A simplified procedure to synthesize zwitterionic cellulose by means of N-protected aspartic anhydride under mild conditions was developed. The preparation of modified cellulose samples was carried ...out under heterogeneous, aqueous conditions by reacting NH
OH-activated cellulose with aspartic anhydrides N-protected with trifluoroacetyl (TFAc) and carbobenzyloxy (Cbz). Modified cellulose samples Cel-Asp-N-TFAc and Cel-Asp-N-Cbz were characterized by Fourier Transform Infrared (FTIR) and
C solid state Nuclear Magnetic Resonance (NMR) spectroscopy. The functionalization degree of each cellulose sample was determined by the
C NMR signal integration values corresponding to the cellulose C1 vs. the Cα of the aspartate residue and corroborated by elemental analysis. In agreement, both analytical methods averaged a grafting degree of 20% for Cel-Asp-N-TFAc and 16% for Cel-Asp-N-Cbz. Conveniently, Cel-Asp-N-TFAc was concomitantly partially N-deprotected (65%) as determined by the ninhydrin method. The zwitterion character of this sample was confirmed by a potentiometric titration curve and the availability of these amino acid residues on the cellulose was inspected by adsorption kinetics method with a 100 mg L
cotton blue dye solution. In addition, the synthesis reported in the present work involves environmentally related advantages over previous methodologies developed in our group concerning to zwitterionic cellulose preparation.
Background. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The ...aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D 25(OH) vitamin D levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. Results. Serum 25(OH) vitamin D levels were lower in MS patients than in controls (p=0.009). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression (p=0.88). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls (p=0.05). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 (p=0.65). In subanalysis, patients with GA+AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls (p=0.03). No increased risk was observed in GT+TT genotypes of CYP27B1 rs10877012 (p=0.63). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. Conclusion. Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA+AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.
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.
Two zwitterionic celluloses were prepared by grafting amphoteric precursors AS (APTES with 1,4 butane sultone) and TAS (Trimethoxysilylpropyldiethylenetriamine with 1,4 butane sultone) onto activated ...cellulose with NH
4
OH in a heterogeneous system. Information about the zwitterionic modification in celluloses was achieved by FT-IR and
13
C/
29
Si NMR CP/MAS spectroscopy. These analyses demonstrated the chemical structure and level of grafting of the zwitterionic precursors onto cellulose. Moreover, grafting degree (GD) of Cel-AS (31.5%) and Cel-TAS (16.6%) was evaluated by Elemental analysis. The amount of free amino groups from the grafted residues in both samples was tested by ninhydrin method. Here, results demonstrated that around a sixth part of the grafting in Cel-AS remains as aminopropylsilane. In the case of Cel-TAS, the half of butane sultone was bonded to a secondary nitrogen resulting in three possible zwitterionic configurations. These zwitterionic materials were used as adsorbents of Congo red dye in aqueous solution at different concentrations. Uptake experimental data fit well with Langmuir model, with a maximum theoretical adsorption capacity of 541.8 mg g
−1
for Cel-TAS and 81.2 mg g
−1
in Cel-AS at pH 6. Kinetics results for these systems showed the limiting rate step driven by chemisorption process, since they followed a pseudo-second order model. Finally, zwitterionic modification of cellulose with TAS conferred an increase on more than eightfold of Congo red adsorption capacity in comparison with unmodified cellulose.
Graphic abstract
To describe disease activity and disability during the first year of follow-up, from rheumatoid arthritis (RA) patients who discontinue tofacitinib after they end participation in a clinical trial. ...From 2008 to 2016, 36 patients were enrolled in the “Long term follow-up study with tofacitinib (and methotrexate) for RA treatment”. At the end of the study, tofacitinib was discontinued and patients were proposed to enter an observational study; 35 agree and had scheduled evaluations at baseline, at 15 and 30 days of follow-up, at month 2 and 3, and thereafter every 3 months. Disease activity was evaluated as per DAS28-ESR and disability as per HAQ. During follow-up, treatment was treat-to-target oriented, only conventional DMARDs were indicated. Descriptive statistics and nonparametric test were used. The study was approved by IRB. Patients were primarily females (
N
= 34), had median (Q25–75) age of 52 years (45–58), and had received tofacitinib for a median of 7.9 years (6.3–8.3). The proportion of patients with remission and low disease activity decreased from day 30 of follow-up and recovered after 270 days, meanwhile patients with high disease activity increased from 0% at baseline to 6.3% at 1 year. At study entry, 20 patients had remission/low disease activity; during follow-up, 85% deteriorated after (median) 30 days; among them, 23.5% recovered their baseline status after a median of 172.5 days. The HAQ showed a similar behavior, but 66.7% recovered. A substantial proportion of RA patients deteriorated outcomes early after tofacitinib cessation; some patients recovered baseline status with traditional DMARDS.
The zwitterion functionalization of cellulose with lysine was achieved in a two-step synthesis. The cellulose modification in each step of the synthesis was corroborated by FTIR and solid state 13C ...NMR spectroscopy. The zwitterionic character in the modified cellulose was determined by its isoelectric point using a titration curve vs. pH. The dye adsorption performance of the modified cellulose was evaluated with malachite green and indigo carmine solutions. Cellulose modification increases laccase immobilization almost 10-fold compared to unmodified cellulose. Ionic and hydrophobic interactions are involved in immobilization, stabilizing laccase and the zwitterionic cellulose system. A novel theoretical approach of this immobilization is also proposed involving the interaction energies of the specific ionic moieties and supported by hydrophobic interactions shared between the enzyme and the zwitterionic cellulose interface. Moreover, immobilization did not affect the bioactivity of the enzyme, but on the contrary increased it by 29%. The laccase and zwitterionic cellulose system (Laccase-Lys-Cel) was tested against malachite green and indigo carmine in a 96-h experiment. The best removal results of about 93% from aqueous solution were observed for indigo carmine after 1 h and 99% after 72 h. Finally, Laccase-Lys-Cel combines two mechanisms: (1) dye adsorption in the early stages and (2) final dye degradation by the enzyme.
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Context.
The CARMENES instrument, installed at the 3.5 m telescope of the Calar Alto Observatory in Almería, Spain, was conceived to deliver high-accuracy radial velocity (RV) measurements with ...long-term stability to search for temperate rocky planets around a sample of nearby cool stars. Moreover, the broad wavelength coverage was designed to provide a range of stellar activity indicators to assess the nature of potential RV signals and to provide valuable spectral information to help characterise the stellar targets.
Aims.
We describe the CARMENES guaranteed time observations (GTO), spanning from 2016 to 2020, during which 19 633 spectra for a sample of 362 targets were collected. We present the CARMENES Data Release 1 (DR1), which makes public all observations obtained during the GTO of the CARMENES survey.
Methods.
The CARMENES survey target selection was aimed at minimising biases, and about 70% of all known M dwarfs within 10 pc and accessible from Calar Alto were included. The data were pipeline-processed, and high-level data products, including 18 642 precise RVs for 345 targets, were derived. Time series data of spectroscopic activity indicators were also obtained.
Results.
We discuss the characteristics of the CARMENES data, the statistical properties of the stellar sample, and the spectroscopic measurements. We show examples of the use of CARMENES data and provide a contextual view of the exoplanet population revealed by the survey, including 33 new planets, 17 re-analysed planets, and 26 confirmed planets from transiting candidate follow-up. A subsample of 238 targets was used to derive updated planet occurrence rates, yielding an overall average of 1.44 ± 0.20 planets with 1
M
⊕
<
M
pl
sin
i <
1000
M
⊕
and 1 day <
P
orb
< 1000 days per star, and indicating that nearly every M dwarf hosts at least one planet. All the DR1 raw data, pipeline-processed data, and high-level data products are publicly available online.
Conclusions.
CARMENES data have proven very useful for identifying and measuring planetary companions. They are also suitable for a variety of additional applications, such as the determination of stellar fundamental and atmospheric properties, the characterisation of stellar activity, and the study of exoplanet atmospheres.
The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus ...of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period.
Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005–2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated.
A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn’s disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab.
Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications.
El objetivo primario fue explorar la tendencia epidemiológica de la enfermedad intestinal inflamatoria pediátrica en América Latina; los secundarios, obtener una visión general del enfoque diagnóstico/terapéutico de miembros de la SLAGHNP y explorar la relación entre la frecuencia de casos y los años del período evaluado.
Se realizó una encuesta en línea a pediatras gastroenterólogos de América Latina con la plataforma SurveyMonkey. Se preguntó la frecuencia anual de pacientes nuevos de 2005 a 2016, su variedad, los segmentos del tubo digestivo afectados, los métodos de diagnóstico y el tratamiento utilizado. Se evaluó la correlación entre la frecuencia anual y los años de estudio.
Se estudió a 607 pacientes; el diagnóstico de colitis ulcerativa se realizó en 475 (78.3%), de enfermedad de Crohn en 104 (17.1%) y de enfermedad intestinal inflamatoria no clasificable en 28 (4.6%). La tendencia de colitis ulcerativa tuvo un incremento lineal con coeficiente de correlación significativo entre la frecuencia de casos nuevos y el año de estudio; 67.6% tuvieron pancolitis. Los métodos de diagnóstico incluyeron datos clínicos, endoscopia y biopsias en más del 99% de los casos; los estudios de imagen se indicaron de manera selectiva. Los esquemas farmacológicos se circunscribieron a derivados del ácido 5-aminosalicílico, azatioprina, 6-mercaptopurina, infliximab y adalimumab.
La enfermedad intestinal inflamatoria pediátrica en América Latina parece incrementarse en el período estudiado con predominio de formas moderadas o graves de colitis ulcerativa; esta tendencia lineal puede indicar la posibilidad predictiva de incremento gradual en la próxima década, lo que es probable que tenga implicaciones epidemiológicas y clínicas.
The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus ...of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period.
Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005 to 2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated.
A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn's disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab.
Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications.
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