Pudexacianinium (ASP5354) chloride for ureter visualization in participants undergoing laparoscopic, minimally invasive colorectal surgery.

BACKGROUND: Intraoperative ureteral injury, a serious complication of abdominopelvic surgeries, can be avoided through ureter visualization. Near-infrared fluorescence imaging offers real-time anatomical visualization of ureters during surgery. Pudexacianinium (ASP5354) chloride is an indocyanine green derivative under investigation for intraoperative ureter visualization during colorectal or gynecologic surgery in adult and pediatric patients. METHODS: In this phase 2 study (NCT04238481), adults undergoing laparoscopic colorectal surgery were randomized to receive one intravenous dose of pudexacianinium 0.3 mg, 1.0 mg, or 3.0 mg. The primary endpoint was successful intraoperative ureter visualization, defined as observation of ureter fluorescence 30 min after pudexacianinium administration and at end of surgery. Safety and pharmacokinetics were also assessed. RESULTS: Participants received pudexacianinium 0.3 mg (n = 3), 1.0 mg (n = 6), or 3.0 mg (n = 3). Most participants were female (n = 10; 83.3%); median age was 54 years (range 24-69) and median BMI was 29.3 kg/m2 (range 18.7-38.1). Successful intraoperative ureter visualization occurred in 2/3, 5/6, and 3/3 participants who received pudexacianinium 0.3 mg, 1.0 mg, or 3.0 mg, respectively. Median intensity values per surgeon assessment were 1 (mild) with the 0.3-mg dose, 2 (moderate) with the 1.0-mg dose, and 3 (strong) with the 3.0-mg dose. A correlation was observed between qualitative (surgeon's recognition/identification of the ureter during surgery) and quantitative (video recordings of the surgeries after study completion) assessment of fluorescence intensity. Two participants experienced serious adverse events, none of which were drug-related toxicities. One adverse event (grade 1 proteinuria) was related to pudexacianinium. Plasma pudexacianinium concentrations were dose-dependent and the mean (± SD) percent excreted into urine during surgery was 22.3% ± 8.0% (0.3-mg dose), 15.6% ± 10.0% (1.0-mg dose), and 39.5% ± 12.4% (3.0-mg dose). CONCLUSIONS: In this study, 1.0 and 3.0 mg pudexacianinium provided ureteral visualization for the duration of minimally invasive, laparoscopic colorectal procedures and was safe and well tolerated.

Metabolomics studies of allelopathy: a review

SUMMARY Introduction: Allelopathy is a harmful effect indirectly or directly produced by one plant to another through the production of chemical substances that enter the environment. Allelopathy has a pertinent significance for systems of ecological, sustainable, and integrated management. These natural reactions have multiple effects, ranging from processes of inhibition and stimulation of growth in neighbor plants to inhibition of seed germination. Metabolomics is a discipline integral that studies all the metabolites in a particular tissue, organ, or organism in a specific developmental stage or under particular environmental conditions, and it allows for the assessment of the contribution of genetic and environmental factors to the modification of metabolism. With the growing number of "omics", new approaches can be used to understand metabolic changes that occur in plants, especially in proteomics and metabolomics, and thus those analyses could be profiled in coming years with the objective of knowing the allelopathome of a larger number of plant species and their interactions. Aim: To provide a recent update on the science of allelopathy in the context of physiology, practical application of metabolomics in allelopathic studies, allelochemicals analyzed by metabolomics in alfalfa, rice, canola, sorghum, rye, wheat and other crops and finally mentionated the biological activity of allelopathic secondary metabolites. Methods: A recent comprehensive literature search of allelopathy and metabolomics in journal databases was carried out. Results: The concept of allelopathy, allelopathic mechanisms, metabolomic studies in allelopathy, allelochemicals analysed by metabolomics in alfalfa, rice, canola, rye sorghum, wheat and other agro-industrially important crops, and the biological activity of allelopathic secondary metabolites are detailed. Conclusions: These studies suggest that a combination of secondary metabolites can be used to attack weeds. In situ and In vitro culture of secondary metabolites (allelochemical types) is recommended to be used as organics compounds in weed organic control in the future.

Introducción: la alelopatía es un efecto nocivo producido directa o indirectamente por una planta a otra a través de la producción de sustancias químicas que ingresan al medio ambiente. La alelopatía es importante para los sistemas de manejo ecológico, sostenible e integrado. Estas reacciones naturales tienen múltiples efectos, que van desde procesos de inhibición y estimulación del crecimiento en plantas vecinas hasta la inhibición de la germinación de semillas. La metabolómica es una disciplina integral que estudia todos los metabolitos en un determinado tejido, órgano u organismo en una determinada etapa de desarrollo o en determinadas condiciones ambientales, y permite evaluar la contribución de los factores genéticos y ambientales a la modificación del metabolismo. Con el creciente número de "ómicas", se pueden utilizar nuevos enfoques para comprender los cambios metabólicos que ocurren en las plantas, especialmente en proteómica y metabolómica, y así esos análisis podrían perfilarse en los próximos años con el objetivo de conocer el alelopatoma de un mayor número. de las especies de plantas y sus interacciones. Objetivo: proporcionar una actualización reciente sobre la ciencia de la alelopatía en el contexto de la fisiología, la aplicación práctica de la metabolómica en los estudios alelopáticos, los aleloquímicos analizados por metabolómica en alfalfa, arroz, canola, sorgo, centeno, trigo y otros cultivos y, finalmente, mencionar los aspectos biológicos. actividad de los metabolitos secundarios alelopáticos. Métodos: se realizó una búsqueda bibliográfica exhaustiva reciente sobre alelopatía y metabolómica en bases de datos de revistas. Resultados: se detalla el concepto de alelopatía, los mecanismos alelopáticos, los estudios metabolómicos en alelopatía, los aleloquímicos analizados por metaboló-mica en alfalfa, arroz, canola, sorgo de centeno, trigo y otros cultivos de importancia agroindustrial, y la actividad biológica de los metabolitos secundarios alelopáticos. Conclusiones: estos estudios sugieren que se puede utilizar una combinación de metabolitos secundarios para atacar a las malas hierbas. Se recomienda el cultivo in situ e in vitro de metabolitos secundarios (de tipo aleloquímico) para ser utilizados como compuestos orgánicos en el control orgánico de las malas hierbas en el futuro.

Introdução: A alelopatia é um efeito nocivo produzido de forma indireta ou direta por uma planta a outra por meio da produção de substâncias químicas que adentram o meio ambiente. A alelopatia é importante para sistemas de manejo ecológico, sustentável e integrado. Essas reações naturais têm múltiplos efeitos, que vão desde processos de inibição e estimulação do crescimento em plantas vizinhas até a inibição da germinação de sementes. A metabolômica é uma disciplina integral que estuda todos os metabólitos em um determinado tecido, órgão ou organismo em um estágio de desenvolvimento específico ou condições ambientais particulares, e permite avaliar a contribuição de fatores genéticos e ambientais para a modificação do metabolismo. Com o crescente número de "ômicas", novas abordagens podem ser utilizadas para entender as alterações metabólicas que ocorrem nas plantas, principalmente em proteômica e metabolómica, e assim essas análises poderão ser perfiladas nos próximos anos com o objetivo de conhecer o alelopatoma de um número maior das espécies vegetais e suas interações. Objetivo: fornecer uma atualização recente sobre a ciência da alelopatia no contexto da fisiologia, aplicação prática da metabolômica em estudos alelopáticos, aleloquímicos analisados por metabolômica em alfafa, arroz, canola, sorgo, centeio, trigo e outras culturas e, finalmente, mencionar atividade de metabólitos secundários alelopáticos. Métodos: uma pesquisa bibliográfica abrangente recente sobre alelopatia e metabolismo foi conduzida em bancos de dados de periódicos. Resultados: o conceito de alelopatia, mecanismos alelopáticos, estudos metabólicos em alelopatia, aleloquímicos analisados por metabolômicos em alfafa, arroz, canola, sorgo de centeio, trigo e outros cultivos agroindustriais importantes, e a atividade biológica dos metabólitos secundários alelopáticos são detalhados. Conclusões: esses estudos sugerem que uma combinação de metabólitos secundários pode ser usada para atacar ervas daninhas. Recomenda-se o cultivo in situ e in vitro de metabólitos secundários (tipo alquímico) para uso como compostos orgânicos no controle de ervas daninhas orgânicas no futuro.

DIVERSIDAD GENÉTICA DE POBLACIONES DE GUANÁBANA (Annona muricata L.) EN NAYARIT, MÉXICO MEDIANTE MARCADORES SSR Y SRAP / Genetic diversity of soursop populations (Annona muricata L.) in Nayarit, Mexico using SSR and SRAP markers

RESUMEN La guanábana (Annona muricata L.) es un cultivo de importancia económica para Nayarit, México. Los frutos han tenido una excelente aceptación en el mercado regional, dificultando su comercialización a lugares lejanos porque la producción es altamente perecedera, aunado a que los árboles de los huertos de guanábana son en su mayoría ecotipos o fenotipos sin ningún plan de mejoramiento genético. Debido a la falta de variedades comerciales y de un banco de germoplasma, es importante conocer la diversidad genética para identificar y seleccionar genotipos; una de las herramientas para este propósito es el uso de marcadores moleculares. El objetivo de esta investigación fue analizar la diversidad genética de guanábana de las principales zonas productoras de Nayarit. Se extrajo ADN genómico de hojas de guanábana, las cuales fueron recolectadas de 11 huertos (poblaciones) de las siguientes zonas: Compostela (cinco poblaciones), Tepic (tres poblaciones) y San Blas (tres poblaciones). Posteriormente, se realizó un análisis mediante marcadores moleculares SSR y SRAP. Los resultados indicaron que los SSR no mostraron polimorfismo entre las poblaciones. Por otro lado, en los marcadores SRAP se obtuvieron 116 loci polimórficos con un promedio de porcentaje de loci polimórfico (P) entre las zonas productoras de 29,55 %. Asimismo, se realizó un AMOVA, el cual mostró que el mayor porcentaje de varianza se encuentra dentro de las poblaciones. Además, los análisis de agrupamiento demostraron la formación de tres grupos independientes. Por tanto, se obtuvo una alta homocigocidad y baja diversidad genética de guanábana entre las zonas y poblaciones estudiadas.

ABSTRACT Soursop (Annona muricata L.) is a crop of economic importance for Nayarit, Mexico. Soursop fruits have had an excellent acceptance in the regional market, making it difficult its commercialization to distant places because the production is highly perishable, in addition to the fact that the trees in the soursop orchards are mostly ecotypes or phenotypes without any genetic improvement plan. Due to the lack of commercial varieties and a germplasm bank, it is important to know the genetic diversity to identify and select genotypes; one of the tools for this purpose is the use of molecular markers. The objective of this research was to analyze the genetic diversity of soursop in the main producing areas of Nayarit. Genomic DNA was extracted from soursop leaves from 11 orchards (populations) in the following areas: Compostela (five populations), Tepic (three populations) and San Blas (three populations). Subsequently, we performed molecular analysis using SSR and SRAP molecular markers. The results indicated that the SSRs showed no polymorphism between the populations. On the other hand, we found 116 polymorphic loci in the SRAP markers with an average percentage of polymorphic loci (P) among the producing areas of 29.55 %. Likewise, an AMOVA was performed, showing that the highest percentage of variance is found within the populations. Furthermore, cluster analyzes demonstrated the formation of three independent groups. Therefore, a high homozygosity and low genetic diversity of soursop were obtained between the areas and populations studied.

Changes on the health care of people with multiple sclerosis from Latin America during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has resulted in uncertain access to medical treatment for people with multiple sclerosis (pwMS) all over the world. However, there is no data regarding its impact on access to health care of pwMS from Latin America. OBJECTIVES: We investigated and described changes in health care delivery for pwMS from Latin America during the COVID-19 pandemic. METHODS: PwMS from 18 patient organizations of the region completed a web-based survey hosted from May to October 2020. RESULTS: A total of 602 pwMS completed the questionnaire. Changes in disease-modifying therapies (DMTs) use: 6.7% of pwMS on continuous DMTs claimed to stopped them; 14.1% of those on infusion therapies declared to postpone their dosing; 68.8% declared delaying the initiation of a DMT. Disruptions in accessing rehabilitation services were reported by 65.7%. Changes in laboratory and MRI monitoring were reported by 30% and 33%, respectively. In a multivariable-adjusted logistic regression model, changes in laboratory monitoring were significantly associated with increased odds of postponing MRI monitoring (OR 4.09 CI95% 2.79-6.00, p < 0.001). CONCLUSIONS: The COVID-19 pandemic has disrupted all aspects of the routine care for pwMS from Latin America. Consequences are yet to be determined.

Evaluation and performance of a newly developed patient-reported outcome instrument for diarrhea-predominant irritable bowel syndrome in a clinical study population.

BACKGROUND: To evaluate the psychometric properties of the newly developed seven-item Irritable Bowel Syndrome - Diarrhea predominant (IBS-D) Daily Symptom Diary and four-item Event Log using phase II clinical trial safety and efficacy data in patients with IBS-D. This instrument measures diarrhea (stool frequency and stool consistency), abdominal pain related to IBS-D (stomach pain, abdominal pain, abdominal cramps), immediate need to have a bowel movement (immediate need and accident occurrence), bloating, pressure, gas, and incomplete evacuation. METHODS: Psychometric properties and responsiveness of the instrument were evaluated in a clinical trial population [ClinicalTrials.gov identifier: NCT01494233]. RESULTS: A total of 434 patients were included in the analyses. Significant differences were found among severity groups (p < 0.01) defined by IBS Patient Global Impression of Severity (PGI-S) and IBS Patient Global Impression of Change (PGI-C). Severity scores for each Diary and Event Log item score and five-item, four-item, and three-item summary scores were calculated. Between-group differences in changes over time were significant for all summary scores in groups stratified by changes in PGI-S (p < 0.05), two of six Diary items, and three of four Event Log items; a one-grade change in PGI-S was considered a meaningful difference with mean change scores on all Diary items -0.13 to -0.86 [standard deviation (SD) 0.79-1.39]. Similarly, for patients who reported being 'slightly improved' (considered a clinically meaningful difference) on the PGI-C, mean change scores on Diary items ranged from -0.45 to -1.55 (SD 0.69-1.39). All estimates of clinically important change for each item and all summary scores were small and should be considered preliminary. These results are aligned with the previous standalone psychometric study regarding reliability and validity tests. CONCLUSIONS: These analyses provide evidence of the psychometric properties of the IBS-D Daily Symptom Diary and Event Log in a clinical trial population.

Diarrhea-predominant irritable bowel syndrome: creation of an electronic version of a patient-reported outcome instrument by conversion from a pen-and-paper version and evaluation of their equivalence.

BACKGROUND: Subjects with diarrhea-predominant irritable bowel syndrome (IBS-D) experience abdominal cramping, bloating, pressure, and pain. Due to an absence of clinical biomarkers for IBS-D severity, evaluation of clinical therapy benefits depends on valid and reliable symptom assessments. A patient-reported outcome (PRO) instrument has been developed, comprising of two questionnaires - the IBS-D Daily Symptom Diary and IBS-D Symptom Event Log - suitable for clinical trials and real-world settings. This program aimed to support instrument conversion from pen-and-paper to electronic format. MATERIALS AND METHODS: Digital technology (Android/iOS) and a traditional mode of administration study in the target population were used to migrate or convert the validated PRO IBS-D pen-and-paper measure to an electronic format. Equivalence interviews, conducted in three waves, each had three parts: 1) conceptual equivalence testing between formats, 2) electronic-version report-history cognitive debriefing, and 3) electronic version usability evaluation. After each inter-view wave, preliminary analyses were conducted and modifications made to the electronic version, before the next wave. Final revisions were based on a full analysis of equivalence interviews. The final analysis evaluated subjects' ability to read, understand, and provide meaningful responses to the instruments across both formats. Responses were classified according to conceptual equivalence between formats and mobile-format usability assessed with a questionnaire and open-ended probes. RESULTS: Equivalence interviews (n=25) demonstrated conceptual equivalence between formats. Mobile-application cognitive debriefing showed some subjects experienced difficulty with font/screen visibility and understanding or reading some report-history charts and summary screens. To address difficulties, minor revisions/modifications were made and landscape orientation and zoom-in/zoom-out features incorporated. CONCLUSION: This study indicates that the two administration modes are conceptually equivalent. Since both formats are conceptually equivalent, both are psychometrically reliable, as established in the pen-and-paper version. Subjects found both mobile applications (Android/iOS) offered many advantages over the paper version, such as real-time assessment of their experience.

Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ASP2408, a Potent Selective T-Cell Costimulation Modulator After Single and Multiple Ascending Doses in Healthy Volunteers and RA Patients.

ASP2408 is a next-generation anti-cytotoxic T lymphocyte antigen-4 fusion protein engineered for improved CD86 binding affinity as a treatment for rheumatoid arthritis (RA). In 72 healthy subjects (n = 6/treatment), ASP2408 was administered as single ascending doses intravenously at 0.003 to 10.0 mg/kg or subcutaneously at 0.3 to 3.0 mg/kg. It showed decreased clearance and prolonged half-life with increasing doses, consistent with target-mediated disposition. The apparent bioavailability was 36.3%-56.7% across single subcutaneous doses. Sixteen RA patients (n = 8/treatment) on stable methotrexate received 3 × 3.0 mg/kg subcutaneously every 4 weeks or every 2 weeks. Similar to single-dose treatment, ASP2408 concentrations peaked 2 to 3 days postdose, with a median t1/2 of approximately 8 days. Using CD86 receptor occupancy (RO) as a mechanistic biomarker, ASP2408 demonstrated dose-dependent binding to its target. ASP2408 3.0 mg/kg subcutaneously every 4 weeks and every 2 weeks led to a mean %CD86 RO ≥ 74.7% and ≥ 81.5%, respectively, within each dosing interval. ASP2408 was well tolerated across studies with no evidence of dose-limiting toxicity or clinically significant changes in clinical laboratory test results, vital signs, or 12-lead electrocardiograms. ASP2408 elicited antidrug antibodies in the majority of patients, but with no clinical sequelae.

Cultural adaptation: translatability assessment and linguistic validation of the patient-reported outcome instrument for irritable bowel syndrome with diarrhea.

BACKGROUND AND OBJECTIVE: Following a 2009 US Food and Drug Administration guidance, a new patient-reported outcome (PRO) instrument was developed to support end points in multinational clinical trials assessing irritable bowel syndrome with diarrhea (IBS-D) symptom severity. Our objective was to assess the translatability of the IBS-D PRO instrument into ten languages, and subsequently perform a cultural adaptation/linguistic validation of the questionnaire into Japanese and US Spanish. MATERIALS AND METHODS: Translatability assessments of the US English version of the IBS-D PRO were performed by experienced PRO translators who were native speakers of each target language and currently residing in target-language countries. Languages were Chinese (People's Republic of China), Dutch (the Netherlands), French (Belgium), German (Germany), Japanese (Japan), Polish (Poland), Portuguese (Brazil), Russian (Russia), Spanish (Mexico), and Spanish (US). The project team assessed the instrument to identify potential linguistic and/or cultural adaptation issues. After the issues identified were resolved, the instrument was translated into Spanish (US) and Japanese through a process of two forward translations, one reconciled translation, and one backward translation. The project team reviewed the translated versions before the instruments were evaluated by cognitive debriefing interviews with samples of five Spanish (US) and five Japanese IBS-D patients. RESULTS: Linguistic and cultural adaptation concerns identified during the translatability assessment required minor revisions, mainly the presentation of dates/times and word structure. During the cognitive debriefing interviews, two of five Spanish respondents misunderstood the term "bowel movement" to mean only diarrhea in the Spanish version. Consequently, the term was changed from "movimiento intestinal" to "evacuaciones". None of the Japanese respondents identified issues with the Japanese version. CONCLUSION: The translatability of the IBS-D PRO instrument into ten target languages was confirmed, with only minor changes made to the translations of the instrument. The translation and linguistic validation into Spanish (US) and Japanese provide evidence that this instrument can be used in multinational trials and clinical settings.

A Phase 1 Dose-Escalation Study of ASP2409, a Selective T-Cell Costimulation Inhibitor, in Stable Rheumatoid Arthritis Patients on Methotrexate Therapy.

ASP2409 represents a new class of CTLA4-Ig molecules with higher binding avidity and selectivity to CD86. This first-in-human study was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ASP2409 in stable rheumatoid arthritis patients on methotrexate therapy with a randomized, double-blind, placebo-controlled dose-escalation study design. Patients were enrolled and randomized in each of 8 dose-escalation cohorts ranging from 0.001 to 3.0 mg/kg to receive either ASP2409 or placebo in a sequential manner. Escalation to higher dose levels occurred in the absence of dose-limiting toxicity. A total of 57 patients completed the study. ASP2409 showed nonlinear PK over the dose range of 0.01 to 3.0 mg/kg following a single intravenous administration, indicating target-mediated drug disposition. Area under the concentration-time curve (AUC) and maximum concentration (Cmax ) increased at a greater than dose-proportional rate. The half-life of ASP2409 increased dose dependently and ranged from 1.57 to 6.68 days. ASP2409 showed a dose-dependent increase in the extent and duration of CD86 receptor occupancy. There were no clinically relevant safety issues up to a single dose of 3.0 mg/kg. No maximum tolerated dose was reached. The incidence and duration of antidrug antibodies did not correlate with adverse events. ClinicalTrials.gov identifier: NCT02171143.

Psychometric assessment of the IBS-D Daily Symptom Diary and Symptom Event Log.

PURPOSE: Diarrhea-predominant irritable bowel syndrome (IBS-D) can considerably impact patients' lives. Patient-reported symptoms are crucial in understanding the diagnosis and progression of IBS-D. This study psychometrically evaluates the newly developed IBS-D Daily Symptom Diary and Symptom Event Log (hereafter, "Event Log") according to US regulatory recommendations. METHODS: A US-based observational field study was conducted to understand cross-sectional psychometric properties of the IBS-D Daily Symptom Diary and Event Log. Analyses included item descriptive statistics, item-to-item correlations, reliability, and construct validity. RESULTS: The IBS-D Daily Symptom Diary and Event Log had no items with excessive missing data. With the exception of two items ("frequency of gas" and "accidents"), moderate to high inter-item correlations were observed among all items of the IBS-D Daily Symptom Diary and Event Log (day 1 range 0.67-0.90). Item scores demonstrated reliability, with the exception of the "frequency of gas" and "accidents" items of the Diary and "incomplete evacuation" item of the Event Log. The pattern of correlations of the IBS-D Daily Symptom Diary and Event Log item scores with generic and disease-specific measures was as expected, moderate for similar constructs and low for dissimilar constructs, supporting construct validity. Known-groups methods showed statistically significant differences and monotonic trends in each of the IBS-D Daily Symptom Diary item scores among groups defined by patients' IBS-D severity ratings ("none"/"mild," "moderate," or "severe"/"very severe"), supporting construct validity. CONCLUSIONS: Initial psychometric results support the reliability and validity of the items of the IBS-D Daily Symptom Diary and Event Log.

Optimization of Alkaline and Dilute Acid Pretreatment of Agave Bagasse by Response Surface Methodology.

Utilization of lignocellulosic materials for the production of value-added chemicals or biofuels generally requires a pretreatment process to overcome the recalcitrance of the plant biomass for further enzymatic hydrolysis and fermentation stages. Two of the most employed pretreatment processes are the ones that used dilute acid (DA) and alkaline (AL) catalyst providing specific effects on the physicochemical structure of the biomass, such as high xylan and lignin removal for DA and AL, respectively. Another important effect that need to be studied is the use of a high solids pretreatment (≥15%) since offers many advantaged over lower solids loadings, including increased sugar and ethanol concentrations (in combination with a high solids saccharification), which will be reflected in lower capital costs; however, this data is currently limited. In this study, several variables, such as catalyst loading, retention time, and solids loading, were studied using response surface methodology (RSM) based on a factorial central composite design of DA and AL pretreatment on agave bagasse using a range of solids from 3 to 30% (w/w) to obtain optimal process conditions for each pretreatment. Subsequently enzymatic hydrolysis was performed using Novozymes Cellic CTec2 and HTec2 presented as total reducing sugar (TRS) yield. Pretreated biomass was characterized by wet-chemistry techniques and selected samples were analyzed by calorimetric techniques, and scanning electron/confocal fluorescent microscopy. RSM was also used to optimize the pretreatment conditions for maximum TRS yield. The optimum conditions were determined for AL pretreatment: 1.87% NaOH concentration, 50.3 min and 13.1% solids loading, whereas DA pretreatment: 2.1% acid concentration, 33.8 min and 8.5% solids loading.

Quality and shelf life of the gonad of lion's paw scallop transported and stored whole in refrigeration / Qualidade e vida de prateleira da gônada do bivalve pata de leão, transportado e armazenado inteiramente em refrigeração

The effect of refrigerated 48h transport and 4 days storage on the quality and shelf life of the whole lion's paw scallop Nodipecten subnodosus gonad was evaluated. Proximal composition, adenosine 5´triphosphate (ATP) and related products, K-value, total volatile bases (TVB-N), trimethylamine (TMA-N), pH, fatty acid profile and microbiological analyses were quantified. Gonad holds a significant composition of essential fatty acids while levels of gonadal ATP were initially low; moreover, K-value of the gonad remained constant. With respect to TVB-N and TMA-N, only the former exceeded allowed limits. The pH level showed no significant variation during storage and, despite the high level of TVB-N, according to the TMA-N as well as microbiological analyses it was demonstrated innocuity after 4 days under the transportation and storage conditions utilized.

Avaliou-se o efeito do transporte em refrigeração por 48 horas e quatro dias de armazenamento sobre a qualidade e vida de prateleira da gônada do bivalve pata de leão, Nodipecten subnodosus. Determinou-se a composição centesimal, a adenosina 5'trifosfato (ATP) e afins, o índice K, bases voláteis totais (TVB-N), trimetilamina (TMA-N), pH, perfil de ácidos graxos e análise microbiológica. A Gônada apresentou uma importante composição de ácidos graxos essenciais e baixos níveis iniciais de ATP, enquanto o índice K manteve-se constante. Quanto a TVB -N e TMA- N, apenas as primeiras ultrapassaram os limites admissíveis. Os valores de pH não mostraram nenhuma mudança significativa durante o armazenamento e, apesar dos altos níveis de TVB -N, de acordo com a análise quantitativa e microbiológica TMA- N, a segurança do produto foi demonstrada após quatro dias sob as condições de transporte e armazenamento utilizado.

Chemically pretreating slaughterhouse solid waste to increase the efficiency of anaerobic digestion.

The combined effect of temperature and pretreatment of the substrate on the anaerobic treatment of the organic fraction of slaughterhouse solid waste was studied. The goal of the study was to evaluate the effect of pretreating the waste on the efficiency of anaerobic digestion. The effect was analyzed at two temperature ranges (the psychrophilic and the mesophilic ranges), in order to evaluate the effect of temperature on the performance of the anaerobic digestion process for this residue. The experiments were performed in 6 L batch reactors for 30 days. Two temperature ranges were studied: the psychrophilic range (at room temperature, 18°C average) and the mesophilic range (at 37°C). The waste was pretreated with NaOH before the anaerobic treatment. The result of pretreating with NaOH was a 194% increase in the soluble chemical oxygen demand (COD) with a dose of 0.6 g NaOH per g of volatile suspended solids (VSS). In addition, the soluble chemical oxygen demand/total chemical oxygen demand ratio (sCOD/tCOD) increased from 0.31 to 0.7. For the anaerobic treatment, better results were observed in the mesophilic range, achieving 70.7%, 47% and 47.2% removal efficiencies for tCOD, total solids (TS), and volatile solids (VS), respectively.

Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure.

BACKGROUND: This study evaluated the efficacy and safety of levosimendan, a positive inotropic drug with vasodilator effects, given intravenously to patients with acutely decompensated heart failure (ADHF). METHODS: We performed 2 sequential trials, the first to develop a new measure of efficacy in 100 patients, and the second to use this measure to evaluate levosimendan in an additional 600 patients. Patients admitted with ADHF received placebo or intravenous levosimendan for 24 h in addition to standard treatment. The primary endpoint was a composite that evaluated changes in clinical status during the first 5 days after randomization. RESULTS: In the 600-patient trial, more levosimendan than placebo patients (58 vs. 44) were improved at all 3 pre-specified time points (6 h, 24 h, and 5 days), whereas fewer levosimendan patients (58 vs. 82) experienced clinical worsening (p = 0.015 for the difference between the groups). These differences were apparent, despite more frequent intensification of adjunctive therapy in the placebo group (79 vs. 45 patients). Improvements in patient self-assessment and declines in B-type natriuretic peptide levels with levosimendan persisted for 5 days and were associated with reduced length of stay (p = 0.009). Similar findings were present in the 100-patient pilot trial. Levosimendan was associated with more frequent hypotension and cardiac arrhythmias during the infusion period and a numerically higher risk of death across the 2 trials (49 of 350 on a regimen of levosimendan vs. 40 of 350 on a regimen of placebo at 90 days, p = 0.29). CONCLUSIONS: In patients with ADHF, intravenous levosimendan provided rapid and durable symptomatic relief. As dosed in this trial, levosimendan was associated with an increased risk of adverse cardiovascular events. (Evaluation of Intravenous Levosimendan Efficacy in the Short Term Treatment of Decompensated Chronic Heart Failure; NCT00048425).

A bifunctional endoglucanase/endoxylanase from Cellulomonas flavigena with potential use in industrial processes at different pH.

Cellulomonas flavigena CDBB-531 was found to secrete a bifunctional cellulase/xylanase with a molecular mass of 49 kDa and pI 4.3. This enzyme was active on Remazol brilliant blue-carboxymethylcellulose (RBB-CMC) and Remazol brilliant blue-xylan (RBB-X). Based on thin-layer chromatographic analysis of the degradation products, the cellulase activity produced glucose, cellobiose, cellotriose, and cellotetraose from CMC as the substrate. When xylan from birchwood was used, end products were xylose, arabinose, and xylobiose. The bifunctional enzyme showed a pH optimum of 6 for cellulase activity and 9 for xylanase activity, which pointed out that this enzyme had separate sites for each activity. In both cases, the apparent optimum temperature was 50 degrees C. The predicted amino acid sequence of purified protein showed similarity with the catalytic domain of several glycosyl hydrolases of family 10.

Differential expression of cellulases and xylanases by Cellulomonas flavigena grown on different carbon sources.

The diversity of cellulases and xylanases secreted by Cellulomonas flavigena cultured on sugar cane bagasse, Solka-floc, xylan, or glucose was explored by two-dimensional gel electrophoresis. C. flavigena produced the largest variety of cellulases and xylanases on sugar cane bagasse. Multiple extracellular proteins were expressed with these growth substrates, and a limited set of them coincided in all substrates. Thirteen proteins with carboxymethyl cellulase or xylanase activity were liquid chromatography/mass spectrometry sequenced. Proteins SP4 and SP18 were identified as products of celA and celB genes, respectively, while SP20 and SP33 were isoforms of the bifunctional cellulase/xylanase Cxo recently sequenced and characterized in C. flavigena. The rest of the detected proteins were unknown enzymes with either carboxymethyl cellulase or xylanase activities. All proteins aligned with glycosyl hydrolases listed in National Center for Biotechnology Information database, mainly with cellulase and xylanase enzymes. One of these unknown enzymes, protein SP6, was cross-induced by sugar cane bagasse, Solka-floc, and xylan. The differences in the expression maps of the presently induced cultures revealed that C. flavigena produces and secretes multiple enzymes to use a wide range of lignocellulosic substrates as carbon sources. The expression of these proteins depends on the nature of the cellulosic substrate.

Effects of intravenous ABT-870 (iron (III)-hydroxide oligosaccharide) on mean arterial pressure and heart rate in the anaesthetized beagle: comparison with other iron-containing haematinic agents.

Iron-deficiency anaemia, a complication of end-stage renal disease (ESRD), is often treated with parenteral iron therapies that have been shown to produce dose-limiting hypotension in patients. ABT-870 (iron-(III)-hydroxide-oligosaccharide) is comprised of elemental iron complexed with oligosaccharide, a composition that we hypothesised would allow the hypotensive effects of parenteral iron therapy to be overcome, thus allowing a rapid rate of infusion to be well tolerated. Mean arterial pressure (MAP) and heart rate (HR) were monitored in anaesthetized dogs following the infusion of ABT-870 and iron sucrose administered at doses of 7.1 and 21.3 mg/kg using a rapid 30 s infusion. ABT-870 and iron sucrose were also monitored at doses of 7.1, 21.3 and 50 mg/kg administered over a 10 min period. Sodium ferric gluconate complex (SFGC) was administered in an identical fashion at doses of 12.5 and 31.2 mg/kg. A 30 s rapid infusion of ABT-870 at doses of 7.1 and 14.3 mg/kg or a 10 min infusion of ABT-870 at doses of 7.1 and 21.3 mg/kg produced little effect on MAP and HR. Infusion of the highest dose of ABT-870 (50 mg/kg) produced no consistent hypotension, but did produce an increase in HR (maximal increase 35 +/- 9 b.p.m.), an effect that lasted only 15 min. A 30 s rapid infusion of iron sucrose at 7.1 mg/kg produced modest increases in MAP and HR (5 +/- 1 mmHg and 5 +/- 2 b.p.m., respectively). However, rapid infusion of iron sucrose at 14.3 mg/kg produced hypotension (to -8 +/- 1 mmHg below baseline) and exerted variable, biphasic effects on HR ranging from -16 to +50 b.p.m. Although 10 min infusion of iron sucrose at 7.1 mg/kg exerted little effect on MAP and HR, at doses of 21.3 and 50 mg/kg iron sucrose elicited a profound dose-dependent decrease in MAP (-34 +/- 11 and -83 +/- 5 mmHg, respectively) and a pronounced increase in HR ranging from 32 to 49 b.p.m. above baseline. A 10 min infusion of SFGC at doses of 12.5 and 31.2 mg/kg produced a dose-dependent decrease in MAP (-28 +/- 18 and -67 +/- 12 mmHg below baseline) and a marked increase in HR (26 +/- 11 and 94 +/- 15 b.p.m. above baseline). In conclusion, unlike iron sucrose and SFGC, high doses of ABT-870 failed to exert consistent hypotensive effects. These data demonstrate that ABT-870 may have a substantial therapeutic window and considerable clinical potential for iron-replacement therapy.

A model for the interim analysis process: a case study.

To evaluate data from a clinical trial before its completion, researchers routinely perform interim analyses. However, if not performed carefully, interim analyses can compromise the integrity of a clinical trial. In the last 10-15 years, regulatory authorities and the pharmaceutical industry have developed procedures and guidelines to allow trial sponsors access to unblinded data in an ongoing clinical trial without affecting the outcome. In December 1996, Abbott Laboratories was codeveloping a drug for treatment of an autoimmune disease. The pivotal phase II/III trial for the new drug application was very expensive, large, long term, and slow-accruing. The trial was initiated with a great deal of uncertainty concerning the safety and efficacy of the proposed treatment. An interim analysis was a logical part of the trial design. Two interim analyses were performed; the second analysis resulted in early termination of the trial. This article describes the interim analysis, including the process used for planning and execution and the lessons learned from the experience. In addition, the methodology for performing an interim analysis and the roles and responsibilities of involved members are discussed.