Influence of glutathione-related genetic variants on the oxidative stress profile of Mexican patients with psychotic disorders

Objective: The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. Methods: The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. Results: GSH levels were significantly reduced and, conversely, GPx activity was higher among patients than controls. GCLC_GAG-7/9 genotype (OR = 4.3, 95%CI = 1.40-14.31, p = 0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR = 6.09, 95%CI = 1.93-22.59, p = 0.003) were found to be risk factors for psychosis. The genetic variants were not related to clozapine/N-desmethylclozapine levels or metabolic ratio. Conclusions: GCLC variants were associated with the oxidative stress profile of patients with psychotic disorders, raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal.

Mejora significativa de la estabilidad a carga axial con el fijador externo pélvico pretensado: análisis biomecánico en un modelo con lesión Tile tipo C / Significant improvement in axial load stability with the pre-tensioned pelvic external fixator: A biomechanical analysis in a model with type C Tile lesion

Objetivo: Comprobar si la aplicación de fijación externa mediante barra curva conectada a clavos de Schanz supraacetabulares confiere mayor estabilidad al anillo pélvico con una lesión tipo Tile C1 cuando se realiza el montaje con la barra pretensada que con el montaje estándar (sin pretensar). Material y métodos: Pelvis sintéticas (N=5) con lesión verticalmente inestable estabilizada con ambos montajes, se sometieron a carga axial progresiva. Se midieron las fuerzas aplicadas y las variaciones en las posiciones de marcadores situados en la articulación sacroilíaca y la sínfisis se registraron con un sistema óptico. Se determinaron los desplazamientos relativos entre las superficies lesionadas, la rigidez, la resistencia y el modo de fallo de cada montaje. Resultados: Con el fijador pretensado, la rigidez del montaje en la articulación sacroilíaca resultó muy superior a la del montaje convencional (p=0,043) multiplicándola por 3,45, siendo 2,06 veces mayor en la sínfisis. La resistencia ante el fallo también fue superior, multiplicándola por 2 (p=0,043). Discusión: El aumento de estabilidad a carga axial con el fijador externo pretensado concuerda con su capacidad de producir compresión activa simultánea en los elementos posteriores y anteriores del anillo pélvico, demostrada previamente. Este resultado soporta los excelentes resultados clínicos preliminares obtenidos como tratamiento provisional. Conclusiones: El fijador externo pretensado aumenta la estabilidad axial de los elementos óseos posteriores del anillo pélvico con lesión tipo Tile C1 en modelo sintético, sin disminuir la capacidad de estabilización anterior propia de la fijación externa anterior.(AU)

Objective: The aim of our work is to check if the use of a pre-tensed bar connected to 2supra-acetabular Schanz pins is more stable in a pelvic with a tile C1 injury. Material and methods: We used synthetic pelvis (N=5) with a unstable vertical injury, stabilized with both the standard and the pre-tensed system. They both were submitted to axial loading. We measured applied forces and the position of markers that were positioned in the sacroiliac and symphysis joints. We determined the relative movements between injured surfaces, rigidity, resistance and when each system failed. Results: When using the pre-tensed fixator, the rigidity was much higher in the sacro-iliac joint (P=.043) being 3.45 times higher, being also 2.06 times higher in pubic symphysis (P=.043). The resistance against failure was 2 times higher too (P=.043). Discussion: The increased axial stability with the pre-tensed external fixator accords with its ability to make active compression in both posterior and anterior elements of the pelvic ring, which was previously demonstrated. This result supports the preliminary clinic outcomes that were obtained. Conclusions: The pre-tensed external fixator increases the axial stability of the pelvic ring's posterior elements in a synthethic pelvis with a Tile C1 injury, without decreasing it's capacity to achieve an anterior stability.(AU)

[Translated article] Significant improvement in axial load stability with the pre-tensioned pelvic external fixator: A biomechanical analysis in a model with type C Tile lesion / Mejora significativa de la estabilidad a carga axial con el fijador externo pélvico pretensado: análisis biomecánico en un modelo con lesión Tile tipo C

Objetivo: Comprobar si la aplicación de fijación externa mediante barra curva conectada a clavos de Schanz supraacetabulares confiere mayor estabilidad al anillo pélvico con una lesión tipo Tile C1 cuando se realiza el montaje con la barra pretensada que con el montaje estándar (sin pretensar). Material y métodos: Pelvis sintéticas (N=5) con lesión verticalmente inestable estabilizada con ambos montajes, se sometieron a carga axial progresiva. Se midieron las fuerzas aplicadas y las variaciones en las posiciones de marcadores situados en la articulación sacroilíaca y la sínfisis se registraron con un sistema óptico. Se determinaron los desplazamientos relativos entre las superficies lesionadas, la rigidez, la resistencia y el modo de fallo de cada montaje. Resultados: Con el fijador pretensado, la rigidez del montaje en la articulación sacroilíaca resultó muy superior a la del montaje convencional (p=0,043) multiplicándola por 3,45, siendo 2,06 veces mayor en la sínfisis. La resistencia ante el fallo también fue superior, multiplicándola por 2 (p=0,043). Discusión: El aumento de estabilidad a carga axial con el fijador externo pretensado concuerda con su capacidad de producir compresión activa simultánea en los elementos posteriores y anteriores del anillo pélvico, demostrada previamente. Este resultado soporta los excelentes resultados clínicos preliminares obtenidos como tratamiento provisional. Conclusiones: El fijador externo pretensado aumenta la estabilidad axial de los elementos óseos posteriores del anillo pélvico con lesión tipo Tile C1 en modelo sintético, sin disminuir la capacidad de estabilización anterior propia de la fijación externa anterior.(AU)

Objective: The aim of our work is to check if the use of a pre-tensed bar connected to 2supra-acetabular Schanz pins is more stable in a pelvic with a tile C1 injury. Material and methods: We used synthetic pelvis (N=5) with a unstable vertical injury, stabilized with both the standard and the pre-tensed system. They both were submitted to axial loading. We measured applied forces and the position of markers that were positioned in the sacroiliac and symphysis joints. We determined the relative movements between injured surfaces, rigidity, resistance and when each system failed. Results: When using the pre-tensed fixator, the rigidity was much higher in the sacro-iliac joint (P=.043) being 3.45 times higher, being also 2.06 times higher in pubic symphysis (P=.043). The resistance against failure was 2 times higher too (P=.043). Discussion: The increased axial stability with the pre-tensed external fixator accords with its ability to make active compression in both posterior and anterior elements of the pelvic ring, which was previously demonstrated. This result supports the preliminary clinic outcomes that were obtained. Conclusions: The pre-tensed external fixator increases the axial stability of the pelvic ring's posterior elements in a synthethic pelvis with a Tile C1 injury, without decreasing it's capacity to achieve an anterior stability.(AU)

Significant improvement in axial load stability with the pre-tensioned pelvic external fixator: A biomechanical analysis in a model with type C Tile lesion. / Mejora significativa de la estabilidad a carga axial con el fijador externo pélvico pretensado: análisis biomecánico en un modelo con lesión Tile tipo C.

OBJECTIVE: The aim of our work is to check if the use of a pre-tensed bar connected to 2supra-acetabular Schanz pins is more stable in a pelvic with a tile C1 injury. MATERIAL AND METHODS: We used synthetic pelvis (N=5) with a unstable vertical injury, stabilized with both the standard and the pre-tensed system. They both were submitted to axial loading. We measured applied forces and the position of markers that were positioned in the sacroiliac and symphysis joints. We determined the relative movements between injured surfaces, rigidity, resistance and when each system failed. RESULTS: When using the pre-tensed fixator, the rigidity was much higher in the sacro-iliac joint (P=.043) being 3.45 times higher, being also 2.06 times higher in pubic symphysis (P=.043). The resistance against failure was 2 times higher too (P=.043). DISCUSSION: The increased axial stability with the pre-tensed external fixator accords with its ability to make active compression in both posterior and anterior elements of the pelvic ring, which was previously demonstrated. This result supports the preliminary clinic outcomes that were obtained. CONCLUSIONS: The pre-tensed external fixator increases the axial stability of the pelvic ring's posterior elements in a synthethic pelvis with a Tile C1 injury, without decreasing it's capacity to achieve an anterior stability.

[Translated article] Significant improvement in axial load stability with the pre-tensioned pelvic external fixator: A biomechanical analysis in a model with type C Tile lesion.

OBJECTIVE: The aim of our work is to check if the use of a pre-tensed bar connected to 2 supra-acetabular Schanz pins is more stable in a pelvic with a tile C1 injury. MATERIAL AND METHODS: We used synthetic pelvis (N = 5) with a unstable vertical injury, stabilized with both the standard and the pre-tensed system. They both were submitted to axial loading. We measured applied forces and the position of markers that were positioned in the sacroiliac and symphysis joints. We determined the relative movements between injured surfaces, rigidity, resistance and when each system failed. RESULTS: When using the pre-tensed fixator, the rigidity was much higher in the sacro-iliac joint(P=.043) being 3.45 times higher, being also 2.06 times higher in pubic symphysis (P=.043). The resistance against failure was 2 times higher too (P=.043). DISCUSSION: The increased axial stability with the pre-tensed external fixator accords with its ability to make active compression in both posterior and anterior elements of the pelvic ring, which was previously demonstrated. This result supports the preliminary clinic outcomes that were obtained. CONCLUSIONS: The pre-tensed external fixator increases the axial stability of the pelvic ring's posterior elements in a synthethic pelvis with a Tile C1 injury, without decreasing it's capacity to achieve an anterior stability.

Influence of glutathione-related genetic variants on the oxidative stress profile of Mexican patients with psychotic disorders.

OBJECTIVE: The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. METHODS: The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. RESULTS: GSH levels were significantly reduced and, conversely, GPx activity was higher in PD patients compared to controls. GCLC_GAG-7/9 genotype (OR=4.3, CI95=1.40-14.31, p=0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR=6.09, CI95=1.93-22.59, p=0.003) were found as risk factors for psychosis. The genetic variants were not related to clozapine/N-desmethylclozapine levels or to metabolic ratio. CONCLUSIONS: GCLC variants were associated with the oxidative stress profile of PD patients raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal.

Leucism: the prevalent congenital malformation in the olive ridley sea turtle of northwestern Mexico.

Despite being the most abundant sea turtle in the world, the olive ridley turtle Lepidochelys olivacea is classified as Vulnerable by the IUCN. There is evidence of congenital malformations in hatchlings, and the associated causes are multifactorial, with both genetic and environmental sources. Santuario Playa Ceuta (SPC) is a sanctuary for the olive ridley, located at the northernmost region of its nesting range in the Mexican Pacific. The objective of this study was to identify and quantify the prevalence and severity of congenital malformations in olive ridley embryos/hatchlings in SPC during the 2017 nesting season. We collected 62907 eggs from 643 relocated nests that were moved to a hatchery, of which 4242 eggs with obvious development did not hatch and were analyzed for this study. Hatching success was 53.9%, with 22.5% of nests (n = 145) and 0.54% of eggs (n = 344) showing embryos or hatchlings with malformations. The nest severity index was 2.4 (range: 1-10) malformed embryos or hatchlings per nest, and the organism severity index was 1.4 (range: 1-7) malformations per malformed embryo or hatchling. Leucism was the most prevalent malformation (34.4%; 170/494 total observed), with the craniofacial region showing the greatest diversity of malformations (17/35 types). Given the geographical position of SPC, extreme environmental conditions (e.g. cold, heat, and dryness) could be one of the main causes of teratogenesis in this species. However, more studies are needed regarding the presence of contaminants, genetic factors, health assessments of nesting females, and malformation rates of nests that remain in situ versus those that are relocated.

Caprylic acid in Vitex mollis fruit and its inhibitory activity against a thiabendazole-resistant Colletotrichum gloeosporioides strain.

BACKGROUND: Colletotrichum gloeosporioides causes anthracnose in a large number of crops. Synthetic fungicides are employed to prevent this disease, even though their effectiveness and safety is questionable. Thus, effective and innocuous antifungal compounds are proposed as natural alternatives against anthracnose. The hexane fraction of Vitex mollis pulp (HF-VM) reduces anthracnose incidence in papaya fruit; however, the active compounds and antifungal mechanism of HF-VM are unknown. The aims of this study were to characterize the activity of HF-VM sub-fractions (sHF1 -sHF7 ) against a thiabendazole-resistant Colletotrichum gloeosporioides strain, identify the chemical components and investigate the mechanism of the most active sub-fraction. RESULTS: The sHF3 showed the highest inhibitory activity against Colletotrichum gloeosporioides with a minimal inhibitory concentration (MIC) of 0.5 mg mL-1 , whereas thiabendazole (TBZ) had a MIC value higher than 2 mg mL-1 . The gas chromatography-mass spectrometry (GC-MS) analysis showed that the compounds in sHF3 were methyl 4-decenoate, caprylic acid, and 24-methylencycloartanol. These compounds are rarely found in fruits and are reported for the first time on Vitex species. The purified 24-methylencycloartanol was inactive (MIC > 0.5 mg mL-1 ). In contrast, the commercial standard of caprylic acid presented an elevated activity (MIC = 0.125 mg mL-1 ), indicating that this compound is the main one responsible for the antifungal properties of sHF3 . Furthermore, the sHF3 inhibited the spore germination and induced membrane disruption in both the spore and mycelium of Colletotrichum gloeosporioides. CONCLUSION: Vitex mollis fruit is a novel source of antifungal caprylic acid that could be employed as a marker to prepare standardized extracts with antifungal properties. © 2022 Society of Chemical Industry.

Leishmaniasis cutánea resistente al antimoniato de meglumina intramuscular / Resistance to Intramuscular Meglumine Antimoniate in Cutaneous Leishmaniasis

La leishmaniasis es una enfermedad causada por pará- sitos protozoarios del género Leishmania. Se clasifica como: cutánea, mucocutánea y visceral. De las ante- riores, la Leishmaniasis cutánea (LC) es la forma más común a nivel mundial, transmitida a humanos por la picadura del mosquito hembra, el cual pertenece a la familia Phlebotominae y Lutzomyia. La cutánea gene- ralmente se manifiesta clínicamente por presentar una pápula ulcerada con exudado seroso, con fondo limpio de aspecto granular y bordes hiperémicos y engrosados. Presentamos el caso de un adolescente de 16 años de edad, procedente de Aldea Peña Blanca Norte, San Pe- dro Sula, con lesión eritemato-costrosa, tumefacta no dolorosa de 2 meses de evolución, en pabellón auri- cular derecho. El paciente fue visto en consulta exter- na de Dermatología Pediátrica del Instituto Hondure- ño de Seguridad Social Regional del Norte (I.H.S.S.), recibiendo tratamiento con antibióticos sistémicos y tópicos (trimetoprim sulfametoxazol, mupirocina un- güento), por 7 días. Previamente había recibido varios tratamientos sistémicos orales y parenterales (amoxici- lina/ ácido clavulánico, dicloxacilina, penicilina benza- tínica, y aplicación tópica de ácido fusídico) sin obtener mejoría clínica alguna; se le envió a realizar microsco- pía directa con tinción de Giemsa de frotis obtenido de la lesión en el Centro de Salud "Miguel Paz Barahona", demostrando la presencia de amastigotes. Se inició al antimoniato de meglumina según esquema estableci- do por la Organización Mundial de la Salud (OMS) a razón de 20 mg/kg/día intramuscular por 30 días. Debido a la falla de tratamiento se deci- de utilizar itraconazol durante 3 meses con buena respuesta y sin efectos adversos...(AU)

Identification based on morphological and molecular characters of Phassus huebneri (Geyer) (Lepidoptera: Hepialidae), a ghost moth feeding on blackberry in Michoacán, Mexico: its biology and parasitoids.

Larvae of an unidentified Lepidopteran hepialid were found boring stems and crown roots of blackberry (Rubus sp.) in Michoacán, Mexico. In this study, the morphological and molecular identification of larvae and adults of this insect was performed. Preliminary aspects of biology, including information on parasitoids associated to larval stage, are also recorded. A total of 109 larvae of various instars were collected and three were reared to adult. The two females and one male were identified as Phassus huebneri (Geyer) (Lepidoptera: Hepialidae) following morphological characters. This identification was corroborated by comparing the cytochrome oxidase I (COI) barcode of two field-collected larvae (IIAFL1 and IIAFL2) with sequences of Phassus spp. obtained from GenBank. A Neighbor-Joining similarity analysis yielded a phenogram with two subclades. The first subclade grouped the IIAFL1 and IIAFL2 sequences with two other Mexican sequences categorized as P. huebneri, whereas in the second subclade other species belonging to the genus Phassus from Guatemala and Costa Rica were grouped together. Larval development of nine instars took about 14 months. Larvae reached a maximum length of 10 cm. The pupal stage lasted 39-41 days. Each of the two females laid over 1,000 unfertilized eggs within a period of 48 h. Larvae were parasitized by Dinera grisescens Fallen (Diptera: Tachinidae) and another unidentified Dinera sp. This study provides additional evidences on the distribution pattern of P. huebneri in western Mexico and presents the first record of this species feeding on one of the most economically important crops in Mexico.

Palbociclib combined with endocrine therapy in heavily pretreated HR+/HER2- advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

BACKGROUND: This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017. PATIENTS AND METHODS: Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR+/HER2- mBC who had progressed on ≥4 treatments for advanced disease were eligible. RESULTS: A total of 219 patients received palbociclib in combination with aromatase inhibitors (110; 50.2%), fulvestrant (87; 39.7%), tamoxifen (8; 3.6%) or as single agent (10; 4.6%). Mean age of the patients was 58 years; 31 patients (16.1%) were premenopausal and 162 (83.9%) were postmenopausal at the beginning of treatment with palbociclib. Patients had received a median of 3 previous lines of endocrine therapy (ET) for advanced disease. Real-world tumor response (rwTR) and clinical benefit rate were 5.9% (n = 13) and 46.2% (n = 101), respectively. The median real world progression-free survival (rwPFS) was 6.0 months (95% CI 5.7-7.0) and the median overall survival was 19.0 months (95% CI 16.4-21.7). Subgroup analysis revealed a significant difference in median rwPFS in patients treated with palbociclib plus fulvestrant depending on the duration of prior treatment with fulvestrant monotherapy (>6 versus ≤6 months; HR 1.93, 95% CI 1.37-2.73, p < 0.001). The most frequently reported toxicities were neutropenia, asthenia, thrombopenia and anemia. CONCLUSIONS: Palbociclib can be an effective and safe treatment option in patients with heavily pretreated endocrine-sensitive mBC, especially in those with longer PFS to previous ET.

In ovo vaccination with herpesvirus of turkey enhances innate and cellular responses in meat-type chickens: Effect of vaccine dose and strain.

In ovo vaccination with herpesvirus of turkey (HVT) or recombinant HVT (rHVT) is commonly used in meat-type chickens. Previous studies showed that in ovo vaccination with HVT enhances innate, cellular, and humoral immune responses in egg-type chicken embryos. This study evaluated if in ovo vaccination with HVT hastens immunocompetence of commercial meat-type chickens and optimized vaccination variables (dose and strain of HVT) to accelerate immunocompetence. A conventional HVT vaccine was given at recommended dose (RD), HVT-RD = 6080 plaque forming units (PFU), double-dose (2x), half-dose (1/2), or quarter-dose (1/4). Two rHVTs were given at RD: rHVT-A = 7380 PFU, rHVT-B = 8993 PFU. Most, if not all, treatments enhanced splenic lymphoproliferation with Concanavalin A and increased the percentage of granulocytes at day of age. Dose had an effect and HVT-RD was ideal. An increase of wing-web thickness after exposure to phytohemagglutinin-L was only detected after vaccination with HVT-RD. Furthermore, compared to sham-inoculated chickens, chickens in the HVT-RD had an increased percentage of CD3+ T cells and CD4+ T-helper cells, and increased expression of major histocompatibility complex (MHC)-II on most cell subsets (CD45+ cells, non-T leukocytes, T cells and the CD8+ and T cell receptor γδ T-cell subsets). Other treatments (HVT-1/2 and rHVT-B) share some of these features but differences were not as remarkable as in the HVT-RD group. Expression of MHC-I was reduced, compared to sham-inoculated chickens, in most of the cell phenotypes evaluated in the HVT-RD, HVT-2x and rHVT-A groups, while no effect was observed in other treatments. The effect of in ovo HVT on humoral immune responses (antibody responses to keyhole limpet hemocyanin and to a live infectious bronchitis/Newcastle disease vaccine) was minimal. Our study demonstrates in ovo vaccination with HVT in meat-type chickens can accelerate innate and adaptive immunity and we could optimize such effect by modifying the vaccine dose.

Genetic Regulation of Redox Balance in ß-Thalassemia Trait.

ß-Thalassemia (ß-thal) trait is a heterogeneous group of genetic defects leading to decreased ß-globin production, ineffective erythropoiesis, and oxidative stress. The aim is to evaluate the cytoprotective response, at transcriptional and systemic levels, of the variations of global redox balance in ß-thal trait patients. Sixty-six subjects (40 healthy and 26 with ß-thal trait) were analyzed at the Universidad Nacional de Tucumán, Tucumán, Argentina, between 2016 and 2017. The following parameters were evaluated: complete blood count, iron status, hemoglobin (Hb) electrophoresis, Hb A2, thiobarbituric acid reactive species (TBARS), serum catalase (CAT), and superoxide dismutase (SOD) activity, FOXO3a, NRF2, SOD, PRDX2, CAT, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) gene expression. The ß-thal trait group showed a decrease in Hb levels, MCV, and MCH with higher TBARS levels. The SOD activity was significantly increased by 32.0% in ß-thal trait patients respect to the control group. Relative expression of NRF2 was 4.7-fold higher in ß-thal trait than in the control group, while FOXO3a expression was similar in both groups. The SOD, PRDX2, and proinflammatory cytokines transcriptional expression was significantly upregulated in ß-thal trait patients. This is the first study on the genetic regulation of redox balance in ß-thal trait patients in which interesting modifications were observed in the transcript levels of some redox regulators that could be associated with changes in the erythrocyte proteome in this disorder. A better understanding of the pathophysiological mechanisms present in these heterozygous patients would allow adequate therapy in situations such as growth, pregnancy, or high performance sports, favoring a personalized treatment.

An ultrasensitive Cystatin C renal failure immunosensor based on a PPy/CNT electrochemical capacitor grafted on interdigitated electrode.

An interdigitated immunosensor for Cystatin C detection based on polypyrrole/carbon nanotube electrochemical capacitor is described. Cystatin C (CysC) is powerful biomarker for early acute renal failure and one predictive for cardiovascular risk, sepsis, cancer and death. Recently, electrochemical immunosensors based on interdigitated electrodes (IDE) have been successfully focused on development of point-of-care testing, due to their miniaturization facilities and higher sensitivity as compared with the screen-printed electrochemical sensing. Herein, a polypyrrole/carbon nanotube nanoyhibrid film was grafted on two gold fingers by electropolymerization obtaining a supercapacitor. Anti-CysC antibodies were immobilized on the IDE by covalent entrapment via ethylenediamine bifunctional agent, followed by glycine blocking in acid and alkaline medium. Under low frequency, capacitive effect of antigen-antibody interaction were observed by double layer capacitance, and analytical responses of this IDE immunosensor to CysC serum were obtained by changes on phase angle a linear range up to 300 ng/mL. The cutoff was calculated for serum samples showing a total reducing of non-specific binding at approximately 28 ng/mL CysC. This immunosensor based on interdigitated electrode (IDE) is a potential tools as portable device,with possibility to use as a practical and rapid test for CysC diagnostic in samples of serum.

Evaluation of therapeutic targeting of CCR7 in acute graft-versus-host disease.

Graft-versus-host disease (GVHD) is the main complication after allogeneic hematopoietic stem cell transplantation. We previously unveiled a correlation between proportions of C-C motif chemokine receptor 7 (CCR7)+ T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in vivo whether apheresis with low proportion of CCR7+ cells or treatment with an anti-human CCR7 monoclonal antibody (mAb) were suitable strategies to prevent or treat acute GVHD in preclinical xenogeneic models. Therapeutic anti-CCR7 mAb was the most effective strategy in both prophylactic and therapeutic settings where antibody drastically reduced in vivo lymphoid organ infiltration of donor CCR7+ T cells, extended lifespan and solved clinical signs. The antibody neutralized in vitro migration of naïve and central memory T cells toward CCR7 ligands and depleted target CCR7+ subsets through complement activation. Both mechanisms of action spared CCR7- subsets, including effector memory and effector memory CD45RA+ T cells which may mediate graft versus leukemia effect and immunity against infections. Accordingly, the numbers of donor CCR7+ T cells in the apheresis were not associated to cytomegalovirus reactivation or the recurrence of the underlying disease. These findings provide a promising new strategy to prevent and treat acute GVHD, a condition where new specific, safety and effective treatment is needed.

A retrospective chart review study describing metastatic melanoma patients profile and treatment patterns in Spain.

PURPOSE: To describe patient characteristics by disease stage, resectability status and current treatment management after first diagnosis of IIIB to IV1c advanced (AM)/metastatic melanoma (MM). METHODS/PATIENTS: Multicentre, retrospective study based on data from medical charts of patients > 18 years at MM first diagnosis, visited by oncologists at 4 reference centres in Spain: Hospital Universitario Gregorio Marañón (Madrid), Hospital General de Valencia (Valencia), Clínica Universidad de Navarra (Pamplona), and Hospital Clínic (Barcelona). RESULTS: Metastatic non-visceral melanoma (IIIB, IIIC, IV M1a) was reported in 139 (48.6%) patients and 40.9% (n = 117) were diagnosed with IV-M1c disease. 160 (55.9%) metastases were resectable. Available therapies under clinical practice were used in 210 patients; 74 were treated under clinical trials (CT). Intention-to-cure surgery (47.6%) was the most common treatment at time of MM diagnosis. Systemic (45.1% overall) therapy included chemo-, targeted- and immunotherapy (19.6%, 14.3%, 8.4%, respectively). At time of data collection, 26 patients were still alive and 120 had progressed to IV-M1c. Median overall survival (OS) was significantly larger in IIIB patients, 28.9 m (25.2-32.7); the shortest for IV-M1c patients, 11.0 m (8.7-13.3). CONCLUSIONS: Novel treatments are undoubtedly a major step forward in AM/MM, however these are often only available in the CT setting because early stages of development or country-specific regulations. Further prospective studies and multifactorial analysis should be performed to clearly identify possible clinical associations for outcome in Spanish patients with AM/MM.

Correction: Body-size structure of Central Iberian mammal fauna reveals semidesertic conditions during the middle Miocene Global Cooling Event.

[This corrects the article DOI: 10.1371/journal.pone.0186762.].

Escenarios de aprendizaje basados en simulación: experiencia multidisciplinaria de la Universidad del Valle de México / Simulation-based learning scenarios: multidisciplinary experience of the University of the Valley of Mexico

Introducción: La simulación ha penetrado rápidamente en el terreno de la educación en ciencias de la salud y ha ganado aceptación como método educativo y herramienta que ofrece seguridad al paciente. Objetivo: Presentar la experiencia del diseño e implementación de centros de simulación con un enfoque multidisciplinar en pregrado. Sujetos y métodos: A partir de 2014 se creó la Dirección Nacional de Tecnologías Educativas en Salud y, con ello, la estandarización en los 12 centros de simulación de la Universidad del Valle de México a lo largo del país. Resultados: A dos años de la implementación de la estandarización de los centros de simulación, se han consolidado 12 centros de simulación en todo el país con un fuerte programa de capacitación al personal administrativo y docente. En la cohorte de febrero a noviembre de 2016 se comunicaron 1.951 escenarios de aprendizaje basados en simulación, y para 2017, en el mismo período, 5.547, de los cuales el 15º tiene componentes multidisciplinares. El propósito es elevar progresivamente el número de prácticas multidisciplinares con el objetivo de contribuir al egreso de profesionales de la salud competentes. Conclusiones: Los escenarios de aprendizaje basados en simulación realizada de forma multidisciplinar ha permitido la reproducción de tareas clínicas y profesionales, con el fin de desarrollar diversas competencias desde habilidades técnicas psicomotoras, habilidades de comunicación y actitudinales, como trabajo en equipo y liderazgo, entre otras tan importantes e indispensables para que los estudiantes de ciencias de la salud sean profesionales con experiencia clínica y profesional

Introduction: Simulation has rapidly penetrated the field of health science education by gaining acceptance as an educational method and a tool that provides patient safety. Aim: To present the experience of the design and implementation of simulation centers with a multidisciplinary approach in undergraduate. Subjects and methods: From 2014 the National Directorate of Educational Technologies in health was created, and thus the standardization in the 12 centers of simulation of University of the Valley of Mexico throughout the country. Results: Two years after the implementation of the standardization of the simulation centers. Twelve simulation centers have been consolidated nationwide with a strong training program for administrative and teaching staff; In the cohort February 2016 to November 2016, 1951 simulation-based learning scenarios were reported. For the 2017 in the same period 5547, of which 15º have multidisciplinary components. The purpose is to progressively increase the number of multidisciplinary practices with the aim of contributing to the discharge of competent health professionals. Conclusions: The simulation-based learning scenarios carried out in a multidisciplinary manner have allowed the reproduction of clinical and professional tasks, in order to develop diverse competencies from psychomotor technical skills, communication and attitudinal as teamwork, leadership among others so important and essential for the students of health sciences are professionals with clinical and professional experience

Surgical Ligation Versus Percutaneous Closure of Patent Ductus Arteriosus in Very Low-Weight Preterm Infants: Which are the Real Benefits of the Percutaneous Approach?

Percutaneous treatment of patent ductus arteriosus (PDA) in extreme premature infants is technically difficult, and therefore, often not consider as an alternative to surgery. The main objective of our work was to compare respiratory status prior and post ductal closure and morbi-mortality, in our series of preterm infants with percutaneous PDA closure versus surgical ligation in the same time-period. Retrospective review of all premature infants submitted to percutaneous and surgical PDA closure from January 2011 to December 2016. All the antenatal, perinatal, and postnatal characteristics were collected. The main outcome was the assessment of the pulmonary status before and after ductal closure using a pulmonary score. Secondary outcomes included moderate-severe disability in neurodevelopment, death before discharge, moderate-severe chronic lung disease, and morbidity at discharge. 25 patients with a mean weight of 1330 g (± 280) underwent percutaneous closure of PDA with ADO-II-AS, and a total of 53 underwent surgical ligation. 28/53 with similar gestational age, birth weight, and procedure weight to those in the percutaneous group, were selected to perform the comparative study. Ductal closure (percutaneous and surgical) resulted in improved respiratory status. However, percutaneous group achieved a fastest respiratory improvement, than surgical group. The surgical closure group associated higher morbidity among survivors (HIV, number of sepsis, need, and duration of inotropics post-interventionism). The incidence of recurrent laryngeal nerve palsy among the surgical group was 17%. Percutaneous closure of PDA in carefully selected low-weight preterm infants is a safe and reliable alternative to surgical ligation.

Non-small cell lung cancer clinical trials requiring biopsies with biomarker-specific results for enrollment provide unique challenges.

BACKGROUND: Clinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated. METHODS: The authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California-Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment. RESULTS: In total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker-eligible patients. CONCLUSIONS: Although the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800-7. © 2017 American Cancer Society.