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We present a benchmark dataset for evaluating physical human activity recognition methods from wrist-worn sensors, for the specific setting of basketball training, drills, and games. Basketball activities lend themselves well for measurement by wrist-worn inertial sensors, and systems that are able to detect such sport-relevant activities could be used in applications of game analysis, guided training, and personal physical activity tracking. The dataset was recorded from two teams in separate countries (USA and Germany) with a total of 24 players who wore an inertial sensor on their wrist, during both a repetitive basketball training session and a game. Particular features of this dataset include an inherent variance through cultural differences in game rules and styles as the data was recorded in two countries, as well as different sport skill levels since the participants were heterogeneous in terms of prior basketball experience. We illustrate the dataset's features in several time-series analyses and report on a baseline classification performance study with two state-of-the-art deep learning architectures.
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Basquetebol , Punho , Humanos , Benchmarking , Exercício Físico , Articulação do PunhoRESUMO
OBJECTIVE: The objective is to describe the main characteristics of patients with systemic lupus erythematosus (SLE) in Argentina and to examine the influence of ethnicity on the expression of the disease. PATIENTS AND METHODS: RELESSAR is a multicentre register carried out by 106 researchers from 67 rheumatologic Argentine centres. It is a cross-sectional study of SLE (1982/1997 ACR) patients. RELESSAR electronic database includes demographic, cumulative SLE manifestations, SELENA-SLEDAI, SLICC-SDI, Katz's severity and Charlson's comorbidity indexes and treatment patterns. RESULTS: We included 1,610 patients, 91.7% were female with a median age at diagnosis of 28.1 ± 12.8; 96.2% met ≥4 ACR 1982/97 criteria. Frequent manifestations were arthritis (83.5%), malar rash (79.5%), photosensitivity (75.3%), haematological (63.8%) and renal disease (47.4%), antinuclear antibodies (96%), anti-dsDNA (66.5%) and anti-Smith antibodies (29%). The mean Selena-SLEDAI score at last visit was 3.18 (SD 4.3) and mean SDI was 1 (SD 1.3). The accumulated treatments most frequently used were antimalarials (90.4%), corticosteroids (90%), azathioprine (31.8%), intravenous cyclophosphamide (30.2%), mycophenolate mofetil or mycophenolic acid (24.5%), methotrexate (19.3%), belimumab 5.3% and rituximab 5.1%. Refractory lupus was diagnosed in 9.3% of the cases. The main causes of death were lupus activity (25.0%), activity and concomitant infections (25.0%), infections (18.2%), vascular disease (13.6%) and cancer (4.5%). Mortality was associated with higher SLEDAI, Katz, damage indexes and comorbidities. Of the 1610 patients included, 44.6% were Caucasian, 44.5% Mestizo, 8.1% Amerindian and 1.2% Afro-Latin American. Mestizo patients had higher male representation, low socioeconomic status, more inadequate medical coverage, fewer formal years of education and shorter disease duration. Polyadenopathies and Raynaud's phenomenon were more frequent in Caucasians. In the logistic regression analysis higher damage index (OR 1.28, CI 95% 1.02-1.61, p = 0.03) remained associated to mestizo ethnicity. CONCLUSIONS: This study represents the largest number of adult patients with SLE studied in Argentina. Caucasian patients were differentiated by having Raynaud's phenomenon and polyadenopathy more frequently, while patients of Mestizo origin had higher damage indexes.
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Etnicidade , Lúpus Eritematoso Sistêmico , Argentina/epidemiologia , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Fenótipo , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To validate the systemic lupus activity questionnaire (SLAQ) in Spanish language. METHODS: The SLAQ questionnaire was translated and adapted in Spanish. Consecutive SLE patients from 8 centers in Argentina were included. A rheumatologist completed a Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, and a physician's assessment. Reliability was assessed by internal consistency (Cronbach's alpha), stability by test-retest reliability (intraclass correlation coefficient), and construct validity by evaluating the correlation with clinically relevant scores. Sensitivity and specificity for clinically significant disease activity (SLEDAI ≥6) of different S-SLAQ cut-off points were evaluated. RESULTS: We included 97 patients ((93% female, mean age: 40 years (SD14.7)). Internal consistency was excellent (Cronbach's alpha = 0.84, p < 0.001), and the intraclass correlation coefficient was 0.95 (p < 0.001). Mean score of S-SLAQ was 8.2 (SD 7.31). Correlation of S-SLAQ was moderate with Patient NRS (r= 0.63 p< 0.001), weak with SLAM-no lab (r = 0.42, p <0.001) and SLAM (r = 0.38, p < 0.0001), and very weak with SLEDAI-2K (r = 0.15, p =0.1394). Using the S-SLAQ cutoff of five points, the sensitivity was 72.2% and specificity was 37.9%, for clinically significant disease activity. CONCLUSIONS: The S-SLAQ showed good validity and reliability. A good correlation, similar to the original instrument, was observed with patient´s global disease activity. No correlation was found between S-SLAQ and gold standard disease activity measures like SLEDAI-2K and SLAM. The S-SLAQ cutoff point of 5 showed a good sensitivity to identify the active SLE population and therefore could be an appropriate screening instrument for disease activity in clinical and epidemiological studies.
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Lúpus Eritematoso Discoide , Lúpus Eritematoso Sistêmico , Adulto , Feminino , Humanos , Idioma , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
PURPOSE: To evaluate the effect of a new nutritional supplement based on melatonin on the intraocular pressure (IOP) in normotensive subjects. PATIENTS AND METHODS: A short-term prospective study was designed. Sixty-seven normotensive subjects were recruited. Patients were divided into two groups. The daily group (DG) (n = 18) was instructed to take the supplement between 22:00 and 23:00 (before sleeping) for 3 consecutive days. IOP was measured from 10.00 to 11.00 am the day before treatment and during the 3 days of experiment. The acute group (AG) (n = 49) was instructed to take the supplement after the second measure (11.00) of the second day. IOP was measured 1 h and just before the intake of the supplement and 1 and 2 h after. All measurements in this group were taken 1 day before without any supplement (control) and the day of experiment. RESULTS: The DG group showed a significant decrease in IOP after supplement intake in all days of experiment, from 14.9 ± 3.4 mm Hg to 13.8 ± 2.9 mm Hg after 3 days of experiment (p value < 0.001). For AG, IOP did not change during the control day; however, a reduction of 1 mm Hg was found 2 and 3 h after supplement intake, from 15.7 ± 2.5 mm Hg to 14.7 ± 2.5 mm Hg and 15.1 ± 2.7 mm Hg, respectively, being statistically significant (p value < 0.001). CONCLUSION: The supplement based on melatonin was able to reduce the IOP in normotensive subjects after 2 h of intake. Moreover, the daily intake showed a reduction in IOP during the 3 days of experiment.
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Pressão Intraocular/efeitos dos fármacos , Melatonina/farmacologia , Apoio Nutricional/métodos , Hipertensão Ocular/tratamento farmacológico , Adulto , Antioxidantes/administração & dosagem , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/fisiopatologia , Estudos Prospectivos , Tonometria Ocular , Adulto JovemRESUMO
In recent years, the rapid emergence of antibiotic-resistant bacteria has become a significant concern in the healthcare field, and although bactericidal dressings loaded with various classes of antibiotics have been used in clinics, in addition to other anti-infective strategies, this alarming issue necessitates the development of innovative strategies to combat bacterial infections and promote wound healing. Electrospinning technology has gained significant attention as a versatile method for fabricating advanced wound dressings with enhanced functionalities. This work is based on the generation of polyvinylpyrrolidone (PVP)-based dressings through electrospinning, using a DomoBIO4A bioprinter, and incorporating graphene oxide (GO)/zinc oxide (ZnO) nanocomposites as a potent antibacterial agent. GO and ZnO nanoparticles offer unique properties, including broad-spectrum antibacterial activity for improved wound healing capabilities. The synthesis process was performed in an inexpensive one-pot reaction, and the nanocomposites were thoroughly characterized using XRD, TEM, EDX, SEM, EDS, and TGA. The antibacterial activity of the dispersions was demonstrated against E. coli and B. subtilis, Gram-negative and Gram-positive bacteria, respectively, using the well diffusion method and the spread plate method. Bactericidal mats were synthesized in a rapid and cost-effective manner, and the fiber-based structure of the electrospun dressings was studied by SEM. Evaluations of their antibacterial efficacy against E. coli and B. subtilis were explored by the disk-diffusion method, revealing an outstanding antibacterial capacity, especially against the Gram-positive strain. Overall, the findings of this research contribute to the development of next-generation wound dressings that effectively combat bacterial infections and pave the way for advanced therapeutic interventions in the field of wound care.
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The COVID-19 pandemic resulted in government restrictions that altered the lifestyle of people worldwide. Studying the impact of these restrictions on exercise behaviors will improve our understanding of the environmental factors that influence individuals' physical activity (PA). We conducted a retrospective analysis using an stringency index of government pandemic policies developed by Oxford University and digitally-logged PA data from more than 7000 runners collected using a wearable exercise-tracking device to compare the relationship between strictness of lockdowns and exercise habits on a global scale. Additionally, the time-of-day of PA globally, and activity-levels of PA in 14 countries, are compared between the pre-pandemic year of 2019 and the first pandemic year of 2020. We found that during the pandemic year there was a major shift in the time-of-day that runners exercised, with significantly more activity counts logged during standard working hours on workdays (p < 0.001) and fewer activities during the same time frame on weekends (p < 0.001). Of the countries examined, Italy and Spain had among the most strict lockdowns and suffered the largest decreases in activity counts, whereas France experienced a minimal decrease in activity counts despite enacting a strict lockdown with certain allowances. This study suggests that there are several factors affecting PA of dedicated runners, including government policy, workplace policy, and cultural norms.
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COVID-19 , Dispositivos Eletrônicos Vestíveis , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Exercício Físico , Hábitos , Humanos , Pandemias , Estudos RetrospectivosRESUMO
BACKGROUND: SPG4 is a subtype of hereditary spastic paraplegia (HSP), an upper motor neuron disorder characterized by axonal degeneration of the corticospinal tracts and the fasciculus gracilis. The few neuroimaging studies that have focused on the spinal cord in HSP are based mainly on the analysis of structural characteristics. METHODS: We assessed diffusion-related characteristics of the spinal cord using diffusion tensor imaging (DTI), as well as structural and shape-related properties in 12 SPG4 patients and 14 controls. We used linear mixed effects models up to T3 in order to analyze the global effects of 'group' and 'clinical data' on structural and diffusion data. For DTI, we carried out a region of interest (ROI) analysis in native space for the whole spinal cord, the anterior and lateral funiculi, and the dorsal columns. We also performed a voxelwise analysis of the spinal cord to study local diffusion-related changes. RESULTS: A reduced cross-sectional area was observed in the cervical region of SPG4 patients, with significant anteroposterior flattening. DTI analyses revealed significantly decreased fractional anisotropy (FA) and increased radial diffusivity at all the cervical and thoracic levels, particularly in the lateral funiculi and dorsal columns. The FA changes in SPG4 patients were significantly related to disease severity, measured as the Spastic Paraplegia Rating Scale score. CONCLUSIONS: Our results in SPG4 indicate tract-specific axonal damage at the level of the cervical and thoracic spinal cord. This finding is correlated with the degree of motor disability.
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Pessoas com Deficiência , Transtornos Motores , Paraplegia Espástica Hereditária , Anisotropia , Imagem de Tensor de Difusão/métodos , Humanos , Tratos Piramidais , Paraplegia Espástica Hereditária/diagnóstico por imagem , Medula Espinal/diagnóstico por imagemRESUMO
BACKGROUND: This research explores how public awareness and attitudes toward donation and transplantation policies may contribute to Spain's success in cadaveric organ donation. MATERIALS AND METHODS: A representative sample of 813 people residing in Andalusia (Southern Spain) were surveyed by telephone or via Internet between October and December 2018. RESULTS: Most participants trust Spain's donation and transplantation system (93%) and wish to donate their organs after death (76%). Among donors, a majority have expressed their consent (59%), and few nondonors have expressed their refusal (14%). Only a minority are aware of the presumed consent system in force (28%) and feel sufficiently informed regarding the requirements needed to be an organ donor (16%). Participants mainly consider that relatives should represent the deceased's preferences and be consulted when the deceased's wishes are unknown, as is the case in Spain. CONCLUSION: Public trust in the transplant system may contribute to Spain's high performance in organ donation. High levels of societal support toward organ donation and transplantation do not correspond with similar levels of public awareness of donation and transplantation policies in Spain.
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Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Políticas , Opinião Pública , Espanha , Doadores de TecidosRESUMO
SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder characterized by progressive spasticity and weakness of the lower limbs caused by degeneration of the corticospinal tract. In other neurodegenerative motor disorders, the thalamus and basal ganglia are affected, with a considerable impact on disease progression. However, only a few works have studied these brain structures in HSP, mainly in complex forms of this disease. Our research aims to detect potential alterations in the volume and shape of the thalamus and various basal ganglia structures by comparing 12 patients with pure HSP and 18 healthy controls. We used two neuroimaging procedures: automated segmentation of the subcortical structures (thalamus, hippocampus, caudate nucleus, globus pallidus, and putamen) in native space and shape analysis of the structures. We found a significant reduction in thalamic volume bilaterally, as well as an inward deformation, mainly in the sensory-motor thalamic regions in patients with pure HSP and a mutation in SPG4. We also observed a significant negative correlation between the shape of the thalamus and clinical scores (the Spastic Paraplegia Rating Scale score and disease duration). Moreover, we found a 'Group × Age' interaction that was closely related to the severity of the disease. No differences in volume or in shape were found in the remaining subcortical structures studied. Our results suggest that changes in structure of the thalamus could be an imaging biomarker of disease progression in pHSP.
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Paraplegia Espástica Hereditária , Atrofia , Gânglios da Base , Humanos , Mutação/genética , Paraplegia , Paraplegia Espástica Hereditária/diagnóstico por imagem , Paraplegia Espástica Hereditária/genética , Espastina/genéticaRESUMO
Ferritin is a multimeric protein composed of light (L-ferritin) and heavy (H-ferritin) subunits that binds and stores iron inside the cell. A variety of mutations have been reported in the L-ferritin subunit gene (FTL gene) that cause the following five diseases: (1) hereditary hyperferritinemia with cataract syndrome (HHCS), (2) neuroferritinopathy, a subtype of neurodegeneration with brain iron accumulation (NBIA), (3) benign hyperferritinemia, (4) L-ferritin deficiency with autosomal dominant inheritance, and (5) L-ferritin deficiency with autosomal recessive inheritance. Defects in the FTL gene lead to abnormally high levels of serum ferritin (hyperferritinemia) in HHCS and benign hyperferritinemia, while low levels (hypoferritinemia) are present in neuroferritinopathy and in autosomal dominant and recessive L-ferritin deficiency. Iron disturbances as well as neuromuscular and cognitive deficits are present in some, but not all, of these diseases. Here, we identified two novel FTL variants that cause dominant L-ferritin deficiency and HHCS (c.375+2T > A and 36_42delCAACAGT, respectively), and one previously reported variant (Met1Val) that causes dominant L-ferritin deficiency. Globally, genetic changes in the FTL gene are responsible for multiple phenotypes and an accurate diagnosis is useful for appropriate treatment. To help in this goal, we included a diagnostic algorithm for the detection of diseases caused by defects in FTL gene.
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Resumen Introducción: el progreso en los tratamientos para el lupus eritematoso sistémico (LES) resultó en una disminución de la mortalidad; sin embargo, la enfermedad cardiovascular y las complicaciones infecciosas aún son las principales causas de muerte. La evidencia apoya la participación del sistema inmunológico en la generación de la placa aterosclerótica, así como su conexión con las enfermedades autoinmunes. Objetivos: describir la frecuencia de eventos cardiovasculares (ECV) en el Registro de Lupus Eritematoso Sistémico de la Sociedad Argentina de Reumatología (RELESSAR) transversal, así como sus principales factores de riesgo asociados. Materiales y métodos: estudio descriptivo y transversal para el cual se tomaron los pacientes ingresados en el registro RELESSAR transversal. Se describieron las variables sociodemográficas y clínicas, las comorbilidades, score de actividad y daño. ECV se definió como la presencia de al menos una de las siguientes patologías: enfermedad arterial periférica, cardiopatía isquémica o accidente cerebrovascular. El evento clasificado para el análisis fue aquel posterior al diagnóstico del LES. Se conformaron dos grupos macheados por edad y sexo 1:2. Resultados: 1515 pacientes mayores de 18 años participaron del registro. Se describieron 80 pacientes con ECV (5,3%). En este análisis se incluyeron 240 pacientes conformando dos grupos. La edad media fue de 47,8 (14,4) y 47,6 (14,2) en el grupo con y sin ECV respectivamente. Los pacientes con ECV tuvieron mayor duración del LES en meses, mayor índice de Charlson, mayor SLICC (Systemic Lupus International Collaborating Clinics/American College of Rheumatology), mayor frecuencia de manifestaciones neurológicas, síndrome antifosfolípido, hospitalizaciones y uso de ciclofosfamida. Las únicas variables asociadas en el análisis multivariado fueron el índice de Charlson (p=0,004) y el SLICC (p<0,001). Conclusiones: los ECV influyen significativamente en nuestros pacientes, y se asocian a mayor posibilidad de daño irreversible y comorbilidades.
Abstract Introduction: progress in treatments for systemic lupus erythematosus (SLE) has resulted in a decrease in mortality; however, cardiovascular and infectious diseases remain the leading causes of death. Evidence supports the involvement of the immune system in the generation of atherosclerotic plaque, as well as its connection to autoimmune diseases. Objectives: to describe the frequency of cardiovascular disease (CVD) in the cross-sectional RELESSAR registry, as well as its associated variables. Materials and methods: a descriptive and cross-sectional study was performed using patients admitted to the cross-sectional RELESSAR registry. Sociodemographic variables, clinical variables, comorbidities, activity and damage scores were described. CVD was defined as at least one of the following: peripheral arterial disease, ischemic heart disease, or cerebrovascular accident. All patients with at least one CVD were included in our analysis (heart attack, central nervous system vascular disease, and peripheral arteries atherosclerotic disease). The event classified for the analysis was that after the diagnosis of SLE. SLE diagnosis was previous to CVD. Two groups matched by age and sex, 1:2 were formed. Results: a total of 1515 patients older than 18 years participated in the registry. Eighty patients with CVD (5.3%) were described in the registry. Two-hundred and forty patients were included, according to two groups. The mean age was 47.8 (SD 14.4) and 47.6 (SD 14.2) in patients with and without CVD, respectively. Patients with CVD had a longer duration of SLE in months, a higher Charlson index, a higher SLICC, increased frequency of neurological manifestations, antiphospholipid syndrome, hospitalizations, and use of cyclophosphamide. The associated variables in the multivariate were the Charlson Index (p=0.004) and the SLICC (p<0.001). Conclusions: CVDs have a significant influence on our patients, being associated with a greater possibility of damage and comorbidities.
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Lúpus Eritematoso Sistêmico , Doenças Cardiovasculares , MortalidadeRESUMO
Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.
Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.
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Humanos , Lúpus Eritematoso Sistêmico , Encaminhamento e Consulta , TerapêuticaRESUMO
Introducción: el lupus es una enfermedad compleja y varias veces de difícil abordaje. Alcanzar la remisión es uno de los objetivos, incorporando opciones terapéuticas. Objetivos: describir las características generales de los pacientes según el estado de la enfermedad y el uso de belimumab. Materiales y métodos: estudio de corte transversal, registro RELESSAR. Se definió el estado de la enfermedad como: remisión: SLEDAI=0 y sin corticoides; baja actividad de la enfermedad: SLEDAI >0 y ≤4 y sin corticoides; control no óptimo: SLEDAI >4 y cualquier dosis de corticoides. Resultados: se incluyeron 1.277 pacientes, 23,4% en remisión, 12,6% en baja actividad y 63,8% con control no óptimo. En este último grupo eran más jóvenes y con menor duración de la enfermedad; presentaban mayores índices de actividad y cronicidad, y mayor empleo de inmunosupresores. Solo el 22,3% de los pacientes con criterio potencial de uso de belimumab (lupus eritematoso sistémico activo a pesar del tratamiento estándar) lo recibía en ese momento. Las variables asociadas a hospitalizaciones fueron: terapia con corticoides, ciclofosfamida y mayor SLICC. Conclusiones: se refleja la complejidad del manejo de estos pacientes y se visualizan aspectos estructurales como la desigualdad. El uso del belimumab resultaría beneficioso en los pacientes seleccionados.
Introduction: lupus is a complex disease and often difficult to approach. Achieving remission is one of the objectives, incorporating therapeutic options. Objectives: to describe the characteristics of the patients and the use of belimumab, according to the status of the disease. Materials and methods: cross-sectional study. Patients of the RELESSAR registry. Stratification: Remission: SLEDAI=0 and without corticosteroids. Low disease activity SLEDAI> 0 and ≤4 and without corticosteroids and non-optimal control: SLEDAI> 4 and any dose of corticosteroids. Results: a total of 1,277 patients were included, 23.4% in remission, 12.6% in low disease activity and 63.8% in non-optimal control. The last group was younger and had a shorter duration of the disease. They had higher activity and chronicity indices and greater use of immunosuppressants. Only 22.3% of the patients with potential criteria for the use of belimumab (activity disease despite standard treatment) were receiving it. The variables associated with hospitalizations were: corticosteroids, cyclophosphamide and higher SLICC. Those associated with severe infection: mycophenolate mofetil, azathioprine, corticosteroids, and higher SLICC. Conclusions: the complexity of the management of these patients is reflected, visualizing structural aspects such as inequality. The use of belimumab could be beneficial in selected patients.
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The co-regulation of DNA replication and gene transcription is still poorly understood. To gain a better understanding of this important control mechanism, we examined the DNA replication and transcription using the Dbf4 origin-promoter and Dbf4 pseudogene models. We found that origin firing and Dbf4 transcription activity were inversely regulated in a cell cycle-dependent manner. We also found that proteins critical for the regulation of replication (ORC, MCM), transcription (SP1, TFIIB), and cohesin (Smc1, Smc3) and Mediator functions (Med1, Med12) interact with specific sites within and the surrounding regions of the Dbf4 locus in a cell cycle-dependent manner. As expected, replication initiation occurred within a nucleosome-depleted region, and nucleosomes flanked the 2 replication initiation zones. Further, the histone H3 in this region was distinctly acetylated or trimethylated on lysine 9 in a cell cycle-dependent fluctuation pattern: H3K9ac was most prevalent when the Dbf4 transcription level was highest whereas the H3K9me3 level was greatest during and just after replication. The KDM4A histone demethylase, which is responsible for the H3K9me3 modification, was enriched at the Dbf4 origin in a manner coinciding with H3K9me3. Finally, HP1γ, a protein known to interact with H3K9me3 in the heterochromatin was also found enriched at the origin during DNA replication, indicating that H3K9me3 may be required for the regulation of replication at both heterochromatin and euchromatin regions. Taken together, our data show that mammalian cells employ an extremely sophisticated and multilayered co-regulation mechanism for replication and transcription in a highly coordinated manner.
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Proteínas de Ciclo Celular/genética , Replicação do DNA , Loci Gênicos , Histonas/metabolismo , Lisina/metabolismo , Regiões Promotoras Genéticas , Transcrição Gênica , Acetilação , Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina/metabolismo , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/metabolismo , Regulação para Baixo/genética , Células HEK293 , Células HeLa , Humanos , Histona Desmetilases com o Domínio Jumonji/metabolismo , Complexo Mediador/metabolismo , Metilação , Nucleossomos/metabolismo , Ligação Proteica , Processamento de Proteína Pós-Traducional/genética , Pseudogenes , Origem de Replicação/genética , CoesinasRESUMO
BACKGROUND AND OBJECTIVES: Arterial Oxygen Saturation (AOS) predicts altitude sickness. OBJECTIVES: To estimate the AOS values with relation to altitude. Furthermore, make a graph to use during activity which assesses the AOS for each altitude and the normal range. PATIENTS AND METHOD: Values of AOS were assessed during eight high mountain activities in the Alps, Himalaya, Caucasus and Andes; 53 mountaineers participated, 17 of them in more than one activity; 761 measurements of AOS were registered. RESULTS: A Logistic Regression Model was made to estimate the AOS values dependent on altitude, adjusted to possible related factors. A strong lineal relationship exists between altitude and AOS (R2=.83, P<.001); .7 points more in women. The AOS in a particular altitude is not related to age, weight, height, smoking, heart rate, or even with previous experiences in mountains. The calculation of the AOS responds to the follow equation: Blood Oxygen Saturation=103.3-(altitude × .0047)+(Z), being Z=.7 in men and 1.4 in women. A scatter plot was made to relate the estimated altitude with the AOS, with their normal limits values: percentiles 2.5 and 97.5. CONCLUSIONS: The simple calculation of the AOS estimated for a particular altitude with the proposed graphic can help in the early decision-making onsite.
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Altitude , Oximetria , Oxigênio/sangue , Adulto , Doença da Altitude/sangue , Doença da Altitude/diagnóstico , Artérias , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Cdc7-Dbf4 serine/threonine kinase is essential for initiation of DNA replication. It was previously found that overexpression of certain replication proteins such as Cdc6 and Cdt1 in fission yeast resulted in multiple rounds of DNA replication in the absence of mitosis. Since this phenomenon is dependent upon the presence of wild-type Cdc7/Hsk1, we hypothesized that high levels of Cdc7 and/or Dbf4 could also cause multiple rounds of DNA replication, or could facilitate entry into S phase. To test this hypothesis, we transiently overexpressed hamster Cdc7, Dbf4 or both in CHO cells. Direct observations of individual cells by fluorescence microscopy and flow cytometric analysis on cell populations suggest that overexpression of Cdc7 and/or Dbf4 does not result in multiple rounds of DNA replication or facilitating entry into S phase. In contrast, moderately increased levels of Dbf4, but not Cdc7, cause cell-cycle arrest in G2/M. This G2/M arrest coincides with hyperphosphorylation of Cdc2/Cdk1 at Tyr-15, raising the possibility that high levels of Dbf4 may activate a G2/M cell-cycle checkpoint. Further increase in Cdc7 and/or Dbf4 by 2-4 fold can arrest cells in G1 and significantly slow down S-phase progression for the cells already in S phase.
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Proteínas de Ciclo Celular/metabolismo , Ciclo Celular/fisiologia , Proteínas/metabolismo , Animais , Células CHO , Proteínas de Ciclo Celular/genética , Cricetinae , Cricetulus , DNA/genética , Replicação do DNA , Feminino , Citometria de Fluxo , Expressão Gênica , Microscopia de Fluorescência , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas/genética , Fase S/fisiologia , Espectrometria de FluorescênciaRESUMO
Objetivos: describir la frecuencia de estenosis arterial (cubital y radial) en pa-cientes con esclerosis sistémica (ES); analizar la relación entre estenosis macro-vascular y úlceras digitales. Método: se incluyeron 57 pacientes con ES, según la clasificación del Colegio Americano de Reumatología de 1980 y 21 pacientes sin ES. Se realizó ecografía doppler arterial de miembros superiores. Resultados: la estenosis en al menos una arteria cubital se objetivó en 31% de pacientes con ES (18/57) (p=0.003). Se objetivó estenosis radial en 9 de 57 pacientes con ES (15%) y en uno de los 21 controles (p=0.19). En el modelo multivariado, los predicto-res de úlceras digitales fueron inicio de Raynaud antes de los 40 años (OR 5.3 IC95% 1.54-18.22, p=0.008) y patrón tardío en la capilaroscopia (OR 4.4 IC95% 1.29-15.63, p=0.018). Conclusiones: un tercio de los pacientes ES presentó este-nosis cubital. El compromiso de los grandes vasos no se asoció a úlceras digitales.
Objectives: to describe the frequency of ulnar and radial stenosis in SSc patients. Analyze the correlation between arterial stenosis and digital ulcers. Methods: we included 57 SSc consecutive patients who fulfilled ACR 1980 classification criteria, and 21 healthy controls. An arterial ecodoppler was performed to all participants. Results: the presence of stenosis in at least one ulnar artery was observed in 18 of 57 patients with SSc (31%) and in none of the 21 controls (p=0.003). Stenosis was present in at least one radial artery in 9 of 57 SSc patients (15%) (p=0.19). In multivariate model, the best predictors of digital ulcers were age at onset of Ray-naud phenomenon before 40 years (OR 5.3 95%CI 1.54-18.22, p=0.008) and late SD pattern (OR 4.4 95%CI 1.29-15.63, p=0.018). Conclusion: in the present series, ulnar stenosis was observed frequently in SSc patients. Stenosis of large vessels was not associated with digital ulcers.
Assuntos
Humanos , Escleroderma Sistêmico/complicações , Úlcera/etiologia , Doenças Vasculares Periféricas , Artéria Ulnar , Artéria Radial , Ultrassonografia DopplerRESUMO
STUDY DESIGN: Case report. OBJECTIVE: To report this rare varicella-zoster virus (VZV) complication in a patient with multiple sclerosis. SUMMARY OF BACKGROUND DATA: Longitudinally extensive transverse myelitis is a spinal cord lesion that extends over 3 or more vertebral segments. A common feature in neuromyelitis optica, longitudinally extensive transverse myelitis can also occur in several other diseases. METHODS: A 15-year-old boy with relapsing-remitting multiple sclerosis, who has been treated with immunomodulators for 6 months, developed a subacute left brachiocrural hemiparesis with ipsilateral decreased sensation in the trunk and limbs. This was interpreted as a new relapse and was treated consequently. During the evolution, the patient developed a cutaneous rash in the left C8 metameres, followed by asymmetric tetraparesis. RESULTS: Magnetic resonance imaging demonstrated an extensive cervical-thoracic myelopathy. Cerebrospinal fluid analysis revealed 17 leukocytes per microliter (95% mononuclear), protein 41 mg/dL, and negative VZV-DNA by polymerase chain reaction, but elevated anti-VZV immunoglobulin G cerebrospinal fluid/serum index, with a normal albumin cerebrospinal fluid/serum index, all of which were consistent with intrathecal synthesis of anti-VZV antibody. We were able to rule out all other causes included in the differential diagnosis, namely, vascular disease, tumor, and autoimmune conditions, especially those associated with neuromyelitis optica spectrum disorders. CONCLUSION: Awareness of the potentially varied presentation of VZV myelitis can enable earlier recognition and specific treatment.
Assuntos
Encefalite por Varicela Zoster/diagnóstico , Esclerose Múltipla/complicações , Mielite/diagnóstico , Adolescente , Anticorpos Antivirais/imunologia , Vértebras Cervicais/virologia , Diagnóstico Diferencial , Encefalite por Varicela Zoster/complicações , Encefalite por Varicela Zoster/virologia , Herpesvirus Humano 3/imunologia , Herpesvirus Humano 3/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Mielite/complicações , Mielite/virologia , Vértebras Torácicas/virologiaRESUMO
BACKGROUND: Exposure to electromagnetic fields has been reported to have analgesic and antinociceptive effects in several organisms. OBJECTIVE: To test the effect of very low-intensity transcranial magnetic stimulation on symptoms associated with fibromyalgia syndrome. METHODS: A double-blinded, placebo-controlled clinical trial was performed in the Sagrado Corazón Hospital, Seville, Spain. Female fibromyalgia patients (22 to 50 years of age) were randomly assigned to either a stimulation group or a sham group. The stimulation group (n=28) was stimulated using 8 Hz pulsed magnetic fields of very low intensity, while the sham group (n=26) underwent the same protocol without stimulation. Pressure pain thresholds before and after stimulation were determined using an algometer during the eight consecutive weekly sessions of the trial. In addition, blood serotonin levels were measured and patients completed questionnaires to monitor symptom evolution. RESULTS: A repeated-measures ANOVA indicated statistically significant improvement in the stimulation group compared with the control group with respect to somatosensory pain thresholds, ability to perform daily activities, perceived chronic pain and sleep quality. While improvement in pain thresholds was apparent after the first stimulation session, improvement in the other three measures occurred after the sixth week. No significant between-group differences were observed in scores of depression, fatigue, severity of headaches or serotonin levels. No adverse side effects were reported in any of the patients. CONCLUSIONS: Very low-intensity magnetic stimulation may represent a safe and effective treatment for chronic pain and other symptoms associated with fibromyalgia.
Assuntos
Fibromialgia/terapia , Magnetoterapia/métodos , Limiar da Dor/efeitos da radiação , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The lamin B2 locus is the only mammalian origin whose replication initiation points (RIPs) have been mapped. Although this paper was published 8 years ago, no further mammalian RIP-mapping studies have been reported, largely due to technical difficulties of ligation-mediated (LM)-PCR used by the authors. Here, we report the development of a simple, one-way PCR-based protocol that allows one to accurately determine RIPs at mammalian origins. The procedure can be completed within 48 h from the time of cell lysis in the agarose gel. Nascent DNA is then isolated from the same gel after DNA is separated by alkaline gel electrophoresis. Subsequently, RIPs are determined by one-way PCR-based primer extension using labeled primers. Using this protocol, we have successfully mapped RIPs in the human DBF4 locus. As one-way PCR is routinely used by many scientists, this protocol will provide a powerful new tool for studying DNA replication in many organisms including mammalian cells.