Purpose: Cervical cancer (CC) is the second most frequent cancer in undeveloped countries. Serum biomarkers could be useful for evaluation of the treatment response and as a complementary means to ...improve diagnosis. The expression of galectin-9 is altered in cancer tissue, and higher concentrations are found in the serum of cancer patients. The objectives of this study were (a) to determine the serum galectin-9 concentration in patients with intraepithelial lesions and CC, (b) to determine if the concentration was related to the clinicopathological characteristics and (c) to determine if the galectin-9 concentration was related to its expression level in tumour tissue. Patients and Methods: In all, 222 serum samples from women with different diagnoses, including premalignant lesions and CC, as well as samples from women with normal cytology were included in the study. The serum galectin-9 concentration was determined by ELISA. To evaluate the expression level of galectin-9 in CC tissue, immunohistochemistry was performed in 34 CC biopsy specimens. Results: The galectin-9 concentration in the serum of CC patients (8.171 ng/mL) was increased compared with serum from women with normal epithelia (4.654 ng/mL) and those with low-grade (4.806 ng/mL) and high-grade (5.354 ng/mL) intraepithelial lesions (p value < 0.0001). The area under the ROC curve considering the CC group and the control group was 0.882. The optimal cut- off value was greater than or equal to6.88 ng/mL, the specificity obtained was 100%, and the sensitivity was 68.2%. In the CC group, the analysis of the clinical stage showed an increase of galectin-9 in the advanced stage IV group. Serum galectin-9 was not related to the level of galectin-9 expression in tissue, which suggests that galectin-9 is not secreted by tumour cells. Conclusion: The serum galectin-9 concentration is related to cancer progression, as the level of this protein is higher in patients with advanced-stage disease. Keywords: galectin-9, serum biomarker, prognostic markers, cervical cancer, premalignant lesions
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive tubular disorder characterized by excessive renal magnesium and calcium excretion and chronic kidney ...failure. This rare disease is caused by mutations in the CLDN16 and CLDN19 genes. These genes encode the tight junction proteins claudin-16 and claudin-19, respectively, which regulate the paracellular ion reabsorption in the kidney. Patients with mutations in the CLDN19 gene also present severe visual impairment. Our goals in this study were to examine the clinical characteristics of a large cohort of Spanish patients with this disorder and to identify the disease causing mutations. We included a total of 31 patients belonging to 27 unrelated families and studied renal and ocular manifestations. We then analyzed by direct DNA sequencing the coding regions of CLDN16 and CLDN19 genes in these patients. Bioinformatic tools were used to predict the consequences of mutations. Clinical evaluation showed ocular defects in 87% of patients, including mainly myopia, nystagmus and macular colobomata. Twenty two percent of patients underwent renal transplantation and impaired renal function was observed in another 61% of patients. Results of the genetic analysis revealed CLDN19 mutations in all patients confirming the clinical diagnosis. The majority of patients exhibited the previously described p.G20D mutation. Haplotype analysis using three microsatellite markers showed a founder effect for this recurrent mutation in our cohort. We also identified four new pathogenic mutations in CLDN19, p.G122R, p.I41T, p.G75C and p.G75S. A strategy based on microsequencing was designed to facilitate the genetic diagnosis of this disease. Our data indicate that patients with CLDN19 mutations have a high risk of progression to chronic renal disease.
Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation.
To identify polymorphisms associated with secukinumab response in psoriasis ...patients in a daily practice setting.
We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed.
A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes.
We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.
Due to their antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic effects, polyphenols are first-rate candidates to prevent or treat chronic diseases in which oxidative stress-induced ...inflammation plays a role in disease pathogenesis. Dry eye disease (DED) is a common pathology, on which novel phenolic compound formulations have been tested as an adjuvant therapeutic approach. However, polyphenols are characterized by limited stability and solubility, insolubility in water, very rapid metabolism, and a very short half-life. Thus, they show poor bioavailability. To overcome these limitations and improve their stability and bioavailability, we evaluated the safety and efficacy of an oral formulation containing among other compounds, polyphenols and omega-3 fatty acids, with the addition of a surfactant in patients with DED. Subjects were randomly assigned to one of four study groups including the study formulation (A), placebo (P), the study formulation + eye lubricant (A + L), and placebo + eye lubricant (P + L). Patients from the A and P groups were instructed to take two capsules every 24 h, while patients in the L groups also added one drop of lubricant twice a day for 12 weeks as well. Regarding safety, non-ocular abnormalities were observed during study formulation therapy. Liver function tests did not show any statistically significant difference (baseline vs. week 4). Concerning efficacy, there was a statistically significant difference between baseline, month 1, and month 3 in the OSDI (Ocular Surface Disease Index) test results in both treatment groups (group A and group A + L). Furthermore, both groups showed statistically significant differences between baseline and month 3 regarding the non-invasive film tear breakup time (NIF-BUT) score and a positive trend related to Shirmer’s test at month 3. The non-invasive average breakup time (NIAvg-BUT) score showed a statistically significant difference at month 3 when compared with baseline in the A + L group. The P + L group showed a statistically significant difference in terms of the OSDI questionary between baseline and month 3. Regarding the lissamine green staining, the A + L group showed a statistical difference between baseline and month 3 (p = 0.0367). The placebo + lubricant group did not show statistically significant differences. Finally, the placebo group did not show any data with statistically significant differences. Consequently, this polyphenol formulation as a primary treatment outperformed the placebo alone, and the polyphenol oral formulation used as an adjuvant to artificial tears was superior to the combination of the placebo and the artificial tears. Thus, our data strongly suggest that this polyphenol oral formulation improves visual strain symptoms and tear film status in patients with mild to moderate DED.
The development of biomaterial scaffolds and implementation of tissue engineering techniques are necessary. Therefore, Polycaprolactone/Sodium Hyaluronate/Multiwalled Carbon Nanotubes/Extract of ...Mimosa tenuiflora composites have been produced by a thermally-induced phase separation method.
The objective of this research was to evaluate the in vitro bioactivity and in vitro biocompatibility of the composites.
The in vitro bioactivity of the composites was assessed by soaking them in simulated body fluid for 7, 14, 21, and 28 days. The structure and composition of the composites were analyzed using scanning electron microscopy coupled with energy dispersive spectroscopy and Fourier transform infrared spectroscopy. Also, the in vitro biocompatibility of the composites was evaluated by means of alkaline phosphatase activity of the osteoblasts and by measuring the metabolic activity of the cells using MTT assay.
The results show a porous and interconnected morphology with enhanced bioactivity. It was observed that the incorporation of Mimosa tenuiflora in the composites promotes increased viability of osteoblasts in the scaffolds.
The results show the efficiency of bioactive and biocompatible composites and their potential as candidates for tissue engineering applications.
Acquisition of Basic Surgical Skills (BSS) are essential for medical students. The objective was to determine it's fidelity impact.
Using four suturing models (SM) (pigskin, sponge, commercial pad, ...and orange), SM-quality and student-SM interaction were evaluated. After a 1-h class, participants were divided into groups and randomly assigned exercises in SM in 15-min intervals. The experiment included completing three individual simple stitches and a 3-stitch continuous suture in each SM.
Eighty-two medical students participated. Suturing quality was better in pigskin and sponge, which were also the preferred models (p < 0.001). Significant differences in quality between the insertion and exit point, and firmness of knots (p < 0.05) in both simple and continuous sutures, as well as between length and distance in continuous ones (p < 0.001) were identified.
Acquisition and quality of BSS are influenced by the intrinsic characteristics of SM. An adequate degree of resistance, consistency, and elasticity are necessary.
To compare the clinical effectiveness of the triple intra-articular injection of platelet-rich plasma (PRP) with respect to the single injection in patients with mild osteoarthritis of the knee.
A ...total of 35 patients with a clinical and radiographic diagnosis of osteoarthritis grade I and II were analyzed. They were randomized into two groups: single application (18 patients) and triple application (17 patients). Both groups were evaluated using the Visual Analogue Scale (VAS), the Western Ontario and McMaster Universities (WOMAC) index, and the Health Survey 12v2 (SF-12) at baseline and at 6, 12, 24, 36 and 48 weeks post-treatment.
Both treatments significantly decreased the level of pain (VAS) (single, from 7.3±2.1 to 4.6±2.7 and triple, from 6.6±2.4 to 0.9±1.4; p lt 0.05) and the total WOMAC (single, from 44.2±19.7 to 26.7±24.9 and triple, from 41.4±15.5 to 7.2±7.3; p lt 0.05) at the end of the study. The triple application showed better improvement in the VAS (p= 0.0007) and the total WOMAC (p= 0.0209) scores when comparing the final results between groups.
The triple infiltration of PRP in patients with mild knee osteoarthritis is clinically more effective than the single application at 48 weeks of follow-up.
Para evaluar la influencia de la harina de coco desgrasada (HCD) en el comportamiento productivo y el rendimiento a la canal para conejos en crecimiento, fueron elaboradas cinco dietas con niveles ...crecientes de esta (0, 10, 20, 30 y 40 %), las cuales fueron suministradas a 130 animales de la raza chinchilla, con un diseño completamente aleatorizado. Fueron determinados los pesos vivo inicial y final, ganancia media diaria, consumo de alimento, conversión alimenticia, rendimiento a la canal y sus cortes valiosos. El período experimental fue de 78 días. El peso vivo final de los animales durante el ciclo de ceba estuvo entre 2060 y 2242 g/animal, en todos los casos por encima de los 2000 g, que es el establecido para el sacrificio de los animales. La ganancia media de peso osciló entre 25.4 y 28.4. La inclusión de la harina de coco desgrasada en la dieta hasta un 40 % no afectó el rendimiento a la canal, sus valores promedios oscilaron entre 49.72 y 53.5%. Los resultados indican que los conejos realizaron una adecuada absorción de los nutrientes al utilizar harina de coco desgrasada para su crecimiento, además se mejora el rendimiento económico del sistema de producción.
We aimed to elucidate the influence on analgesic effect of genetic polymorphisms in enzymes responsible for biotransformation of tramadol and ibuprofen or other possible genes involved in their ...mechanism of action.
The study population comprised 118 patients from a multicenter, randomized, double-blind, placebo-controlled, Phase III clinical trial that assessed the analgesic efficacy and tolerability of a single dose of ibuprofen (arginine)/tramadol 400/37.5 mg compared with ibuprofen arginine 400 mg alone, tramadol 50 mg alone, and placebo in patients with moderate to severe pain after dental surgery. We analyzed 32 polymorphisms in the cytochrome P450 (CYP) enzymes COMT, ABCB1, SLC22A1, OPRM1, and SLC22A1.
We did not find any statistically significant difference among CYP2C9 phenotypes related to ibuprofen response, although CYP2C9 poor metabolizers had a longer effect (higher pain relief at 6 hours). Likewise, we did not find any statistically significant difference among PTGS2 genotypes, contradicting previously publications.
There was not a clear effect of CYP2D6 phenotype on tramadol response, although CYP2D6 poor metabolizers had a slower analgesic effect. Concerning the transport of CYP2D6, we observed a better response in individuals carrying ABCB1 mutated alleles, which might correlate with higher tramadol plasma levels. Finally, we found a statistically significant better response in patients carrying the OPRM1 A118G G allele, which contradicts the previous reports. Measuring the active metabolite O-desmethyl-tramadol formation would be of great importance to better evaluate this association because O-desmethyl-tramadol has a higher μ-opioid receptor affinity compared with the parent drug. EudraCT.ema.europa.eu identifier: 2013-004637-33.
The skin is a fundamental organ in the transition from intrauterine to extrauterine life. The newborn infant experiences physiological changes and often presents benign, transient skin ...characteristics that vary according to maternal, gestational, and neonatal factors.
To estimate the frequency of various dermatologic findings during the first 72 hours of life and to identify their association with maternal, gestational, or neonatal factors.
Descriptive, observational, cross-sectional study from April to July 2015 and July to November 2017 in the maternity ward of Centro Hospitalario Pereira Rossell. We examined the skin of neonates within 72 hours of birth. Proportions and 95% CIs were calculated for all findings. Associations between findings and factors were analyzed.
A total of 2811 neonates were included. We observed at least 1 neonatal skin finding in all of the neonates and found a median (interquartile range) of 8 (6–9) findings (minimum–maximum, 1–16). We observed 42 of the 46 possible characteristics we looked for; 99.9% of the findings were benign and transient. Among the findings were lanugo (98%; 95% CI, 97.7%–98.7%), physiological scaling (79.7%; 95% CI, 78.2%–81.1%), and sebaceous hyperplasia (73.3%; 95% CI, 71.6%–74.9%). Lanugo (P = .001), physiological scaling (P < .001), and erythema toxicum (P = .001) were observed significantly more often in full- and late-term neonates. Sebaceous hyperplasia (P = .001) and transient hyperpigmentation (P < .001) were found more often in newborn males. Erythema toxicum was more common after vaginal births (P = .008). Transient hyperpigmentation (P < .001) and dermal melanocytosis (P < .001) were seen more often in neonates of African descent.
All neonates have skin characteristics that are part of their adaptation to extrauterine life. Most are benign and transient. Maternal age, type of delivery, and certain neonatal factors such as gestational age, birth weight, sex, and ethnicity are associated with specific findings.
La piel es fundamental en la transición de la vida intrauterina a la extrauterina. El recién nacido presenta cambios fisiológicos, siendo frecuente observar hallazgos cutáneos benignos y transitorios que varían según las características maternas, neonatales y de la gestación.
Estimar la frecuencia de diferentes hallazgos dermatológicos en neonatos en las primeras 72 horas de vida e identificar la existencia de diferencias de proporciones estadísticamente significativas con factores neonatales, maternos y de la gestación.
Se realizó un estudio descriptivo, observacional de corte transversal entre abril a julio 2015 y de julio a noviembre de 2017 en la maternidad del Centro Hospitalario Pereira Rossell. Se incluyeron neonatos de hasta 72 horas de vida, a los que se les practicó un examen dermatológico completo. Se presenta la proporción de cada uno de los hallazgos con el intervalo de confianza correspondiente. Se analiza la relación entre los hallazgos y determinados factores asociados.
Se incluyeron 2811 neonatos. El 100% presentó al menos 1 hallazgo a nivel de la piel. La mediana fue de 8 lesiones por paciente (IIQ. 6 -9/Mn-Mx: 1-16). De los 46 hallazgos explorados clínicamente se encontraron 42. Las lesiones benignas y transitorias correspondieron a 99,9%. Entre ellas se observó: lanugo 98% (IC 97,7-98,7), descamación fisiológica 79,7% (IC 78,2-81,1) e hiperplasia sebácea 73,3% (IC 71,6-74,9). El lanugo (p = 0,001), la descamación fisiológica (p < 0,001), el eritema tóxico neonatal (p 0,001) se observaron con más frecuencia en los neonatos de término y postérmino. La hiperplasia sebácea (p = 0,001) y la hiperpigmentación transitoria neonatal (p < 0,001) se encontraron con mayor frecuencia en varones. El eritema tóxico neonatal aumentó en los nacimientos por parto vaginal (p 0,008). La hiperpigmentación neonatal transitoria (p < 0,001) y la melanocitosis dérmica (p < 0,001) se observaron en mayor proporción en afrodescendientes.
El 100% de los neonatos presenta cambios a nivel de la piel, la mayoría benignos y transitorios como parte de la adaptación a la vida extrauterina. La edad materna, la vía de nacimiento, las características del neonato como la edad gestacional, el peso al nacer, el sexo, así como la etnia se asocian con la aparición de hallazgos específicos.
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