Validation of Math Model Using Porous Media for Determining Alveolar co2 in Ventilated Patients.

OBJECTIVES: To validate a mathematical model using porous media theory for alveolar CO2 determination in ventilated patients. DESIGN: Mathematical modeling study with prospective clinical validation to simulate CO2 exchange from bloodstream to airway entrance. SETTING: ICU. PATIENTS: Thirteen critically ill patients without chronic or acute lung disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Model outcomes compared with patient data showed correlations for end-tidal CO2 (EtCO2), area under the CO2 curve, and PaCO2 of 0.918, 0.954, and 0.995. Determination coefficients (R2) were 0.843, 0.910, and 0.990, indicating precision and predictive power. CONCLUSIONS: The mathematical model shows potential in pulmonary critical care. Although promising, practical application demands further validation, clinician training, and patient-specific adjustments. The path to clinical use will be iterative, involving validation and education.

Nanocatalytic performance of pectinase immobilized over in situ prepared magnetic nanoparticles.

Immobilization of enzymes is one of the protein engineering methods used to improve their thermal and long-term stabilities. Immobilized pectinase has become an essential biocatalyst for optimization in the food processing industry. Herein, nanostructured magnetic nanoparticles were prepared in situ for use as supports to immobilize pectinase. The structural, morphological, optical and magnetic features and the chemical compositions of the nanoparticles were characterized. Nanoparticle agglomeration and low porosity were observed due to the synthetic conditions. These nanoparticles exhibited superparamagnetic behavior, which is desirable for biotechnological applications. The maximum retention rate for the enzyme was observed at pH 4.5 with a value of 1179.3 U/mgNP (units per milligram of nanoparticle), which was equivalent to a 65.6% efficiency. The free and immobilized pectinase were affected by the pH and temperature. The long-term instability caused 40% and 32% decreases in the specific activities of the free and immobilized pectinase, respectively. The effects of immobilization were analyzed with kinetic and thermodynamic studies. These results indicated a significant affinity for the substrate, a decreased reaction rate, and improved thermal stability of the immobilized pectinase. The reusability of the immobilized pectinase was preserved effectively during cycling, with only a 21.2% decrease in activity observed from the first to the last use. Therefore, alternative magnetic nanoparticles are presented for immobilizing and maintaining the thermostability of pectinase.

Relación entre la cantidad y el tipo de alcohol (destilado versus fermentado) consumido y el riesgo de aparición de deterioro cognitivo compatible con un síndrome demencial en personas mayores de 60 años: revisión sistemática / Relationship between the amount and type of alcohol (distilled versus fermented) consumed and the risk of cognitive impairment compatible with a dementia syndrome in people over 60 years of age: A systematic review

Introducción: el alcohol es la sustancia más consumida en la cultura occidental y su consumo es un factor causal en más de 200 enfermedades y trastornos. El objetivo fue conocer la relación entre la cantidad y el tipo de alcohol (destilado o fermentado) consumido en individuos mayores de 60 años y la aparición del deterioro cognitivo compatible con un síndrome demencial como consecuencia de un consumo excesivo y prolongado.Desarrollo: búsqueda en las bases de datos Medline, PsycInfo y Web of Science. Se acotó la búsqueda a artículos publicados entre los años 2010 y 2021, a partir de la combinación de diversos términos relacionados con la demencia, el consumo y tipo de alcohol y la vejez. Se obtuvieron 157 artículos, se eliminaron aquellos repetidos y los no relacionados con el tema, quedando un total de 9 artículos. Esta revisión sistemática se ha llevado a cabo de acuerdo con los criterios de la declaración PRISMA.Conclusiones: la mayoría de los estudios encontrados (7 de 9) sugirieron una asociación entre el consumo de alcohol y la aparición de la demencia. Respecto al tipo de bebidas, todo y la objetivación de algunos resultados poco concluyentes, en general se sugiere que el consumo de vino (bebida fermentada) se asocia a una disminución del deterioro cognitivo y el consumo de licor (bebida destilada) a un aumento del deterioro cognitivo; no queda claro el papel de la cerveza. Por ello se puede concluir que la asociación entre el consumo de alcohol, y el mayor o menor deterioro cognitivo depende tanto del consumo excesivo y prolongado, como también del tipo de bebidas consumidas (destiladas o fermentadas).(AU)

Introduction: Alcohol is the most consumed substance in Western culture and its consumption is a causal factor in more than 200 diseases and disorders. The objective was to determine the relationship between the amount and type of alcohol (distilled or fermented) consumed, in individuals over 60 years of age, and the appearance of cognitive deterioration compatible with a dementia syndrome as a consequence of excessive and prolonged consumption.Development: Search in Medline, PsycInfo and Web of Science databases. The search was limited to articles published between 2010 and 2021, based on the combination of various terms related to dementia, alcohol consumption and type, and old age. 157 articles were obtained, those repeated and those not related to the topic were eliminated, leaving a total of 9 articles. This systematic review has been carried out in accordance with the criteria of the PRISMA statement.Conclusions: Most of the studies found (7 out of 9) suggested an association between alcohol consumption and the onset of dementia. Regarding the type of beverages, everything and the objectification of some inconclusive results, in general it is suggested that the consumption of wine (fermented beverage) is associated with a decrease of cognitive deterioration and the consumption of liquor (distilled beverage) to a increased cognitive decline; the role of beer is not clear. Therefore, it can be concluded that the association between alcohol consumption and greater or lesser cognitive impairment depends both on excessive and prolonged consumption, as well as on the type of beverages consumed (distilled or fermented).(AU)

Tolerance and response to ketogenic therapy in neonates and infants younger than 4 months. Case series in a hospital center in Medellin, Colombia. / Tolerancia y respuesta a la terapia cetógena en neonatos y lactantes menores de 4 meses. Serie de casos en un centro hospitalario de Medellín, Colombia.

INTRODUCTION: Ketogenic therapy (KT) studies have focused in children older than 2 years and adults. Recently its efficacy in infants has been reported, but there are few studies in this age group. PATIENTS AND METHODS: We report a case series of nine newborn and children younger than 4 months of age with refractory epilepsy treated with KT. We retrospectively reviewed charts of children treated at our center between 2015-2021. RESULTS: Data was collected on seven patients. Six patients began having seizures on day one of life, one had seizures starting on day 45. Different epilepsy etiologies were found. KT was started as soon as 9 days of life. The average age at which ketogenic therapy was started was 24 days of life. Initially, the diet was started at 1:1 or 2:1 ratio, and was progressed to a 4:1 ratio. After one month of KT 5/7 patients experienced a significant reduction in seizure frequency (>50%) and 2/7 had complete seizure control. At six months, 4/7 patients achieve complete seizure freedom and 1/7 had >50% seizure reduction. Two patients were lost to follow-up. None of our patients reported gastrointestinal side effects that required diet adjustments. One patient had mild and one mild hypertriglyceridemia. CONCLUSION: Even though evidence about KT in young children are starting to emerge, our experience shows it can be successful in controlling seizure burden without considerable adverse effects. There is great research potential regarding KT in young children.

TITLE: Tolerancia y respuesta a la terapia cetógena en neonatos y lactantes menores de 4 meses. Serie de casos en un centro hospitalario de Medellín, Colombia.Introducción. Los estudios para terapia cetógena (TC) se han concentrado en niños mayores de 2 años y adultos. Su eficacia en lactantes se ha descrito, pero hay pocos estudios en este grupo de edad. Pacientes y métodos. Se describe una serie de casos de nueve neonatos y lactantes menores de 4 meses de edad con epilepsia refractaria que recibieron tratamiento con TC. Se evaluaron, retrospectivamente, los registros clínicos de niños tratados entre 2015 y 2021. Resultados. Se recolectaron datos de siete pacientes. Seis pacientes iniciaron con crisis epilépticas el primer día de vida, y uno, el día 45. La etiología de la epilepsia fue variada (metabólica, genética y estructural). La TC se inició tan temprano como a los 9 días de vida. La edad promedio de inicio fue los 24 días de vida. Se inició con una tasa cetógena de 1:1 o 1:2, y se progresó posteriormente a 4:1. Después de un mes de TC, 5/7 pacientes presentaron una reducción significativa en la frecuencia de las crisis (>50%) y 2/7 experimentaron un control completo. A los seis meses, 4/7 pacientes lograron un control completo y 1/7 un control >50%. Dos pacientes se perdieron en el seguimiento. No se notificaron efectos gastrointestinales que obligaran al ajuste o la suspensión de la dieta. Se notificaron hipoglucemia e hipertrigliceridemia. Conclusión. A pesar de que la evidencia en la TC en lactantes y neonatos apenas está empezando a aparecer, nuestra experiencia muestra que puede ser una buena opción terapéutica para el control de las crisis epilépticas, sin efectos adversos importantes. Existe un gran potencial de investigación en el área de la TC en lactantes y neonatos.

Tolerancia y respuesta a la terapia cetógena en neonatos y lactantes menores de 4 meses. Serie de casos en un centro hospitalario de Medellín, Colombia / Tolerance and response to ketogenic therapy in neonates and infants younger than 4 months. Case series in a hospital center in Medellín, Colombia

Introducción: Los estudios para terapia cetógena (TC) se han concentrado en niños mayores de 2 años y adultos. Su eficacia en lactantes se ha descrito, pero hay pocos estudios en este grupo de edad. Pacientes y métodos: Se describe una serie de casos de nueve neonatos y lactantes menores de 4 meses de edad con epilepsia refractaria que recibieron tratamiento con TC. Se evaluaron, retrospectivamente, los registros clínicos de niños tratados entre 2015 y 2021. Resultados: Se recolectaron datos de siete pacientes. Seis pacientes iniciaron con crisis epilépticas el primer día de vida, y uno, el día 45. La etiología de la epilepsia fue variada (metabólica, genética y estructural). La TC se inició tan temprano como a los 9 días de vida. La edad promedio de inicio fue los 24 días de vida. Se inició con una tasa cetógena de 1:1 o 1:2, y se progresó posteriormente a 4:1. Después de un mes de TC, 5/7 pacientes presentaron una reducción significativa en la frecuencia de las crisis (>50%) y 2/7 experimentaron un control completo. A los seis meses, 4/7 pacientes lograron un control completo y 1/7 un control >50%. Dos pacientes se perdieron en el seguimiento. No se notificaron efectos gastrointestinales que obligaran al ajuste o la suspensión de la dieta. Se notificaron hipoglucemia e hipertrigliceridemia. Conclusión: A pesar de que la evidencia en la TC en lactantes y neonatos apenas está empezando a aparecer, nuestra experiencia muestra que puede ser una buena opción terapéutica para el control de las crisis epilépticas, sin efectos adversos importantes. Existe un gran potencial de investigación en el área de la TC en lactantes y neonatos.(AU)

Introduction: Ketogenic therapy (KT) studies have focused in children older than 2 years and adults. Recently its efficacy in infants has been reported, but there are few studies in this age group. Patients and methods: We report a case series of nine newborn and children younger than 4 months of age with refractory epilepsy treated with KT. We retrospectively reviewed charts of children treated at our center between 2015-2021. Results: Data was collected on seven patients. Six patients began having seizures on day one of life, one had seizures starting on day 45. Different epilepsy etiologies were found. KT was started as soon as 9 days of life. The average age at which ketogenic therapy was started was 24 days of life. Initially, the diet was started at 1:1 or 2:1 ratio, and was progressed to a 4:1 ratio. After one month of KT 5/7 patients experienced a significant reduction in seizure frequency (>50%) and 2/7 had complete seizure control. At six months, 4/7 patients achieve complete seizure freedom and 1/7 had >50% seizure reduction. Two patients were lost to follow-up. None of our patients reported gastrointestinal side effects that required diet adjustments. One patient had mild and one mild hypertriglyceridemia. CONCLUSION. Even though evidence about KT in young children are starting to emerge, our experience shows it can be successful in controlling seizure burden without considerable adverse effects. There is great research potential regarding KT in young children.(AU)

Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Estimated 10-Year Risk of Major and Hip Osteoporotic Fractures in Rheumatoid Arthritis: A Cross-Sectional Study.

BACKGROUND: Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. METHODS: Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. RESULTS: The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). CONCLUSION: High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

Multiphoton Excitation Fluorescence Microscopy and Spectroscopic Multianalytical Approach for Characterization of Historical Glass Grisailles.

The preservation of the integrity of artworks and cultural heritage items during characterization and conservation operations is of high priority, therefore, the application of non-invasive techniques is commonly suggested and recommended. Nonlinear optical microscopies (NLOM), based on the use of tightly focused pulsed femtosecond lasers, are emerging techniques for structural and chemical analysis of heritage objects with micrometric lateral and axial resolution. The results obtained with a set of optical and spectroscopic techniques for the chemical and physical characterization of grisaille paint layers on historical stained glasses, from different chronologies and provenance in Spain, are presented in this work. Optical behaviour and chemical composition were investigated by NLOM, using a laboratory set-up in the modality of Multi-Photon Excitation Fluorescence (MPEF), and by a multi-analytical combination of Field Emission Scanning Electron Microscopy-Energy Dispersive X-ray Spectrometry (FESEM-EDS), Laser Induced Breakdown Spectrosocopy (LIBS) and Laser Induced Fluorescence (LIF). Thicknesses values of the historical grisaille paint layers measured with MPEF were compared with those retrieved through FESEM, showing significant consistency and agreement. Under proper conditions, analysis via MPEF microscopy avoids the photochemical and physical damage to the examined materials, thus ensuring their preservation. This approach paves the way for future in-situ, non-invasive stratigraphic investigations on cultural heritage objects.

Axial and peripheral spondyloarthritis: does psoriasis influence the clinical expression and disease burden? Data from REGISPONSER registry.

OBJECTIVE: To evaluate whether the presence of psoriasis influences the clinical expression, disease activity and disease burden in both axial and peripheral phenotypes of spondyloarthritis (SpA). METHODS: Patients from the Spanish REGISPONSER registry classified as having SpA according to the ESSG criteria were included. Patients were classified as psoriatic or non-psoriatic depending on the presence of cutaneous or nail psoriasis; thereafter, they were classified as having either axial [presence of radiographic sacroiliitis OR inflammatory back pain (IBP)] or peripheral phenotype (absence of radiographic sacroiliitis AND absence of IBP AND presence of peripheral involvement). Pair-wise univariate and multivariate analyses among the four groups (psoriatic/non-psoriatic axial phenotypes and psoriatic/non-psoriatic peripheral phenotypes) were performed with adjustment for treatment intake. RESULTS: A total of 2296 patients were included in the analysis. Among patients with axial phenotype, psoriasis was independently associated (P < 0.05) with HLA-B27+ [odds ratio (OR) 0.27], uveitis (OR 0.46), synovitis (ever) (OR 2.59), dactylitis (OR 2.78) and the use of conventional synthetic DMARDs (csDMARDs) (OR 1.47) in comparison with non-psoriatic patients. Among patients with peripheral phenotype and adjusting for csDMARD intake, psoriasis was independently associated with higher age at disease onset (OR 1.05), HLA-B27+ (OR 0.14) and heel enthesitis (OR 0.22). Higher scores for patient-reported outcomes and greater use of treatment at the time of the study visit were observed in psoriatic patients with either axial or peripheral phenotype. CONCLUSION: These findings suggest that, among all patients with SpA, psoriasis is associated with differences in clinical expression of SpA, a greater disease burden and increased use of drugs.

Perfil de los nuevos diagnósticos de infección por VIH y factores de riesgo asociados al diagnóstico tardío en una consulta especializada durante el periodo 2014-2018 / Profile of new HIV diagnoses and risk factors associated with late diagnosis in a specialized outpatient clinic during the 2014-2018 period

INTRODUCCIÓN: El diagnóstico tardío (DT) de la infección por el VIH se asocia con un aumento de su morbimortalidad y su transmisibilidad. El objetivo de este estudio fue definir las características clínicas de los nuevos diagnósticos y clarificar los factores de riesgo (FR) asociados al DT con o sin enfermedad avanzada (EA) entre el año 2014 y 2018. MÉTODOS: Se incluyeron a los pacientes con nuevo diagnóstico de infección por el VIH atendidos en una consulta especializada de un hospital de tercer nivel. El DT con o sin EA se definió como el recuento de CD4 < 350 cel/mm3 o CD4 < 200 cel/mm3 respectivamente y/o condición definitoria de sida al diagnóstico. Se realizó un análisis mediante regresión logística binaria para analizar los FR asociados al DT y a la EA. RESULTADOS: De los 205 nuevos diagnósticos, 102 (50%) fueron DT. La edad ≥32 años [(OR, IC95%); 2,92 (1,52-5,59)], la transmisión distinta a la de hombres que tienen sexo con hombres [3,39 (1,56-7,34)] y la hospitalización en el diagnóstico [9,68 (2,63-35,68)] fueron FR asociados al DT. Por otro lado, tener una enfermedad de transmisión sexual (ETS) concomitante [0,37 (0,17-0,77)] se asoció con un diagnóstico precoz. Los resultados fueron similares al analizar el DT con EA excepto para la ETS. CONCLUSIÓN: El conocimiento de las características clínicas y epidemiológicas de los nuevos diagnósticos de infección por el VIH y de los FR para el DT con o sin EA constituyen una oportunidad para el diagnóstico precoz y para disminuir la transmisibilidad

INTRODUCTION: Late diagnosis (LD) of HIV infection is associated with an increase in morbidity and mortality and transmissibility. The aim of this study was to define the clinical characteristics of new diagnoses and clarify the risk factors (RF) associated with LD with or without advanced disease (AD) between 2014 and 2018. METHODS: Patients with a new diagnosis of HIV infection treated in a specialised outpatient clinic of a third level hospital were included. LD with or without AD was defined as aCD4 count < 350 cel/mm3 or CD4 < 200 cel/mm3 respectively and/or the presence of any AIDS condition on diagnosis. An analysis was performed using binary logistic regression to analyse the RF associated with LD and the AD. RESULTS: Of the 205 new diagnoses, 102 (50%) were LD. Age ≥ 32 years [(OR, 95% CI); 2.92 (1.52-5.59)], transmission different than in men who have sex with men [3.39 (1.56-7.34)] and hospitalisation on diagnosis [9.68 (2.63-35.68)] were RF associated with LD. On the other hand, having a concomitant sexually transmitted disease (STD) [.37 (.17-.77)] was associated with an early diagnosis. The results were similar when analysing the LD with AD except for the STD. CONCLUSION: Knowledge of the clinical and epidemiological characteristics of new diagnoses of HIV infection and of the RF for LD with or without AD provides an opportunity for early diagnosis and to reduce transmissibility

No radiographic sacroiliitis progression was observed in patients with early spondyloarthritis at 6 years: results of the Esperanza multicentric prospective cohort.

OBJECTIVE: To estimate the 6-year radiographic progression of sacroiliitis in patients with early spondyloarthritis (SpA). PATIENTS AND METHODS: Sacroiliac joint (SIJ) radiographs (baseline and 6 years) of 94 patients with recent-onset SpA from the Esperanza cohort were scored, blindly and in a random order, by nine readers. The modified New York criteria were used to define the presence of sacroiliitis. As the gold standard for radiographic (r) sacroiliitis, the categorical opinion of at least five readers was used. Progression was defined as the shift from non-radiographic (nr) to r-sacroiliitis. RESULTS: In the 94 SIJ radiographs (baseline and 6 years), 78/94 (83%) pairs of radiographs had not changed from baseline to 6 years. Sacroiliitis was present in 20 patients at baseline (21.3%) and in 18 (19.2%) patients at 6 years; 11 patients had sacroiliitis at both the baseline and final visits; 9 patients changed from baseline r-sacroiliitis to nr-sacroiliitis at 6 years, and 7 changed from baseline nr-sacroiliitis to r-sacroiliitis at 6 years. The mean continuous change score (range: -8 to +8) was 2.80 at baseline and 2.55 at 6 years (mean net progression of -0.25). The reliability of the readers was fair (mean inter-reader kappa of 0.375 (0.146-0.652) and mean agreement of 73.7% (58.7-90%)). CONCLUSION: In the early SpA Esperanza cohort, progression from nr-axSpA to r-axSpA over 6 years was not observed, although the SIJ radiographs scoring has limitations to detect low levels of radiographic progression.

Measuring Spinal Mobility Using an Inertial Measurement Unit System: A Validation Study in Axial Spondyloarthritis.

Portable inertial measurement units (IMUs) are beginning to be used in human motion analysis. These devices can be useful for the evaluation of spinal mobility in individuals with axial spondyloarthritis (axSpA). The objectives of this study were to assess (a) concurrent criterion validity in individuals with axSpA by comparing spinal mobility measured by an IMU sensor-based system vs. optical motion capture as the reference standard; (b) discriminant validity comparing mobility with healthy volunteers; (c) construct validity by comparing mobility results with relevant outcome measures. A total of 70 participants with axSpA and 20 healthy controls were included. Individuals with axSpA completed function and activity questionnaires, and their mobility was measured using conventional metrology for axSpA, an optical motion capture system, and an IMU sensor-based system. The UCOASMI, a metrology index based on measures obtained by motion capture, and the IUCOASMI, the same index using IMU measures, were also calculated. Descriptive and inferential analyses were conducted to show the relationships between outcome measures. There was excellent agreement (ICC > 0.90) between both systems and a significant correlation between the IUCOASMI and conventional metrology (r = 0.91), activity (r = 0.40), function (r = 0.62), quality of life (r = 0.55) and structural change (r = 0.76). This study demonstrates the validity of an IMU system to evaluate spinal mobility in axSpA. These systems are more feasible than optical motion capture systems, and they could be useful in clinical practice.

Hip and Shoulder Involvement and Their Management in Axial Spondyloarthritis: a Current Review.

PURPOSE OF REVIEW: Hip and shoulder disease can occur in patients with spondyloarthritis (SpA). While hip involvement has been widely assessed in axial SpA patients, studies in the overall SpA population as well as studies focused on shoulder involvement are scarce. Here, we review the most recent studies on the epidemiology, evaluation, and treatment of root joint involvement in SpA patients. RECENT FINDINGS: Radiological hip involvement can affect up to 25% of patients with SpA, reflecting more severe disease and associated with functional impairment. Shoulder involvement in SpA patients is characterized by cuff tendinitis and enthesitis, while primary glenohumeral joint involvement is rare. Anti-tumor necrosis factor (anti-TNF) treatment in SpA patients seems to have an effect on hip arthritis, showing a change in trend in the frequency of hip replacement in this population. The majority of studies evaluating hip involvement have focused on axial SpA patients, but further studies evaluating root joint involvement in the overall SpA population are needed. Anti-TNF therapy should be considered in patients with hip involvement, and root joint involvement should be assessed routinely in clinical practice.

Profile of new HIV diagnoses and risk factors associated with late diagnosis in a specialized outpatient clinic during the 2014-2018 period. / Perfil de los nuevos diagnósticos de infección por VIH y factores de riesgo asociados al diagnóstico tardío en una consulta especializada durante el periodo 2014-2018.

INTRODUCTION: Late diagnosis (LD) of HIV infection is associated with an increase in morbidity and mortality and transmissibility. The aim of this study was to define the clinical characteristics of new diagnoses and clarify the risk factors (RF) associated with LD with or without advanced disease (AD) between 2014 and 2018. METHODS: Patients with a new diagnosis of HIV infection treated in a specialised outpatient clinic of a third level hospital were included. LD with or without AD was defined as aCD4 count < 350 cel/mm3 or CD4 < 200 cel/mm3 respectively and/or the presence of any AIDS condition on diagnosis. An analysis was performed using binary logistic regression to analyse the RF associated with LD and the AD. RESULTS: Of the 205 new diagnoses, 102 (50%) were LD. Age ≥ 32 years [(OR, 95% CI); 2.92 (1.52-5.59)], transmission different than in men who have sex with men [3.39 (1.56-7.34)] and hospitalisation on diagnosis [9.68 (2.63-35.68)] were RF associated with LD. On the other hand, having a concomitant sexually transmitted disease (STD) [.37 (.17-.77)] was associated with an early diagnosis. The results were similar when analysing the LD with AD except for the STD. CONCLUSION: Knowledge of the clinical and epidemiological characteristics of new diagnoses of HIV infection and of the RF for LD with or without AD provides an opportunity for early diagnosis and to reduce transmissibility.

How to calculate the ASDAS based on C-reactive protein without individual questions from the BASDAI: the BASDAI-based ASDAS formula.

OBJECTIVES: To develop a new equation to calculate the Ankylosing Spondylitis Disease Activity Score based on CRP (ASDAS-CRP) using only the BASDAI total score and CRP. METHODS: Axial SpA (axSpA) patients from the Cordoba Spondyloarthritis Registry cohort were recruited as a derivation cohort, while a retrospective sample from the Spanish Rheumatology Society National Registry of Spondyloarthropathies and Ibero American Spondyloarhtritis Registry registers was used as a validation cohort. We built a new equation based only on the BASDAI and CRP, defining a new formula: the BASDAI-based ASDAS (BASDAS). Linear regression analysis was used to determine the coefficients of the equation in the derivation cohort and it was subsequently validated in the validation cohort. RESULTS: A total of 52 axSpA patients in the derivation cohort and 3359 patients in the validation cohort were included. In the derivation cohort, the mean BASDAS [2.24 (s.d. 0.90)] was very similar to the ASDAS-CRP [2.23 (s.d. 0.95)], with a very strong correlation (r = 0.96, P < 0.001). In the validation cohort, the mean BASDAS was 3.31 (s.d. 1.37) and the ASDAS-CRP was 3.19 (s.d. 1.27), which also had a very strong correlation (r = 0.95, P < 0.001). Intraclass correlation coefficients were excellent in both cohorts (0.963 and 0.947, respectively). CONCLUSION: The BASDAS performs similarly to the ASDAS-CRP and can be calculated with only the BASDAI total score and CRP, allowing evaluation of disease activity in retrospective studies where the individual items of the BASDAI are not available.

Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.

13Check_RNA: a tool to evaluate 13C chemical shift assignments of RNA.

Motivation: Chemical shifts (CS) are an important source of structural information of macromolecules such as RNA. In addition to the scarce availability of CS for RNA, the observed values are prone to errors due to a wrong re-calibration or miss assignments. Different groups have dedicated their efforts to correct CS systematic errors on RNA. Despite this, there are not automated and freely available algorithms for evaluating the referencing of RNA 13 C CS before their deposition to the BMRB or re-reference already deposited CS with systematic errors. Results: Based on an existent method we have implemented an open source python module to correct 13 C CS (from here on 13Cexp) systematic errors of RNAs and then return the results in 3 formats including the nmrstar one. Availability and implementation: This software is available on GitHub at https://github.com/BIOS-IMASL/13Check_RNA under a MIT license. Supplementary information: Supplementary data are available at Bioinformatics online.

Collagenase nanocapsules: An approach to fibrosis treatment.

Fibrosis is a common lesion in different pathologic diseases and defined by the excessive accumulation of collagen. Different approaches have been used to treat different conditions characterized by fibrosis. The FDA and EMA approved the use of collagenase to treat palmar fibromatosis (Dupuytren's contracture). The EMA approved additionally its use in severe Peyronie's disease, but it has been used off label in other conditions [1,2]. The approved treatment includes up to three (in palmar fibromatosis) or up to eight (in penile fibromatosis) injections followed by finger extension or penile modeling procedures, typically causing severe pain. Frequent single injections are adequate to treat palmar fibromatosis [3]. The need to repeatedly inject doses of this enzyme can be due to the labile nature of collagenase, which exhibits a complete activity loss after a short period of time. This study presents a novel strategy to manage this enzyme based on the synthesis of polymeric nanocapsules that contain collagenase encapsulated within their matrix. These nanocapsules have been engineered for achieving a gradual release of the encapsulated enzyme for a longer time, which can be up to ten days. The efficacy of these nanocapsules has been tested in a murine model of local dermal fibrosis, and the results demonstrate a reduction in fibrosis greater than that with the injection of free enzyme; this type of treatment showed a significant improvement compared to conventional therapy of free collagenase. STATEMENT OF SIGNIFICANCE: The use of proteins as therapeutic molecules has recently attracted great interest. Collagenase injection is the current treatment for fibrotic diseases. Unfortunately, proteins have a low stability and presume several repetition cycles to obtain an effective treatment. This article describes a novel treatment for these types of diseases using collagenase nanocapsules designed to exhibit a sustainable release of the encapsulated enzyme, which maintains the enzymatic activity for a long period of time. The therapeutic effect of nanocapsules was tested in a murine mouse model of local dermal fibrosis, and the results showed an important improved effect compared to the effect of the administration of free enzyme. These results indicate a high potential for this novel system to improve the current treatment for fibrotic diseases.

Evaluation of quality of life in patients with axial spondyloarthritis and its association with disease activity, functionality, mobility, and structural damage.

To evaluate quality of life (QoL) in patients with axial spondyloarthritis (axSpA) and its association with disease activity, functionality, structural damage, and spinal mobility, using patient-reported outcomes. This was an observational, cross-sectional, and single-center study in which 100 consecutive patients with axSpA were included. We obtained from all patients' sociodemographic data and values related to disease activity, functionality, structural damage, mobility, and quality of life. The Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) was considered as the primary outcome. Pearson r statistic, Student's T test, and univariate and multivariate linear regressions were performed to relate ASQoL with the studied covariates. Mean ASQoL score in all patients was 4.02 ± 2.81, with statistically significant differences between male and female (3.61 ± 2.80 vs. 4.83 ± 2.70). Patients with high disease activity (measured by the ASAS-endorsed Disease Activity Score, ASDAS > 2.1) showed higher mean score in ASQoL than those with low disease activity (ASDAS ≤ 2.1) (3.21 ± 0.74 vs. 1.43 ± 0.43, p < 0.001). ASQoL presented a significant linear correlation with BASDAI, BASFI, and ASDAS (r > 0.60). However, disease duration was not significantly correlated with ASQoL. Finally, the 68.9% of the ASQoL variability (R2 = 0.689) was determined by BASDAI, BASFI, and mSASSS, presenting mSASSS a negative regression coefficient (- 0.035). In our study, the impairment of QoL was mainly associated with disease activity (BASDAI) and worsening of functionality (BASFI). However, there is an inverse relationship between the worsening of QoL and structural damage. In addition, disease duration does not seem to influence the patient's welfare.

Michael addition of carbonyl compounds to nitroolefins under the catalysis of new pyrrolidine-based bifunctional organocatalysts.

Novel bifunctional pyrrolidine-based organocatalysts for the asymmetric Michael addition of carbonyl compounds to nitroolefins have been synthesised from homoallylamines, which are easily obtained from (R)-glyceraldehyde as a chiral precursor. Under optimal reaction conditions, these bifunctional organocatalysts showed a high catalytic efficiency (almost quantitative yield in most cases) and stereoselectivity in the Michael addition reactions of a variety of aldehydes (up to 98 : 2 dr and 97% ee) and ketones (up to 98 : 2 dr and 99% ee) to nitroolefins.