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BACKGROUND: Documentation of lingual tumors is scarce in nonhuman primates. METHODS: Through a multi-institutional retrospective study we compile cases of primary and metastatic neoplasia in non-human primates. RESULTS: We describe five cases of lingual neoplasia. Three cases are primary lingual tumors: chondro-osteoblastic lipoma in a howler monkey, squamous cell carcinoma, and fibroma in two baboons. We describe two cases of metastatic lymphoma in the tongue in rhesus macaques. A literature review of published lingual neoplasia in nonhuman primates is included in this manuscript. CONCLUSION: Lingual neoplasia is seldom reported in non-human primates.
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Doenças dos Macacos , Papio , Neoplasias da Língua , Animais , Doenças dos Macacos/patologia , Doenças dos Macacos/diagnóstico , Masculino , Feminino , Neoplasias da Língua/patologia , Neoplasias da Língua/veterinária , Neoplasias da Língua/diagnóstico , Estudos Retrospectivos , Macaca mulatta , Carcinoma de Células Escamosas/veterinária , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico , Lipoma/veterinária , Lipoma/patologia , Lipoma/diagnósticoRESUMO
Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.
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Encéfalo , Macaca mulatta , Caracteres Sexuais , Transcriptoma , Animais , Macaca mulatta/genética , Encéfalo/metabolismo , Feminino , Masculino , Humanos , Evolução MolecularRESUMO
Background: The COVID-19 pandemic affected older adults worldwide. Sedentary older adults experienced more severe adverse health effects due to their shelter-in-place. Physical activity was strongly recommended during periods of social distancing. The present study evaluated the impact of a virtually supervised exercise program on the physical fitness and mental health of Mexican older adults during the pandemic's lockdown. Methods: Participants were 44 older adults who were assigned to one of four physical fitness groups: a healthy control group (Ctrl-H, n = 15), a comorbidity control group (Ctrl-COM, n = 9), an exercise group without comorbidities (Exe-H, n = 11), and an exercise group with comorbidities (Exe-COM, n = 9). The participants engaged in a 60-min, virtually-supervised concurrent exercise session three times/week for 12 weeks. Fitness was measured using the online Senior Fitness Tests and the 4-m Gait Speed Test. Mental health was evaluated through virtual interviews using the Hamilton Depression Rating Scale, the Geriatric Depression Scale, and the Connor-Davidson Resilience Scale. Within-subject pre vs. post-intervention comparisons tested for significant differences, between-groups and over time. Results: Significant interactions were found in the scores of the Geriatric Depression Scale (p ≤ 0.0001; ηp2 = 0.35), the Hamilton Depression Scale (p ≤ 0.0001; ηp2 = 0.35), resilience scores (p ≤ 0.0001; ηp2 = 0.46), lower-body strength (p ≤ 0.0001; ηp2 = 0.32), timed up-and-go test (p = 0.018; ηp2 = 0.18), the 6MWT distance scores (p ≤ 0.0001; ηp2 = 0.39), and the 4-m gait speed test scores (p = 0.011; ηp2 = 0.20). Conclusion: A long-term virtually-supervised exercise program conducted during the COVID-19 lockdown period led to marked improvements in both the fitness and mental health of older Mexican adults. Comorbidities did not diminish these benefits. These findings provide empirical support for online exercise programs in the daily routines of older adults to make clinically meaningful improvements in both physical and mental well-being.
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COVID-19 , Comorbidade , Saúde Mental , Aptidão Física , Humanos , COVID-19/psicologia , Idoso , Masculino , Feminino , México , Exercício Físico/psicologia , Terapia por Exercício/métodos , Idoso de 80 Anos ou mais , SARS-CoV-2 , Pandemias , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To assess the predictive value of four cardiovascular (CV) risk algorithms for identifying high-risk psoriatic arthritis (PsA) patients. METHODS: Evaluation of patients with PsA enrolled in the Spanish prospective project CARdiovascular in RheuMAtology. Baseline data of 669 PsA patients with no history of CV events at the baseline visit, who were followed in rheumatology outpatient clinics at tertiary centres for 7.5 years, were retrospectively analysed to test the performance of the Systematic Coronary Risk Assessment (SCORE), the modified version (mSCORE) European Alliance of Rheumatology Associations (EULAR) 2015/2016, the SCORE2 algorithm (the updated and improved version of SCORE) and the QRESEARCH risk estimator version 3 (QRISK3). RESULTS: Over 4790 years of follow-up, there were 34 CV events, resulting in a linearised rate of 7.10 per 1000 person-years (95% CI 4.92 to 9.92). The four CV risk scales showed strong correlations and all showed significant associations with CV events (p<0.001). SCORE, mSCORE EULAR 2015/2016 and QRISK3 effectively differentiated between low and high CV risk patients, although the cumulative rate of CV events observed over 7.5 years was lower than expected based on the frequency predicted by these risk scales. Additionally, model improvement was observed when combining QRISK3 with any other scale, particularly the combination of QRISK3 and SCORE2, which yielded the lowest Akaike information criterion (411.15) and Bayesian information criterion (420.10), making it the best predictive model. CONCLUSIONS: Risk chart algorithms are very useful for discriminating PsA at low and high CV risk. An integrated model featuring QRISK3 and SCORE2 yielded the optimal synergy of QRISK3's discrimination ability and SCORE2's calibration accuracy.
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Artrite Psoriásica , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/complicações , Estudos Prospectivos , Estudos Retrospectivos , Artrite Psoriásica/complicações , Teorema de Bayes , Seguimentos , AlgoritmosRESUMO
Zika virus (ZIKV) infection during pregnancy poses significant threats to maternal and fetal health, leading to intrauterine fetal demise and severe developmental malformations that constitute congenital Zika syndrome (CZS). As such, the development of a safe and effective ZIKV vaccine is a critical public health priority. However, the safety and efficacy of such a vaccine during pregnancy remain uncertain. Historically, the conduct of clinical trials in pregnant women has been challenging. Therefore, clinically relevant animal pregnancy models are in high demand for testing vaccine efficacy. We previously reported that a marmoset pregnancy model of ZIKV infection consistently demonstrated vertical transmission from mother to fetus during pregnancy. Using this marmoset model, we also showed that vertical transmission could be prevented by pre-pregnancy vaccination with Zika purified inactivated virus (ZPIV) vaccine. Here, we further examined the efficacy of ZPIV vaccination during pregnancy. Vaccination during pregnancy elicited virus neutralizing antibody responses that were comparable to those elicited by pre-pregnancy vaccination. Vaccination also reduced placental pathology, viral burden and vertical transmission of ZIKV during pregnancy, without causing adverse effects. These results provide key insights into the safety and efficacy of ZPIV vaccination during pregnancy and demonstrate positive effects of vaccination on the reduction of ZIKV infection, an important advance in preparedness for future ZIKV outbreaks.
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Industrially fabricated medicines have a well-defined shelf life supported by rigorous studies before their approval for commercialization. However, the shelf life of extemporaneous compounding topical formulations prepared at hospitals tends to be shorter, especially when no data are available to prove a longer stability period. Also, the storage conditions are unknown in many circumstances. Accelerated Predictive Stability (APS) studies have been shown to be a useful tool to predict in a faster and more accurate manner the chemical stability of extemporaneously compounded formulations requiring a minimum amount of formulation, thereby reducing the chemical drug waste per study. Shelf life will be allocated based on scientific data without compromising drug efficacy or safety. In this work, the APS approach was applied to the commercially available Cristalmina® (CR) and an extemporaneously compounded formulation of chlorhexidine (DCHX). A different degradation kinetic was found between DCHX and CR (Avrami vs. zero-order kinetics, respectively). This can explain the different shelf life described by the International Council for Harmonisation of Technical Requirements Registration Pharmaceuticals Human Use (ICH) conditions between both formulations. A predicted stability for the DCHX solution was obtained from the extrapolation of the degradation rate in long-term conditions from the Arrhenius equation. The estimated degradation from the Arrhenius equation for DCHX at 5 °C, 25 °C, and 30 °C at 365 days was 3.1%, 17.4%, and 25.9%, respectively. The predicted shelf life, in which the DCHX content was above 90%, was 26.67 months under refrigerated conditions and 5.75 and 2.24 months at 25 and 30 °C, respectively. Currently, the Spanish National Formulary recommends a shelf life of no longer than 3 months at room temperature for DCHX solution. Based on the predicted APS and confirmed by experimental long-term studies, we have demonstrated that the shelf life of DCHX extemporaneously compounded formulations could be prolonged by up to 6 months.
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Clorexidina , Humanos , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de MedicamentosRESUMO
INTRODUCTION: Inflammatory rheumatic diseases usually affect women of childbearing age treated with biologic drugs. However, there is a lack of literature on the efficacy and toxicity of biologic disease-modifying drugs during pregnancy. The aim of this study was to determine the presence of pregnant patients treated with bDMARDs in a real-world dataset and to examine the impact of pregnancy and lactation on the evolution of rheumatic disease in a registry of Spanish patients. METHOD: This was a multicentre prospective study with a real-world setting. Information was obtained from BIOBADASER registry. Patients included are women who got pregnant until November 2020 from 19 rheumatology units. We conducted proportions, means, and standard deviations (SD) to describe the study population and the use of treatments. T-test and Chi-square test were applied to assess differences between groups. RESULT: Ninety cases of pregnancy were registered (n=68 full-term pregnancies; n=22 spontaneous miscarriages). Most of the cases discontinued bDMARDs during pregnancy (78.9%) but 13 cases continued treatment during pregnancy, mainly using certolizumab pegol. These cases were obtaining better management of rheumatic disease, although the differences were not statistically significant [DAS28-CRP, 2.9 (SD: 1.6) vs. 2.0 (1.2), p=.255; DAS28-ESR, 2.2 (1.0) vs. 1.7 (.5), p=.266]. No serious adverse events were reported during pregnancy and lactation. CONCLUSION: Being pregnant is still an uncommon condition in patients with rheumatic diseases and using bDMARDs. Our results show that rheumatic disease tended to progress better during pregnancy in patients who continued to take bDMARDs.
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Produtos Biológicos , Doenças Reumáticas , Reumatologia , Gravidez , Humanos , Feminino , Masculino , Estudos Prospectivos , Doenças Reumáticas/tratamento farmacológico , Sistema de RegistrosRESUMO
A pseudo-outbreak of Aspergillus caused by false positive cultures can have a high sanitary impact. We determined the effectiveness (fungal load elimination) of a non-touch disinfection system, vs conventional disinfection methods, to solve steady contamination of culture plates with Aspergillus niger at a clinical microbiology laboratory. Routine cleaning-disinfection (RCD), intensive cleaning-disinfection (ICD), and terminal airborne disinfection (TAD) were employed in stages. Air sampling was carried out before and after each procedure. The effectiveness of TAD on contact surfaces was tested by surface sampling. After RCD, ICD, and TAD, there was a mean decrease of 5.4 (95% CI = 1.8-9.0), 19.2 (95% CI = 12.4-26.0), and 4.4 (95% CI = 2.5-6.3) CFU per tested area, and 46.2%, 21.7%, and 95.5% of contaminated areas became sterile, respectively. There was a mean decrease of 30.6 CFU per tested surface (p < 0.0007) and 50% of tested surfaces became sterile. Global effectiveness of RCD, ICD, and TAD was 68.8% (95% CI = 68.5-69.1), 82.2% (95% CI = 82.1-82.3), and 99.0% (95% CI = 98.8-99.2), respectively. The effectiveness was higher with TAD (4.1 CFU/cm2 less than with ICD; p = 0.0290). No further contamination has occurred since then. When construction and renovation activities are discarded and RCD and ICD practices are insufficient, non-touch disinfection remove residual dust contamination and avoid recurrence.
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Aspergillus niger , Infecção Hospitalar , Humanos , Infecção Hospitalar/microbiologia , Espanha , Desinfecção/métodosRESUMO
Cromoglycate (SCG) is widely used for allergy processes, and inflammatory states acting as a mast cell membrane stabilizer that inhibits the histamine and mediator release. Currently, SCG topical extemporaneous compounding formulations are prepared in hospitals and community pharmacies, as no industrial fabricated medicines are available in Spain. The stability of these formulations is unknown. Additionally, there are no clear guidelines on which concentration and vehicle are more suitable to enhance permeation across the skin. In this work, the stability of commonly prescribed topical SCG formulations in clinical practice was evaluated. Different vehicles commonly employed by pharmacists daily for formulating topical SCG were investigated (Eucerinum, Acofar Creamgel, and Beeler's base) at different concentrations, ranging from 0.2 to 2%. The stability of topical extemporaneous compounded SCG formulations can be extended for up to three months at room temperature (25 °C). Creamgel 2% formulations significantly improved the topical permeation of SCG across the skin, being 4.5-fold higher than formulations prepared with Beeler's base. The reason attributed to this performance can be related to the lower droplet size formed upon dilution in aqueous media combined with a lower viscosity, which facilitates its application and extensibility on the skin. The higher the SCG concentration in Creamgel formulations, the higher the permeability across both synthetic membranes and pig skin (p-value < 0.05). These preliminary results can be used as a guide to prompt a rational prescription of topical SCG formulations.
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Zika virus (ZIKV) infection during pregnancy causes severe developmental defects in newborns, termed congenital Zika syndrome (CZS). Factors contributing to a surge in ZIKV-associated CZS are poorly understood. One possibility is that ZIKV may exploit the antibody-dependent enhancement of infection mechanism, mediated by cross-reactive antibodies from prior dengue virus (DENV) infection, which may exacerbate ZIKV infection during pregnancy. In this study, we investigated the impact of prior DENV infection or no DENV infection on ZIKV pathogenesis during pregnancy in a total of four female common marmosets with five or six fetuses per group. The results showed that negative-sense viral RNA copies increased in the placental and fetal tissues of DENV-immune dams but not in DENV-naïve dams. In addition, viral proteins were prevalent in endothelial cells, macrophages, and neonatal Fc receptor-expressing cells in the placental trabeculae and in neuronal cells in the brains of fetuses from DENV-immune dams. DENV-immune marmosets maintained high titers of cross-reactive ZIKV-binding antibodies that were poorly neutralizing, raising the possibility that these antibodies might be involved in the exacerbation of ZIKV infection. These findings need to be verified in a larger study, and the mechanism involved in the exacerbation of ZIKV infection in DENV-immune marmosets needs further investigation. However, the results suggest a potential negative impact of preexisting DENV immunity on subsequent ZIKV infection during pregnancy in vivo.
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Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Animais , Feminino , Gravidez , Callithrix , Anticorpos Neutralizantes , Anticorpos Antivirais , Células Endoteliais , Placenta , Reações CruzadasRESUMO
The expression of indoleamine 2,3-dioxygenase (IDO), a robust immunosuppressant, is significantly induced in macaque tuberculosis (TB) granulomas, where it is expressed on IFN-responsive macrophages and myeloid-derived suppressor cells. IDO expression is also highly induced in human TB granulomas, and products of its activity are detected in patients with TB. In vivo blockade of IDO activity resulted in the reorganization of the granuloma with substantially greater T cells being recruited to the core of the lesions. This correlated with better immune control of TB and reduced lung M. tuberculosis burdens. To study if the IDO blockade strategy can be translated to a bona fide host-directed therapy in the clinical setting of TB, we studied the effect of IDO inhibitor 1-methyl-d-tryptophan adjunctive to suboptimal anti-TB chemotherapy. While two-thirds of controls and one-third of chemotherapy-treated animals progressed to active TB, inhibition of IDO adjunctive to the same therapy protected macaques from TB, as measured by clinical, radiological, and microbiological attributes. Although chemotherapy improved proliferative T cell responses, adjunctive inhibition of IDO further enhanced the recruitment of effector T cells to the lung. These results strongly suggest the possibility that IDO inhibition can be attempted adjunctive to anti-TB chemotherapy in clinical trials.
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Mycobacterium tuberculosis , Tuberculose Pulmonar , Tuberculose , Animais , Humanos , Granuloma , Indolamina-Pirrol 2,3,-Dioxigenase , Macrófagos/metabolismo , Mycobacterium tuberculosis/metabolismoRESUMO
OBJECTIVE: Real-world studies are needed to identify factors associated with response to biologic therapies in patients with axial spondyloarthritis (SpA). The objective was to assess sex differences in response to tumor necrosis factor inhibitors (TNFi) and to explore possible risk factors associated with TNFi efficacy. METHODS: A total of 969 patients with axial SpA (315 females, 654 males) enrolled in the BIOBADASER registry (2000-2019) who initiated a TNFi (first, second, or further lines) were studied. Statistical and artificial intelligence (AI)-based data analyses were used to explore the association of sex differences and other factors to TNFi response, using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), to calculate the BASDAI50, with an improvement of at least 50% of the BASDAI score, and using the Ankylosing Spondylitis Disease Activity Score, calculated using the C-reactive protein level (ASDAS-CRP). RESULTS: Females had a lower probability of reaching a BASDAI50 response with a first line TNFi treatment at the second year of follow-up (P = 0.018) and a lesser reduction of the ASDAS-CRP at this time point. The logistic regression model showed lower BASDAI50 responses to TNFi in females (P = 0.05). Other factors, such as older age (P = 0.004), were associated with unfavorable responses. The AI data analyses reinforced the idea that age at the beginning of the treatment was the main factor associated with an unfavorable response. The combination of age with other clinical characteristics (female sex or cardiovascular risk factors and events) potentially contributed to an unfavorable response to TNFi. CONCLUSION: In this national multicenter registry, female sex was associated with less response to a first-line TNFi by the second year of follow-up. A higher age at the start of the TNFi was the main factor associated with an unfavorable response to TNFi.
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Espondilartrite , Espondilite Anquilosante , Humanos , Feminino , Masculino , Espondilite Anquilosante/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Inteligência Artificial , Fator de Necrose Tumoral alfa , Resultado do Tratamento , Sistema de Registros , Índice de Gravidade de DoençaRESUMO
AIM: To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors. METHODS: Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) database, assessing all adults who had ever started golimumab >6 months before the analysis for an approved indication (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA]). RESULTS: Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0-73.9) at year 1% and 37.7% (95% CI: 33.3-42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p < 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first-line therapy (hazard ratio [HR] for discontinuation 1.52 for second- and 1.79 for third/later-line vs. first-line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation. CONCLUSION: Based on this retrospective analysis of the BIOBADASER registry, nearly two-fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic.
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Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Espondiloartrite Axial , Espondilartrite , Adulto , Humanos , Artrite Psoriásica/tratamento farmacológico , Estudos Retrospectivos , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: To determine weight, height and body mass index (BMI) of schoolchildren from the La Mancha-Centro health area and compare them with those determined by the Spanish Cross-sectional Growth Study 2010 (SCGS-2010). METHODS: Cross-sectional study of 954 schoolchildren aged 6-12 years. Mean, standard deviation, and percentile distributions of weight, height, and BMI by gender and age were obtained. Differences in each 6-month age group were analyzed. RESULTS: There was a progressive increase in BMI with age, which was significant in girls from nine years of age on and in boys from 8.5 years on. From age 10, average BMI was 2.3 kg/m2 higher than at younger ages (p < 0.001). The biggest difference between genders occurred at age 12: 2 ± 0.98 kg/m2 higher in boys (p = 0.042). Overall, no significant differences were found in weight, height and BMI vs. SCGS-2010, although mean weight of male children from La Mancha-Centro aged between 8.5 and 11.5 years was 3.9 kg higher than that of the rest of Spanish male children. CONCLUSIONS: Anthropometric parameters of schoolchildren from La Mancha-Centro do not significantly differ from national standards; however, preadolescent males from La Mancha-Centro weigh almost 4 kg more.
OBJETIVOS: Determinar peso, talla e índice de masa corporal (IMC) de escolares del área de salud La Mancha-Centro y compararlos con los definidos en el Estudio Transversal Español de Crecimiento 2010 (ETEC-2010). MÉTODOS: Estudio transversal de 954 escolares entre 6 y 12 años. Se obtuvieron media, desviación estándar y distribuciones percentilares de peso, talla e IMC por sexo y edad. Se analizaron las diferencias en cada grupo semestral de edad. RESULTADOS: Existió incremento progresivo del IMC con la edad, significativo en las niñas a partir de los nueve años y en los niños desde los 8.5 años. Desde los 10 años, el IMC promedio resultó 2.3 kg/m2 superior al de edades menores (p < 0.001); la mayor diferencia entre los sexos ocurrió a los 12 años: 2 ± 0.98 kg/m2 más en los varones (p = 0.042). Globalmente no se hallaron diferencias significativas de peso, talla e IMC con el ETEC-2010, aunque el peso medio de los niños manchegos de 8.5 a 11.5 años fue 3.9 kg mayor que el del resto de los niños españoles. CONCLUSIONES: Los parámetros antropométricos de los escolares manchegos no difieren de los estándares nacionales; sin embargo, los varones preadolescentes manchegos pesan casi 4 kg más.
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Estudos Transversais , Criança , Humanos , Masculino , Feminino , Lactente , Antropometria , Índice de Massa CorporalRESUMO
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), along with the World Health Organization (WHO), has provided a set of guidelines (ICH Q1A-E, Q3A-B, Q5C, Q6A-B) intended to unify the standards for the European Union, Japan, and the United States to facilitate the mutual acceptance of stability data that are sufficient for registration by the regulatory authorities in these jurisdictions. Overall, ICH stability studies involve a drug substance tested under storage conditions and assess its thermal stability and sensitivity to moisture. The long-term testing should be performed over a minimum of 12 months at 25 °C ± 2 °C/60% RH ± 5% RH or at 30 °C ± 2 °C/65% RH ± 5% RH. The intermediate and accelerated testing should cover a minimum of 6 months at 30 °C ± 2 °C/65% RH ± 5% RH (which is not necessary if this condition was utilized as a long-term one) and 40 °C ± 2 °C/75% RH ± 5% RH, respectively. Hence, the ICH stability testing for industrially fabricated medicines is rigorous and tedious and involves a long period of time to obtain preclinical stability data. For this reason, Accelerated Predictive Stability (APS) studies, carried out over a 3-4-week period and combining extreme temperatures and RH conditions (40-90 °C)/10-90% RH, have emerged as novel approaches to predict the long-term stability of pharmaceutical products in a more efficient and less time-consuming manner. In this work, the conventional ICH stability studies versus the APS approach will be reviewed, highlighting the advantages and disadvantages of both strategies. Furthermore, a comparison of the stability requirements for the commercialization of industrially fabricated medicines versus extemporaneous compounding formulations will be discussed.
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Aging is accompanied by a host of social and biological changes that correlate with behavior, cognitive health and susceptibility to neurodegenerative disease. To understand trajectories of brain aging in a primate, we generated a multiregion bulk (N = 527 samples) and single-nucleus (N = 24 samples) brain transcriptional dataset encompassing 15 brain regions and both sexes in a unique population of free-ranging, behaviorally phenotyped rhesus macaques. We demonstrate that age-related changes in the level and variance of gene expression occur in genes associated with neural functions and neurological diseases, including Alzheimer's disease. Further, we show that higher social status in females is associated with younger relative transcriptional ages, providing a link between the social environment and aging in the brain. Our findings lend insight into biological mechanisms underlying brain aging in a nonhuman primate model of human behavior, cognition and health.
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Doenças Neurodegenerativas , Feminino , Masculino , Humanos , Animais , Macaca mulatta , Transcriptoma , Envelhecimento/genética , Meio Social , Núcleo SolitárioRESUMO
Attention Deficit/Hyperactivity Disorder is the most prevalent neurodevelopmental disorder worldwide. Choice treatment includes psychostimulants, but parents tend to be reluctant to administer them due to side effects, and alternatives are needed. Saffron extract is a natural stimulant that has been proven safe and effective for treating a variety of mental disorders. This study compares the efficacy of saffron and the usual treatment with methylphenidate, using objective and pen-and-paper tests. We performed a non-randomized clinical trial with two groups, methylphenidate (n = 27) and saffron (n = 36), in children and adolescents aged 7 to 17. Results show that the efficacy of saffron is comparable to that of methylphenidate. Saffron is more effective for treating hyperactivity symptoms, while methylphenidate is more effective for inattention symptoms.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Crocus , Metilfenidato , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Criança , Humanos , Metilfenidato/uso terapêutico , PaisRESUMO
Resumen Objetivos: Determinar peso, talla e índice de masa corporal (IMC) de escolares del área de salud La Mancha-Centro y compararlos con los definidos en el Estudio Transversal Español de Crecimiento 2010 (ETEC-2010). Métodos: Estudio transversal de 954 escolares entre 6 y 12 años. Se obtuvieron media, desviación estándar y distribuciones percentilares de peso, talla e IMC por sexo y edad. Se analizaron las diferencias en cada grupo semestral de edad. Resultados: Existió incremento progresivo del IMC con la edad, significativo en las niñas a partir de los nueve años y en los niños desde los 8.5 años. Desde los 10 años, el IMC promedio resultó 2.3 kg/m2 superior al de edades menores (p < 0.001); la mayor diferencia entre los sexos ocurrió a los 12 años: 2 ± 0.98 kg/m2 más en los varones (p = 0.042). Globalmente no se hallaron diferencias significativas de peso, talla e IMC con el ETEC-2010, aunque el peso medio de los niños manchegos de 8.5 a 11.5 años fue 3.9 kg mayor que el del resto de los niños españoles. Conclusiones: Los parámetros antropométricos de los escolares manchegos no difieren de los estándares nacionales; sin embargo, los varones preadolescentes manchegos pesan casi 4 kg más.
Abstract Objectives: To determine weight, height and body mass index (BMI) of schoolchildren from the La Mancha-Centro health area and compare them with those determined by the Spanish Cross-sectional Growth Study 2010 (SCGS-2010). Methods: Cross-sectional study of 954 schoolchildren aged 6-12 years. Mean, standard deviation, and percentile distributions of weight, height, and BMI by gender and age were obtained. Differences in each 6-month age group were analyzed. Results: There was a progressive increase in BMI with age, which was significant in girls from nine years of age on and in boys from 8.5 years on. From age 10, average BMI was 2.3 kg/m2 higher than at younger ages (p < 0.001). The biggest difference between genders occurred at age 12: 2 ± 0.98 kg/m2 higher in boys (p = 0.042). Overall, no significant differences were found in weight, height and BMI vs. SCGS-2010, although mean weight of male children from La Mancha-Centro aged between 8.5 and 11.5 years was 3.9 kg higher than that of the rest of Spanish male children. Conclusions: Anthropometric parameters of schoolchildren from La Mancha-Centro do not significantly differ from national standards; however, preadolescent males from La Mancha-Centro weigh almost 4 kg more.