Prevalence and predictors of colon and prostate cancer screening among volunteer firefighters: The United States Firefighter Cancer Assessment and Prevention Study.

BACKGROUND: Although firefighters have increased risk for colon and prostate cancer, limited information exists on screening practices for these cancers in volunteer firefighters who compose two-thirds of the US fire service. We estimated the prevalence of colon and prostate cancer screening among volunteer firefighters using eligibility criteria from 4 evidence-based screening recommendations and evaluated factors influencing screening. METHODS: We evaluated colon (n = 569) and prostate (n = 498) cancer screening prevalence in a sample of US volunteer firefighters using eligibility criteria from the US Preventive Services Taskforce (USPSTF), National Fire Protection Association, American Cancer Society, and National Comprehensive Cancer Network. We assessed associations with fire service experience, demographics, and cancer risk perception based on USPSTF guidelines. RESULTS: For those eligible based on USPSTF guidelines, colon and prostate cancer screening prevalence was 51.7% (95% CI: 45.7, 57.8) and 48.8% (95% CI: 40.0, 57.6), respectively. Higher odds of colon and prostate cancer screening were observed with older age and with some college education compared to those with less education. Fire service experience and cancer risk perception were not associated with screening practices. CONCLUSION: This is the first large study to assess colon and prostate cancer screening among US volunteer firefighters based on different screening guidelines. Our findings suggest gaps in cancer prevention efforts in the US volunteer fire service. Promoting cancer screening education and opportunities for volunteer firefighters by their fire departments, healthcare professionals, and public health practitioners, may help to address the gaps.

Firefighter Well-Being Defined and Operationalized at the Organizational and Worker Level: A Qualitative Study.

OBJECTIVE: The aim of the study is to define and explore organizational- and worker-level factors of firefighter well-being. METHODS: Qualitative data were collected using interviews and focus group sessions among 17 career firefighters across 4 fire departments. Interviews were recorded and transcribed, and a general inductive approach was used to code similar concepts into themes. RESULTS: Firefighters defined well-being as being content with oneself and being able to balance ones' emotional, mental, and physical health. Themes contributing to firefighter well-being include the nature of the job, the influence of others, and physical health. Subthemes mapping to themes include dealing with trauma, compartmentalizing work and home life, coworkers and station culture, the role of superiors on attitudes and practices, being a reliable firefighter, and lack of sleep. CONCLUSIONS: Career firefighters describe well-being as a holistic approach to balancing emotional, mental, and physical health.

Safety evaluation of a multiallergen immunotherapy treatment in polyallergic patients. APOLO observational study.

Aim: Assessment of safety, tolerability and changes in global clinical impression with an multiallergen immunotherapy treatment without dilutional effect in polyallergic patients. Patients & methods: This observational prospective study included patients with allergic rhinitis-rhinoconjunctivitis with or without asthma between 5 and 60 years old receiving immunotherapy treatment with a mixture of two allergenic sources. All adverse events were recorded. Global clinical impression, tolerability subjective assessment and satisfaction were also assessed. Results: 130 patients were analyzed. Nine clinically relevant local adverse reactions were reported in six patients (4.6%). Six systemic reactions (grades 0-I) occurred in four patients (3.1%). Patients improved significantly in their global clinical impression. Good tolerability subjective assessment and satisfaction values were also observed. Conclusion: This multiallergen immunotherapy treatment without dilutional effect can be considered as a potential therapeutic alternative for polyallergic patients suffering from allergic rhinitis.

Preclinical Development of U3-1784, a Novel FGFR4 Antibody Against Cancer, and Avoidance of Its On-target Toxicity.

The FGFR4/FGF19 signaling axis is overactivated in 20% of liver tumors and currently represents a promising targetable signaling mechanism in this cancer type. However, blocking FGFR4 or FGF19 has proven challenging due to its physiological role in suppressing bile acid synthesis which leads to increased toxic bile acid plasma levels upon FGFR4 inhibition. An FGFR4-targeting antibody, U3-1784, was generated in order to investigate its suitability as a cancer treatment without major side effects.U3-1784 is a high-affinity fully human antibody that was obtained by phage display technology and specifically binds to FGFR4. The antibody inhibits cell signaling by competing with various FGFs for their FGFR4 binding site thereby inhibiting receptor activation and downstream signaling via FRS2 and Erk. The inhibitory effect on tumor growth was investigated in 10 different liver cancer models in vivo The antibody specifically slowed tumor growth of models overexpressing FGF19 by up to 90% whereas tumor growth of models not expressing FGF19 was unaffected. In cynomolgus monkeys, intravenous injection of U3-1784 caused elevated serum bile acid and liver enzyme levels indicating potential liver damage. These effects could be completely prevented by the concomitant oral treatment with the bile acid sequestrant colestyramine, which binds and eliminates bile acids in the gut. These results offer a new biomarker-driven treatment modality in liver cancer without toxicity and they suggest a general strategy for avoiding adverse events with FGFR4 inhibitors.

Tolerability and surrogate efficacy parameters of a polymerized depot mixture pollen extracts without dilutional effect.

Aim: To evaluate tolerability of subcutaneous immunotherapy, in a polymerized mixture (Olea europaea/Phleum pratense) depot presentation. Patients & methods: A total of 47 poly-allergic patients received: an abbreviated schedule with three injections at weekly intervals or a cluster schedule with two administrations in 1 day. Both treatments continued with 3 monthly maintenance administrations. Results: Two systemic reactions, (4.3%). One grade 0 and one grade I. No local reactions. Immunoglobulin levels, increased significantly at final visit versus baseline in sIgG and sIgG4; in both schedules and allergens, no significant changes in specific immunoglobulin E levels were detected. Cutaneous reactivity at final visit decreased significantly. Conclusion: Both administration schedules with polymerized mixture of O. europaea/P. pratense, presented an excellent tolerability profile and induced preliminary efficacy changes.

Search for normality criteria of auditory brain responses and auditory steady state response with free-field stimulation. / Búsqueda de criterios de normalidad de potenciales evocados auditivos de tronco cerebral y potenciales evocados auditivos de estado estable con estímulo en campo libre.

OBJECTIVE: To discover the thresholds of normality of the tests of ABR and ASSR in free-field stimulation compared with headphones. METHODS: Descriptive study of a series of cases of children without hearing loss carried out between April 2016 and January 2017. The ABR and conventional ASR were performed using insert headphones and free-field stimulation. RESULTS: Fifty-four ears were evaluated with absolute criteria of normality. The mean age was 16.7 months (SD=5.7). The evocation of the action potential at 70 dBs in the free-field showed a mean on wave I of 3.47ms, on wave II of 4.01, on wave III of 5.97, on wave IV of 6.71 and on wave V of 8.22. There is a statistically significant difference (p<.05) between the value obtained with insert earphones and the free-field on wave I (mean difference 1.91), on wave III (1.88), on wave IV (1.69) and on wave V (1.95), their being higher in stimulus in free field. There were no statistically significant differences in the interlatencies. The responses in the ASSR with free-field showed an increase of 1.56minutes compared to the headphones. CONCLUSIONS: The thresholds obtained in ABR by free-field were differentiated from those obtained by headphones in the increase of latencies, caused by delayed stimulation of the ear due to the distance between the sound source and the eardrum. Both tests are feasible by free-field stimulation, which would allow them to be applied routinely to patients on whom conventional tests cannot be performed.

Tolerability and positive efficacy results after subcutaneous immunotherapy with Parietaria judaica depot extract.

AIM: To evaluate tolerability and efficacy of Parietaria judaica subcutaneous immunotherapy on patients with allergic rhinoconjunctivitis. PATIENTS & METHODS: 51 patients were assigned to build-up scheme (six increasing doses) of P. judaica depot native extract, plus three maintenance monthly administrations. RESULTS: Out of 470 administered doses, only 3.8% elicited systemic reactions (1.5% nonspecific and 2.3% grade I). Concerning the exploratory efficacy parameters: cutaneous reactivity at the final visit versus baseline was significantly decreased; specific titers of IgG and IgG4 increased significantly and patients showed a significant decrease in the rhinitis symptoms score. CONCLUSION: P. judaica subcutaneous immunotherapy (Allergovac® depot ROXALL Medicina España S.A., Zamudio, Spain) with an abbreviated up-dosing scheme showed an adequate safety and tolerability profile and induced preliminary efficacy changes.

Musculoskeletal Pain and Interest in Meditation and Yoga in Home Health Aides: Evidence From the Home Health Occupations Musculoskeletal Examinations (HHOME) Study.

Home healthcare aides (HHAs) are a growing U.S. workforce highly susceptible to workplace stressors and musculoskeletal pain. In the present study we: 1) examine the association of musculoskeletal pain to life satisfaction and emotional exhaustion; and 2) characterize interest in meditation and yoga in a sample of HHAs. A nonprobabilistic sample of HHAs employed at home healthcare agencies in Florida, Massachusetts, and Oregon (n = 285 total) completed a self-administered questionnaire with standard survey measures on musculoskeletal pain location, duration, and severity; life satisfaction; emotional exhaustion; and interest in meditation techniques and yoga. Among HHAs responding, 48.4% reported pain in the last 7 days and 46.6% reported pain in the last 3 months. Home healthcare aides who reported current pain and chronic pain had a significant (P < .05) decrease in satisfaction with life score and a significant increase in emotional exhaustion score. The majority of HHAs reported an interest in learning about the benefits (65.6%) and practice (66.4%) of meditation and a willingness to participate in a yoga class (59.2%) or stress management meeting (59.1%). The HHAs reported both acute and chronic musculoskeletal pain that was correlated with lower life satisfaction and greater emotional exhaustion. More efforts are needed to reduce the sources of injury and emotional exhaustion.

Diabetes Drug Discovery: hIAPP1-37 Polymorphic Amyloid Structures as Novel Therapeutic Targets.

Human islet amyloid peptide (hIAPP1-37) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP1-37) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP1-37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP1-37. When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP1-37. Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP1-37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A-F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities.

Antibacterial Activities of Hibiscus sabdariffa Extracts and Chemical Sanitizers Directly on Green Leaves Contaminated with Foodborne Pathogens.

Leafy greens have been associated with foodborne disease outbreaks in different countries. To decrease microbial contamination of leafy greens, chemical agents are commonly used; however, a number of studies have shown these agents to have limited antimicrobial effect against pathogenic bacteria on vegetables. The objective of this study was to compare the antibacterial effect of Hibiscus sabdariffa calyx extracts (water, methanol, acetone, and ethyl acetate), sodium hypochlorite, acetic acid, and colloidal silver against foodborne bacteria on leafy greens. Thirteen foodborne bacteria were used in the study: Listeria monocytogenes, Shigella flexneri, Salmonella serotypes Typhimurium Typhi, and Montevideo, Staphylococcus aureus, Escherichia coli O157:H7, five E. coli pathotypes (Shiga toxin-producing, enteropathogenic, enterotoxigenic, enteroinvasive, and enteroaggregative), and Vibrio cholerae O1. Each foodborne bacterium was separately inoculated on romaine lettuce, spinach, and coriander leaves. Separately, contaminated leafy greens were immersed in four hibiscus extracts and in sanitizers for 5 min. Next, green leaves were washed with sterile tap water. Separately, each green leaf was placed in a bag that contained 0.1% sterile peptone water and was rubbed for 2 min. Counts were done by plate count using appropriate dilutions (in sterile peptone water) of the bacterial suspensions spread on Trypticase soy agar plates and incubated at 35 ± 2°C for 48 h. Statistically significant differences ( P < 0.05) were calculated with an analysis of variance and Duncan's test. All 13 foodborne bacteria attached to leafy greens. Roselle calyx extracts caused a significantly greater reduction ( P < 0.05) in concentration of all foodborne bacteria on contaminated romaine lettuce, spinach, and coriander than did the sodium hypochlorite, colloidal silver, and acetic acid. Dry roselle calyx extracts may potentially be a useful addition to disinfection procedures for romaine lettuce, spinach, and coriander.

Distribución y abundancia espacial y temporal de Stomolophus meleagris (Rhizostomae: Stomolophidae) en un sistema lagunar del sur del Golfo de México / Spatial and temporal abundance and distribution of Stomolophus meleagris (Rhizostomae: Stomolophidae) in a lagoon system Southern Gulf of Mexico

ResumenLas escifomedusas se alimentan principalmente de crustáceos microscópicos, huevos y larvas de peces, moluscos y de otras medusas. La distribución y abundancia de la escifomedusa tiene una importancia económica y ecológica ya que son depredadores que influyen en la dinámica poblacional de otras pesquerías. El presente trabajo se realizó de septiembre 2013 hasta agosto 2014 en el sistema lagunar Arrastradero-Redonda, Tabasco, con el objetivo de aportar información sobre la distribución y abundancia espacial y temporal de la escifomedusa Stomolophus meleagris y su relación con los parámetros ambientales. Para su realización se efectuaron recorridos mensuales durante un ciclo anual y se recolectaron muestras biológicas; realizándose tres arrastres en cada una de las estaciones, en una área de 1 km2, con una duración de 5 a 10 min con un chinchorro playero de monofilamento de 20 m de longitud por 3 m de altura y luz de malla de 1.5 cm, con esos datos se realizó el análisis de eficiencia pesquera, (CPUE con Org./Unidad de superficie evaluada) y se determinó la relación con los parámetros ambientales. Se estableció que la mayor abundancia se presentó de la estación 1 a la 3 con 7 a 19 Org/km2 en los meses de abril hasta agosto 2014 y su menor abundancia se observó en las estaciones 6 a 10 con un promedio de 1 Org./km2 desde octubre 2013 a marzo 2014. El análisis de correlación múltiple por pasos indicó que existe una fuerte asociación entre la CPUE y algunas variables ambientales estudiadas, observándose el 70.9 % de la variabilidad de los datos. La salinidad fue la variable más influyente explicando el 64.3 % de la variabilidad, seguida por la temperatura con un 3.6 % mientras el oxígeno disuelto explica solo el 2.9 % de variabilidad, principalmente debido a que en la zona confluyen una serie de factores geológicos, oceanográficos y biológicos favorables para la proliferación de esta especie debido al aporte de agua marina de la barra de Tupilco. Sin embargo falta realizar mayores investigaciones que permita cuantificar este recurso y establecer zonas de explotación comercial y realizar estudios sobre el aspecto biológico, principalmente hábitos reproductivos y alimenticios; que aporten información necesaria para diseñar planes adecuados sobre su posible uso de manera adecuada. Así mismo con los datos obtenidos en el presente trabajo podamos determinar el potencial pesquero de este recurso en el estado de Tabasco.

Abstract:The scyphomedusae feed mainly on microscopic crustaceans, eggs and fish larvae, molluscs and some other jellyfishes. The distribution and abundance of the scyphomedusae has an economic and ecological impact as they are predators that have an influence on the population dynamics of other fisheries. This investigation took place in the lagoon system 'ArrastraderoRedonda', Tabasco, from September 2013 to August 2014, with the purpose to provide information on the distribution, and spatial and temporal abundance of Stomolophus meleagris; along with its relation to environmental parameters. A total of 10 stations were defined and biological samples were taken on a monthly basis during this annual cycle. For this purpose, three pulls with a beach seine monofilament (20 m long by 3 m height, mesh opening 1.5 cm, 5 to 10 minutes) per station were made within a 1 km2 area. Information obtained was used to calculate the fishing efficiency analysis (CPUE con org./Evaluated Area Unit) and to determine the relationship with the environmental parameters. Our results showed that the abundance in the stations 1 to 3 was from 7 to 19 org./km2 from April to August 2014; less organisms were observed in stations 6 to 10 (an average of 1 org./ km2) from October 2013 to March 2014. The multiple correlation steps analysis indicated that there is a strong association between the CPUE and some environmental investigated variables, and a 70.9 % variability of the data was observed. The salinity resulted the most important variable because it determined a 64.3 % of variation; it was followed by the temperature with a 3.6 %; meanwhile, dissolved oxygen explained only the 2.9 %, this was mainly because within the area there are several geological, oceanographic and biological factors that favor the distribution of this species due to seawater contribution through the Tupilco bar. With the provided data with this investigation we were able to determine the fishery potential of this resource for Tabasco state. However, additional research is required to allow an extended quantification of this resource, to determine the commercial exploitation areas, and drive studies about reproductive and feeding habits, that may provide the necessary information to establish plans for sustainable use. Rev. Biol. Trop. 65 (1): 167-179. Epub 2017 March 01.

[Spatial and temporal abundance and distribution of Stomolophus meleagris (Rhizostomae: Stomolophidae) in a lagoon system southern Gulf of Mexico]. / Distribución y abundancia especial y temporal de Stomolophus meleagris (Rhizostomae: Stomolophidae) en un sistema lagunar del sur del Golfo de México.

The scyphomedusae feed mainly on microscopic crustaceans, eggs and fish larvae, molluscs and some other jellyfishes. The distribution and abundance of the scyphomedusae has an economic and ecological impact as they are predators that have an influence on the population dynamics of other fisheries. This investigation took place in the lagoon system 'Arrastradero-Redonda', Tabasco, from September 2013 to August 2014, with the purpose to provide information on the distribution, and spatial and temporal abundance of Stomolophus meleagris; along with its relation to environmental parameters. A total of 10 stations were defined and biological samples were taken on a monthly basis during this annual cycle. For this purpose, three pulls with a beach seine monofilament (20m long by 3m height, mesh opening 1.5 cm, 5 to 10 minutes) per station were made within a 1 km2 area. Information obtained was used to calculate the fishing efficiency analysis (CPUE con org./Evaluated Area Unit) and to determine the relationship with the environmental parameters. Our results showed that the abundance in the stations 1 to 3 was from 7 to 19 org./km2 from April to August 2014; less organisms were observed in stations 6 to 10 (an average of 1 org./km2) from October 2013 to March 2014. The multiple correlation steps analysis indicated that there is a strong association between the CPUE and some environmental investigated variables, and a 70.9 % variability of the data was observed. The salinity resulted the most important variable because it determined a 64.3 % of variation; it was followed by the temperature with a 3.6 %; meanwhile, dissolved oxygen explained only the 2.9 %, this was mainly because within the area there are several geological, oceanographic and biological factors that favor the distribution of this species due to seawater contribution through the Tupilco bar. With the provided data with this investigation we were able to determine the fishery potential of this resource for Tabasco state. However, additional research is required to allow an extended quantification of this resource, to determine the commercial exploitation areas, and drive studies about reproductive and feeding habits, that may provide the necessary information to establish plans for sustainable use.

Kinesiotaping. Evidencia actual / Kinesiotaping. Current evidence

En este artículo se revisa la función y el uso de los vendajes tipo Kinesiotaping en la medicina deportiva actual y la Ortopedia. Se estudian las diferentes lesiones dentro de la medicina del deporte en la cual se pueden usar y la evidencia clínica existente. Esta revisión concluye que la utilidad del kinesiotaping es confusa. La literatura no aporta evidencia clínica probada sobre el uso de este vendaje e incluso podría intuirse un fin mercantilista en su uso

This paper reviews the function and use of Kinesiotaping in today’s Sports Medicine and Orthopedics. The different sports medicine injuries in which could be used and the current clinical evidence are reviewed. This review concludes the utility of Kinesiotaping is not clear. Literature shows lack of proved clinical evidence about the use of this bandage and even a mercantilist purpose could be suspected

Timothy grass pollen therapeutic vaccine: optimal dose for subcutaneous immunotherapy.

AIMS: To establish the optimal dose of Phleum pratense subcutaneous immunotherapy (SCIT) in patients with allergic rhinoconjunctivitis with/without asthma. MATERIALS & METHODS: One hundred and fifty-one patients were randomized to receive SCIT 0.25, 0.5, 1.0, 2.0 or 4.0 skin-prick test units (SPT) or placebo. The primary end point was the variation in the concentration of Phleum pratense extract needed to produce a positive nasal provocation test from baseline (V0) to final visit (FV). RESULTS: After 17 weeks, a dose-dependent trend was apparent in the concentration of P. pratense extract needed to produce a positive nasal provocation response. Systemic adverse reactions occurred with 3.2% of administered doses. Grade III (n = 2) and IV (n = 2) events were observed only at the two highest doses. CONCLUSION: P. pratense depot SCIT showed signs of clinical and immunological efficacy by dose-dependently decreasing the allergen sensitization rate. Risk-benefit favored doses below 1.0 SPT units for confirmatory trials.

Changes in body composition in heart failure patients after a resistance exercise program and branched chain amino acid supplementation.

BACKGROUND & AIMS: Heart Failure (HF) is a complex syndrome, which can include the physiological, neural hormonal and metabolic complications known as "Cardiac Cachexia" (CC). In the development of CC there is a release of catabolic cytokines (Tumor Necrosis Factor-α, interleukins 1 and 6) that cause a decrease of fat free mass and fat mass. These changes in body composition might be reversed with a therapeutic combination of resistance exercise and branched chain amino acid supplementation (BCAA). AIM: Evaluate changes in body composition after a resistance exercise program and BCAA supplementation in patients with HF. METHODS: In a randomized clinical trial with 3 month of follow-up anthropometric body composition analysis and stress tests were evaluated at the beginning and in the end of the study. Patients were divided into two groups; the experimental group performed the resistance exercise program and received 10 g/day BCAA supplementation, and the control group only performed the resistance exercise program. Both groups were provided with individualized diets and conventional medical treatment. RESULTS: Changes were found in hip circumference between the groups (p = 0.02), and muscle strength was increased in the experimental group (8%) and the control group (11.4%) with no difference between them. METS and VO2Max also increased in experimental and control groups (16.6% and 50.1% respectively). Regarding changes in symptoms, improvements in fatigue (45.4%), decubitus intolerance (21.8%) and dyspnea (25.4%) were observed in the overall sample. CONCLUSION: Improvements in physical and functional capacities are attributed to resistance exercise program but not to the BCAA supplementation. CLINICAL TRIALS IDENTIFIER: NCT02240511.

Dystonia in Machado-Joseph disease: Clinical profile, therapy and anatomical basis.

INTRODUCTION: Dystonia is frequent in Machado-Joseph disease, but several important aspects are not yet defined, such as the detailed clinical profile, response to treatment and anatomical substrate. METHODS: We screened 75 consecutive patients and identified those with dystonia. The Burke-Marsden-Fahn Dystonia Rating Scale was employed to quantify dystonia severity. Patients with dystonia received levodopa 600 mg/day for 2 months and were videotaped before and after treatment. A blinded evaluator rated dystonia in the videos. Patients with disabling dystonia who failed to respond to levodopa treatment received botulinum toxin. Finally, volumetric T1 and diffusion tensor imaging sequences were obtained in the dystonic group using a 3T-MRI scanner to identify areas of gray and white matter that were selectively damaged. RESULTS: There were 21 patients with dystonia (28%): 9 classified as generalized and 12 as focal/segmental. Patients with dystonia had earlier onset and larger (CAG) expansions (28.9 ± 11.7 vs 40.6 ± 11.4; p < 0.001 and 75 vs 70; p < 0.001, respectively). Although group analyses failed to show benefit on levodopa (p = 0.07), some patients had objective improvement. In addition, ten patients received botulinum toxin resulting in a significant change in dystonia scores after 4 weeks (p = 0.03). Patients with dystonia had atrophy at pre- and paracentral cortices; whereas, non-dystonic patients had occipital atrophy. Basal ganglia volume was reduced in both groups, but atrophy at the thalami, cerebellar white matter and ventral diencephali was disproportionately higher in the dystonic group. CONCLUSION: Dystonia in Machado-Joseph disease is frequent and often disabling, but may respond to levodopa. It is associated predominantly with structural abnormalities around the motor cortices and in the thalami.

A Phase I clinical trial with subcutaneous immunotherapy vaccine of Timothy grass pollen extract according to EMA guidelines.

AIM: A double-blind placebo-controlled study was conducted according to EMA guidelines, to evaluate safety, tolerability and short-term treatment effects of three up-dosing regimens of Phleum pratense subcutaneous immunotherapy. MATERIALS & METHODS: Forty-two patients were randomized to groups: A (6 weekly doses), B (8 weekly doses) or C (eight doses, two clustered increasing doses over 3 weeks). RESULTS: The most frequent adverse events were local reactions. No serious adverse events were found. Higher number and more severe systemic reactions were reported in group C. A decrease in cutaneous responses and an increase of specific antibodies was shown in all active groups even at very short-term. CONCLUSION: Phleum pratense subcutaneous immunotherapy in depot presentation exhibited good safety and tolerability. Group A seemed to show the best profile.

Public health 101 nanocourse: a condensed educational tool for non-public health professionals.

Graduate students and postdoctoral fellows-including those at the Harvard School of Public Health (HSPH)-have somewhat limited opportunities outside of traditional coursework to learn holistically about public health. Because this lack of familiarity could be a barrier to fruitful collaboration across disciplines, HSPH postdocs sought to address this challenge. In response, the Public Health 101 Nanocourse was developed to provide an overview of five core areas of public health (biostatistics, environmental health sciences, epidemiology, health policy and management, and social and behavioral sciences) in a two half-day course format. We present our experiences with developing and launching this novel approach to acquainting wider multidisciplinary audiences with the field of public health.

In vitro and in vivo evaluation of water-soluble iminophosphorane ruthenium(II) compounds. A potential chemotherapeutic agent for triple negative breast cancer.

A series of organometallic ruthenium(II) complexes containing iminophosphorane ligands have been synthesized and characterized. Cationic compounds with chloride as counterion are soluble in water (70-100 mg/mL). Most compounds (especially highly water-soluble 2) are more cytotoxic to a number of human cancer cell lines than cisplatin. Initial mechanistic studies indicate that the cell death type for these compounds is mainly through canonical or caspase-dependent apoptosis, nondependent on p53, and that the compounds do not interact with DNA or inhibit protease cathepsin B. In vivo experiments of 2 on MDA-MB-231 xenografts in NOD.CB17-Prkdc SCID/J mice showed an impressive tumor reduction (shrinkage) of 56% after 28 days of treatment (14 doses of 5 mg/kg every other day) with low systemic toxicity. Pharmacokinetic studies showed a quick absorption of 2 in plasma with preferential accumulation in the breast tumor tissues when compared to kidney and liver, which may explain its high efficacy in vivo.

Diseño asistido por computadora de la inmovilización covalente de bromelina y papaína / Computer-aided design of bromelain and papain covalent immobilization

Enzymes as immobilized derivatives have been widely used in Food, Agrochemical, Pharmaceutical and Biotechnological industries. Protein immobilization is probably the most used technology to improve the operational stability of these molecules. Bromelain (Ananas comosus) and papain (Carica papaya) are cystein proteases extensively used as immobilized biocatalyst with several applications in therapeutics, racemic mixtures resolution, affinity chromatography and others industrial scenarios. The aim of this work was to optimize the covalent immobilization of bromelain and papain via rational design of immobilized derivatives strategy (RDID) and RDID1.0 program. Were determined the maximum protein quantity to immobilize, the optimum immobilization pH (in terms of functional activity retention), was predicted the most probable configuration of the immobilized derivative and the probabilities of multipoint covalent attachment. As support material was used Glyoxyl-Sepharose CL 4B. The accuracy of RDID1.0 program´s prediction was demonstrated comparing with experimental results. Bromelain and papain immobilized derivatives showed desired characteristics for industrial biocatalysis, such as: elevate pH stability retaining 95% and 100% residual activity at pH 7.0 and 8.0, for bromelain and papain, respectively; high thermal stability at 30 °C retaining 90% residual activity for both immobilized enzymes; a catalytic configuration bonded by immobilization at optimal pH; and the ligand load achieve ensure the minimization of diffusional restrictions.

Las enzimas inmovilizadas han sido ampliamente utilizadas en las industrias Alimentaria, Agroquímica, Farmacéutica y Biotecnológica. La inmovilización de proteínas es, probablemente, la tecnología más empleada para elevar la estabilidad operacional de estas moléculas. La bromelina (Ananas comosus) y la papaína (Carica papaya) son cisteín proteasas extensamente usadas como biocatalizadores inmovilizados con disímiles aplicaciones en la terapéutica, resolución de mezclas racémicas, cromatografía de afinidad, entre otros escenarios industriales. El objetivo del presente trabajo fue optimizar la inmovilización covalente de las enzimas bromelina y papaína a través de la estrategia de diseño racional de derivados inmovilizados (RDID) y el programa RDID1.0. Se predijo la cantidad máxima de proteína a inmovilizar, el pH óptimo de inmovilización (en términos de retención de la actividad funcional), la configuración más probable del derivado inmovilizado y la probabilidad de enlazamiento covalente multipuntual. Como soporte de inmovilización de empleó Glioxil-Sepharose CL 4B. La precisión de las predicciones llevadas a cabo con el programa RDID1.0 fue validada comparando con los resultados experimentales obtenidos. Los derivados inmovilizados de bromelina y papaína mostraron características deseadas para la biocatálisis a nivel industrial, tales como: elevada estabilidad al pH reteniendo el 95% y 100% de actividad residual a pH 7.0 y 8.0, para la bromelina y la papaína, respectivamente; una elevada estabilidad térmica con la retención del 90% de actividad residual a 30 °C para ambas enzimas; al pH de inmovilización óptimo la configuración obtenida es catalíticamente competente; y la carga de ligando alcanzada asegura la disminución de las restricciones difusionales.