade de Vida , Idoso , Seguimentos , Humanos , Pessoa de Meia-Idade
19.
Compr Psychiatry ; 109: 152258, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34252633

RESUMO

BACKGROUND: Impairment of social cognition is documented in bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH). In healthy individuals, women perform better than men in some of its sub-domains. However, in BD and SCH the results are mixed. Our aim was to compare emotion recognition, affective Theory of Mind (ToM) and first- and second-order cognitive ToM in BD, SCH and healthy subjects, and to investigate sex-related differences. METHODS: 120 patients (BD = 60, SCH = 60) and 40 healthy subjects were recruited. Emotion recognition was assessed by the Pictures of Facial Affect (POFA) test, affective ToM by the Reading the Mind in the Eyes Test (RMET) and cognitive ToM by several false-belief stories. Group and sex differences were analyzed using parametric (POFA, RMET) and non-parametric (false-belief stories) tests. The impact of age, intelligence quotient (IQ) and clinical variables on patient performance was examined using a series of linear/logistic regressions. RESULTS: Both groups of patients performed worse than healthy subjects on POFA, RMET and second-order false-belief (p < 0.001), but no differences were found between them. Instead, their deficits were related to older age and/or lower IQ (p < 0.01). Subthreshold depression was associated with a 6-fold increased risk of first-order false-belief failure (p < 0.001). Sex differences were only found in healthy subjects, with women outperforming men on POFA and RMET (p ≤ 0.012), but not on first/second-order false-belief. LIMITATIONS: The cross-sectional design does not allow for causal inferences. CONCLUSION: BD and SCH patients had deficits in emotion recognition, affective ToM, and second-order cognitive ToM, but their performance was comparable to each other, highlighting that the differences between them may be subtler than previously thought. First-order cognitive ToM remained intact, but subthreshold depression altered their normal functioning. Our results suggest that the advantage of healthy women in the emotional and affective aspects of social cognition would not be maintained in BD and SCH.


Assuntos
Transtorno Bipolar , Transtornos Psicóticos , Esquizofrenia , Teoria da Mente , Idoso , Transtorno Bipolar/diagnóstico , Cognição , Estudos Transversais , Feminino , Humanos , Masculino , Esquizofrenia/diagnóstico , Caracteres Sexuais , Cognição Social
20.
Neurol Sci ; 42(9): 3673-3680, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33439388

RESUMO

OBJECTIVE: To compare the presence of allodynia, pain catastrophizing, and the impact of headaches on patients with cluster headache (CH) and healthy individuals. Our second aim was to analyze the relationship between catastrophism, psychological comorbidities, and the impact in CH. METHODS: We designed this cross-sectional study to compare various factors among 47 patients diagnosed with CH and 40 healthy controls, and then focus on catastrophism, anxiety, depression, and impact in the CH group. RESULTS: There were statistically significant differences between CH and the asymptomatic group in Allodynia Symptom Checklist (ASC) (p < 0.001), Pain Catastrophizing Scale (p < 0.001), and HIT-6 (p < 0.001) scores. We found a correlation among ASC, PCS, anxiety-depression, EuroQoL, and HIT-6 for the CH group. In this group, we observed a strong positive correlation between PCS and anxiety (rho = 0.69; p < 0.001), PCS and depression (rho = 0.62; p < 0.001) and depression and EuroQoL (rho = - 0.68; p < 0.001). The regression model showed that the combination of anxiety and HIT-6 was a significant predictor of PCS (adjusted R2 = 0.52). DISCUSSION: Our findings reveal significant differences regarding allodynia, pain catastrophism, and impact in CH group compared with controls. We found a significant relationship between psychological comorbidity, pain catastrophism, and quality of life in CH patients. Anxiety and HIT-6 were a predictor (adjusted R2 = 52%) of pain catastrophism. Screening for these comorbidities should be implemented through a multidisciplinary approach.


Assuntos
Cefaleia Histamínica , Ansiedade/epidemiologia , Cefaleia Histamínica/epidemiologia , Estudos Transversais , Humanos , Dor , Qualidade de Vida
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