Using patient-reported outcome measures to evaluate care for patients with inflammatory chronic rheumatic disease

Objectives: Few countries integrate Patient-Reported Outcome Measures (PROMs) in routine performance assessment, and those that do focus on elective surgery. This study addresses the challenges of using PROMs to evaluate care in chronic conditions. We set out a modelling strategy to assess the extent to which changes over time in self-reported health status by patients with inflammatory chronic rheumatic disease are related to their biological drug therapy and Rheumatology centre primarily responsible for their care. Methods: Using data from the Portuguese Register of Rheumatic Diseases, we assess the health status using the Health Assessment Questionnaire-Disability Index (HAQ-DI) for rheumatic patients receiving biological drugs between 2000 and 2017. We employ a fixed effects model using the Least Squares Dummy Variables estimator. Results: Patients receiving infliximab or rituximab report lower health status than those on etanercept (the most common therapy) and patients in 4 of the 26 Rheumatology centres report higher health status than those at other centres. Conclusions: PROMs can be used for those with chronic conditions to provide the patient’s perspective about the impact on their health status of the choice of drug therapy and care provider. Care for chronic patients might be improved if healthcare organisations monitor PROMs and engage in performance assessment initiatives on a routine basis

A Multicenter, Non-Interventional Study to Evaluate the Disease Activity in Multiple Sclerosis after Withdrawal of Natalizumab in Portugal

Objectives: Natalizumab (NTZ) is very effective for treatment of relapsing-remitting multiple sclerosis (RRMS), its use is mainly limited by safety issues. Discontinuation of NTZ is associated with recurrence of disease activity (reactivation and rebound). The best strategy for subsequent therapy and the predictive factors for recurrence in such patients are areas of active research. We aimed to evaluate predictors of reactivation in a multicentric study. Patients and methods: Multicentric retrospective observational study in five portuguese MS referral centers. Demographic, clinical and imagiological data were collected in the year prior, during and in the year following NTZ discontinuation. Predictors of reactivation and rebound after NTZ suspension were studied using a multivariate Cox model. Results: Sixty-nine patients were included. They were mainly non-naïve patients (97%), with a mean age of 29.1 ± 8.3 years at diagnosis, and a mean age of 37.2 ± 10.3 years at NTZ initiation. The mean annualized relapse rate (ARR) previous, during and after NTZ was 1.6 ± 1.2, 0.2 ± 0.5 and 0.6 ± 1.0, respectively. The median EDSS before, during and after NTZ was 3.5 (IQR 3.3), 3.5 (IQR 3.5) and 4.0 (IQR 3.8), respectively. The median number of infusions was 26.0 (IQR 12.5) and the main reason to NTZ discontinuation was progressive multifocal leukoencephalopathy (PML) risk (70%). After NTZ suspension, reactivation was observed in 25 (36%) patients after a median time of 20.0 (IQR 29.0) weeks. Reactivation predictors in our sample included NTZ suspension for reasons other than PML (adjusted HR = 0.228, 95% CI [0.084- 0.616], p = 0.004), ARR before NTZ (adjusted HR = 1.914 95% [CI 1.330-2.754], p < 0.001) and a longer disease duration at time of NTZ initiation (adjusted HR = 1.154, 95% CI [1.020-1.306], p = 0.023). Rebound occurred in 5 (7%) patients after a median time of 20 (IQR 34.5) weeks. Conclusion: Significant predictors of disease reactivation in our cohort were discontinuation of NTZ for reasons other than PML risk, higher disease activity before NTZ treatment, and longer disease duration. Our study provides valuable data of portuguese patients after NTZ withdrawal.info:eu-repo/semantics/publishedVersio

Urbanization and seasonality strengthens the CO2 capacity of the Red River Delta, Vietnam

Tropical rivers are dynamic CO2 sources. Regional patterns in the partial pressure of CO2 (pCO2) and relationships with other a/biotic factors in densely populated and rapidly developing river delta regions of Southeast Asia are still poorly constrained. Over one year, at 21 sites across the river system in the Red River Delta (RRD), Vietnam, we calculated pCO2 levels from temperature, pH, and total alkalinity and inter-linkages between pCO2 and phytoplankton, water chemistry and seasonality were then assessed. The smaller, more urbanized, and polluted Day River had an annual median pCO2 of 5000 ± 3300 µatm and the larger Red River of 2675 ± 2271 µatm. pCO2 was 1.6 and 3.2 times higher during the dry season in the Day and Red rivers respectively than the rainy season. Elevated pCO2 levels in the Day River during the dry season were also 2.4-fold higher than the median value (2811 ± 3577 µatm) of calculated and direct pCO2 measurements in >20 sub/tropical rivers. By further categorizing the river data into Hanoi City vs. other less urban-populated provinces, we found significantly higher nutrients, organic matter content, and riverine cyanobacteria during the dry season in the Day River across Hanoi City. Forward selection also identified riverine cyanobacteria and river discharge as the main predictors explaining pCO2 variation in the RRD. After accounting for the shared effects (14%), river discharge alone significantly explained 12% of the pCO2 variation, cyanobacteria uniquely a further 21%, while 53% of the pCO2 variance was unexplained by either. We show that the urbanization of rivers deltas could result in increased sources of riverine pCO2, water pollution, and harmful cyanobacterial blooms. Such risks could be mitigated through water management to increase water flows in problem areas during the dry season

Influence of homogenization conditions on physical properties and antioxidant activity of fully biodegradable pea protein-alpha-tocopherol films

In this study, antioxidant biodegradable films based on pea protein and alpha-tocopherol were successfully developed by solution casting. The effect of both the homogenization conditions (rotor stator and microfluidizer) and the relative humidity (RH) on the microstructure and physical properties (transparency, tensile, oxygen and water vapour barrier properties) of pea protein/alpha-tocopherol-based films was evaluated. The addition of alpha-tocopherol produced minimal changes in the films transparency, while providing them with antioxidant properties and improved water vapour and oxygen barrier properties (up to 30 % in both water vapour and oxygen permeability) when films were at low and intermediate RH. The addition of alpha-tocopherol in microfluidized films gave rise to an increase in their resistance to break and extensibility (up to 27 % in E values) at intermediate and high RH. These results add a new insight into the potential of employing pea protein and alpha-tocopherol in the development of fully biodegradable antioxidant films which are of interest in food packagingThe authors acknowledge the financial support from the Spanish Ministerio de Educacion y Ciencia throughout the project AGL2010-20694, co-funded by FEDER. Author M.J.Fabra is a recipient of a Juan de la Cierva contract from the Spanish Ministerio de Economia y Competitividad.Fabra, MJ.; Jiménez, A.; Talens Oliag, P.; Chiralt, A. (2014). Influence of homogenization conditions on physical properties and antioxidant activity of fully biodegradable pea protein-alpha-tocopherol films. Food and Bioprocess Technology. 7(12):3569-3578. https://doi.org/10.1007/s11947-014-1372-0S35693578712ASTM (1995). Standard test methods for water vapor transmission of materials. Standards Desingnations: E96-95. In: Annual Book of ASTM Standards (pp. 406-413); American Society for Testing and Materials: Philadelphia, PA.ASTM (2001). Standard test method for tensile properties of thin plastic sheeting. Standard D882. In: Annual book of American Standard Testing Methods (pp 162-170). D882. Philadelphia:ASTM.Bertan, L. C., Tanada-Palmu, P. S., Siani, A. C., & Grosso, C. R. F. (2005). Effect of fatty acids and “Brazilian elemi” on composite films based on gelatin. Food Hydrocolloids, 19(1), 73–82.Byun, Y., Kim, Y. T., & Whiteside, S. (2010). Characterization of an antioxidant polylactic acid (PLA) film prepared with alpha-tocopherol, BHT and polyethylene glycol using film cast extruder. Journal of Food Engineering, 100, 239–244.Cerqueira, M. A., Costa, M. J., Fuciños, C., Pastrana, L. M., & Vicente, A. A. (2014). Development of active and nanotechnology-based smart edible packaging systems: physical-chemical characterization. Food and Bioprocess Technology, 7(5), 1472–1482.Choi, W. S., & Han, J. H. (2001). Physical and mechanical properties of pea–protein-based edible films. Journal of Food Science, 66, 319–322.Choi, W. S., & Han, J. H. (2002). Film-forming mechanism and heat denaturation effects on the physical and chemical properties of pea-protein-isolate edible films. Journal of Food Science, 67, 1399–1406.Fabra, M. J., Talens, P., & Chiralt, A. (2009). Microstructure and optical properties of sodium caseinate films containing oleic acidebeeswax mixtures. Food Hydrocolloids, 23, 676–683.Fabra, M. J., Talens, P., & Chiralt, A. (2010). Water sorption isotherms and phase transitions of sodium caseinate–lipid films as affected by lipid interactions. Food Hydrocolloids, 24, 384–391.Fabra, M. J., Hambleton, A., Talens, P., Debeaufort, F., & Chiralt, A. (2011). Effect of ferulic acid and α-tocopherol antioxidants on properties of sodium caseinate edible films. Food Hydrocolloids, 25, 1441–1447.Fabra, M. J., Talens, P., Gavara, R., & Chiralt, A. (2012). Barrier properties of sodium caseinate films as affected by lipid composition and moisture content. Journal of Food Engineering, 109, 372–379.Frankel, E. N., Huang, S. W., Kanner, J., & German, J. B. (1994). Interfacial phenomena in the evaluation of antioxidants: bulk oils vs emulsions. Journal of Agriculture and Food Chemistry, 42(5), 1054–1059.Gómez-Estaca, J., Giménez, B., Montero, P., & Gómez-Guillén, M. C. (2009). Incorporation of antioxidant borage extract into edible films based on sole skin gelatin or a commercial fish gelatin. Journal of Food Engineering, 92, 78–85.Huang, S. W., Frankel, E. N., & German, J. B. (1994). Antioxidant activity of alpha.- and.gamma.-tocopherols in bulk oils and in oil-in-water emulsions. Journal of Agriculture and Food Chemistry, 42(10), 2108–2114.Hutchings, J. B. (1999). Food and colour appearance (2nd ed.). Gaithersburg: Chapman and Hall Food Science Book, Aspen Publication.Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2010). Effect of lipid self-association on the microstructure and physical properties of hydroxypropylmethylcellulose edible films containing fatty acids. Carbohydrate Polymers, 82(3), 585–593.Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2013). Physical properties and antioxidant capacity of starch-sodium caseinate films containing lipids. Journal of Food Engineering, 116(3), 695–702.Jung, M. Y., & Min, D. B. (1990). Effects of alpha-. γ-, and δ-tocopherols on oxidative stability of soybean oil. Journal of Food Science, 55(5), 1464–1465.López-de-Dicastillo, C., Alonso, J. M., Catalá, R., Gavara, R., & Hernández-Muñoz, P. (2010). Improving the antioxidant protection of packaged food by incorporating natural flavonoids into ethylene-vinyl alcohol copolymer (EVOH) films. Journal of Agricultural and Food Chemistry, 58, 10958–10964.Ma, W., Tang, C.-H., Yin, S.-W., Yang, X. Q., Qi, J. R., & Xia, N. (2012). Effect of homogenization conditions on properties of gelatin-olive oil composite films. Journal of Food Engineering, 113(1), 136–142.Mauer, L. J., Smith, D. E., & Labuza, T. P. (2000). Water vapor permeability, mechanical, and structural properties of edible β-casein films. International Dairy Journal, 10(5–6), 353–358.Mc Hugh, T. H., Avena-Bustillos, R., & Krochta, J. M. (1993). Hydrophobic edible films:modified procedure for water vapor permeability and explanation of thickness effects. Journal of Food Science, 58(4), 899–903.McHugh, T. H., & Krochta, J. M. (1994). Dispersed phase particle size effects on water vapour permeability of whey protein–beeswax emulsion films. Journal of Food Processing and Preservation, 18, 173–188.Ozkan, G., Simsek, B., & Kuleasan, H. (2007). Antioxidant activities of Satureja cilicica essential oil in butter and in vitro. Journal of Food Engineering, 79, 1391–1396.Pereira de Abreu, D. A., Paseiro Losada, P., Maroto, J., & Cruz, J. M. (2011). Natural antioxidant active packaging film and its effect on lipid damage in frozen blue shark (Prionace glauca). Innovative Food Science and Emerging Technologies, 12, 50–55.Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., & Rice-Evans, C. (1999). Antioxidant activity applying an improved ABTS radical cation decoloration assay. Free Radical Biology and Medicine, 26, 1231–1237.Roos, Y. H. (1995). Phase transitions in food. San Diego: Academic Press.Salgado, P. R., Molina Ortiz, S. E., Petruccelli, S., & Mauri, A. N. (2010). Biodegradable sunflower protein films naturally activated with antioxidant compounds. Food Hydrocolloids, 24(5), 525–533.Salgado, P. R., Fernández, G. B., Drago, S. R., & Mauri, A. N. (2011). Addition of bovine plasma hydrolysates improves the antioxidant properties of soybean and sunflower protein-based films. Food Hydrocolloids, 25, 1433–1440.Samaranayaka, A. G. P., & Li-Chan, E. C. Y. (2008). Autolysis-assisted production of fish protein hydrolysates with antioxidant properties form Pacific hake (Merluccius productus). Food Chemistry, 107, 768–776.Souza, B. W. S., Cerqueira, A., Casariego, A., Lima, A. M. P., Teixeira, J. A., & Vicente, A. A. (2009). Effect of moderate electric fields in the permeation properties of chitosan coatings. Food Hydrocolloids, 23, 2110–2115

HÁBITOS ALIMENTARIOS DE LAS MUJERES EN RELACIÓN CON EL NIVEL DE CONOCIMIENTOS SOBRE EL CLIMATERIO

Objectives: Knowing the behaviors related to food and toxic habits of women aged 30-60 years in the health area of Vigo.Determine whether menopausal women have healthier behaviors than non menopausal ones. Identify whether any of the socio-demographic variables has an influence on feeding habits or toxic behaviors.Determine whether women with high-very high knowledge have proper habits.Methods: Comparative, observational cross study made of 425 women between 30 and 60 years of age. We used a booklet with personally answered questionnaires, one about menopause and the other about feeding behaviors during the climacteric stage, which includes socio-demographic variables. Data analysis was carried out using SPSS 14.0.Results: A result of 74.3% of the women in the sample has a high/very high level of knowledge but behaviors that do not correlate with this.Conclusions: Women know what they must do to maintain a healthy life, but the majority does not put this into practice. We think it is necessary to introduce in health centers a program about the climacteric stage, coordinated by nurses and midwives and focused on applying to daily life the knowledge that women already have, with the aim of helping them to achieve a better quality of life.This study is part of a wider research on &ldquo;Knowledge and behaviors related to climacteric stage in women between 30 and 60 years of age in the health area of Vigo sponsored by the &ldquo;Fondo de Investigaciones Sanitarias&rdquo; (Spanish Health Research Fund) in 2007Objetivos: Conocer los comportamientos relacionados con la alimentaci&oacute;n y h&aacute;bitos t&oacute;xicos de las mujeres de edad comprendida entre 30-60 a&ntilde;os del &aacute;rea sanitaria de Vigo.Averiguar si las mujeres menop&aacute;usicas tienen comportamientos m&aacute;s saludables que las no menop&aacute;usicas.Identificar si alguna de las variables sociodemogr&aacute;ficas influye en los comportamientos sobre la alimentaci&oacute;n y h&aacute;bitos t&oacute;xicos. Determinar si las mujeres con conocimientos altos-muy altos tienen comportamientos adecuadosM&eacute;todos: Estudio comparativo, observacional, transversal, realizado a 425 mujeres de 30-60 a&ntilde;os. Se utiliz&oacute; un cuadernillo con dos cuestionarios autocumplimentados, uno de conocimientos sobre la menopausia y otro sobre los comportamientos relacionados con la alimentaci&oacute;n en la etapa del climaterio, incluidas las variables sociodemogr&aacute;ficas. El an&aacute;lisis de los datos se realiz&oacute; mediante SPSS 14.0.Resultados: Las mujeres de nuestra muestra tienen conocimientos altos-muy altos en un 74,3% y unos comportamientos que no se correlacionan con el nivel de conocimientos.Conclusiones: Las mujeres conocen qu&eacute; es lo que deben realizar para mantener una vida saludable, pero a la hora de ponerlo en pr&aacute;ctica no lo hacen mayoritariamente. Consideramos necesaria la implantaci&oacute;n en los Centros de Salud, de un programa coordinado por el equipo deEnfermer&iacute;a Global N&ordm; 20 Octubre 2010 P&aacute;gina 2salud, dirigido a aplicar los conocimientos que han demostrado poseer las mujeres a los comportamientos diarios, con el objetivo de alcanzar una mayor calidad de vida. Este estudio forma parte de una investigaci&oacute;n m&aacute;s amplia realizada sobre los &ldquo;Conocimientos y comportamientos relacionados con el climaterio de las mujeres de 30-60 a&ntilde;os del &Aacute;rea Sanitaria de Vigo&rdquo; becado por el Fondo de Investigaciones Sanitarias (2007)

Consenso Português para a Identificação Precoce de Esclerose Múltipla Secundária Progressiva: Painel Delphi

Introduction: Multiple sclerosis is a disease with a heterogeneous evolution. The early identification of secondary progressive multiple sclerosis is a clinical challenge, which would benefit from the definition of biomarkers and diagnostic tools applicable in the transition phase from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis. We aimed to reach a Portuguese national consensus on the monitoring of patients with multiple sclerosis and on the more relevant clinical variables for the early identification of its progression. Material and methods: A Delphi panel which included eleven Portuguese Neurologists participated in two rounds of questions between July and August of 2021. In the first round, 39 questions which belonged to the functional, cognitive, imaging, biomarkers and additional evaluations were included. Questions for which no consensus was obtained in the first round (less than 80% of agreement), were appraised by the panel during the second round. Results: The response rate was 100% in both rounds and consensus was reached for a total of 33 questions (84.6%). Consensus was reached for monitoring time, evaluation scales and clinical variables such as the degree of brain atrophy and mobility reduction, changes suggestive of secondary progressive multiple sclerosis. Additionally, digital devices were considered tools with potential to identify disease progression. Most questions for which no consensus was obtained referred to the cognitive assessment and the remaining referred to both functional and imaging domains. Conclusion: Consensus was obtained for the determination of the monitorization interval and for most of the clinical variables. Most questions that did not reach consensus were related with the confirmation of progression taking into account only one test/domain, reinforcing the multifactorial nature of multiple sclerosis.Introdução: A esclerose múltipla é uma doença de evolução heterogénea. A identificação precoce da forma secundária progressiva é um desafio clínico, carecendo da definição de biomarcadores e ferramentas de diagnóstico aplicáveis na fase de transição da forma surto-remissão para a forma secundária progressiva. Este trabalho teve como objetivo estabelecer um consenso nacional português sobre a monitorização dos doentes e das variáveis clínicas mais relevantes para a identificação precoce da progressão da esclerose múltipla. Material e Métodos: Um painel Delphi constituído por 11 neurologistas portugueses respondeu a duas rondas de perguntas entre julho e agosto de 2021. Na primeira ronda foram incluídas 39 questões relacionadas com a avaliação funcional, cognitiva, imagiológica, de biomarcadores e outras, e na segunda, as questões para as quais não foi atingido consenso (menos de 80% de concordância) na primeira ronda voltaram a ser submetidas a avaliação pelo painel. Resultados: A taxa de resposta foi de 100% em ambas as rondas e 33 das 39 questões (84,6%) atingiram concordância. Foi atingido consenso relativamente ao tempo de monitorização dos doentes, às escalas de avaliação a empregar e a variáveis clínicas tais como o grau de atrofia cerebral ou redução da mobilidade, cuja alteração é sugestiva de esclerose múltipla secundária progressiva. Adicionalmente, os dispositivos digitais foram considerados ferramentas com potencial para identificar a progressão da doença. A maioria das questões para as quais não foi obtido consenso dizem respeito à avaliação cognitiva, estando as restantes inseridas nos domínios funcional e imagiológico. Conclusão: Foi obtido consenso para a determinação do intervalo de monitorização e para a maioria das variáveis clínicas. A maioria das questões sem consenso estavam relacionadas com a confirmação do diagnóstico de progressão tendo em conta apenas um teste/domínio, realçando a natureza multifatorial da esclerose múltipla.info:eu-repo/semantics/publishedVersio

Pressure-dependent EPANET extension

In water distribution systems (WDSs), the available flow at a demand node is dependent on the pressure at that node. When a network is lacking in pressure, not all consumer demands will be met in full. In this context, the assumption that all demands are fully satisfied regardless of the pressure in the system becomes unreasonable and represents the main limitation of the conventional demand driven analysis (DDA) approach to WDS modelling. A realistic depiction of the network performance can only be attained by considering demands to be pressure dependent. This paper presents an extension of the renowned DDA based hydraulic simulator EPANET 2 to incorporate pressure-dependent demands. This extension is termed “EPANET-PDX” (pressure-dependent extension) herein. The utilization of a continuous nodal pressure-flow function coupled with a line search and backtracking procedure greatly enhance the algorithm’s convergence rate and robustness. Simulations of real life networks consisting of multiple sources, pipes, valves and pumps were successfully executed and results are presented herein. Excellent modelling performance was achieved for analysing both normal and pressure deficient conditions of the WDSs. Detailed computational efficiency results of EPANET-PDX with reference to EPANET 2 are included as well

Cerebrospinal Fluid Cytokines in Multiple System Atrophy: a Cross-Sectional Catalan MSA Registry Study

Introduction: Neuroinflammation is a potential player in neurodegenerative conditions, particularly the aggressive ones, such as multiple system atrophy (MSA). Previous reports on cytokine levels in MSA using serum or cerebrospinal fluid (CSF) have been inconsistent, including small samples and a limited number of cytokines, often without comparison to Parkinson's disease (PD), a main MSA differential diagnosis. Methods: Cross-sectional study of CSF levels of 38 cytokines using a multiplex assay in 73 participants: 39 MSA patients (19 with parkinsonian type [MSAp], 20 with cerebellar type [MSAc]; 31 probable, 8 possible), 19 PD patients and 15 neurologically unimpaired controls. None of the participants was under non-steroidal anti-inflammatory drugs at the time of the lumbar puncture. Results: There were not significant differences in sex and age among participants. In global non-parametric comparisons FDR-corrected for multiple comparisons, CSF levels of 5 cytokines (FGF-2, IL-10, MCP-3, IL-12p40, MDC) differed among the three groups. In pair-wise FDR-corrected non-parametric comparisons 12 cytokines (FGF-2, eotaxin, fractalkine, IFN-α2, IL-10, MCP-3, IL-12p40, MDC, IL-17, IL-7, MIP-1β, TNF-α) were significantly higher in MSA vs. non-MSA cases (PD + controls pooled together). Of these, MCP-3 and MDC were the most significant ones, also differed in MSA vs. PD, and were significant MSA-predictors in binary logistic regression models and ROC curves adjusted for age. CSF levels of fractalkine and MIP-1α showed a strong and significant positive correlation with UMSARS-2 scores. Conclusion: Increased CSF levels of cytokines such as MCP-3, MDC, fractalkine and MIP-1α deserve consideration as potential diagnostic or severity biomarkers of MSA.info:eu-repo/semantics/publishedVersio

The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch

The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with Ssubstitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T) as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening

Cardiospondylocarpofacial syndrome as a distinct hereditary connective tissue disorder: novel missense variant in MAP3K7 in two unrelated patients

CDKL5 deficiency disorder is a rare X-linked condition that results in early onset of impairedmotor and cognitive skills such as motor rigidity, stereotypical hand movements and deficient language acquisition aswell as recurrent seizures. It is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene, which encodes a serine/threonine kinase involved in important neuronal processes such as cell signaling and neuron morphogenesis.FCT: UID/Multi/04326/2019 (CCMAR)info:eu-repo/semantics/publishedVersio