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1.
RNA ; 28(9): 1197-1209, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35760522

RESUMEN

Guanine-rich regions of DNA or RNA can form structures with two or more consecutive G-quartets called G-quadruplexes (GQ). Recent studies reveal the potential for these structures to aggregate in vitro. Here, we report effects of in vivo concentrations of additives-amino acids, nucleotides, and crowding agents-on the structure and solution behavior of RNAs containing GQ-forming sequences. We found that cytosine nucleotides destabilize a model GQ structure at biological salt concentrations, while free amino acids and other nucleotides do not do so to a substantial degree. We also report that the tendency of folded GQs to form droplets or to aggregate depends on the nature of flanking sequence and the presence of additives. Notably, in the presence of biological amounts of polyamines, flanking regions on the 5'-end of the RNA drive more droplet-like phase separation, while flanking regions on the 3'-end, as well as both the 5'- and 3'-ends, induce more condensed, granular structures. Finally, we provide an example of a biological sequence in the presence of polyamines and show that crowders such as PEG and dextran can selectively cause its phase separation. These findings have implications for the participation of GQS in LLPS in vivo.


Asunto(s)
G-Cuádruplex , Aminoácidos/genética , Nucleótidos , Poliaminas , ARN/química , ARN/genética
2.
Dev Neurosci ; 44(4-5): 394-411, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35613558

RESUMEN

The variability of severity in hypoxia-ischemia (HI)-induced brain injury among research subjects is a major challenge in developmental brain injury research. Our laboratory developed a novel injury scoring tool based on our gross pathological observations during hippocampal extraction. The hippocampi received scores of 0-6 with 0 being no injury and 6 being severe injury post-HI. The hippocampi exposed to sham surgery were grouped as having no injury. We have validated the injury scoring tool with T2-weighted MRI analysis of percent hippocampal/hemispheric tissue loss and cell survival/death markers after exposing the neonatal mice to Vannucci's rodent model of neonatal HI. In addition, we have isolated hippocampal nuclei and quantified the percent good quality nuclei to provide an example of utilization of our novel injury scoring tool. Our novel injury scores correlated significantly with percent hippocampal and hemispheric tissue loss, cell survival/death markers, and percent good quality nuclei. Caspase-3 and Poly (ADP-ribose) polymerase-1 (PARP1) have been implicated in different cell death pathways in response to neonatal HI. Another gene, sirtuin1 (SIRT1), has been demonstrated to have neuroprotective and anti-apoptotic properties. To assess the correlation between the severity of injury and genes involved in cell survival/death, we analyzed caspase-3, PARP1, and SIRT1 mRNA expressions in hippocampi 3 days post-HI and sham surgery, using quantitative reverse transcription polymerase chain reaction. The ipsilateral (IL) hippocampal caspase-3 and SIRT1 mRNA expressions post-HI were significantly higher than sham IL hippocampi and positively correlated with the novel injury scores in both males and females. We detected a statistically significant sex difference in IL hippocampal caspase-3 mRNA expression with comparable injury scores between males and females with higher expression in females.


Asunto(s)
Lesiones Encefálicas , Hipoxia-Isquemia Encefálica , Animales , Animales Recién Nacidos , Encéfalo/metabolismo , Lesiones Encefálicas/metabolismo , Caspasa 3/metabolismo , Femenino , Humanos , Hipoxia-Isquemia Encefálica/patología , Isquemia , Masculino , Ratones , ARN Mensajero/metabolismo , Sirtuina 1
3.
Crim Behav Ment Health ; 32(4): 284-294, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35938636

RESUMEN

BACKGROUND: Following several high-profile police shootings of Black Americans, renewed debate has focused on race as a predictor of police violence. Past research has been inconsistent on this score. Some scholars argue that socioeconomic issues are better predictors of police-related violence than are race and ethnicity. AIMS: To test relationships between complaints of excessive use of police violence and racial/ethnic population demographics, allowing for social and mental health variables. METHODS: We examined records from all 195 municipal police departments in California to identify complaints of excessive force by police and tested for associations between such complaints and health, socio-economic and demographic data from county records, using multivariate analyses. RESULTS: There was no difference in reporting between communities according to Black or White American residency proportions; communities with more Latino Americans were less likely to complain formally of excessive use of police force. The strongest associate of complaints to police departments that their employees had used excessive force was experiencing mental distress in the community. CONCLUSIONS: Our findings are limited by reliance on complaints to police authorities rather than actual incidence of police use of excessive force and by having to map municipal data on to county data, but the finding that factors other than or in addition to any inherent police problems may contribute to excessive use of force by the police offers new lines for remedying the problem. In particular, our findings suggest that more training for police in recognising and managing mental distress and more provision of mental health experts to work alongside police would be worth evaluating as a next step.


Asunto(s)
Etnicidad , Policia , Negro o Afroamericano , Hispánicos o Latinos , Humanos , Estados Unidos , Violencia
4.
Am Heart J ; 224: 85-97, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32353587

RESUMEN

BACKGROUND: Children with congenital heart disease are at risk for growth failure due to inadequate nutrient intake and increased metabolic demands. We examined the relationship between anthropometric indices of nutrition (height-for-age z-score [HAZ], weight-for-age z-score [WAZ], weight-for-height z-score [WHZ]) and outcomes in a large sample of children undergoing surgery for congenital heart disease. METHODS: Patients in the Society of Thoracic Surgeons Congenital Heart Surgery Database having index cardiac surgery at age 1 month to 10 years were included. Indices were calculated by comparing patients' weight and height to population norms from the World Health Organization and Centers for Disease Control and Prevention. Outcomes included operative mortality, composite mortality or major complication, major postoperative infection, and postoperative length of stay. For each outcome and index, the adjusted odds ratio (aOR) (for mortality, composite outcome, and infection) and adjusted relative change in median (for postoperative length of stay) for a 1-unit decrease in index were estimated using mixed-effects logistic and log-linear regression models. RESULTS: Every unit decrease in HAZ was associated with 1.40 aOR of mortality (95% CI 1.32-1.48), and every unit decrease in WAZ was associated with 1.33 aOR for mortality (95% CI 1.25-1.41). The relationship between WHZ and outcome was nonlinear, with aOR of mortality of 0.84 (95% CI 0.76-0.93) for 1-unit decrease when WHZ ≥ 0 and a nonsignificant association for WHZ < 0. Trends for other outcomes were similar. Overall, the incidence of low nutritional indices was similar for 1-ventricle and 2-ventricle patients. Children between the age of 1 month and 1 year and those with lesions associated with pulmonary overcirculation had the highest incidence of low nutritional indices. CONCLUSIONS: Lower HAZ and WAZ, suggestive of malnutrition, are associated with increased mortality and other adverse outcomes after cardiac surgery in infants and young children. Higher WHZ over zero, suggestive of obesity, is also associated with adverse outcomes.


Asunto(s)
Antropometría/métodos , Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas/cirugía , Estado Nutricional , Complicaciones Posoperatorias/epidemiología , Sociedades Médicas , Cirugía Torácica/estadística & datos numéricos , Peso Corporal , Niño , Preescolar , Bases de Datos Factuales , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Factores de Riesgo , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiología
5.
J Pediatr ; 173: 235-7, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26996725

RESUMEN

A 35-day-old female with severe combined immunodeficiency developed cytomegalovirus (CMV) meningitis before undergoing hematopoietic stem cell transplantation. Strategies for timely diagnosis of neonates with congenital or acquired CMV infection and prevention of CMV acquisition in the era of universal newborn severe combined immunodeficiency screening are needed.


Asunto(s)
Infecciones por Citomegalovirus/complicaciones , Meningitis Viral/complicaciones , Inmunodeficiencia Combinada Grave/complicaciones , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/tratamiento farmacológico , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Recién Nacido , Janus Quinasa 3/deficiencia , Meningitis Viral/diagnóstico , Meningitis Viral/tratamiento farmacológico , Inmunodeficiencia Combinada Grave/terapia
6.
Rheumatol Int ; 35(12): 2029-35, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26346588

RESUMEN

The aim of this paper was to assess the validity and reliability of the touch-screen standard Portuguese version of the following patient-reported outcomes (PROs), compared with paper format, in patients with rheumatoid arthritis (RA) and spondyloarthritis: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Quality of Life scale (ASQoL), Short-Form 36 (SF-36), Health Assessment Questionnaire (HAQ) and visual analogue scales (VAS) measuring pain and burden of disease. Adult patients with RA and spondyloarthritis attending the Portuguese Institute of Rheumatology were recruited from March 2013 to January 2014. Patients filled the paper and touch-screen formats of the standard Portuguese versions of the PROs. Two groups of VAS were used, RA and psoriatic arthritis (Global VAS) and another specific for spondyloarthrites (Spa-VAS). Paper questionnaires were filled 15 min before touch-screen formats. Agreement between formats (validity) was assessed by intraclass correlation coefficient (ICC), while internal consistency of scales (reliability) was assessed by Cronbach's alpha. Overall, 134 patients were included with a mean age of 51 years, 74.6 % female and 57.5 % presenting RA. BASDAI, BASFI, HAQ and ASQoL showed high ICC between paper and touch-screen formats (0.977, 0.958, 0.974 and 0.940, respectively). ICC for Global VAS ranged from 0.906 to 0.921, while Spa-VAS ranged from 0.867 to 0.943. The mean ICC for all SF-36 domains was 0.889 (ICC for each domain ranged from 0.781 to 0.944). Touch-screen standard Portuguese formats of these PROs may be valid and reliable tools for PRO measurement in rheumatology.


Asunto(s)
Artritis Reumatoide/diagnóstico , Computadores , Espondiloartritis/diagnóstico , Adulto , Anciano , Artritis Reumatoide/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Portugal , Calidad de Vida , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Espondiloartritis/fisiopatología , Encuestas y Cuestionarios , Evaluación de Síntomas , Traducciones
7.
Nat Commun ; 14(1): 5535, 2023 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-37684277

RESUMEN

Phosphorylation of the translation initiation factor eIF2α to initiate the integrated stress response (ISR) is a vital signalling event. Protein kinases activating the ISR, including PERK and GCN2, have attracted considerable attention for drug development. Here we find that the widely used ATP-competitive inhibitors of PERK, GSK2656157, GSK2606414 and AMG44, inhibit PERK in the nanomolar range, but surprisingly activate the ISR via GCN2 at micromolar concentrations. Similarly, a PKR inhibitor, C16, also activates GCN2. Conversely, GCN2 inhibitor A92 silences its target but induces the ISR via PERK. These findings are pivotal for understanding ISR biology and its therapeutic manipulations because most preclinical studies used these inhibitors at micromolar concentrations. Reconstitution of ISR activation with recombinant proteins demonstrates that PERK and PKR inhibitors directly activate dimeric GCN2, following a Gaussian activation-inhibition curve, with activation driven by allosterically increasing GCN2 affinity for ATP. The tyrosine kinase inhibitors Neratinib and Dovitinib also activate GCN2 by increasing affinity of GCN2 for ATP. Thus, the mechanism uncovered here might be broadly relevant to ATP-competitive inhibitors and perhaps to other kinases.


Asunto(s)
Desarrollo de Medicamentos , Factor 2 Eucariótico de Iniciación , Fosforilación , Inhibición Psicológica , Adenosina Trifosfato
8.
Rheumatol Int ; 32(12): 4047-52, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21915758

RESUMEN

To evaluate a standardised enthesis ultrasound training method, a workshop was conducted to train rheumatologists on enthesis ultrasound. After a theoretical session about ultrasound elementary enthesis lesions (changes in tendon architecture/thickness, bone proliferation/erosion, bursitis or Doppler signal), a reading exercise of 28 entheses' ultrasonographic images (plantar fasciae, Achilles, origin and insertion of patellar tendon) was completed. Participants scored through an electronic multiple-choice device with six possible lesions in each enthesis. To assess the adequacy and efficacy of the workshop, we explored the following: (1) subjective outcomes: a 12-item structured satisfaction questionnaire (graded 1-5 using Likert scale) and (2) objective outcomes of reliability: sensitivity (Se), specificity (Sp) and percentage of correctly classified cases (CC). Forty-nine participants attended the workshop. The satisfaction questionnaire demonstrated a 4.7 mean global value. The inter-reader Kappa reliability coefficient was moderate for the plantar fascia (0.47), Achilles tendon (0.47), and distal patellar tendons (0.50) and good for the proximal patellar tendon (0.63). The whole group means comparing to teachers' consensus were as follows: (a) plantar fascia: Se, 73.2%; Sp, 87.7%; CC, 83.3%; (b) Achilles: Se, 66.9%; Sp, 85.0%; CC, 79.5%; (c) distal patellar tendon: Se, 74.6%; Sp, 85.3%; CC, 82.1%; and (d) proximal patellar tendon: Se, 82.2%; Sp, 90.6%; CC, 88%. The proposed learning method seemed to be simple, easily performed, effective and well accepted by the target audience.


Asunto(s)
Enfermedades Reumáticas/diagnóstico por imagen , Ultrasonografía Doppler , Tendón Calcáneo/diagnóstico por imagen , Educación , Fascia/diagnóstico por imagen , Pie/diagnóstico por imagen , Humanos , Ligamento Rotuliano/diagnóstico por imagen , Reproducibilidad de los Resultados , Espondiloartropatías/diagnóstico por imagen
9.
J Pediatric Infect Dis Soc ; 11(Supplement_4): S132-S140, 2022 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-36063366

RESUMEN

Coronavirus disease 2019 (COVID-19) is an important cause of morbidity in children in the United States (U.S.). Moreover, the U.S. has witnessed significant disparities affecting American Indian/Alaska Native, Black, and Hispanic/Latino children, stemming from systemic racism and social-structural inequalities and not differences in innate biological susceptibility. We review what is known on COVID-19 and health disparities in disease burden, access to care, pharmaceutical interventions, and clinical research in children, with a focus on the U.S. context. In addition, we propose strategies to communicate scientific data in ways that do not promote racism and biological susceptibility themes, and to address pediatric disparities in clinical infectious diseases research.


Asunto(s)
COVID-19 , Niño , Humanos
10.
ARP Rheumatol ; 1(1): 42-48, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35633576

RESUMEN

BACKGROUND: Axial spondyloarthritis (axSpA), particularly ankylosing spondylitis was historically considered a male's disease and has been under-recognized in women. Emerging evidence reveals sex differences in pathophysiology, disease presentation and therapeutic efficacy. OBJECTIVE: To identify differences between sexes in a Portuguese cohort of patients with axSpA regarding clinical manifestations, disease activity, functional capacity, patient related outcomes and presence of sacroiliitis on x-ray or magnetic resonance imaging. METHODS: Patients with ≥18 years fulfilling the ASAS- Assessment of Spondyloarthritis International Society classification criteria for axSpA registered in the electronic Rheumatic Diseases Portuguese Register (Reuma.pt) were included in this multicentric cross-sectional study. Sociodemographic data, clinical features and imaging were collected from the first record in Reuma.pt. These variables were compared between sexes using Mann-Whitney test and Chi-Square test. Variables with a significant association with variable sex were considered in the multiple variable analysis to adjust the sex effect on the outcome variables. Statistical analysis was performed with R version 4.0.2 and p <0.05 was considered statistically significant. RESULTS: A total of 1995 patients were included, 1114 (55.9%) men and 881 (44.1%) women. Men had an earlier disease onset (25.1 vs 28.4, p <0.001), were younger at diagnosis (26.9 vs 30.4, p<0.001) and were more frequently smokers (32.1% vs 15.7%, p <0.001). Comparing to women, men had worse Bath Ankylosing Spondylitis Metrological Index scores (4.0 vs 3.4, p<0.001), higher levels of C-Reactive Protein (10.5 vs 6.9 mg/L, p <0.001) and were more often Human Leukocyte Antigen-B27 positive (67.8% vs 54%, p <0.001). In contrast, women more frequently had inflammatory bowel disease (8.8% vs 4.9%, p =0.004), higher levels of erythrocyte sedimentation rate (25.0 vs 21.0mm/h, p=0.003) and worse patient-related outcomes- Bath Ankylosing Spondylitis Disease Activity Index (5.7 vs 4.5, p<0.001), Patient Global Assessment (60.0 vs 50.0, p <0.001) and fatigue (6.2 vs 5.0, p <0.001). DISCUSSION: In this large multicentric study from a Portuguese axSpA cohort, we confirmed sex differences in patients with axSpA. This work brings awareness to these differences, resulting in less underdiagnosis and misdiagnosis, optimizing treatment strategies, and improving outcomes in axSpA.


Asunto(s)
Espondiloartritis Axial , Espondiloartritis , Espondilitis Anquilosante , Estudios Transversales , Femenino , Humanos , Masculino , Portugal/epidemiología , Caracteres Sexuales , Espondiloartritis/diagnóstico , Espondilitis Anquilosante/diagnóstico
11.
Front Med (Lausanne) ; 9: 901817, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35770002

RESUMEN

Objective: To identify risk factors for SARS-CoV-2 infection and for severe/critical COVID-19, and to assess the humoral response after COVID-19 in these patients. Methods: Nationwide study of adult patients with inflammatory RMDs prospectively followed in the Rheumatic Diseases Portuguese Register-Reuma.pt-during the first 6 months of the pandemic. We compared patients with COVID-19 with those who did not develop the disease and patients with mild/moderate disease with those exhibiting severe/critical COVID-19. IgG antibodies against SARS-CoV-2 were measured ≥3 months after infection and results were compared with matched controls. Results: 162 cases of COVID-19 were registered in a total of 6,363 appointments. Patients treated with TNF inhibitors (TNFi; OR = 0.160, 95% CI 0.099-0.260, P < 0.001) and tocilizumab (OR 0.147, 95% CI 0.053-0.408, P < 0.001) had reduced odds of infection. Further, TNFi tended to be protective of severe and critical disease. Older age, major comorbidities, and rituximab were associated with an increased risk of infection and worse prognosis. Most patients with inflammatory RMDs (86.2%) developed a robust antibody response. Seroconversion was associated with symptomatic disease (OR 13.46, 95% CI 2.21-81.85, P = 0.005) and tended to be blunted by TNFi (OR 0.17, 95% CI 0.03-1.05; P = 0.057). Conclusions: TNFi and tocilizumab reduced the risk of infection by SARS-CoV-2. Treatment with TNFi also tended to reduce rates of severe disease and seroconversion. Older age, general comorbidities and rituximab were associated with increased risk for infection and worse prognosis, in line with previous reports. Most patients with RMDs developed a proper antibody response after COVID-19, particularly if they had symptomatic disease.

12.
Am J Obstet Gynecol ; 205(4): 324.e1-7, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21777898

RESUMEN

OBJECTIVE: The objective of the study was to characterize endometrial inflammation associated with common genital tract pathogens. STUDY DESIGN: The design of the study was the immunohistochemical characterization of the endometrial leukocyte subpopulations from 37 controls and 45 women infected with Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis. RESULTS: Compared with uninfected women, endocervical infection with C trachomatis, N gonorrhoeae, or T vaginalis was associated with significant increases in endometrial T cells, B cells, plasma cells, and polymorphonuclear leukocytes. Even more substantial increases in T cell, B cell, and plasma cell numbers were detected among women infected endocervically and endometrially with C trachomatis. CONCLUSION: Because lower genital tract C trachomatis, N gonorrhoeae, or T vaginalis infections were associated with comparable increases in the same endometrial leukocyte subpopulations, our results suggest the underappreciated involvement of T vaginalis in upper genital tract inflammatory processes. The more robust inflammatory infiltrate associated with C trachomatis endometrial ascension may offer insight into host inflammatory responses associated with pelvic inflammatory disease development.


Asunto(s)
Infecciones por Chlamydia/inmunología , Chlamydia trachomatis , Endometrio/inmunología , Gonorrea/inmunología , Leucocitos , Infecciones del Sistema Genital/inmunología , Endometrio/citología , Femenino , Humanos , Inmunohistoquímica , Vaginitis por Trichomonas
13.
Violence Vict ; 26(4): 395-409, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21882665

RESUMEN

Previous research offered little guidance on sentencing outcomes for protection order (PO) violations in cases of domestic assault and whether PO violation charges affected offender recidivism rates. Using data from local court records, this study examined the effect of PO violation charges on the odds of case conviction relative to dismissal, and whether case conviction or a PO violation charge results in lower domestic violence rearrest rates compared to offenders not receiving these sanctions. The models indicate that PO violation charges has no significant effect on the odds of conviction or recidivism rates, and these trends were not significantly different for convicted versus dismissed offenders. Findings are discussed in relation to previous research with recommendations for future areas of study.


Asunto(s)
Víctimas de Crimen/legislación & jurisprudencia , Criminales/legislación & jurisprudencia , Violencia Doméstica/legislación & jurisprudencia , Salud de la Mujer/legislación & jurisprudencia , Víctimas de Crimen/estadística & datos numéricos , Criminales/estadística & datos numéricos , Conducta Peligrosa , Violencia Doméstica/estadística & datos numéricos , Femenino , Humanos , Relaciones Interpersonales , Aplicación de la Ley , Masculino , Factores de Riesgo , Prevención Secundaria , Factores Socioeconómicos , Maltrato Conyugal/legislación & jurisprudencia , Estados Unidos
15.
J Rheumatol ; 47(5): 690-700, 2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-31371659

RESUMEN

OBJECTIVE: To assess longterm effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA) registered in the Rheumatic Diseases Portuguese Register, exposed to at least 1 TNFi, prospectively followed between 2001 and 2017. METHODS: Kaplan-Meier analysis was performed for first-, second-, and third-line TNFi. Responses included European League Against Rheumatism (EULAR) criteria, Disease Activity Index for Psoriatic Arthritis (DAPSA), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) at 3 and 6 months. Baseline predictors of discontinuation and response were studied using Cox and multivariable multinomial/logistic regression models. RESULTS: The 750 patients with PsA showed drug retention of 4.1 ± 3.4 years (followup 5.8 ± 3.8 yrs) for first TNFi. Switching to a second (189 patients) or third (50 patients) TNFi further decreased survival by 1.1 years. Female sex, higher baseline 28-joint count Disease Activity Score, and infliximab were predictors of first TNFi discontinuation. After 6 months of the first TNFi, 48.7% of patients achieved a good EULAR criteria response and 20.9% were in DAPSA remission. There were 11.4% in MDA, and 56.4% had a good ASDAS. Responses to the second TNFi were significantly inferior compared to responses to the first TNFi. Female sex and higher baseline Health Assessment Questionnaire-Disability Index were negatively associated with good EULAR response at 3 months, and obesity decreased the chance of response at 6 months. CONCLUSION: In this study, switching to a second or third TNFi was associated with significantly lower drug survival and response rates for patients with axial and peripheral PsA subtypes. More successful therapeutic approaches will require considering the effect of sex and obesity on TNFi effectiveness.


Asunto(s)
Antirreumáticos , Artritis Psoriásica , Enfermedades Reumáticas , Inhibidores del Factor de Necrosis Tumoral , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Femenino , Humanos , Masculino , Portugal , Sistema de Registros , Enfermedades Reumáticas/tratamiento farmacológico , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa
16.
J Pediatr ; 155(6): 904-908.e3, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19683724

RESUMEN

OBJECTIVE: To examine the multivariate nature of risk factors for youth violence including delinquent peer associations, exposure to domestic violence in the home, family conflict, neighborhood stress, antisocial personality traits, depression level, and exposure to television and video game violence. STUDY DESIGN: A population of 603 predominantly Hispanic children (ages 10-14 years) and their parents or guardians responded to multiple behavioral measures. Outcomes included aggression and rule-breaking behavior on the Child Behavior Checklist (CBCL), as well as violent and nonviolent criminal activity and bullying behavior. RESULTS: Delinquent peer influences, antisocial personality traits, depression, and parents/guardians who use psychological abuse in intimate relationships were consistent risk factors for youth violence and aggression. Neighborhood quality, parental use of domestic violence in intimate relationships, and exposure to violent television or video games were not predictive of youth violence and aggression. CONCLUSION: Childhood depression, delinquent peer association, and parental use of psychological abuse may be particularly fruitful avenues for future prevention or intervention efforts.


Asunto(s)
Agresión/psicología , Trastorno Depresivo/psicología , Relaciones Familiares , Medios de Comunicación de Masas , Medio Social , Violencia/psicología , Adolescente , Trastorno de Personalidad Antisocial/complicaciones , Trastorno de Personalidad Antisocial/etnología , Trastorno de Personalidad Antisocial/psicología , Niño , Estudios de Cohortes , Trastorno Depresivo/complicaciones , Trastorno Depresivo/etnología , Femenino , Hispánicos o Latinos/psicología , Humanos , Masculino , Análisis Multivariante , Grupo Paritario , Factores de Riesgo , Violencia/etnología
17.
PLoS One ; 14(2): e0212029, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30753206

RESUMEN

BACKGROUND: The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) resulted in the recommended use of clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) for suspected S. aureus infections. The objective of this study was to determine the resistance to methicillin, clindamycin, and TMP-SMX in S. aureus isolates during a 10-year period. METHODS: Retrospective review of the antimicrobial susceptibilities of all S. aureus isolates in the outpatient and inpatient settings at Nationwide Children's Hospital from 1/1/2005 to 12/31/2014. Duplicate isolates from the same site and year and those obtained for MRSA surveillance or from patients with cystic fibrosis were excluded. RESULTS: Of the 57,788 S. aureus isolates from 2005-2014, 40,795 (71%) were included. In the outpatient setting, methicillin resistance decreased from 54% to 44% (p<0.001) while among inpatient isolates, no significant change was observed. From 2009-2014, resistance to clindamycin among outpatient isolates increased from 16% to 17% (p = 0.002) but no significant trend was observed among inpatient isolates (18% to 22%). Similarly, TMP-SMX resistance increased in outpatient S. aureus isolates from 2005-2014 (0.9% to 4%, p<0.001) but not among inpatient isolates. Among both inpatient and outpatient isolates, methicillin-susceptible S. aureus (MSSA) exhibited higher resistance to both clindamycin and TMP-SMX than MRSA. In addition, resistance to methicillin, clindamycin and TMP-SMX varied widely according to the site of specimen collection. CONCLUSION: In a decade where >40,000 S. aureus isolates were identified at a large pediatric hospital, substantial changes in methicillin, clindamycin, and TMP-SMX resistance occurred. These findings highlight the importance of ongoing surveillance of the local antimicrobial resistance in S. aureus in order to guide empiric antimicrobial therapy.


Asunto(s)
Farmacorresistencia Bacteriana , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/efectos de los fármacos , Niño , Preescolar , Clindamicina/farmacología , Femenino , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Masculino , Meticilina/farmacología , Vigilancia de la Población , Estudios Retrospectivos , Staphylococcus aureus/aislamiento & purificación , Combinación Trimetoprim y Sulfametoxazol/farmacología
19.
Acta Reumatol Port ; 42(3): 269-270, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28605749

RESUMEN

INTRODUCTION: Spinal involvement is infrequent in chronic gout. However, some cases of back pain with radiculopathy secondary to this etiology have been reported. CASE REPORT: 56-year old male patient, with history of arterial hypertension, hypertriglyceridemia, obesity, glucose intolerance and alcohol abuse, diagnosed with gout in his fifth decade of life. The patient was started on urate lowering therapy, with poor compliance, and evolved with sustained hyperuricemia, recurrent episodes of arthritis, and growth of gouty tophi on the elbows, wrists, hands and knees. In 2011, the patient presented with radiculopathy. When pain recurred, a Computed Tomography was performed and it showed alterations compatible with spinal tophi formation and nerve root involvement. DISCUSSION/CONCLUSIONS: Our clinical case is another example of how gout can produce spinal inflammation and nerve damage and superimpose on previously damaged joints and how patients' compliance to therapeutics may have an important impact on prognosis.


Asunto(s)
Artritis Gotosa/complicaciones , Artritis Gotosa/diagnóstico por imagen , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Enfermedades de la Columna Vertebral/etiología , Vértebras Torácicas/diagnóstico por imagen , Enfermedad Crónica , Femenino , Humanos , Persona de Mediana Edad
20.
Biomed Res Int ; 2015: 279890, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26000286

RESUMEN

OBJECTIVES: To compare the effectiveness of TNF inhibitors (TNFi) and tocilizumab in rheumatoid arthritis (RA) treatment, according to different response criteria. METHODS: We included RA patients registered in the Rheumatic Diseases Portuguese Register treated with TNFi or tocilizumab for at least 6 months, between January 2008 and July 2013. We assessed remission/low disease activity (LDA) at 6 months according to DAS28, CDAI, and SDAI, as well as Boolean ACR/EULAR remission and EULAR response rate, adjusting for measured confounders. RESULTS: Tocilizumab-treated patients (n = 95) presented higher baseline disease activity and were less frequently naïve to biologics compared to TNFi users (n = 429). Multivariate logistic regression analysis including the propensity score for receiving tocilizumab showed that patients treated with tocilizumab were more likely to achieve remission or LDA according to DAS28 (OR = 11.0/6.2, 95% CI 5.6-21.6/3.2-12.0), CDAI (OR = 2.8/2.6, 95% CI 1.2-6.5/1.3-5.5), or SDAI (OR = 3.6/2.5, 95% CI 1.5-8.7/1.1-5.5), as well as a good EULAR response (OR = 6.4, 95% CI 3.4-12.0). However, both groups did not differ in Boolean remission (OR = 1.9, 95% CI 0.8-4.8) or good/moderate EULAR response (OR = 1.8, 95% CI 0.8-4.5). CONCLUSIONS: Compared with TNFi, tocilizumab was associated with greater likelihood of achieving DAS28, CDAI, and SDAI remission/LDA and EULAR good response. Boolean remission and EULAR good/moderate response did not differ significantly between groups.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Sistema de Registros , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Portugal , Inducción de Remisión , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismo
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