Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

BACKGROUND: Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. PATIENTS AND METHODS: Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. RESULTS: Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. CONCLUSIONS: Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

Usefulness of bilateral mucoplasty plus reboot surgery in severe type-2 chronic rhinosinusitis with nasal polyps.

BACKGROUND: Although extended endoscopic sinus surgery (ESS) constitutes an alternative approach in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), the surgical techniques proposed so far do not allow for an optimal control of the disease. This study introduces bilateral mucoplasty as a complementary technique to extended ESS such as reboot surgery, analyzing its benefits in healing and quality of life (QoL). METHODS: Patients diagnosed with severe Type-2 CRSwNP were selected for a prospective cohort study in two surgery groups: reboot surgery plus bilateral mucoplasty versus reboot surgery only. In the first group, an autologous endonasal mucosal graft from the nostril floor was placed bilaterally onto the ethmoidal roof. Endoscopic, radiological and QoL outcomes were compared before and one year after surgery between the two groups using Modified Lund Kennedy (LKM), Meltzer and Lund Mackay (LM) scores, and the Sino-Nasal Outcome Test 22 (SNOT-22). RESULTS: 64 patients with homogeneous baseline characteristics were included: 17 patients underwent a reboot surgery plus a bilateral mucoplasty and 47 a reboot surgery only. LKM, Meltzer and SNOT-22 scores showed significant differences before and after surgery in both groups, with higher improvement in the mucoplasty group. A greater mean improvement of 20.5 ± 6.4 points in SNOT-22 change was associated with bilateral mucoplasty. CONCLUSION: Bilateral mucoplasty plus reboot surgery constitutes a useful surgical resource in Type-2 CRSwNP patients, showing improved endoscopic, radiological and QoL outcomes one year after surgery. Further studies are needed to determine their long-term benefits.

[Clinical experience with erenumab during the first year of treatment]. / Experiencia clínica con erenumab durante el primer año de tratamiento.

INTRODUCTION: Erenumab, a calcitonin gene-related peptide antagonist, has been approved for migraine prophylaxis. It represents an alternative for patients with multiple treatment failures, who have a low quality of life and high associated disability. AIM: To analyse the effectiveness and safety of erenumab during the first year of treatment and to assess its impact on quality of life and disability. PATIENTS AND METHODS: It is a longitudinal prospective observational study conducted over 15 months. Patients who met the funding criteria for erenumab were included. Data concerning years of illness, migraine days/month, pain intensity, previous treatments, doses and adverse effects were collected. In addition, quality of life and disability were assessed using the Migraine-Specific Quality Of Life Questionnaire 2.1 and Migraine Disability Assessment Scale, repeated at three and 12 months. RESULTS: Forty-three patients were included, 79.1% female, 95.3% with chronic migraine and with a mean age of 48.2 years. Prior to erenumab they had 20 migraine days/month, a pain intensity of 8.2 and a 30.6% quality of life, and 72.5% had very severe disability. Fifteen patients stopped taking erenumab due to inefficacy and one due to intolerance. Thirteen received erenumab for one year and 14 continued with the treatment. All four effectiveness variables were significantly improved with erenumab by the third month. Fifteen patients (34.9%) had adverse effects, most of which were mild. Constipation was the most frequent. CONCLUSIONS: Erenumab proved effective in most patients for migraine prophylaxis in the first three months, significantly reducing the number of migraine days/month, pain intensity and associated disability. Moreover, it significantly improved their quality of life . It is a safe drug.

TITLE: Experiencia clínica con erenumab durante el primer año de tratamiento.Introducción. El erenumab, un antagonista del péptido relacionado con el gen de la calcitonina, ha sido autorizado para la profilaxis de la migraña. Se presenta como una alternativa para pacientes con múltiples fracasos terapéuticos, los cuales presentan baja calidad de vida y alta discapacidad asociada. Objetivo. Analizar la efectividad y la seguridad del erenumab durante el primer año de tratamiento y evaluar su impacto en la calidad de vida y la discapacidad. Pacientes y métodos. Estudio observacional prospectivo longitudinal realizado durante 15 meses. Se incluyó a los pacientes que cumplían los criterios de financiación del erenumab. Se recogieron años de enfermedad, días de migraña/mes, intensidad del dolor, tratamientos previos, dosis y efectos adversos. Además, se evaluaron la calidad de vida y la discapacidad mediante los cuestionarios Migraine-Specific Quality Of Life Questionnaire 2.1 y Migraine Disability Assessment Scale, que se repitieron a los tres y a los 12 meses. Resultados. Se incluyó a 43 pacientes, el 79,1% mujeres, el 95,3% con migraña crónica y con una edad media de 48,2 años. Previamente al erenumab presentaban 20 días de migraña/mes, intensidad de dolor 8,2, un 30,6% de calidad de vida y el 72,5% tenía discapacidad muy grave. Quince pacientes suspendieron el erenumab por ineficacia y uno por intolerancia. Trece recibieron erenumab durante un año y 14 continuaban en tratamiento. Las cuatro variables de efectividad mejoraron significativamente con el erenumab al tercer mes. Quince pacientes (34,9%) presentaron efectos adversos, en su mayoría leves. El estreñimiento fue el más frecuente. Conclusiones. El erenumab mostró efectividad en la mayoría de los pacientes para profilaxis de migraña en los tres primeros meses, reduciendo significativamente los días de migraña/mes, la intensidad del dolor y la discapacidad asociada. Además, mejoró significativamente la calidad de vida. Es un fármaco seguro.

Efficacy of complementary treatment with autologous platelet concentrates and/or mesenchymal stem cells in chemical osteonecrosis of the jaw. Systematic review of the literature.

The aim of this systematic review was to establish the current status of the subject and find out what scientific evidence we have on the use of autologous plasma concentrates (APCs) and mesenchymal stem cells (MSCs) as complementary therapies at the management of Medication-related Osteonecrosis of the jaw (MRONJ). We performed a literature search of articles published between December 2019 to January 2020 in electronic databases, in accordance to PRISMA system. The variables analyzed were: the number of patients, age, sex, medical history, origin of MRONJ, imaging studies, treatment performed, and evolution of MRONJ. The articles included in the review were grouped into two groups (Group A "Therapy with APCs" and Group B "Therapy with APCs and MSCs"). Newcastle-Ottawa scale (NOS) was used to assess the quality of the articles. Fisher's exact test was used to evaluate eventual differences between groups. Of the 306 patients who were included, 297 belonged to Group A and 9 to Group B. In our sample, women predominated against men and no significant differences in age were observed. Osteoporosis was the most frequent underlying disease in both groups. The most common origin of MRONJ was oral surgery in group A. Conservative surgery was performed in all patients, but complementary treatment was applied in different ways in each group. The resolution of the pathology was achieved in 90% of cases in both groups without significant differences between them. The mean score of the reviewed studies at NOS was 4. There are currently no published scientific data that can sufficiently support the use of APCs and MSCs for the treatment of established MRONJs.

The determination of fertiliser quality of the formed struvite from a WWTP.

Struvite from nutrient-rich wastewaters has been identified as a potential substitute for commercial mineral fertilisers, with the added benefit of reducing threats to global food security by prolonging phosphate rock reserves. A fertilisation test using grass (Brachiaria brizantha Marandú) and a sand column leaching test was conducted to determine the agronomic effectiveness of struvite precipitates produced from the supernatant of dewatered sewage sludge (centrate) from a municipal Wastewater Treatment Plant (WWTP). The performance of this struvite as a fertiliser was compared with biosolids and commercial fertilisers (Urea and Triple15). The results show that the concentration of heavy metals in struvite was lower than in biosolids and below the limits of Colombia and European fertiliser regulations. Struvite increased the uptake of N and P in grass, resulting in crop yields similar to other treatments tested. Struvite use as an effective slow-release fertiliser is highly dependent on the size of crystal particles, particularly in achieving low P losses, but resulted in high N loss in the sand columns tested; N loses from struvite were higher than in the commercial fertilisers due to the struvite small particle size. Therefore, struvite represents a suitable opportunity to recover and recycle nutrients from municipal sewage sludge, facilitating the effective reuse of P and N in agriculture and uptake by plants.

Exogenous fibrolytic enzymes and recombinant bacterial expansins synergistically improve hydrolysis and in vitro digestibility of bermudagrass haylage.

Four experiments were conducted to examine the effects of a recombinant bacterial expansin-like protein (BsEXLX1) from Bacillus subtilis and a commercial exogenous fibrolytic enzyme (EFE) preparation for ruminants on hydrolysis of pure substrates (cellulose and xylan) and in vitro digestibility of bermudagrass haylage (BMH). Recombinant Escherichia coli BL21 strain was used to express BsEXLX1; the protein was purified using an affinity column. In experiment 1, carboxymethylcellulose, Whatman #1 filter paper (General Electric, Boston, MA) and oat-spelt xylan substrates were subjected to 4 treatments (1) sodium citrate buffer (control), (2) BsEXLX1 (162 µg/g of substrate), (3) EFE (2.3 mg/g of substrate), and (4) EFE + BsELX1 in 3 independent runs. Samples were incubated at optimal conditions for both additives (pH 5 and 50°C) or at ruminal (pH 6 and 39°C) or ambient (pH 6 and 25°C) conditions for 24 h and sugar release was measured. In experiment 2, digestibility in vitro of BMH was examined after treatment with the following: (1) control (buffer only), (2) BsEXLX1 (162 µg/g of dry matter), (3) EFE (2.2 mg/g of dry matter), and (4) EFE + BsEXLX1 in 3 independent runs at 39°C for 24 h. Experiment 3 examined effects of EFE and BsEXLX1 on simulated preingestive hydrolysis and profile of released sugars from BMH after samples were suspended in deionized water with sodium azide at 25°C for 24 h in 2 independent runs. In experiment 4, the sequence of the BsEXLX1 purified protein was compared with 447 ruminal bacterial genomes to identify similar proteins from the rumen. In experiment 1, compared with EFE alone, EFE and BsEXLX1 synergistically increased sugar release from carboxymethylcellulose and Whatman #1 filter paper under all simulated conditions; however, hydrolysis of xylan was not improved. In experiment 2, compared with EFE alone, treatment with EFE and BsEXLX1 increased neutral detergent fiber and acid detergent fiber digestibility of bermudagrass haylage (by 5.5 and 15%, respectively) and total volatile fatty acid concentrations, and decreased acetate-propionate ratio. In experiment 3, compared with EFE alone. The EFE and BsEXLX1 synergistically reduced concentrations of neutral detergent fiber and acid detergent fiber and increased release of sugars by 9.3%, particularly cellobiose (72.5%). In experiment 4, a similar sequence to that of BsEXLX1 was identified in Bacillus licheniformis, and similar hypothetical protein sequences were identified in Ruminococcus flavefaciens strains along with different protein structures in E. xylanophilum and Lachnospiraceae. This study showed that an expansin-like protein synergistically increased the hydrolysis of pure cellulose substrates and the hydrolysis and digestibility in vitro of BMH.

Aproximación para establecer y evaluar la relevancia clínica de las interacciones medicamentosas en el tratamiento de pacientes infectados con virus de hepatitis C, revisión estructurada (actualización 2015-2017) / Structured review of establishing and evaluating clinical relevance of drug interactions in hepatitis C virus treatment (Update 2015 - 2017)

Resumen Objetivo: establecer y evaluar la relevancia clínica de las interacciones medicamentosas en el tratamiento de pacientes con hepatitis C. Método: se realizó una búsqueda en PubMed/MedLine de artículos publicados en inglés y en español, desde el 1 de enero de 2015 hasta el 30 de marzo de 2017, utilizando los términos Mesh: Hepatitis C AND drug interactions OR herb-drug interactions OR food-drug interactions, de estudios realizados en humanos. La relevancia clínica de las interacciones medicamentosas se estableció y evaluó con base en la probabilidad de ocurrencia y la gravedad de la interacción. Resultados: se identificaron 184 artículos, de los cuales 92 se seleccionaron por el título y resumen para revisión completa, a 2 de ellos no fue posible acceder al texto completo. De estos, 57 aportaban interacciones, lo que permitió identificar 155 parejas de interacciones medicamentosas, de las cuales 154 (99,4 %) fueron farmacocinéticas y 1 (0,6 %) farmacodinámica. Por su parte, de las 155 parejas, 34 (21,9 %) se valoraron de nivel 1; 73 (47,1 %) de nivel 2; 48 (31,0 %) de nivel 3; y 0 (0,0 %) de nivel 4. Además, se identificaron 29 parejas agrupadas como interacciones con evidencia de ausencia de relevancia clínica. Conclusiones: más de 99 % de las interacciones medicamentosas de relevancia clínica son farmacocinéticas, asociadas con cambios en el metabolismo y el transporte de fármacos; el simeprevir y la terapia 3D (Paritaprevir/Ritonavir+ Ombitasvir+Dasabuvir) fueron los medicamentos con mayor número de interacciones.

Abstract Objective: This study-s objective is to establish and evaluate the clinical relevance of drug interactions during treatment of patients with hepatitis C. Method: A PubMed/MedLine search was conducted for articles published in English and Spanish from January 1, 2015 to March 30, 2017 using the terms Mesh: Hepatitis C AND drug interactions OR herb-drug interactions OR food-drug interactions, from studies conducted in humans. The clinical relevance of drug interactions was established and evaluated based on probability of occurrence and severity of interactions. Results: Of the 184 four articles identified, 92 were selected by title and abstract for full review. The full texts of two articles could not be accessed. Of the remaining articles, 57 describ ed relevant interactions. Of the 155 pairs of drugs that interact that were identified, 154 (99.4%) were pharmacokinetic, and one (0.6%) was pharmacodynamic. Thirty-four of the 155 pairs (21.9%) were assessed at level 1; 73 (47.1%) were assessed at level 2; 48 (31.0%) were assessed at level 3, none were assessed at level 4. In addition, 29 pairs of interacting drugs had no evidence of clinical relevance. Conclusions: More than 99% of clinically relevant drug interactions are pharmacokinetics and are associated with changes in metabolism and transport of drugs. Simeprevir and 3D (Paritaprevir/Ritonavir+ Ombitasvir+Dasabuvir) therapy had the greatest number of interactions.

Blueberries as an additive to increase the survival of Lactobacillus johnsonii N6.2 to lyophilisation.

Effective cultivation methods, total cost, and biomass preservation are key factors that have a significant impact on the commercialisation and effectiveness of probiotics, such as Lactobacillus. Sugar polymers, milk and whey proteins have been suggested as good additives for industrial preparations. Alternative compounds, such as phytophenols, are a more attractive option, given their potential benefits to human health. The overall goal of this study was to determine if the addition of blueberry phytophenols improves the survival of Lactobacillus johnsonii N6.2 during the freeze-drying process. The addition of blueberry aqueous extract (BAE) stimulated the growth of L. johnsonii under aerobic conditions and improved the stationary phase survival of the bacteria. Furthermore, the addition of BAE to the culture media improved the endurance of L. johnsonii N6.2 to freeze-drying stress, as well as to storage at 4 °C for up to 21 weeks. Moreover, blueberry extract performed more effectively as a lyophilising additive compared to skim milk and microencapsulation with whey protein/sodium alginate. In sum, this study demonstrates that BAE is an effective additive to increase the growth and survival of L. johnsonii N6.2 when added to the culture medium and/or used as a lyophilising preservative. Moreover, BAE or other polyphenols sources might likely enhance growth and increase survival of more probiotic lactic acid bacterial strains.

Quantitative assessment of the metabolic products of iron oxide nanoparticles to be used as iron supplements in cell cultures.

Iron nanoparticles (NPs) metabolism is directly associated to human health due to their use as anemia treatment and should be studied in detail in cells. Here we present a speciation strategy for the determination of the metabolic products of iron oxide nanoparticles coated by tartaric and adipic acids in enterocytes-like cell models (Caco-2 and HT-29). Such methodology is based on the use of SDS-modified reversed phase high performance liquid chromatography (HPLC) separation using inductively coupled plasma-mass spectrometry (ICP-MS) as Fe selective detector. Post-column isotope dilution analysis is used as quantification tool by adding 57Fe as isotopically enriched standard. To assess the separation capability of the method, two different iron nanostructures: iron sucrose nanoparticles -Venofer®- used as model suspension and iron tartrate/adipate-modified nanoparticles, both of about 4 nm (core size) were evaluated. The two nanostructures were injected into the system showing good peak profiles and quantitative elution recoveries (>80%) in both cases. In addition, both nanoparticulate fractions could be based-line separated from ionic iron species, which needed to be complexed with 1 mM citrate to elute from the column. Exposed cells up to 0.5 mM of iron tartrate/adipate-modified nanoparticles were specifically treated to extract the internalized NPs and the extracts examined using the proposed strategy. The obtained results revealed the presence of three different fractions corresponding to nanoparticle aggregates, dispersed nanoparticles and soluble iron respectively in a single chromatographic run. Quantitative experiments (column recoveries ranging from 60 to 80%) revealed the presence of the majority of the Fe in the nanoparticulated form (>75%) by summing up the dispersed and aggregate particles. Such experiments point out the high uptake and low solubilization rate of the tartrate/adipate NPs making these structures highly suitable as Fe supplements in oral anemia treatments.

Routine HIV Screening in Cancer Patients in the Emergency Department.

Treatment of human immunodeficiency virus(HIV) in cancer patients improves outcomes and reduces transmission of this oncogenic virus. HIV testing rates of cancer patients are similar to the general population (15-40%), despite the association with cancer. Our aim was to increase HIV screening in the Emergency Department(ED) of a comprehensive cancer center through a quality initiative. Testing increased significantly during the intervention (p<0.001; 0.15/day to 2.69/day). Seropositive HIV rate was 1.4% (12/852), with incidence of 0.3%. All patients were linked to care. Incident cases were between 36 and 55 years of age. Barriers encountered included confusion regarding the need for written consent for HIV testing, failure to consider ordering the test, and concerns regarding linkage to care.

Desarrollo de un Sistema con Potencial Aplicación de Fototerapia para Ictericia Neonatal / Design of a System with a Potential Application to Neonatal Jaundice Phototherapy

RESUMEN En este proyecto se diseñó y construyó un prototipo con potencial aplicación a un sistema de fototerapia para ictericia neonatal utilizando por primera vez LEDs de 10 W de alta potencia. Se describe la metodología aplicada para el diseño de los diferentes circuitos electrónicos que se utilizaron para la alimentación de la corriente de excitación de los LEDs, se describe el método de control de corriente mediante el uso de la modulación por ancho de pulsos, Pulse Width Modulation (PWM, por sus siglas en inglés), generados por el circuito integrado 555. Se diseñó la placa de circuito impreso mediante la ayuda del simulador Orcad Layout. Se utilizaron dos LEDs de alta potencia de 10 W para el propósito de conservar la intensidad requerida para el tratamiento, minimizando el espacio utilizado por la cantidad de LEDs utilizados en los equipos convencionales. Entre las limitaciones que se presentaron en esta investigación fue el uso de la plataforma Arduino, ya que se tienen varias oportunidades de mejora para darle el mejor uso al microcontrolador, y de esta manera digitalizar el sistema de una forma más completa, reduciendo la circuitería de control. El prototipo presentado cumple con los requerimientos necesarios para un sistema de fototerapia.

ABSTRACT This project consisted in the design and construction of a prototype with potential application to a phototherapy system for neonatal jaundice using for the first-time high power 10 W LEDs. The methodology for the design of different electronic circuits which were used for feeding the drive current of the LEDs, the current control method described using pulse width modulation (PWM) generated by the known 555 integrated circuit is described. The printed circuit board was designed with the help of the Orcad Layout simulator. Two high-power 10 W LEDs were used for maintaining the intensity required for the treatment, minimizing the space used by the number of LEDs used in the conventional equipment. Among the limitations presented in this research was the use of the Arduino platform, due to several improve that can be used to improve and increase the use of this microcontroller, and in this way to digitize the system, reducing the circuitry of control. The prototype presented meets the requirements for a phototherapy system according to the different references used.

FPI: Consolidando alternativas de tratamiento / No disponible

La fibrosis pulmonar idiopática es una patología sobre la cual se está incidiendo tanto en el diagnóstico, a través de estudios acerca de las alteraciones genéticas que modifican el curso de la enfermedad, como en estudios que nos aportan diferentes alternativas en cuanto al tratamiento. Actualmente disponemos de dos fármacos que han demostrado mejorar tanto el pronóstico de la enfermedad como la calidad de vida de los pacientes que se someten a dichos tratamientos, ellos son Pirfenidona y Nintedanib

Idiopathic pulmonary fibrosis is a pathology that is affecting both the diagnosis, through studies about genetic alterations that modify the course of the disease and studies that provide us with different treatment alternatives. We currently have two drugs that have been shown to improve both the prognosis of the disease and the quality of life of patients who undergo such treatments, such as Pirfenidone and Nintedanib

Interventional Cultural and Language Assistance Program: Associations between Cultural and Linguistic Factors and Satisfaction with Cancer Care.

Addressing language and cultural nuance is required to improve the quality of care among all patients. The tenth version of the National Standards for Culturally and Linguistically Appropriate Services in Health Care (CLAS) recommends implementing ongoing assessments to integrate specific actions into measurement and continuous quality improvement activities. To this end, we have created the Interventional Cultural and Language Assistance Program (ICLAP). As part of ICLAP, we conducted a cross-sectional needs assessment survey with 564 consecutive patients receiving outpatient Positron emission tomography-computed tomography (PET/CT) imaging at a comprehensive cancer center in the five most prevalent languages of New York City: English, Spanish, Russian, Chinese, and Arabic. The purpose of this study is to describe the language assistance characteristics and needs of a sample of patients receiving care in the cancer center. We examined the relationship between race, ethnicity, birthplace, communication and language assistance characteristics and the satisfaction with the care received. Our results show that race and ethnicity, birthplace, cultural beliefs, language assistance, and communication characteristics were all factors associated with patients' satisfaction with care, illustrating that there is an unmet need among cancer patients to have cultural and linguistic sensitive services.

Association between waist circumference and magnesium and uric acid in indigenous Argentinean children living at high altitude.

BACKGROUND: Studies in adults show that central obesity increases the likelihood of Type 2 diabetes (T2DM). OBJECTIVE: To determine the association between waist circumference (WC) and non-traditional risk factors such as magnesium (Mg), phosphorus, and uric acid in indigenous children living at high altitudes. METHODS: A total of 354 (166 M) indigenous school children, aged 9.6 + 2.3 years, were enrolled in a cross-sectional study in November 2011. Central obesity was defined as WC > 90th percentile according to age and sex. Low Mg and phosphorus levels were defined as serum Mg <1.8 mg/dL and phosphorus <2.4 mg/dL . Hyperuricemia was defined as serum uric acid > 7 mg/dL. RESULTS: The prevalence of central obesity was 6.8% (24/354). None of the children had hyperuricemia or low P levels. HypoMg was identified in 21.7% (57/263). There was a significant association between WC (z-score) and Mg (r-015), uric acid (r0.28), phosphorus (r-0.30), HOMA-IR (r0.49), Triglycerides (r0.24), and HDL-C (r0.24). However, calcium, sodium, and potassium were not significantly associated with WC. As z-WC quartiles increased Mg and phosphorus levels significantly decreased, whereas uric acid levels increased. Multiple linear regression analysis showed that z-WC was associated significantly and directly with uric acid (B0.31), triglycerides (B0.004), and HOMA-IR (B0.35); and inversely with Mg (B-0.83) and phosphorus (B-0.25), adjusted for confounding variables (R2 0.34). CONCLUSION: Our results indicate that central obesity was significantly and inversely associated with Mg and phosphorus and directly with uric acid in indigenous school children. Supplementation with Mg and/or phosphorus could prevent future cardiovascular disease. Prospective and randomized studies should be performed to confirm these findings.

Effect of adding cofactors to exogenous fibrolytic enzymes on preingestive hydrolysis, in vitro digestibility, and fermentation of bermudagrass haylage.

Our objectives were to examine if adding metal ion cofactors (COF) to exogenous fibrolytic enzymes (EFE) would increase the beneficial effects of the EFE on the preingestive hydrolysis and in vitro digestibility and fermentation of bermudagrass haylage. In experiment 1, 5 COF (Mn(2+), Co(2+), Fe(2+), Ca(2+), and Mg(2+)) were screened to select the best candidates for synergistically enhancing release of water-soluble carbohydrates (WSC) from bermudagrass haylage by 5 EFE. The 5 EFE (1A, 2A, 11C, 13D, and 15D) were sourced from Trichoderma reesei and Aspergillus oryzae and they were the most effective of 12 EFE at increasing the neutral detergent fiber digestibility of bermudagrass haylage in a previous trial. Adding 1mM of each of the COF to EFE 2A or 11C synergistically increased release of WSC from bermudagrass haylage, as did adding (1mM) Fe(2+) to 1A, Mn(2+), Co(2+), or Fe(2+) to 13D, or Co(2+)or Fe(2+) to 15D. The greatest release of WSC responses were obtained by adding Mn(2+) to 11C (38%) or by adding Fe(2+) to 2A or 13D (10 and 21.9%, respectively). In experiment 2, the effect of increasing the COF dose on in vitro digestibility and fermentation of bermudagrass haylage was examined using the best EFE-COF combinations from experiment 1. Effects of adding increasing doses of these COF on EFE-mediated changes in vitro digestibility depended on the COF-EFE combination. Adding 10mM Mn(2+) alone to bermudagrass haylage increased DMD and NDFD by 2.7 and 6.3% and adding 11C alone increased these measures by 6.6 and 15.5%, respectively. However, adding 10mM Mn(2+) with 11C resulted in 3.5 and 8.1% increases in DMD and NDFD, respectively, beyond the increases caused by adding 11C alone. Adding Fe(2+) to 2A had no effects on EFE-mediated digestibility responses, but 2A prevented adverse effects of adding Fe(2+) alone on DMD and NDFD. In contrast, adding Fe(2+) to 13D reduced the increases in DMD and NDFD caused by adding the EFE alone. This study shows that adding COF to EFE can synergistically increase, decrease, or not affect the hydrolytic effects of EFE on bermudagrass haylage cell walls. The outcome depends on the specific EFE-COF combination and the COF dose. More research is required to understand the mechanisms resulting in these outcomes to exploit beneficial effects of COF on EFE.

Screening exogenous fibrolytic enzyme preparations for improved in vitro digestibility of bermudagrass haylage.

Our objectives were to evaluate the effects of 12 exogenous fibrolytic enzyme products (EFE) on ruminal in vitro neutral detergent fiber digestibility (NDFD) and preingestive hydrolysis of a 4-wk regrowth of bermudagrass haylage (BH), to examine the accuracy of predicting NDFD with EFE activity measures, and to examine the protein composition of the most and least effective EFE at increasing NDFD. In experiment 1, effects of 12 EFE on NDFD of BH were tested. Enzymes were applied in quadruplicate to culture tubes containing ground BH. The suspension was incubated for 24 h at 25 °C before addition of rumen fluid media and further incubation for 24 h at 39 °C. The experiment was repeated twice. In addition, regression relationships between EFE activity measures and NDFD were examined. Compared with the values for the control, 9 EFE-treated substrates had greater NDFD (37.8 to 40.4 vs. 35.6%), 6 had greater total VFA concentration (59.1 to 61.2 vs. 55.4 mM), and 4 had lower acetate-to-propionate ratios (3.03 to 3.16 vs. 3.24). In experiment 2, EFE effects on preingestive fiber hydrolysis were evaluated by incubating enzyme-treated and untreated bermudagrass suspensions in quadruplicate for 24 h at 25 °C and examining fiber hydrolysis measures. Compared with values for the control, 3 EFE reduced neutral detergent fiber concentration (62.8 to 63.7 vs. 67.3%), 10 increased release of water-soluble carbohydrates (26.8 to 58.5 vs. 22.8 mg/g), and 8 increased release of ferulic acid (210 to 391 vs. 198 µg/g). Regression analyses revealed that enzyme activities accurately [coefficient of determination (R(2)) = 0.98] predicted preingestive hydrolysis measures (water-soluble carbohydrates, ferulic acid), moderately (R(2) = 0.47) predicted neutral detergent fiber hydrolysis, but poorly (R(2) ≤ 0.1) predicted dry matter and NDFD. In experiment 3, proteomic tools were used to examine the protein composition of the most and least effective EFE at improving NDFD. Relative to the least effective, the most effective EFE at increasing NDFD contained 10 times more endoglucanase III, 17 times more acetylxylan esterase with a cellulose-binding domain 1, 33 times more xylanase III, 25 times more ß-xylosidase, and 7.7 times more polysaccharide monooxygenase with cellulose-binding domain 1 and 3 times more swollenin. The most effective EFE had a much greater quantity of fibrolytic enzymes and key proteins necessary for hemicellulose and lignocellulase deconstruction. This study identified several EFE that increased the NDFD and in vitro fermentation of 4-wk BH and revealed why some EFE are more effective than others.

Camptocormia: cifosis lumbar adquirida progresiva reductible / Camptocormia: Progressive and acquired reducible lumbar kyphosis

La camptocormia es una enfermedad invalidante para el paciente que la presenta pues le limita en sus actividades de la vida diaria, así como para la marcha. Es una entidad poco frecuente, relativamente conocida, y en la que se debe pensar ante la presencia de una cifosis lumbar adquirida, progresiva y reductible en un paciente de edad avanzada. Su diagnóstico es fundamentalmente clínico y se confirma tras realización de pruebas complementarias como TAC de columna y RNM. El tratamiento en muchos casos no resulta muy efectivo y se basa en prescripción de rehabilitación, ortesis, productos de apoyo o ayudas técnicas para la marcha y tratamiento farmacológico sintomático. Presentamos el caso de una mujer de 81 a˜nos remitida desde el servicio de neurología, que fue valorada y tratada en nuestro servicio con mejoría de la clínica y de su patrón de marcha y postural (AU)

Camptocormia is a disabling disease that limits activities of daily living in affected individuals as well as their gait. It is uncommon but relatively well-known disease that should be considered in patients with progressive and reducible lumbar kyphosis acquired at advanced age. The diagnosis is mainly clinical and is confirmed by complementary tests such as spinal computed tomography and magnetic resonance imaging. Treatment is often ineffective and is based on rehabilitation, the use of orthoses, supports or technical aids for walking, and symptomatic drug therapy. We report the case of an 81-year-old woman who was referred by the neurology service and was evaluated and treated in our service. The patient showed improvements in her clinical symptoms, posture and gait (AU)

Transgenic soybean pollen (Glycine max L.) in honey from the Yucatán peninsula, Mexico.

Using precise pollen species determination by conventional microscopic methods, accompanied by molecular genetic markers, we found bees collect GMO (genetically modified) soybean pollen and incorporate it in Yucatan honey. Honey comb samples from Las Flores, Campeche, Mexico, often contained soybean pollen. Pollen in honey was analyzed in nine samples; six contained substantial soy pollen and two tested positive for soybean GMO. Our analyses confirm field observations that honey bees, Apis mellifera, gather soybean pollen and nectar. The resultant risk for honey production in the Yucatán Peninsula and Mexico is evident in wholesale price reduction of 12% when GMO products are detected and honey consignments are rejected. Although this affects only 1% of current export honey (2011-2013) GMO soybean is an unacknowledged threat to apiculture and its economics in one of the world's foremost honey producing areas.

The effect of estradiol, progesterone, and melatonin on estrous cycling and ovarian aromatase expression in intact female mice.

OBJECTIVE: Melatonin and progesterone levels decline during the perimenopause. Both hormones inhibit estrogen action and endometrial cancer, but little is known about how they act in combination. Therefore, the interplay of progesterone (P4) and melatonin was investigated in intact female mice. STUDY DESIGN: Three P4 doses, low (25mg), mid (50mg), and high (100mg), combined with 0.5mg 17ß-estradiol (E), were administered in the diet (per 1800kcal) for 30 days. Hormone therapy (HT) with the low P4 dose (estradiol/low progesterone replacement therapy (EPLRT)) was used to create an excess estrogen environment to mimic perimenopause. Half the mice were treated with melatonin (M) 15mg/L in the drinking water at night. RESULTS: The unbalanced EPLRT treatment increased estrogen-regulated responses. Specifically, mice treated with EPLRT had significantly higher levels of ovarian aromatase mRNA versus control, which was prevented in the presence of higher doses of P4 and/or the addition of melatonin. The number of days in estrus also increased in EPLRT-treated versus control mice with no change in the length or number of complete estrous cycles. Melatonin, combined with all doses of P4, increased the number of days spent in estrus, but not the length or number of estrous cycles compared to melatonin alone; however, two-way ANOVA revealed a significant interaction between melatonin and P4 dose for days in estrus and for number of cycles. Although none of the E2 and P4 combinations significantly affected uterine weight compared to control, melatonin addition to the low or mid P4 HT resulted in slightly higher uterine weights compared to melatonin-treated mice. Melatonin significantly increased uterine estrogen receptor alpha (ERα) and progesterone receptor A levels compared to control animals. HT, added in combination with melatonin, reduced ERα levels back to control levels, but PR levels remained elevated albeit intermediary to those achieved with melatonin alone. CONCLUSION: The findings that melatonin supplementation inhibits ovarian aromatase expression and increases uterine receptors in mice given an HT that mimics perimenopause may have important clinical applications for the improvement of menopause-related conditions, like menorrhagia, associated with high levels of E2 and low levels of P4.