Study protocol for a randomized controlled trial of the NEIVATECH virtual reality system to improve visual function in children with anisometropic amblyopia.

BACKGROUND: Interest in developing alternative methods for the treatment of amblyopia has long been a topic of interest among clinicians and researchers, as prescribed occlusion and penalization therapies do not always provide an effective response and are associated with a high risk of recurrence and non-compliance. Here, we present the protocol of a small-scale RCT to evaluate the safety and clinical efficacy of a novel VR-based system designed to provide binocular vision training to children with anisometropic amblyopia. METHODS: We aim to recruit a total of 60 children with anisometropic amblyopia aged 5-17 years with no previous treatment for amblyopia other than refractive correction from the pediatric ophthalmology units of the University Clinical Hospital of Valladolid and the Vithas Medimar International Hospital of Alicante. Children who meet the eligibility criteria and consent to participate will be randomly assigned to a three-month intervention group of 18 half-hour in-office therapy sessions with the NEIVATECH system (group A) or to a parallel group receiving 2 hours of conventional patching per day at home for the same period of time (group B). Assessments of visual function will be carried out before the intervention and at 1, 2 and 3 months, with changes in distance BCVA being the primary outcome measure to be considered. Patient safety, compliance, satisfaction and acceptance to treatment will also be assessed after therapy as other valuable outcome measures. In addition, a rsfMRI scan will be performed on a subgroup of 5 patients from each group at the pre-intervention visit and at the post-intervention visit to test the effects of both therapies on neural plasticity in the visual cortex. DISCUSSION: The NEIVATECH system has been conceived as a serious game designed to provide binocular vision training to anisometropic amblyopic children by complementing the concepts of perceptual learning, dichoptic training and gamification in an immersive VR environment. We hope that this novel approach may lead to greater improvements in vision performance than those provided so far by conventional patching in anisometropic amblyopic children. TRIAL REGISTRATION: This protocol was registered with ClinicalTrials.gov ( NCT04819386 ) on 29 March 2021.

Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density.

BACKGROUND AND AIMS: Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors. METHODS AND RESULTS: In a cross-sectional study, atherosclerosis burden was compared between 112 female SLE patients and 31 controls. Plaque number and carotid intima-media wall thickness (cIMT) were assessed by ultrasonography. In a retrospective study, BMD determinations obtained 5-years before the ultrasonography assessment were analyzed in a subgroup of 62 patients. Plaque frequency was increased in SLE, even in patients without CV events or carotid wall thickening. cIMT was increased in patients with CVD, positively correlated with body mass index (BMI). Interestingly, a paradoxical effect of BMI on carotid parameters was observed. Whereas underweight patients (BMI < 20) showed increased prevalence of carotid plaques with low cIMT, those with BMI > 30 showed higher cIMT and plaque burden. Overweight patients (25 < BMI<30) exhibited both elevated cIMT and plaque number. BMI was an independent predictor of BMD. In our retrospective study, patients with either clinical or subclinical CVD exhibited lower BMD levels than their CV-free counterparts. A low lumbar spine BMD independently predicted CVD development after adjusting for confounders. CONCLUSION: SLE was associated with a higher subclinical atherosclerosis burden, a bimodal effect being observed for BMI. Decreased BMD can be a CV risk biomarker in SLE.

Relationship between serum levels of VIP, but not of CGRP, and cranial autonomic parasympathetic symptoms: A study in chronic migraine patients.

Background Cranial autonomic parasympathetic symptoms (CAPS) appear in at least half of migraine patients theoretically as a result of the release of peptides by the trigemino-vascular system (TVS). Cranial pain pathways become sensitised by repeated episodes of TVS activation, leading to migraine chronification. Objective The objective of this article is to correlate the presence of CAPS with serum levels of vasoactive intestinal peptides (VIP) and calcitonin gene-related peptide (CGRP). Patients and methods Patients with chronic migraine (CM) were asked about the presence - during migraine attacks - of five CAPS, which were scored from 0 to 10 by using a quantitative scale. Serum VIP and CGRP levels were determined by ELISA. Results We interviewed 87 CM patients (82 females; mean age 44.7 ± 10.6 years). Seventeen had no CAPS, while 70 reported at least one CAPS. VIP levels ranged from 20.8 to 668.2 pg/ml (mean 154.5 ± 123.2). There was a significant positive correlation between scores in the CAPS scale and VIP levels (Spearman correlation coefficient = 0.227; p = 0.035). VIP levels were significantly higher in CM patients by at least one point in the scale vs those with 0 points ( p = 0.002). Analysing symptoms individually, VIP levels were numerically higher in those patients with symptoms, though they were significantly higher only in those patients with lacrimation vs those without it ( p = 0.013). There was no significant correlation between CGRP levels and the score in the CAPS scale. Conclusions Serum VIP, but not CGRP, levels seem to reflect the rate of activation of the parasympathetic arm of the TVS in migraine.

Effect of bovine ABCG2 Y581S polymorphism on concentrations in milk of enrofloxacin and its active metabolite ciprofloxacin.

The ATP-binding cassette transporter G2 (ABCG2) is involved in the secretion of several drugs into milk. The bovine Y581S ABCG2 polymorphism increases the secretion into milk of the fluoroquinolone danofloxacin in Holstein cows. Danofloxacin and enrofloxacin are the fluoroquinolones most widely used in veterinary medicine. Both enrofloxacin (ENRO) and its active metabolite ciprofloxacin (CIPRO) reach milk at relatively high concentrations. The aim of this work was to study the effect of the bovine Y581S ABCG2 polymorphism on in vitro transport as well as on concentrations in plasma and in milk of ENRO and CIPRO. Experiments using cells overexpressing bovine ABCG2 showed the effects of ABCG2 on the transport of CIPRO, demonstrating more efficient in vitro transport of this antimicrobial by the S581 variant as compared with the Y581 variant. Animal studies administering 2.5mg/kg of ENRO subcutaneously to Y/Y 581 and Y/S 581 cows revealed that concentrations in plasma of ENRO and CIPRO were significantly lower in Y/S animals. Regardless of the genotype, the antimicrobial profile in milk after the administration of ENRO was predominantly of CIPRO. With respect to the genotype effects on the amounts of drugs present in milk, AUC0-24 values were more than 1.2 times higher in Y/S cows for ENRO and 2.2 times for CIPRO, indicating a greater capacity of Y581S to transfer these drugs into milk. These results emphasize the clinical relevance of this polymorphism as a factor affecting the concentrations in plasma and in milk of drugs of importance in veterinary medicine.

Short communication: The gain-of-function Y581S polymorphism of the ABCG2 transporter increases secretion into milk of danofloxacin at the therapeutic dose for mastitis treatment.

The ATP-binding cassette transporter ABCG2 restricts the exposure of certain drugs and natural compounds in different tissues and organs. Its expression in the mammary gland is induced during lactation and is responsible for the active secretion of many compounds into milk, including antimicrobial agents. This particular function of ABCG2 may affect drug efficacy against mastitis and the potential presence of drug residues in the milk. Previous in vitro and in vivo studies showed increased transport of several compounds, including fluoroquinolones, by the bovine ABCG2 Y581S polymorphism. Our main purpose was to study the potential effect of this bovine ABCG2 polymorphism on the secretion into milk of the antimicrobial danofloxacin administered at the therapeutic dose of 6mg/kg used for mastitis treatment. In addition, the effect of this polymorphism on the relative mRNA and protein levels of ABCG2 by quantitative real-time PCR and Western blot were studied. Danofloxacin 18% (6mg/kg) was administered to 6 Y/Y homozygous and 5 Y/S heterozygous cows. Danofloxacin levels in milk and milk-to-plasma concentration ratios were almost 1.5- and 2-fold higher, respectively, in Y/S cows compared with the Y/Y cows, showing a higher capacity of this variant to transport danofloxacin into milk. Furthermore, the higher activity of this polymorphism is not linked to higher ABCG2 mRNA or protein levels. These results demonstrate the relevant effect of the Y581S polymorphism of the bovine ABCG2 transporter in the secretion into milk of danofloxacin after administration of 6mg/kg, with potentially important consequences for mastitis treatment and for milk residue handling.

[Survival of out-hospital cardiac arrests attended by a mobile intensive care unit in Asturias (Spain) in 2010]. / Supervivencia de las paradas cardiacas extrahospitalarias atendidas por una unidad de vigilancia intensiva móvil de Asturias en 2010.

OBJECTIVE: To evaluate attendance timings, out- and in-hospital characteristics, and survival of cardiac arrests attended by an advanced life support unit in Asturias (Spain) in 2010. Factors related to survival upon admission and at discharge were also analyzed. DESIGN: A retrospective, observational trial was carried out involving a cohort of out-hospital cardiac arrests (OHCA) occurring between 1 January 2010 and 31 December 2010, with one year of follow-up from OHCA. SETTING: Health Care Area IV of the Principality of Asturias, with a population of 342,020 in 2010. PATIENTS: All patients with OHCA and attended by an advanced life support unit were considered. MAIN VARIABLES: Demographic data, the etiology of cardiac arrest, bystander cardiopulmonary resuscitation (CPR), attendance timings and survival upon admission, at discharge and after one year. RESULTS: A total of 177 OHCA were included. Of these, 120 underwent CPR by the advanced life support team. Sixty-six of these cases (55%) were caused by presumed heart disease. A total of 63 patients (52.5%) recovered spontaneous circulation, and 51 (42.5%) maintained circulation upon admission to hospital. Thirteen patients (10.8%) were discharged alive. After one year, 11 patients were still alive (9.2%) - 9 of them (7.5%) with a Cerebral Performance Category (CPC) score of 1. Ventricular fibrillation and short attendance timings were related to increased survival. CONCLUSIONS: The survival rate upon admission was better than in other series and similar at discharge. Initial rhythm and attendance timings were related. Public automated external defibrillators (AED) were not used, and bystander CPR was infrequent.

Involvement of breast cancer resistance protein (BCRP/ABCG2) in the secretion of danofloxacin into milk: interaction with ivermectin.

Danofloxacin, a veterinary fluoroquinolone antimicrobial drug, is actively secreted into milk by an as yet unknown mechanism. One of the main determinants of active drug secretion into milk is the transporter (BCRP/ABCG2). The main purpose was to determine whether danofloxacin is an in vitro substrate for Bcrp1/BCRP and to assess its involvement in danofloxacin secretion into milk. In addition, the role of potential drug-drug interactions in this process was assessed using ivermectin. Danofloxacin was transported in vitro by Bcrp1/BCRP, and ivermectin efficiently blocked this transport. Experiments with Bcrp1(-/-) mice showed no evidence of the involvement of Bcrp1 in plasma pharmacokinetics of danofloxacin. However, the milk concentration and milk-to-plasma ratio of danofloxacin were almost twofold higher in wild-type compared with Bcrp1(-/-) mice. The in vivo interaction with ivermectin was studied in sheep after co-administration of danofloxacin (1.25 mg/kg, i.m.) and ivermectin (0.2 mg/kg, s.c.). Ivermectin had no significant effect on the plasma levels of danofloxacin but significantly decreased danofloxacin concentrations in milk by almost 40%. Concomitant administration of multiple drugs, often used in veterinary therapy, may not only affect their pharmacological activity but also their secretion into milk, because of potential drug-drug interactions mediated by BCRP.

Bilateral ankyloblepharon: more than a simple malformation. / Anquilobléfaron bilateral: Algo más que una simple malformación.

"Ankyloblepharon filiforme adnatum" is a congenital anomaly characterized by partial or complete adhesion of upper and lower eyelids. The lid margins remain fused until the end of the fifth month of gestational age. Complete separation usually is completed about the seventh fetal month. Ankyloblepharon may be an isolated manifestation or may be associated with abnormalities in other organs and / or systems. The case is presented on a newborn male with family history of hypohydrotic ectodermal dysplasia (mother and maternal grandfather). It revealed extensible bands of skin in right and in left eye. Apart from this, he presented cleft lip, complete absence of palate, nail and ungueal dysplasia and supernumerary nipples.

Milk secretion of nitrofurantoin, as a specific BCRP/ABCG2 substrate, in assaf sheep: modulation by isoflavones.

Studies on residues in milk used for human consumption have increased due to health concerns and priority interest in the control of potentially risky drugs. The protein BCRP/ABCG2, present in the mammary epithelia, actively extrudes drugs into milk and can be modulated by isoflavones. Nitrofurantoin is a specific BCRP substrate which is actively excreted into milk by this transporter. In this research, we studied nitrofurantoin transport into milk in four experimental groups: G1-calves fed forage with isoflavones; G2-calves fed forage with isoflavones and administered exogenous genistein and daidzein; G3-calves fed forage without isoflavones; G4-calves fed forage without isoflavones and administered exogenous genistein and daidzein. Results show increased levels of nitrofurantoin in milk from calves without isoflavones (G3) and decreased nitrofurantoin residues in milk when isoflavones were present, either by forage (G1 and G2) or by exogenous administration (G4). The values of C(max) in milk were significantly lower in those groups with isoflavones in forage (G1, G2). Plasma levels were low and unmodified among the groups. Inter-individual variation was high. All these results seem to point to a feasible control of drug secretion into milk through isoflavones in the diet when the drug is a good BCRP/ABCG2 substrate.

[Appraisal of cerebral atrophy in multiple sclerosis by means of the corpus callosum index]. / Valoracion de la atrofia cerebral en la esclerosis multiple mediante el indice de cuerpo calloso.

INTRODUCTION: The course of multiple sclerosis is characterised by the development of cerebral atrophy. It is of interest to monitor it in order to evaluate the treatment response, and the preferred technique consists in performing brain volume analyses, which are currently restricted to the field of research. AIM: To analyse the corpus callosum index (CCI) as a possible alternative to the methods based on brain segmentation. SUBJECTS AND METHODS: Our sample was made up of 109 patients with recently diagnosed demyelinating diseases (90 relapsing-remitting multiple sclerosis, 7 primary progressive forms and 12 isolated demyelinating syndromes), and the CCI was calculated in their first magnetic resonance brain scan, together with 101 healthy controls. The sequences of the patients were submitted to a volumetric analysis using the software package MSmetrix. RESULTS: The mean value of the CCI was 0.377 in patients and 0.411 in the controls, and the difference was statistically significant (p < 0.001). The CCI also showed a statistically significant correlation with the brain volume (p < 0.001; r = 0.444) and with the lesional volume in the FLAIR sequence (p < 0.001; r = -0.521), while no association was observed with the volume of grey matter (p = 0.058). CONCLUSIONS: The CCI is related to the overall brain volume obtained by volumetric techniques and may reflect the presence of atrophy in the initial stages of demyelinating diseases, which makes it a fast and easy to calculate alternative.

TITLE: Valoracion de la atrofia cerebral en la esclerosis multiple mediante el indice de cuerpo calloso.Introduccion. La esclerosis multiple se caracteriza en su evolucion por el desarrollo de atrofia cerebral. Su monitorizacion resulta de interes para evaluar la respuesta al tratamiento, y son de eleccion los analisis volumetricos cerebrales, actualmente confinados al ambito de la investigacion. Objetivo. Analizar el indice de cuerpo calloso (ICC) como una posible alternativa a los metodos basados en la segmentacion cerebral. Sujetos y metodos. Se reune a 109 pacientes con enfermedades desmielinizantes de reciente diagnostico (90 con esclerosis multiple remitente recurrente, 7 con formas primarias progresivas y 12 con sindrome desmielinizante aislado) y se calcula el ICC en su primer estudio de resonancia magnetica cerebral, asi como en 101 controles sanos. Las secuencias de los pacientes se someten a analisis volumetrico mediante el programa MSmetrix. Resultados. El valor medio del ICC es de 0,377 en los pacientes y 0,411 en los controles, y la diferencia es estadisticamente significativa (p < 0,001). El ICC muestra una correlacion estadisticamente significativa con el volumen encefalico (p < 0,001; r = 0,444) y con el volumen lesional en secuencia FLAIR (p < 0,001; r = ­0,521), mientras que no se demuestra asociacion con el volumen de la sustancia gris (p = 0,058). Conclusiones. El ICC se relaciona con el volumen encefalico global obtenido mediante tecnicas volumetricas y puede reflejar la presencia de atrofia ya en los estadios iniciales de las enfermedades desmielinizantes, por lo que se presenta como una alternativa de rapido y sencillo calculo.

Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid.

The ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP) is an efflux protein involved in the bioavailability and milk secretion of endogenous and exogenous compounds, actively affecting milk composition. A limited number of physiological substrates have been identified. However, no studies have reported the specific effect of this polymorphism on the secretion into milk of compounds implicated in milk quality such as vitamins or endogenous compounds. The bovine ABCG2 Y581S polymorphism is described as a gain-of-function polymorphism that increases milk secretion and decreases plasma levels of its substrates. This work aims to study the impact of Y581S polymorphism on plasma disposition and milk secretion of compounds such as riboflavin (vitamin B2), enterolactone, a microbiota-derived metabolite from the dietary lignan secoisolariciresinol and uric acid. In vitro transport of these compounds was assessed in MDCK-II cells overexpressing the bovine ABCG2 (WT-bABCG2) and its Y581S variant (Y581S-bABCG2). Plasma and milk levels were obtained from Y/Y homozygous and Y/S heterozygous cows. The results show that riboflavin was more efficiently transported in vitro by the Y581S variant, although no differences were noted in vivo. Both uric acid and enterolactone were substrates in vitro of the bovine ABCG2 variants and were actively secreted into milk with a two-fold increase in the milk/plasma ratio for Y/S with respect to Y/Y cows. The in vitro ABCG2-mediated transport of the drug mitoxantrone, as a model substrate, was inhibited by enterolactone in both variants, suggesting the possible in vivo use of this enterolignan to reduce ABCG2-mediated milk drug transfer in cows. The Y581S variant was inhibited to a lesser extent probably due to its higher transport capacity. All these findings point to a significant role of the ABCG2 Y581S polymorphism in the milk disposition of enterolactone and the endogenous molecules riboflavin and uric acid, which could affect both milk quality and functionality.

Comparative study of hyaluronic derivatives: rheological behaviour, mechanical and chemical degradation.

Depolymerisation by oxytetracycline (OTC) as well as the progressive cleavage of hyaluronic acid induced by ultrasound was investigated in nine commercially available hyaluronic polymers. Sample solutions differed in molecular weight, from 500 to 7000 kDa, and in their source. The hyaluronic acid concentration in each sample was analysed by HPLC. The concentration range was over 8.39-10.18 mg ml(-1) in samples with a nominal concentration of 1%, and 14.05 mg ml(-1) in one sample with a nominal concentration of 1.5%. It was found that stability was dependent on both molecular weight and the concentration of the samples. The rheological parameters n (power law index) and K (consistency coefficient) were good predictors regarding the degradation behaviour. Although many factors are involved in obtaining a therapeutic response, the results obtained in this work support the notion that both mechanical and chemical degradation are reduced in hyaluronate solutions with low molecular weight, the final concentration of the product being a critical factor.

Protection of Panax ginseng in injured muscles after eccentric exercise.

Panax ginseng C.A. Meyer, the root of an Araliaceae plant has been shown to possess various biological effects. Ginseng treatment (100 mg kg(-1)) protected muscles from eccentric exercise injuries. It was effective in preserving mitochondrial membrane integrity and reduced nitrate concentration in vastus and rectus (46% and 26%, respectively). It also reduced carbonyl contents by approximately 27% in all the muscles studied.

Effect of chronic ethanol ingestion and exercise training on skeletal muscle in rat.

The aim of this study was to investigate the interactive effects of exercise training and chronic ethanol consumption on metabolism, capillarity, and myofibrillar composition in rat limb muscles. Male Wistar rats were treated in separate groups as follows: non exercised-control; ethanol (15%) in animals' drinking water for 12 weeks; exercise training in treadmill and ethanol administration plus exercise for 12 weeks. Ethanol administration decreased capillarity and increased piruvate kinase and lactate dehydrogenase activities in white gastrocnemius; in plantaris muscle, ethanol increased citrate synthase activity and decreased cross-sectional area of type I, IIa, and IIb fibres. Exercise increased capillarity in all four limb muscles and decreased type I fibre area in plantaris. The decreased capillarity effect induced by ethanol in some muscles, was ameliorated when alcohol was combined with exercise. While alcoholic myopathy affects predominantly type IIb fibres, ethanol administration and aerobic exercise in some cases can affect type I and type IIa fibre areas. The exercise can decrease some harmful effects produced by ethanol in the muscle, including the decrease in the fibre area and capillary density.

Influence of ethanol on gastric absorption and metabolism of albendazole and mebendazole.

The effect of ethanol administration on gastric absorption in rats of two benzimidazole derivatives has been studied. The ethanol administration was carried out as both acute (5%, 10% and 15% w/v of ethanol in the perfusion solution), and chronic (15, 30 and 120 days) forms. Two benzimidazole derivatives were used: albendazole (ABZ) and mebendazole (MBZ). The administration of ethanol did not affect the kinetic mechanism of the absorption process (simple diffusion) but the absorption rate decreased in all treatments except in 5% acute ethanol, presumably due to the improved solubility of the drugs. Plasma, bile and liver levels after gastric perfusion suggest a possible interference of ethanol metabolism with drug hepatic metabolism.

Effects of ethanol on the pharmacokinetics of cephalexin and cefadroxil in the rat.

Data are presented on the effect of ethanol on the intestinal absorption and excretion in rats of two beta-lactam antibiotics, cephalexin (CFX) and cefadroxil (CFD). A recirculating perfusion technique within an antibiotic concentration range of 0.5 to 50 mM was used. Ethanol was administered either in an acute form into the intestine or in a chronic form as a 15% drinking solution for 2 months. The results are normalized in relation to the metabolic body weight, intestinal length, and osmotic conditions. Acute ethanol treatment decreases the antibiotic absorption; biliary excretion of CFD is increased, while urinary excretion of CFX is lowered. Chronic treatment shows slight negative effects on the absorption of CFX and CFD. Results are interpreted on the basis of the effect of ethanol on biological membranes. Enhanced urinary excretion after acute ethanol treatment, as well as differences between transport mechanisms, are invoked to explain these effects.