Cytochrome P450 from Plants: Platforms for Valuable Phytopharmaceuticals

Cytochrome P450 enzymes are important for biotechnology due to their capacity to modify diverse secondary metabolites that may produce chemicals with pharmacological properties. Most terpenes, flavonoids and alkaloids require P450 catalytic functions to reach their biological activity. In the last ten years, several efforts have focused on the expression and production of these three main types of secondary metabolites in engineered microorganisms and plants using P450 of ethnobotanical origin. Despite this, several P450 coding sequences from plant sources are discovered yearly but only a few have been screened by functional genomics. Amongst them, only a few have shown potentials for use in sustainable production of novel drugs and highly valuable products. Cytochrome P450 involvement in the biosynthesis of these products is discussed in this work.Keywords: Biotechnological platforms, Cytochrome P450, Phytopharmaceuticals, Yield improvement, Terpenes, Flavonoids, Alkaloids, Microbial expressio

Quantifying the contribution of single joint kinematics to the overall ergonomic discomfort

Work-related musculoskeletal disorders (WMSDs) represent one of the major issues concerning the occupational safety and health of workers. Thus, a reliable evaluation of workers’ exposure to the risk factors that may contribute to WMSDs development is mandatory, above all, within an industrial context. At present, standard synthetic indices are widely used in this frame, presenting – however - several limitations due to poor reliability and time efficiency. The aim of this work was to investigate the contribution of the displacement quantified for each single joint during the execution of simple reaching tasks, to the overall discomfort of the worker evaluated by means of standard observational methods. Forty-five healthy volunteers were included in the analysis; each subject was asked to reach and rotate 2 spheres placed on a custom-made rack in standardized positions, i.e., above the head and one at floor level at centre side. Whole-body kinematics was acquired via a system based on wearable inertial measurement units. Standard ergonomic scales including RULA (Rapid Upper Limb Assessment), REBA (Rapid Entire Body Assessment), and MMGA (Method for Movement and Gesture Assessment), were assessed for each subject and each sphere position. Moreover, a quantitative index based on actual joint kinematics, i.e., W1 index, was computed for each joint angle involved in the task. Correlation analysis was performed for W1 relative to each joint with respect to RULA, REBA, and MMGA scores. Considering REBA and MMGA scores, the most comfortable reaching areas were the ones in which the sphere was positioned at the top; in contrast, the lowest positions evidenced the most increased discomfort indexes. The RULA did not result sensitive to the different positions, while REBA and MMGA seemed to be more influenced by the range of motion of the lower limb joint angles than the upper limb ones. This study underlines the necessity to focus on multiple potential contributors to WMSDs and underlines the importance of subject-specific approaches toward risk assessment by exploiting quantitative measurements and wearable technologies, which indeed represent key enabling approaches even in consideration of the novel “Industry 5.0” perspective

ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population

Quantum effects:heat flow in atomic bottlenecks

The Wiedemann–Franz law linking electrical and thermal conductance has now been verified experimentally in atomic junctions

Pensando un rediseño de agroecosistemas campesinos del Chaco Semiárido argentino: el caso de la asociación campesinos del Valle del Conlara (San Luis, Argentina)

La expansión del modelo de agricultura industrial en la región chaqueña ha generado fuertes cambios ambientales y sociales (desmontes masivos, pérdida de biodiversidad, expulsión de campesinos). Desde 2009, estudiantes, docentes e investigadores de la Universidad de Buenos Aires trabajan junto a campesinos y técnicos locales de la Asociación Campesinos del Valle del Conlara (San Luis, Argentina; ACVC), en pensar cómo mejorar la cantidad, calidad y estabilidad de la oferta forrajera del monte nativo. Partimos de una caracterización preliminar de los agroecosistemas campesinos, publicada en SOCLA (2013). Aquí, nos proponemos compartir las reflexiones sobre alternativas de rediseño y manejo agroecológico, así como los trabajos que se realizaron en la ACVC en este sentido. Este trabajo se enmarca dentro de un proyecto interdisciplinario, cuyo propósito es contribuir al fortalecimiento de la autonomía ecológica y económica de los campesinos, una alternativa al modelo hegemónico.Eje: B5 Sistemas de conocimiento (Relatos de experiencias)Facultad de Ciencias Agrarias y Forestale

Pensando un rediseño de agroecosistemas campesinos del Chaco Semiárido argentino: el caso de la asociación campesinos del Valle del Conlara (San Luis, Argentina)

La expansión del modelo de agricultura industrial en la región chaqueña ha generado fuertes cambios ambientales y sociales (desmontes masivos, pérdida de biodiversidad, expulsión de campesinos). Desde 2009, estudiantes, docentes e investigadores de la Universidad de Buenos Aires trabajan junto a campesinos y técnicos locales de la Asociación Campesinos del Valle del Conlara (San Luis, Argentina; ACVC), en pensar cómo mejorar la cantidad, calidad y estabilidad de la oferta forrajera del monte nativo. Partimos de una caracterización preliminar de los agroecosistemas campesinos, publicada en SOCLA (2013). Aquí, nos proponemos compartir las reflexiones sobre alternativas de rediseño y manejo agroecológico, así como los trabajos que se realizaron en la ACVC en este sentido. Este trabajo se enmarca dentro de un proyecto interdisciplinario, cuyo propósito es contribuir al fortalecimiento de la autonomía ecológica y económica de los campesinos, una alternativa al modelo hegemónico.Eje: B5 Sistemas de conocimiento (Relatos de experiencias)Facultad de Ciencias Agrarias y Forestale

Relationship of metabolic syndrome and its components with -844 G/A and HindIII C/G PAI-1 gene polymorphisms in Mexican children

<p>Abstract</p> <p>Background</p> <p>Several association studies have shown that -844 G/A and <it>HindIII </it>C/G <it>PAI-1 </it>polymorphisms are related with increase of PAI-1 levels, obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia, which are components of metabolic syndrome. The aim of this study was to analyze the allele and genotype frequencies of these polymorphisms in <it>PAI-1 </it>gene and its association with metabolic syndrome and its components in a sample of Mexican mestizo children.</p> <p>Methods</p> <p>This study included 100 children with an age range between 6-11 years divided in two groups: a) 48 children diagnosed with metabolic syndrome and b) 52 children metabolically healthy without any clinical and biochemical alteration. Metabolic syndrome was defined as the presence of three or more of the following criteria: fasting glucose levels ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, HDL-cholesterol < 40 mg/dL, obesity BMI ≥ 95^thpercentile, systolic blood pressure (SBP) and diastolic blood pressure (DBP) ≥ 95^thpercentile and insulin resistance HOMA-IR ≥ 2.4. The -844 G/A and <it>HindIII </it>C/G <it>PAI-1 </it>polymorphisms were analyzed by PCR-RFLP.</p> <p>Results</p> <p>For the -844 G/A polymorphism, the G/A genotype (OR = 2.79; 95% CI, 1.11-7.08; <it>p </it>= 0.015) and the A allele (OR = 2.2; 95% CI, 1.10-4.43; <it>p </it>= 0.015) were associated with metabolic syndrome. The -844 G/A and A/A genotypes were associated with increase in plasma triglycerides levels (OR = 2.6; 95% CI, 1.16 to 6.04; <it>p </it>= 0.02), decrease in plasma HDL-cholesterol levels (OR = 2.4; 95% CI, 1.06 to 5.42; <it>p </it>= 0.03) and obesity (OR = 2.6; 95% CI, 1.17-5.92; <it>p </it>= 0.01). The C/G and G/G genotypes of the <it>HindIII </it>C/G polymorphism contributed to a significant increase in plasma total cholesterol levels (179 vs. 165 mg/dL; <it>p </it>= 0.02) in comparison with C/C genotype.</p> <p>Conclusions</p> <p>The -844 G/A <it>PAI-1 </it>polymorphism is related with the risk of developing metabolic syndrome, obesity and atherogenic dyslipidemia, and the <it>HindIII </it>C/G <it>PAI-1 </it>polymorphism was associated with the increase of total cholesterol levels in Mexican children.</p

Risk Factors for Thyroid Dysfunction in Pregnancy:An Individual Participant Data Meta-Analysis

Background:International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin &gt;10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age &gt;30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied &lt;2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p &lt; 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p &lt; 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p &lt; 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p &lt; 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.</p

Os alunos de administração estão em sintonia com o mercado de trabalho?

This article provides a survey of the demands placed by the labor market in relation to the profile of business administration professionals. It describes the characteristics of such profile and analyzes how UNESP/Tupa´s administration students fare in relation to such questions. The points raised show that the labor market is interested not only in technical-academic knowledge but also in knowledge and interpersonal and extracurricular skills. These points were identified through studies of the pertinent literature study and based on consultation of apprenticeship and employment forms of UNESP/Tupa´s job extension project for Internships and Jobs. The comparison between these sources made it possible to identify the main skills sought by companies when searching for an administrator. With the characterization of the object of study it was possible to compare the stage level in which the student was placed (3rd , 5th and 7th semesters), in regard to both day and night shifts, verifying whether these skills evolved with the student´s trajectory through the program. The study also concludes that it is not enough for administration students to restrict their training to academic knowledge. An appropriate profile demands the development of extracurricular activities that enhance competencies such as computer skills and languages. Relevant findings demonstrated that the education of students and how they react to demands are strongly connected to market demands.O presente artigo realiza o levantamento de demandas em relação ao perfil dos profissionais de Administração pelo mercado de trabalho, descreve tais características e analisa como os alunos do curso de Administração da UNESP/Tupã se encontram em relação a tais quesitos. Os pontos levantados demonstram interesses do mercado de trabalho não somente para conhecimentos de formação técnica-acadêmica, como também, conhecimentos e habilidades interpessoais e extracurriculares. Estes pontos foram identificados através de um estudo bibliográfico e da consulta a formulários de vagas de estágio e emprego do projeto de extensão Balcão de Estágios e Empregos, na UNESP/Tupã. A partir da comparação entre estas fontes, foi possível identificar as principais competências procuradas pelas empresas no perfil de um administrador. Com caracterização do objeto de estudo foi possível realizar comparações em relação ao termo em que o aluno se encontrava no curso (3º, 5º e 7º semestres), tanto como em relação ao período (diurno e noturno), verificando se tais competências evoluíam com o passar do curso. O trabalho conclui também que não basta para os alunos de administração restringir sua formação apenas com os conhecimentos acadêmicos, sendo necessário para a formação de um perfil adequado, o desenvolvimento de atividades extracurriculares que incrementem competências como conhecimento de informática e idiomas. Constatações relevantes demonstraram que a formação dos alunos, e a forma como reagem às demandas, estão fortemente conectadas às exigências de mercado.Universidade Estadual Paulista Julio de Mesquita FilhoUniversidade Estadual Paulista Julio de Mesquita Filh