TET enzymes and 5hmC epigenetic mark: new key players in carcinogenesis and progression in gynecological cancers.

DNA methylation is an epigenetic mechanism involving the transfer of a methyl group onto the C5 position of the cytosine to form 5-methylcytosine (5mC). In general, DNA methylation in cancer is associated with the repression of the expression of tumor suppressor genes (TSG) and the demethylation with the overexpression of oncogenes. DNA methylation was considered a stable modification for a long time, but in 2009, it was reported that DNA methylation is a dynamic modification. The Ten-Eleven-Translocations (TET) enzymes include TET1, TET2, and TET3 and participate in DNA demethylation through the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC). The 5hmC oxidates to 5-formylcytosine (5fC) and 5-carboxylcitosine (5caC), which are replaced by unmodified cytosines via Thymine-DNA Glycosylase (TDG). Several studies have shown that the expression of TET proteins and 5hmC levels are deregulated in gynecological cancers, such as cervical (CC), endometrial (EC), and ovarian (OC) cancers. In addition, the molecular mechanisms involved in this deregulation have been reported, as well as their potential role as biomarkers in these types of cancers. This review shows the state-of-art TET enzymes and the 5hmC epigenetic mark in CC, EC, and OC.

Soil characteristics and allometric models for biometric characteristics and nutrient amounts for high yielding "Bolaina" (Guazuma crinita) trees.

The Peruvian amazon is very diverse in native forestry species, the Guazuma crinita "Bolaina" being one of the most planted species in the country; however, little or no information about soil requirements and nutrient demands is known. The objective of this work was to assess the general conditions of soil fertility, biomass and macro- and micronutrient amounts in high-productivity Guazuma crinita plantations. Fields of high yielding Bolaina of different ages (1-10 years) were sampled in two regions. Soil and plant samples were collected in each field and biometric measurements of fresh weight, diameter at breast height and height were performed. For soil and plant analysis, both macro- (N, P, K, Ca, Mg, S) and micronutrients (B, Cu, Fe, Mn, Zn) were determined. Finally, allometric equations were constructed for biometric and nutrient amounts. This study is the first to assess and model macro- and micronutrient amounts in the productive cycle in this species, which grows in fertile soils. In the case of biometric equations, the logarithmic and logistic models performed better. For nutrient amounts, this species followed a pattern of Ca > N > K > P > S > Mg for macronutrients and Fe > B > Mn > Zn > Cu for micronutrients. The best prediction models for nutrients were the square root and logistic models.

Microbiome-induced Increases and Decreases in Bone Tissue Strength can be Initiated After Skeletal Maturity.

Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n=143 total, n=12-17/group/sex) were allocated into five study groups:1) Unaltered, 2) Continuous (dosing 4-24 weeks of age), 3) Delayed (dosing only 16-24 weeks of age), 4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and 5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25-35% less than expected from geometry in mice from the Continuous (p= 0.001), Delayed (p= 0.005), and Initial (p=0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota, however, led to a bone matrix strength similar to Unaltered animals (p=0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating sex-related differences in the response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed (Raman spectroscopy). Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) is small; however, this suggests that microbiome-induced changes in bone matrix occur without osteoblast/osteoclast turnover using an, as of yet unidentified mechanism. These findings add to evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.

Serological and molecular survey of canine distemper virus in red foxes (Vulpes vulpes): Exploring cut-off values and the use of protein A in ELISA tests.

The wide distribution and ecological plasticity of the red fox (Vulpes vulpes) make it a potential reservoir for many infectious diseases shared with domestic and wild carnivores. One of such diseases is canine distemper, which is caused by an RNA virus and its main domestic reservoir is the dog. However, other carnivores can also participate in its maintenance, as shown by the recent upsurge of reported cases in wildlife in many parts of the world, and by the fact that red foxes may act as true reservoirs for canine distemper virus (CDV). The lack of validated serological tests for wildlife or other non-target species may be a handicap for monitoring this virus. In this study, serological assays were compared in 147 red fox sera using a commercial ELISA validated for its use in dogs and a non-specific modified ELISA with Protein A peroxidase conjugate to detect bound antibodies. In addition, the presence of CDV RNA in brain, spleen, lung, and liver samples from 144 foxes was investigated by a RT-qPCR. Through the comparison of the results of both ELISAs and the use of a finite mixture model of the optical density values obtained by both techniques, we adjusted the cut-off point of the commercial ELISA to obtain the seroprevalence in foxes. The overall seroprevalence detected was 53.7% (79/147) and 57.1% (84/147) by the commercial and modified ELISA, respectively, with a moderate agreement according to Cohen's Kappa statistic (κ = 0.491, z = 5.97, p < 0.0001). CDV RNA was detected in 30 out of 144 foxes, which resulted in 20.8% of CDV-infected foxes. At individual level, the results obtained by relating the serological status and the presence/absence of RNA in different organs were explained in terms of the pathogenesis of the infection. Our results highlight the convenience of adjusting the cut-off point when using an ELISA assay developed in domestic dogs for its use in foxes. Moreover, Protein A is confirmed to be a good alternative to be used in red foxes, presenting a good reactivity towards its IgG.

Papilla of Vater morphology as an influencing factor in successful cannulation during resident training in advanced endoscopy. A prospective clinical study.

INTRODUCTION AND AIM: Endoscopic retrograde cholangiopancreatography (ERCP) is a complex procedure. Clinical guidelines assess competence in ERCP through a defined number of procedures, but multiple factors are involved. Our aim was to analyze the morphology of the papilla of Vater as an independent factor in selective common bile duct cannulation during resident training. MATERIAL AND METHODS: Patients that underwent ERCP were studied consecutively. All ERCPs were begun by a resident in training. The type of papilla was classified according to Haraldsson, including those with previous sphincterotomy. Cannulation difficulty and success and their relation to the type of papilla were documented. The analysis was divided into three 4-month periods. RESULTS: Of the 429 patients, cannulation was difficult in 101 (23.5%). The residents achieved selective cannulation of the common bile duct in 276 (64.3%) and the cannulation success rate at the end of their training was 81.7%. Cannulation was performed with the least difficulty in papillae with previous sphincterotomy (2.8%), unlike the type 4 papilla, which was difficult to cannulate in 50% of the cases. The lowest overall cannulation success was in the type 2 papilla (81.8%). CONCLUSION: Papilla type can influence cannulation success, but it is not the only related factor. Patients that underwent previous sphincterotomy appear to be the cases in whom ERCP training can be started.

Experiencia con el Biofire FilmArray® para meningitis/encefalitis infecciosa en una institución de alta complejidad en Bogotá, Colombia / Experience with the Biofire FilmArray® for infectious meningitis/encephalitis in a high complexity institution in Bogotá, Colombia

Introducción: La meningoencefalitis infecciosa (MEI) es una emergencia neurológica con importante morbimortalidad. El panel Biofire FilmArray? para meningitis/encefalitis (FAME) en el líquido cefalorraquídeo (LCR) ha demostrado ser una valiosa herramienta para el diagnóstico etiológico de la MEI, facilitando una terapia antimicrobiana dirigida. El objetivo es determinar el impacto del panel FAME en las decisiones terapéuticas antimicrobianas en pacientes con sospecha de MEI en las primeras 24 horas de la valoración clínica. Pacientes y métodos: Estudio observacional descriptivo que comenta las manifestaciones cínicas, los resultados de neuroimágenes y paraclínicos, y la antibioticoterapia de pacientes con sospecha de MEI. Se realizó un análisis del impacto que tiene el FAME en la terapia antimicrobiana en las primeras 24 horas de la valoración clínica de los pacientes. Resultados: Se incluyó a 44 pacientes. El tiempo promedio para obtener el resultado del panel FAME en el LCR fue de nueve horas, con un 20,4% (9/44) de pruebas positivas. En las primeras 24 horas de la valoración clínica, su resultado tuvo impacto en las decisiones terapéuticas antimicrobianas en el 75% (33/44) de los casos. En pacientes con alta sospecha clínica de MEI, el resultado del FAME permitió cambiar la terapia empírica inicial a una dirigida en el 15% (3/20) y suspender la terapia empírica inicial en el 35% (7/20) de los sujetos. En pacientes con baja sospecha clínica de MEI, su resultado permitió que al 25% (6/24) se le confirmara la sospecha y se le iniciara antibioticoterapia dirigida; y que al 70,8% (17/24) se le descartara el diagnóstico y no se le iniciara tratamiento. Conclusiones: El resultado del panel FAME en el LCR tiene alto impacto en la toma de decisiones terapéuticas antimicrobianas en las primeras 24 horas de la valoración clínica. Sin embargo, su interpretación debe hacerse con el contexto clínico, la epidemiología local y otros estudios diagnósticos.(AU)

Introduction: Infectious meningoencephalitis (IME) is a neurological emergency with a significant rate of morbidity and mortality. The Biofire FilmArray® meningitis/encephalitis (FAME) panel for testing in cerebrospinal fluid (CSF) has proven to be a valuable tool for the aetiological diagnosis of IME, facilitating targeted antimicrobial therapy. The aim is to determine the impact of the FAME panel on antimicrobial therapeutic decisions in patients with suspected IME in the first 24 hours of clinical assessment. Patients and methods: This is a descriptive observational study that comments on the clinical manifestations, the neuroimaging and paraclinical findings, and the antibiotic therapy of patients with suspected IME. An analysis was performed to determine the impact of FAME on antimicrobial therapy in the first 24 hours of the clinical assessment of patients. Results: Altogether 44 patients were included. The average time required to obtain the result of the FAME panel for testing in CSF was nine hours, with 20.4% (9/44) of tests yielding positive results. Within 24 hours of clinical assessment, their outcome had an impact on antimicrobial treatment decisions in 75% (33/44) of cases. In patients with a high clinical suspicion of IME, the result of FAME made it possible to change the initial empirical therapy to a targeted therapy in 15% (3/20) of cases and to discontinue the initial empirical therapy in 35% (7/20) of the subjects. In patients with low clinical suspicion of IME, their result allowed 25% (6/24) to have their suspicion confirmed and they were started on targeted antibiotic therapy; in contrast, 70.8% (17/24) had their diagnosis ruled out and were not started on treatment. Conclusions: The result of the FAME panel for testing in CSF has a high impact on antimicrobial therapeutic decisions within 24 hours of clinical assessment. However, it must be interpreted with the clinical context, local epidemiology and other diagnostic studies.(AU)

Effect of coadministration of Lactiplantibacillus fabifermentans and linear/branched fructans mixtures on the intestinal health of Wistar rats.

A completely randomized experimental design was conducted to evaluate the effect of the coadministration of Lactiplantibacillus fabifermentans (Lpb. fabifermentans) and inulin/agave fructans mixtures on gut microbiota of healthy Wistar rats. Inulin, Agave salmiana fructans or fructan mixtures (1:1) at 12.5 % w/w, and Lpb. fabifermentans at 109 CFU/mL/day were used in the rats' diet for 35 days. Biochemical parameters, short-chain fatty acids (SCFA), structural changes and the bacterial abundance in rats' cecum were evaluated. A significant decrease (p < 0.05) in glucose, cholesterol and triglycerides levels with fructan mixtures combined with Lpb. Fabifermentans was observed. The weight of the small and large intestines, and cecum was higher than the control; no changes were observed in the heart, liver, spleen and kidneys. SCFA concentration mainly, propionate and butyrate was improved (p < 0.05) throughout the gastrointestinal tract in all treatments. Finally, the administration of Lpb. fabifermentans alone or combined with the fructan mixtures promoted an increase in the abundance of cecum intestinal microbiota: Lactobacillus, Bifidobacterium, Prevotella, Blautia, Faecalibacterium, Butyricimonas, Coprococcus, Akkermansia, Methanobrevibacter, Adlercreutzia, Collinsella, Odoribacter, and Roseburia. The inclusion of fructan mixtures in combination with Lpb. fabifermentans could be a good alternative for the development of functional foods that enhance consumer health.

[Experience with the Biofire FilmArray® for infectious meningitis/encephalitis in a high complexity institution in Bogota, Colombia]. / Experiencia con el Biofire FilmArray® para meningitis/encefalitis infecciosa en una institución de alta complejidad en Bogotá, Colombia.

INTRODUCTION: Infectious meningoencephalitis (IME) is a neurological emergency with a significant rate of morbidity and mortality. The Biofire FilmArray® meningitis/encephalitis (FAME) panel for testing in cerebrospinal fluid (CSF) has proven to be a valuable tool for the aetiological diagnosis of IME, facilitating targeted antimicrobial therapy. The aim is to determine the impact of the FAME panel on antimicrobial therapeutic decisions in patients with suspected IME in the first 24 hours of clinical assessment. PATIENTS AND METHODS: This is a descriptive observational study that comments on the clinical manifestations, the neuroimaging and paraclinical findings, and the antibiotic therapy of patients with suspected IME. An analysis was performed to determine the impact of FAME on antimicrobial therapy in the first 24 hours of the clinical assessment of patients. RESULTS: Altogether 44 patients were included. The average time required to obtain the result of the FAME panel for testing in CSF was nine hours, with 20.4% (9/44) of tests yielding positive results. Within 24 hours of clinical assessment, their outcome had an impact on antimicrobial treatment decisions in 75% (33/44) of cases. In patients with a high clinical suspicion of IME, the result of FAME made it possible to change the initial empirical therapy to a targeted therapy in 15% (3/20) of cases and to discontinue the initial empirical therapy in 35% (7/20) of the subjects. In patients with low clinical suspicion of IME, their result allowed 25% (6/24) to have their suspicion confirmed and they were started on targeted antibiotic therapy; in contrast, 70.8% (17/24) had their diagnosis ruled out and were not started on treatment. CONCLUSIONS: The result of the FAME panel for testing in CSF has a high impact on antimicrobial therapeutic decisions within 24 hours of clinical assessment. However, it must be interpreted with the clinical context, local epidemiology and other diagnostic studies.

TITLE: Experiencia con el Biofire FilmArray® para meningitis/encefalitis infecciosa en una institución de alta complejidad en Bogotá, Colombia.Introducción. La meningoencefalitis infecciosa (MEI) es una emergencia neurológica con importante morbimortalidad. El panel Biofire FilmArray? para meningitis/encefalitis (FAME) en el líquido cefalorraquídeo (LCR) ha demostrado ser una valiosa herramienta para el diagnóstico etiológico de la MEI, facilitando una terapia antimicrobiana dirigida. El objetivo es determinar el impacto del panel FAME en las decisiones terapéuticas antimicrobianas en pacientes con sospecha de MEI en las primeras 24 horas de la valoración clínica. Pacientes y métodos. Estudio observacional descriptivo que comenta las manifestaciones cínicas, los resultados de neuroimágenes y paraclínicos, y la antibioticoterapia de pacientes con sospecha de MEI. Se realizó un análisis del impacto que tiene el FAME en la terapia antimicrobiana en las primeras 24 horas de la valoración clínica de los pacientes. Resultados. Se incluyó a 44 pacientes. El tiempo promedio para obtener el resultado del panel FAME en el LCR fue de nueve horas, con un 20,4% (9/44) de pruebas positivas. En las primeras 24 horas de la valoración clínica, su resultado tuvo impacto en las decisiones terapéuticas antimicrobianas en el 75% (33/44) de los casos. En pacientes con alta sospecha clínica de MEI, el resultado del FAME permitió cambiar la terapia empírica inicial a una dirigida en el 15% (3/20) y suspender la terapia empírica inicial en el 35% (7/20) de los sujetos. En pacientes con baja sospecha clínica de MEI, su resultado permitió que al 25% (6/24) se le confirmara la sospecha y se le iniciara antibioticoterapia dirigida; y que al 70,8% (17/24) se le descartara el diagnóstico y no se le iniciara tratamiento. Conclusiones. El resultado del panel FAME en el LCR tiene alto impacto en la toma de decisiones terapéuticas antimicrobianas en las primeras 24 horas de la valoración clínica. Sin embargo, su interpretación debe hacerse con el contexto clínico, la epidemiología local y otros estudios diagnósticos.

Acute stroke in COVID-19 patients: A first year experience in a Colombian hospital.

Background: COVID-19 may be a new risk factor for stroke. Stroke in COVID-19 varies from 1.1 to 8.1%. Various pathophysiological pathways predispose SARS-CoV-2 infected patients to stroke. Aim: To describe COVID-19 patients with acute stroke in one Colombian Center. Methods: From March 6 2020 and March 6 2021 records of patients with acute stroke and in-hospital positive PCR (Polymerase Chain Reaction) test for Sars-CoV-2 infection were reviewed. Demographic, stroke and COVID-19 characteristics were extracted. Continuous variables were reported in means and ranges. Categorical variables were presented in frequencies and percentage. A descriptive narrative was performed. Results: Of 328 acute stroke patients 14 (4.2%) tested positive for PCR SARS-CoV-2. Mean age 56.4 years with 57% males. Five were (35.7%) without vascular risk factors but 9 (64.3%) overweight. Brain infarct diagnosed in 11 (78.5%), 53% with anterior circulation syndromes. Mean NIHSS score 11.8 and 7 (63%) received intravenous thrombolysis. Acute inflammatory blood biomarkers (D-dimer, ferritin, LDH elevated) were positive in all. 11 (78.5%) had symptomatic COVID-19 before stroke with a mean latency of 7 days. 12 (85.7%) had severe COVID-19 and 6 (42.8%) required mechanical ventilation. Outcome was unfavorable in 9 (64.3%) (The Modified Rankin Scale (mRS) > 2), mean hospital stay was 21.8 days and in-hospital case fatality rate was 14.2%. Conclusion: In susceptible individuals COVID-19 predisposes to stroke. Hypercoagulation and immune thrombosis may be at the culprit for this state. In Colombia, COVID-19 patients with stroke have similar characteristics to the described worldwide.

Reproducibilidad de la densidad vascular peripapilar, cabeza del nervio óptico y área macular por OCT-A de acuerdo con la severidad del glaucoma / Reproducibility of peripapillary, optic nerve head and macular vessel density by OCT-A according to glaucoma severity staging

Objetivo Evaluar la reproducibilidad de la densidad vascular (DV) peripapilar, cabeza del nervio óptico (ONH-PP) y área macular mediante angiografía por tomografía de coherencia óptica de dominio espectral (SD OCT-A) en pacientes con glaucoma y en sujetos sanos. Métodos Estudio transversal que evaluó 63 ojos de 63 sujetos, incluyendo 33 pacientes con glaucoma y 30 sujetos sanos. El glaucoma se clasificó en leve, moderado o avanzado. Dos exploraciones consecutivas fueron adquiridas por Spectralis Module OCT-A (Heidelberg, Alemania) y proporcionaron imágenes del complejo vascular superficial (SVC), del plexo vascular de la capa de fibra nerviosa (NFLVP) y del plexo vascular superficial (SVP); del complejo vascular profundo (DVC), del plexo capilar intermedio (ICP) y del plexo capilar profundo (DCP). La DV (%) fue calculada mediante AngioTool. Se calcularon los coeficientes de correlación intraclase (ICC) y los coeficientes de variación (CV). Resultados Respecto a la DV de ONH-PP, el mejor ICC lo presentó el glaucoma avanzado (0,86-0,96) y moderado (0,83-0,97) en comparación con el glaucoma leve (0,64-0,86). Para la DV macular, los resultados de ICC para las capas retinianas superficiales fueron mejores para el glaucoma leve (0,94-0,96), seguido por el glaucoma moderado (0,88-0,93) y por el avanzado (0,85-0,91), y para las capas retinianas más profundas el ICC fue más alto para el glaucoma moderado (0,95-0,96), seguido por el glaucoma avanzado (0,80-0,86) y por el leve (0,74-0,91). Los CV oscilaron entre el 2,2% y el 10,94%. Entre los sujetos sanos, los ICC para las mediciones de DV ONH-PP (0,91-0,99) y para las mediciones de la DV macular (0,93-0,97) fueron excelentes en todas las capas, con CV del 1,65% al 10,33% (AU)

Objective To assess the reproducibility of peripapillary, optic nerve head (ONH-PP) and macular vessel density (VD) by spectral domain optical coherence tomography angiography (SD OCT-A) in glaucoma patients and healthy subjects. Methods Cross-sectional study assessing 63 eyes of 63 subjects, including 33 glaucoma patients and 30 healthy subjects. Glaucoma was classified in mild, moderate, or advanced. Two consecutive scans were acquired by spectralis module OCT-A (Heidelberg, Germany), and provided images of the superficial vascular complex (SVC), nerve fiber layer vascular plexus (NFLVP), superficial vascular plexus (SVP), deep vascular complex (DVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP). VD (%) was calculated by AngioTool. Intraclass correlation coefficients (ICCs) and coefficients of variation (CV) were calculated. Results Among ONH-PP VD, better ICC presented advanced (0.86-0.96) and moderate glaucoma (0.83-0.97) compared with mild glaucoma (0.64-0.86). For the macular VD reproducibility, ICC results for superficial retinal layers were better for mild glaucoma (0.94-0.96) followed by moderated (0.88-0.93) and advanced glaucoma (0.85-0.91), and for deeper retinal layers ICC was better for moderate glaucoma (0,95-0,96) followed by advanced (0.80-0.86) and mild glaucoma (0.74-0.91). CVs ranged from 2.2%% to 10.94%. Among healthy subjects, ICCs for the ONH-PP VD measurements (0.91-0.99) and for the macular VD measurements (0.93-0.97) were excellent in all layers, with CVs from 1.65% to 10.33%. Conclusions SD OCT-A used to quantify macular and ONH-PP VD showed excellent and good reproducibility in most layers of the retina, both in healthy subjects and in glaucoma patients regardless of the severity of the disease (AU)

Reproducibility of peripapillary, optic nerve head and macular vessel density by OCT-A according to glaucoma severity staging.

OBJECTIVE: To assess the reproducibility of peripapillary, optic nerve head (PP-ONH) and macular vessel density (VD) by Spectral Domain optical coherence tomography angiography (SD OCT-A) in glaucoma patients and healthy subjects. METHODS: Cross-sectional study assessing 63 eyes of 63 subjects, including 33 glaucoma patients and 30 healthy subjects. Glaucoma was classified in mild, moderate, or advanced. Two consecutive scans were acquired by Spectralis Module OCT-A (Heidelberg, Germany), and provided images of the superficial vascular complex (SVC), nerve fiber layer vascular plexus (NFLVP), superficial vascular plexus (SVP); deep vascular complex (DVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP). VD (%) was calculated by AngioTool. Intraclass correlation coefficients (ICCs) and coefficients of variation (CV) were calculated. RESULTS: Among PP-ONH VD, better ICC presented advanced (ICC 0.86-0.96) and moderate glaucoma (ICC 0.83-0.97) compared with mild glaucoma (0.64-0.86). For the macular VD reproducibility, ICC results for superficial retinal layers were better for mild glaucoma (0.94-0.96) followed by moderated (0.88-0.93) and advanced glaucoma (0.85-0.91), and for deeper retinal layers ICC was better for moderate glaucoma (0.95-0.96) followed by advanced (0.80-0.86) and mild glaucoma (0.74-0.91). CVs ranged from 2.2% to 10.94%. Among healthy subjects, ICCs for the PP-ONH VD measurements (0.91-0.99) and for the macular VD measurements (0.93-0.97) were excellent in all layers, with CVs from 1.65% to 10.33%. CONCLUSIONS: SD OCT-A used to quantify macular and PP-ONH VD showed excellent and good reproducibility in most layers of the retina, both in healthy subjects and in glaucoma patients regardless of the severity of the disease.

Early beginning of alemtuzumab: Changing the multiple sclerosis treatment paradigm. Interim analysis of the LEMVIDA study.

INTRODUCTION: LEMVIDA is a real-world prospective study of 3-year follow-up on quality of life of patients with multiple sclerosis (MS) receiving alemtuzumab in Spain. METHODS: This is an interim analysis evaluating the baseline characteristics of patients who started alemtuzumab between October 2016-September 2018. For 3 additional subanalysis patients were categorised by baseline EDSS score; time of alemtuzumab initiation during the recruitment period (cohort 1: October 2016-March 2017, cohort 2: April-September 2017, cohort 3: October 2017-March 2018 and cohort 4: April-September 2018); and the presence of highly active MS criteria. RESULTS: 161 patients were analysed: 67.1% female, age 38.7 ± 9.4 years, MS duration 8.5 ± 6.0 years, EDSS 3.3 ± 1.7 and number of relapses in the previous 2 years 1.8 ± 1.3. 48.3% of patients presented gadolinium-enhanced (Gd+) lesions (mean: 5.2 ± 6.9) and 63.1% had received prior treatment with fingolimod or natalizumab. Baseline EDSS scores and number of Gd+ lesions were higher in cohort 1 than in cohort 4 (4.1 ± 1.8 vs 3.2 ± 1.7; P = .040 and 10.9 ± 11.9 vs 4.5 ± 5.7; P = .020). The frequency of prior treatment with fingolimod and natalizumab was lower in cohort 4 (60.6%) than in cohort 1 (70.6%) (comparison between groups not analysed). CONCLUSIONS: Unlike phase 3 studies of alemtuzumab, the patients included in LEMVIDA are older, have a longer duration of MS, higher disability and have received previous immunosuppressants. However, throughout the recruitment period, there is a tendency towards an early beginning of treatment with alemtuzumab, probably due to the evidence of higher effectiveness in the early stages of MS.

Agave fructans enhance the effects of fermented milk products on obesity biomarkers: a randomised trial.

Dysbiosis has been implicated in childhood obesity. Oral intake of fermented milk containing Lacticaseibacillus casei strain Shirota preserves gut microbiota (GM) diversity in children and adults. This study was a double-blind trial involving 37 overweight or obese children aged 6-10 years. Children were followed over a 6-week intervention period in which they received different fermented milk products containing L. casei Shirota: 10 in the first group received just L. casei Shirota; 13 received L. casei Shirota with 3 g/day of inulin (L. casei+inulin); and 14 received L. casei Shirota with 3 g/day of fructans from Agave salmiana (L. casei+fructans). Principal component analysis showed the relationship between microbial abundance, GM metabolites, and other obesity-related markers. Supplementation with probiotics and synbiotics improved the HDL-cholesterol levels of overweight and obese children, although no changes in body composition were detected. We observed an increase in butyrate or propionate concentrations in the L. casei+fructans group compared to the end of the intervention (P<0.03). A diminished level of ANGPTL4 within the L. casei+fructans group (P=0.04) was also found, but no differences when lipopolysaccharide-binding protein was evaluated. The FFAR2+ cell frequency decreased between baseline and at the end of 6-week intervention in L. casei+inulin (P=0.02) and L. casei+fructans groups (P=0.04). In contrast, the percentage of CD14+FFAR3+ frequency increased in the same groups (P=0.04). The L. casei Shirota with inulin or fructans modulates GM, which improves the lipid profile and changes at a molecular level, such as expression of FFAR3 and FFAR2, ANGPTL4, propionate, and butyrate. It, therefore, could be considered an interesting therapeutic possibility for treating childhood overweight and obesity. The study was registered at ClinicalTrials.gov (ID: NCT05423015).

Retinal sensitivity and gaze fixation evaluated by microperimetry in subjects with type 2 diabetes: two independent parameters that explore different neuronal circuits.

BACKGROUND AND AIMS: Retinal sensitivity (RS) and gaze fixation (GF) assessed by retinal microperimetry are useful and complementary tools for identifying mild cognitive impairment (MCI) in patients with type 2 diabetes (T2D). The hypothesis is that RS and GF examine different neural circuits: RS depends only on the visual pathway while GF reflects white matter complex connectivity networks. The aim of the study is to shed light to this issue by examining the relationship of these two parameters with visual evoked potentials (VEP), the current gold standard to examine the visual pathway. MATERIALS AND METHODS: Consecutive T2D patients > 65 years were recruited from the outpatient clinic. Retinal microperimetry (MAIA 3rd generation) and visual evoked potentials (VEP) (Nicolet Viking ED). RS (dB), GF (BCEA63%, BCEA95%) (MAIA) and VEP (Latency P100ms, Amplitude75-100 uV) were analyzed. RESULTS: Thirty three patients (45% women, 72.1 ± 4.6 years) were included. VEP parameters significantly correlated with RS but not with GF. CONCLUSIONS: These results confirm that RS but not GF depends on the visual pathway, reinforcing the concept that they are complementary diagnostic tools. Used together can further increase the value of microperimetry as screening test for identifying T2D population with cognitive impairment.

Are universal adhesives in etch-and-rinse mode better than old 2-step etch-and-rinse adhesives? One-year evaluation of bonding properties to dentin.

OBJECTIVES: This study compared the bonding properties of dentin of three 2-step etch-and-rinse adhesives (2-ERAs) to those of three universal adhesives (UAs) applied with an etch-and-rinse strategy (ER), immediately and after 1 year of water storage. METHODS: Sixty caries-free molars were divided into 6 groups according to the adhesive systems used (n = 10). The 2-ERA systems included were: 1) Adper Single Bond 2 (SB), 2) Tetric N-Bond (TB), and 3) Ambar (AM); and the UAs systems were: 4) Single Bond Universal (SBU) 5) Tetric N-Bond Universal (TBU), and 6) Ambar Universal (AMU). The occlusal third of each tooth was removed and the adhesives were applied. After the composite build-up, specimens were sectioned and tested for microtensile bond strength (µTBS) and nanoleakage (NL) immediately and after 1 year of water storage. In situ degree of conversion (DC) was only evaluated in the immediate time. For water sorption (WS), solubility (SO), and mass change (MC) tests, 48 disk-shaped specimens were prepared (n = 8) and assessed according to ISO 4049:2009. RESULTS: UAs showed higher µTBS and lower NL values than 2-ERAs did after 1 year of water storage (p = 0.001). Regarding DC, 2-ERAs showed higher DC values than UAs (p = 0.001). Regarding WS, 2-ERAs showed higher WS values than those of UAs (p = 0.00001), except for AM and AMU. Lower WS was observed for AM than for other 2-ERAs (p = 0.00001). CONCLUSION: The use of UAs applied with the ER strategy seems to be a more effective technique for maintaining adhesion to dentin substrate than 2-ERAS. CLINICAL SIGNIFICANCE: This study may support clinicians in selecting the most adequate adhesive system to be used in ER strategy in dentin, demonstrating that UAs were more effective, considering the longevity of the resin restorations.

Background rates of 41 adverse events of special interest for COVID-19 vaccines in 10 European healthcare databases - an ACCESS cohort study.

BACKGROUND: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. METHODS: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. FINDINGS: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. INTERPRETATION: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. FUNDING: The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.

Caracterización fenotípica psicomotora y psicolingüística en el síndrome de Wolf-Hirschhorn: un estudio de 18 casos / PSYCHOMOTOR AND PSYCHOLINGUISTIC PHENOTYPIC CHARACTERIZATION IN WOLF-HIRSCHHORN SYNDROME: A STUDY OF 18 CASES

Introducción. El síndrome de Wolf-Hirschhorn (SWH) es una enfermedad rara de origen genético causado por una deleción parcial en la región terminal del brazo corto del cromosoma 4. La finalidad de este estudio es explorar variables del fenotipo cognitivo y su relación con el desarrollo evolutivo motor, visuoespacial, visuomotriz y del lenguaje en niños/as con esta patología. Pacientes y método. La investigación se dirige a una muestra incidental de 18 pacientes con diagnóstico clínico en el SWH, entre 1 y 23 años de edad, procedentes de diferentes países de habla hispana. Variables e instrumentos. Se recogieron diferentes variables diagnósticas, clínicas y neuropsicológicas como el desarrollo somático (desarrollo físico, motor y sensorial) y desarrollo cognitivo (desarrollo visuoespacial, visuomotriz, lenguaje comprensivo y expresivo). Se utilizaron dos instrumentos de medida: Cuestionario ad hoc de evaluación del desarrollo motor, visuoespacial, visuomotriz y del lenguaje, y la versión española de la Escala Barthel. La recogida de datos fue realizada mediante la información proporcionada por los progenitores. Resultados. El principal hallazgo de este estudio es que los/as niños/as con baja talla actual, bajo peso actual, menor perímetro craneal actual y con estatus epiléptico presentan mayor incidencia de problemas en el desarrollo evolutivo, en comparación con aquellos/as que actualmente presentan mayor talla, más peso, mayor perímetro craneal y sin estatus epiléptico. Conclusiones. Se constata un doble fenotipo cognitivo específico acorde a la muestra estudiada que puede ayudar a crear un primer perfil neuroevolutivo del SWH en la praxis sanitaria, educativa y/o social. (AU)

Introduction. Wolf-Hirschhorn Syndrome (WHS) is a rare genetic disorder caused by a partial deletion in the terminal region of the short arm of chromosome 4. The purpose of this study is to explore cognitive phenotype variables and their relationship with motor, visuospatial, visuomotor and language development in children with WHS. Patients and method. The research targets an incidental sample of 18 patients clinically diagnosed with WHS, aged between 1 and 23 years, from various Spanish-speaking countries. Variables and instruments. Different diagnostic, clinical and neuropsychological variables were collected, including somatic development (physical, motor and sensory) and cognitive development (visuospatial, visuomotor, receptive and expressive language). Two measurement instruments were utilized: an ad hoc questionnaire assessing motor, visuospatial, visuomotor and language development, and the Spanish version of the Barthel Scale. Data collection relied on information provided by the parents. Results. The main finding of this study indicates that children with lower current height, weight, and head circumference, as well as those experiencing status epilepticus, demonstrate a higher incidence of developmental problems compared to those with higher current measurements of those variables, and with no status epilepticus. Conclusions. A distinct double cognitive phenotype was observed within the studied sample, which may help to create an initial neurodevelopmental profile of WHS for clinical, educational, and social purposes. (AU)

Flying across Europe: the case of the spread of Chaunocephalus ferox on a black stork (Ciconia nigra).

The annual migration of birds involves a very large number of inter-continental and intra-continental movements in which thousands of bird species participate. These migrations have been associated with the spread of pathogens worldwide, including bacteria, viruses and parasites. This study describes the case of a black stork (Ciconia nigra) that was ringed at the nest in Latvia and died five months later in the south-east of the Iberian Peninsula. Post-mortem examination revealed that the cause of death was electrocution. In addition, a massive infection by the trematode Chaunocephalus ferox (Digenea: Echinostomatidae) causing severe granulomatous lesions throughout the small intestine was detected. This is the first report of C. ferox infection in a black stork in the Iberian Peninsula, a trematode that, due to the severe lesions it causes, can affect the health of C. ferox-infected wild birds, particularly in severely infected long-distance migrants. The dispersal of platyhelminths associated with migratory birds is discussed. After the ringing at the nest, the black stork was sighted in Central Europe one month before its capture, and the trematodes found by necropsy were mostly mature adults. Consequently, we estimate that this juvenile animal acquired the infection during its migration in a European area other than the Iberian Peninsula, evidencing a long-distance parasite spread through its migratory host. Our study highlights that bird ringing can be used to understand the epidemiological implications that bird migratory behaviour may have on the dispersal of parasites.

Assessment of the patient safety culture in the ICU of a second level hospital at the end of the third COVID-19 wave.

INTRODUCTION: Current healthcare settings and ICUs especially are complex, highly technical, and multidisciplinary, with interactions between healthcare professionals and users, in which there may be errors at different levels. Our objective was to assess the perception of patient safety in our unit at the end of the third wave of the COVID pandemic, with the intention of conducting subsequent improvement actions. METHODS: Observational, cross-sectional, and descriptive study. The perception of Safety Culture was estimated using the HSOPS questionnaire translated into Spanish. Some questions were posed in a positive sense, and others in a negative sense. The response was also rated as positive, negative, or neutral. Our findings were compared visually, not mathematically, with those found in the previous national study «Analysis of the culture on patient safety in the hospital setting of the Spanish National Health System¼ published in 2009. A subgroup analysis was performed according to professional group and seniority as a health worker. The Student's t, χ2 and ANOVA tests were used. RESULTS: Sixty-two professionals responded to the questionnaire, 73.90% of the total. The median time working in ICU 2 years (interquartile range 2-4.5 years). The rating for the degree of safety was 8.06 (SD 1.16). The majority (91.20%) had not reported any adverse event in the last year. A total of 30.90% had recently received patient safety training. The dimensions considered as weaknesses were 9 ("Staffing", with 27.57% of positive responses) and 10 ("Support of the hospital management in safety", with 17.64% of positive responses). The dimensions considered as strengths were 3 ("Expectation of actions by management/supervision of the service") with 85.29% of positive responses, and 5 ("Teamwork") with 95.58% of positive responses. The Cronbach's alpha index values suggest that the questionnaire has adequate internal consistency. In general, our data are more positive than those collected in the 2011 national survey, although the 2 dimensions considered weaknesses were already considered such in the previous work. CONCLUSIONS: The perception of patient safety in the ICU of our hospital after the end of the third wave of the COVID pandemic is adequate, with a more positive rating than that of the national study on safety culture at the hospital level carried out in 2009. The constant quest for patient safety should prioritize activity in the 2 dimensions considered weaknesses: staffing, and support from hospital management in everything related to patient safety.