Integrated Approach from Sample-to-Answer for Grapevine Varietal Identification on a Portable Graphene Sensor Chip.

Identifying grape varieties in wine, related products, and raw materials is of great interest for enology and to ensure its authenticity. However, these matrices' complexity and low DNA content make this analysis particularly challenging. Integrating DNA analysis with 2D materials, such as graphene, offers an advantageous pathway toward ultrasensitive DNA detection. Here, we show that monolayer graphene provides an optimal test bed for nucleic acid detection with single-base resolution. Graphene's ultrathinness creates a large surface area with quantum confinement in the perpendicular direction that, upon functionalization, provides multiple sites for DNA immobilization and efficient detection. Its highly conjugated electronic structure, high carrier mobility, zero-energy band gap with the associated gating effect, and chemical inertness explain graphene's superior performance. For the first time, we present a DNA-based analytic tool for grapevine varietal discrimination using an integrated portable biosensor based on a monolayer graphene field-effect transistor array. The system comprises a wafer-scale fabricated graphene chip operated under liquid gating and connected to a miniaturized electronic readout. The platform can distinguish closely related grapevine varieties, thanks to specific DNA probes immobilized on the sensor, demonstrating high specificity even for discriminating single-nucleotide polymorphisms, which is hard to achieve with a classical end-point polymerase chain reaction or quantitative polymerase chain reaction. The sensor was operated in ultralow DNA concentrations, with a dynamic range of 1 aM to 0.1 nM and an attomolar detection limit of ∼0.19 aM. The reported biosensor provides a promising way toward developing decentralized analytical tools for tracking wine authenticity at different points of the food value chain, enabling data transmission and contributing to the digitalization of the agro-food industry.

Extracellular matrix in skin diseases: The road to new therapies.

BACKGROUND: The extracellular matrix (ECM) is a vital structure with a dynamic and complex organization that plays an essential role in tissue homeostasis. In the skin, the ECM is arranged into two types of compartments: interstitial dermal matrix and basement membrane (BM). All evidence in the literature supports the notion that direct dysregulation of the composition, abundance or structure of one of these types of ECM, or indirect modifications in proteins that interact with them is linked to a wide range of human skin pathologies, including hereditary, autoimmune, and neoplastic diseases. Even though the ECM's key role in these pathologies has been widely documented, its potential as a therapeutic target has been overlooked. AIM OF REVIEW: This review discusses the molecular mechanisms involved in three groups of skin ECM-related diseases - genetic, autoimmune, and neoplastic - and the recent therapeutic progress and opportunities targeting ECM. KEY SCIENTIFIC CONCEPTS OF REVIEW: This article describes the implications of alterations in ECM components and in BM-associated molecules that are determinant for guaranteeing its function in different skin disorders. Also, ongoing clinical trials on ECM-targeted therapies are discussed together with future opportunities that may open new avenues for treating ECM-associated skin diseases.

Hydroxypropyl methylcellulose-based micro- and nanostructures for encapsulation of melanoidins: Effect of electrohydrodynamic processing variables on morphological and physicochemical properties.

Electrohydrodynamic processing (EHDP) allows the use of a wide range of biopolymers and solvents, including food-grade biopolymers and green solvents, for the development of micro- and nanostructures. These structures present a high surface-area-to-volume ratio and different shapes and morphologies. The aim of this work was to design and produce hydroxypropyl methylcellulose (HPMC)-based micro- and nanostructures through EHD processing using green solvents, while exploring the influence of process and solution parameters, and incorporating a bioactive extracted from a food by-product. Low (LMW) and high (HMW) molecular weight HPMC have been used as polymers. The design-of-experiments methodology was used to determine the effects of process parameters (polymer concentration, flow rate, tip-to-collector distance, and voltage) of EHDP on the particle and fibre diameter, aspect ratio, diameter distribution, aspect ratio distribution, and percentage of fibre breakage. Additionally, melanoidins extracted from spent coffee grounds were encapsulated into the HPCM-based structures at a concentration of 2.5 mg melanoidins/mL of the polymer solution. Polymer solutions were characterised regarding their viscosity, surface tension and conductivity, and showed that the incorporation of melanoidins increased the viscosity and conductivity values of the polymer solutions. The developed structures were characterised regarding their thermal properties, crystallinity and morphology before and after melanoidin incorporation and it was observed that melanoidin incorporation did not significantly influence the characteristics of the produced micro- and nanostructures. Based on the results, it is possible to envision the use of the produced micro- and nanostructures in a wide range of applications, both in food and biomedical fields.

Dielectric spectroscopy of melt-extruded polypropylene and as-grown carbon nanofiber composites.

In this work, different weight contents of as-grown carbon nanofibers (CNFs), produced by chemical vapor deposition, were melt-extruded with polypropylene (PP) and their morphologic, structure and dielectric properties examined. The morphologic analysis reveals that the CNFs are randomly distributed in the form of agglomerates within the PP matrix, whereas the structural results depicted by Raman analysis suggest that the degree of disorder of the as-received CNFs was not affected in the PP/CNF composites. The AC conductivity of PP/CNF composites at room temperature evidenced an insulator-conductor transition in the vicinity of 2 wt.%, corresponding to a remarkable rise of the dielectric permittivity up to [Formula: see text] 12 at 400 Hz, with respect to the neat PP ([Formula: see text] 2.5). Accordingly, the AC conductivity and dielectric permittivity of PP/CNF 2 wt.% composites were evaluated by using power laws and discussed in the framework of the intercluster polarization model. Finally, the complex impedance and Nyquist plots of the PP/CNF composites are analyzed by using equivalent circuit models, consisting of a constant phase element (CPE). The analysis gathered in here aims at contributing to the better understanding of the enhanced dielectric properties of low-conducting polymer composites filled with carbon nanofibers.

Switching from originator recombinant growth hormone (Genotropin™) to biosimilar (CRISCY™): Results from a 6-month, multicentric, non-inferiority, extension trial.

OBJECTIVE: A previous 12-month comparative trial with Criscy™ (r-hGH Cristália), a biosimilar recombinant growth hormone, demonstrated equivalent efficacy and safety to Genotropin™. This extension trial evaluated the effects of switching patients treated with Genotropin™ to the biosimilar Criscy™ over an additional 6-month treatment period, comparing efficacy, safety, and immunogenicity parameters with patients remaining in the Criscy™ arm. DESIGN: This extension study included 11 research centers and 81 patients who participated in the CERES study (Czepielewski et al., 2019 [1]). Participants from the Genotropin™ arm (n = 39) had the drug replaced by Criscy™ and the remaining participants were kept in the Criscy™ arm (n = 42) for an additional 6-month period to evaluate immunogenicity, efficacy (growth rate, height SDS), and safety (laboratory tests, and adverse events). RESULTS: Before the switch, both Criscy™ and Genotropin groups were similar concerning demographics, and auxological measures: age, sex, height, height SDS, weight, and BMI. Height velocity (HV) after 18 months of treatment was 8.7 ± 1.56 cm/year for Criscy™ group and 8.9 ± 1.36 cm/year for Genotropin™ group in the ITT population (p = 0.43). The auxological parameters and IGF-1 and IGFBP-3 SDS were comparable between both groups of patients. No participants were excluded from the study due to adverse events. There were no clinical or statistical relevant differences between the treatment groups concerning frequency, distribution, intensity, and AEs outcome. Similarly, no new anti-r-hGH (ADA) cases among patients that switched from Genotropin™ to Criscy™ were reported. No neutralizing antibody (nAb) was detected in either group. CONCLUSIONS: This trial showed that switching from originator recombinant human growth hormone to Criscy™ had no impact on efficacy, safety, nor immunogenicity as compared to continued treatment with Criscy™. Growth rates and ADA incidence remained the same as seen before the switch.

Oxígeno hiperbárico para la cistitis inducida por radioterapia: un seguimiento a largo plazo / Hyperbaric oxygen for radiation-induced cystitis: A long-term follow-up

INTRODUCCIÓN Y OBJETIVOS: Alrededor del 12% de los pacientes tratados con radioterapia pélvica desarrollan complicaciones en la vejiga. La terapia de oxígeno hiperbárico (TOHB) es una opción para el manejo de la cistitis hemorrágica inducida por radioterapia (CHIR). El objetivo de este estudio fue evaluar la eficacia de la TOHB para tratar la cistitis por radioterapia e identificar factores predictivos para un resultado exitoso. MATERIAL Y MÉTODOS: Revisamos retrospectivamente a 105 pacientes diagnosticados de CHIR que recibieron un tratamiento de TOHB entre 2007 y 2016 en nuestro centro. Los pacientes recibieron oxígeno al 100% en una cámara hiperbárica multiplaza a 2,4 ATA durante 80 min. Todos los pacientes cumplimentaron un cuestionario en el que se documentaba la gravedad de los síntomas previos a la TOHB y tras el período de seguimiento. RESULTADOS: Después de una media de 40 sesiones de TOHB, hubo una tasa de éxito del 92,4% en el control de la hematuria. Durante el período de seguimiento (mediana de 63 meses), el 24,7% de los pacientes presentaron recurrencia de la hematuria. La puntuación media de las variables evaluadas en el cuestionario -disuria, frecuencia urinaria y hematuria- fue significativamente menor después del período de seguimiento (p <0,05). Nuestros datos muestran que cuanto antes se administre la TOHB después del primer episodio de hematuria, se logran mejores tasas de respuesta y se registran menores recurrencias en relación con la hematuria (p <0,05). No se observaron complicaciones graves. CONCLUSIONES: Nuestros resultados apoyan la seguridad y los beneficios a largo plazo de la TOHB para la CHIR y otros síntomas molestos de la vejiga, lo que supondría una mejora en la calidad de vida de nuestros pacientes

INTRODUCTION AND OBJECTIVES: Bladder complications may be seen in up to 12% of patients treated with pelvic irradiation. Hyperbaric oxygen therapy (HBOT) is an option for the management of radiation-induced hemorrhagic cystitis (RIHC). The aim of this study was to evaluate the efficacy of HBOT in radiation cystitis and to identify the predictive factors for a successful outcome. MATERIAL AND METHODS: We retrospectively reviewed 105 patients diagnosed with RIHC which were treated with HBOT between 2007 and 2016 in our institution. Patients received 100% oxygen in a multiplace hyperbaric chamber at 2.4atm for 80minutes. All patients fulfilled a questionnaire documenting symptom severity pre-HBOT and at the end of the follow-up period. RESULTS: After a median of 40 HBOT sessions, there was success rate of 92,4% in the control of hematuria. During our follow-up period (median of 63 months) 24,7% patients presented with recurrence of hematuria. The mean score of the questionnaire-assessed variables: dysuria, urinary frequency and hematuria, was significantly lower after the follow-up period (P<.05). Our data shows that the sooner HBOT is delivered after the first episode of hematuria, better response rates are achieved and lower recurrences concerning hematuria were registered (P<.05). No serious complications were observed. CONCLUSIONS: Our results support the safety and long-term benefits of HBOT on RIHC and other distressful bladder symptoms, which represents an expected improvement of quality of life in our patients

Analysis of the freezing point of milk by precision method and by Fourier Transform Infrared (FTIR) spectroscopy / [Análise do ponto de congelamento do leite pelo método de precisão e por espectroscopia no infravermelho por transformada de Fourier (FTIR)]

A total of 480 milk samples were analyzed in four repetitions with four preservative treatments (no preservative, Bronopol, Bronolat and Brononata), three storage times at temperatures up to 4 °C (24, 48 and 72hours after reception), five different water additions (0.0, 2.5, 5.0, 7.5 and 10.0%) and two analytical instruments (electronic cryoscope and FTIR). The objective of this study was to evaluate the effect of these parameters in the determination of the freezing point by the reference method and by Fourier transform infrared spectroscopy, thus determining the best analytical conditions and establishing a mathematical equation for electronic determination by FTIR spectroscopy. Bronolat was the best preservative and Brononata was the worst and is not recommended to analyze freezing point by FTIR. The storage time of the samples did not interfere in the analytical determinations by the precision method and by FTIR.(AU)

Foram analisadas 480 amostras de leite em quatro repetições em relação a quatro tratamentos por conservantes (sem conservante, bronopol, bronolat e brononata), três tempos de armazenamento, em temperatura até 4ºC desde a recepção da amostra (24, 48 e 72 horas), cinco porcentagens de adição de água (0,0; 2,5; 5,0; 7,5 e 10,0%) e dois instrumentos analíticos (crioscópio eletrônico e FTIR). O objetivo foi avaliar o efeito desses parâmetros na determinação do índice crioscópico pelo método de precisão em crioscópio eletrônico e por espectroscopia com transformada de Fourier no infravermelho, determinando-se, assim, as melhores condições analíticas. Entre os conservantes utilizados, bronolat foi o melhor e brononata foi o menos eficiente, não sendo, portanto, recomendado para análise de crioscopia por FTIR. O tempo de armazenamento das amostras não interferiu nas determinações analíticas pelo método de precisão e por FTIR.(AU)

Hyperbaric oxygen for radiation-induced cystitis: A long-term follow-up. / Oxígeno hiperbárico para la cistitis inducida por radioterapia: un seguimiento a largo plazo.

INTRODUCTION AND OBJECTIVES: Bladder complications may be seen in up to 12% of patients treated with pelvic irradiation. Hyperbaric oxygen therapy (HBOT) is an option for the management of radiation-induced hemorrhagic cystitis (RIHC). The aim of this study was to evaluate the efficacy of HBOT in radiation cystitis and to identify the predictive factors for a successful outcome. MATERIAL AND METHODS: We retrospectively reviewed 105 patients diagnosed with RIHC which were treated with HBOT between 2007 and 2016 in our institution. Patients received 100% oxygen in a multiplace hyperbaric chamber at 2.4atm for 80minutes. All patients fulfilled a questionnaire documenting symptom severity pre-HBOT and at the end of the follow-up period. RESULTS: After a median of 40 HBOT sessions, there was success rate of 92,4% in the control of hematuria. During our follow-up period (median of 63 months) 24,7% patients presented with recurrence of hematuria. The mean score of the questionnaire-assessed variables: dysuria, urinary frequency and hematuria, was significantly lower after the follow-up period (P<.05). Our data shows that the sooner HBOT is delivered after the first episode of hematuria, better response rates are achieved and lower recurrences concerning hematuria were registered (P<.05). No serious complications were observed. CONCLUSIONS: Our results support the safety and long-term benefits of HBOT on RIHC and other distressful bladder symptoms, which represents an expected improvement of quality of life in our patients.

Chemical composition of rainwater under two events of aerosol transport: A Saharan dust outbreak and wildfires.

A one-year campaign of joint sampling of aerosols and precipitation, carried out in León, Spain, allowed to study the impact of two special events that affected the air quality in the north of the country, on rainfall in the city: a period with wildfires and a Saharan dust intrusion. The wildfires that occurred in northern Portugal and northwestern Spain in August 2016 affected the chemistry of rainfall on 15 August 2016, causing an increase in concentrations of NH4+, Na+, Cl-, K+, Mg2+, Ca2+, SO42- and NO3- and in the concentrations of organic acids, which was reflected in the levels of soluble and insoluble organic carbon. This led to acidification of rainwater (pH = 4.8). The second precipitation event was registered between 11 and 14 February 2017, during which the rainwater was collected in four daily fractions (P1, P2, P3 and P4). The rain sample of 12 February (P2) coincided with a Saharan dust intrusion that reached northern Iberia that day. The chemical composition of P2 showed an increase in the Ca2+ (>800%), Mg2+ (71%), Cl- (62%), and SO42- (33%) concentrations, with respect to P1. The input of crustal elements to the atmosphere helped to neutralize the P2 rainwater, causing pH values higher than 6.5. Once the dust intrusion left the north of the Peninsula, the composition of rainwater P3 and P4 revealed a mixture of marine contribution with local anthropogenic emissions, as well as a decrease in ion concentrations and conductivity, and an increase in pH values.

Índice de CMP em leite pasteurizado comercializado em Minas Gerais, Brasil, durante os anos de 2011 a 2017 / Caseinomacropeptide index in pasteurized milk retailed in Minas Gerais, Brazil from 2011 to 2017

Cheese whey is a nutritious byproduct in the dairy industry, however, due to low commercial value, its use as a milk adulterant is a common practice not easily detected by routine analysis. In Brazil, quantification of caseinomacropeptide (CMP) index, using High Performance Liquid Chromatography (HPLC), is officially used to investigate illegal cheese whey addition to milk. Milk with CMP index above 30mg/L is considered not suitable for human consumption. The objective of this research was to report the CMP index in 185 samples of pasteurized milk, representing 73 commercial brands produced in 51 counties and ten mesoregions of the state of Minas Gerais, from 2011 to 2013 (58 samples) and 2015 to 2017 (127 samples). CMP index was considered normal (up to 30mg/L) in 75.1% of the samples. However, 21.1% presented CMP index above 75mg/L and 3.8% from 31 to 75mg/L. CMP index above 75mg/L was found in 17.4% of the samples produced during the dry season (April to September) and in 24.7% during the rainy season (October to March). These data point to the need of more efficient monitoring and inspection processes to hinder adulteration with cheese whey addition to milk.(AU)

Viability of Staphylococcus aureus and expression of its toxins (SEC and TSST-1) in cheeses using Lactobacillus rhamnosus D1 or Weissella paramesenteroides GIR16L4 or both as starter cultures.

Staphylococcus aureus is one of the main causative agents of food poisoning. This bacterium is an important component of cheese microbiota and plays an important role in foodborne diseases. Another important component of the microbiota is the lactic acid bacterium, which actively participates in processes that define the physicochemical, sensorial, and microbiological features of cheese. Of the various microbiological interactions in cheese, the interaction between lactic acid bacteria and Staph. aureus is most relevant. To this end, we evaluated the viability of Staph. aureus strains and the expression of their enterotoxins in cheeses produced experimentally, using Weissella paramesenteroides GIR16L4 or Lactobacillus rhamnosus D1 or both as starter cultures. Over 7 d, we observed that the presence of lactic acid bacteria did not impair Staph. aureus growth. However, via qPCR we observed a change in the gene expression of staphylococcal enterotoxins, suggesting that molecular communication exists between Staph. aureus strains and lactic acid bacteria in cheese.

Cognitive appraisal in fish: stressor predictability modulates the physiological and neurobehavioural stress response in sea bass.

The role of cognitive factors in triggering the stress response is well established in humans and mammals (aka cognitive appraisal theory) but very seldom studied in other vertebrate taxa. Predictability is a key factor of the cognitive evaluation of stimuli. In this study, we tested the effects of stressor predictability on behavioral, physiological and neuromolecular responses in the European sea bass (Dicentrarchus labrax). Groups of four fish were exposed to a predictable (signalled) or unpredictable (unsignalled) stressor. Stressor predictability elicited a lower behavioural response and reduced cortisol levels. Using the expression of immediate early genes (c-fos, egr-1, bdnf and npas4) as markers of neuronal activity, we monitored the activity of three sea bass brain regions known to be implicated in stressor appraisal: the dorsomedian telencephalon, Dm (putative homologue of the pallial amygdala); and the dorsal (Dld) and ventral (Dlv) subareas of the dorsolateral telencephalon (putative homologue of the hippocampus). The activity of both the Dm and Dlv significantly responded to stressor predictability, suggesting an evolutionarily conserved role of these two brain regions in information processing related to stressor appraisal. These results indicate that stressor predictability plays a key role in the activation of the stress response in a teleost fish, hence highlighting the role of cognitive processes in fish stress.

Comparison of antibody repertories against Staphylococcus aureus in healthy and infected dairy cows with a distinct mastitis history and vaccinated with a polyvalent mastitis vaccine.

Staphylococcus aureus is one of the pathogens most frequently isolated from cases of mastitis worldwide. To decrease the effect of S. aureus mastitis in dairy farming, alternative strategies for controlling mastitis are needed that depend on a better knowledge of cow-to-cow variations in S. aureus antibody production. The present study sought to explore the diversity of S. aureus antibodies produced by dairy cows with a distinct mastitis history and vaccinated with a polyvalent mastitis vaccine. We obtained protein extracts from S. aureus isolates derived from persistent subclinical mastitis. Proteins were fractionated using 2-dimensional gel electrophoresis and Western blotting. Then, Western blotting membranes were exposed to sera from 24 dairy cows that had been divided into the following groups: vaccinated dairy cows that were infected with S. aureus, further subdivided according to whether they (a) remained infected by S. aureus or (b) recovered from the intramammary infection; unvaccinated dairy cows infected with S. aureus; and vaccinated healthy dairy cows with no history of S. aureus mastitis. Proteins found to be reactive by Western blot were identified by mass spectrometry (MALDI/TOF-TOF). Our most important finding was that F0F1 ATP synthase subunit α, succinyl-diaminopimelate desuccinylase, and cysteinyl-tRNA synthetase were potential candidate proteins for the prevention of S. aureus mastitis. This study strengthens the notion that variations among animals should not be ignored and shows that the heterogeneity of antibody production against anti-staphylococcal antigens in animals may enable the identification of new immunotherapy targets.

Electrosprayed whey protein-based nanocapsules for ß-carotene encapsulation.

In this work an electrohydrodynamic process (electrospray) was used to produce ß-carotene loaded nanocapsules based on whey protein isolate (WPI). WPI solutions were prepared in aqueous solutions with different concentrations of ethanol (5, 10 and 15%) which were used for ß-carotene solubilization. Different electrospray conditions were tested and the morphology and molecular organization of the nanocapsules were studied on dried and hydrated state. The size of the dried nanocapsules ranged between 227 and 283 nm. After hydration, there was a significant increase in the mean size of the nanocapsules, being the sizes higher for nanocapsules produced with increasing concentrations of ethanol. Results, obtained from the reactivity of free sulfhydryl groups and fluorescence analysis, showed that the increase of ethanol concentration had a destabilizing effect on the protein unfolding. Electrosprayed WPI-based nanocapsules can be used for the encapsulation of ß-carotene answering the industrial demand for novel encapsulation technologies to protect sensitive bioactive compounds.

Mid-term post-fire losses of nitrogen and phosphorus by overland flow in two contrasting eucalypt stands in north-central Portugal.

Wildfires affect vast areas of Mediterranean forests, thereby triggering changes in hydrological and geomorphological processes that can negatively affect both terrestrial and aquatic ecosystems. Although several studies have evaluated the post-fire hydrological and erosive response in burnt forest areas, an important knowledge gap remains with respect to nutrient mobilization by overland flow. To address this gap, a recently burnt area was selected near the Ermida village (north-central Portugal). The study area was instrumented shortly after a wildfire that occurred in July 2010, to evaluate the export of dissolved (nitrate - NO3-N and orthophosphate - PO4-P) and total nitrogen (TN) and phosphorus (TP) forms by overland flow. This was done in two burnt eucalyptus plantations due to their contrasting slope aspects (south-east vs. north-west). Bounded micro-plots were installed in August 2010 and monitored over two years. During this period, overland flow samples were collected on a 1- to 2-weekly basis, depending on the occurrence of rain. Results showed that the north west-facing slope (BE-N) presented higher nutrient losses than the south east-facing slope (BE-S), contradicting the findings of previous studies in the Mediterranean region. A logging operation that had taken place at the BE-N site shortly before the fire might account for these findings, by causing soil compaction and/or reducing the protective vegetation and litter cover. TN and TP exports were particularly pronounced during the first four months following the wildfire. After this initial period, further peaks in TN and TP exports occurred sporadically, mainly associated to intense rainfall events. The observed mid-term post-fire nutrient losses not only suggested a threat to the soil nutrient balance of Mediterranean eucalypt forests but also a potential risk of eutrophication of downstream water bodies.

Laser surface texturing of Ti-6Al-4V by nanosecond laser: Surface characterization, Ti-oxide layer analysis and its electrical insulation performance.

The development of smart biomedical implants with intrinsic communication system between sensors and actuators, or between implant and patient, remains a challenge for scientific community. Titanium and its alloys, especially Ti6Al4V, are the most used materials in the implant's fabrication. The present work is concerned with implant internal communication printing process and presents a detailed study on titanium alloy (Ti6Al4V) surface texturing and their characterization (morphological and chemical) produced by a Nd: YAG laser, aiming to create localized electrical insulation zones, necessary to accommodate electrical communication systems. The characterization of the textured surface was carried out by scanning electron microscopy and the heat affected zone was analyzed by X-ray diffraction. The results showed the formation of α-Ti, Ti6O and Ti2O phases on the textured surface. Through simulations in TINA software, the outer oxide layer formed during laser texturing had efficiency above 90% as insulator when an electrical current was applied.

Efficacy and safety of a biosimilar recombinant human growth hormone (r-hGH Cristalia) compared with reference r-hGH in children with growth hormone deficiency (CERES study): A randomized, multicentric, investigator-blind, phase 3 trial.

OBJECTIVE: The CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant human growth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD). DESIGN: A total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received either r-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C. RESULTS: The auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = -0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups. CONCLUSIONS: The clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders.

Effect of seasonal conditions and milk management practices on bulk milk quality in Minas Gerais State - Brazil / Efeito da sazonalidade e práticas de manejo na qualidade do leite de tanque no estado de Minas Gerais - Brasil

The influence of seasonality and the training and implementation of good dairy farming practices on raw milk production and quality was evaluated on dairy farms in Minas Gerais State, Brazil. The physico-chemical composition, somatic cell count (SCC) and total bacterial count (TBC) were determined in 3,096 milk samples collected from bulk tanks originated from 43 dairy farms over a three-year period and correlated with key climatic factors. The recommended milking management practices were applied through a training program and correlated with the seasonal data in three stages: I) prior to training (dry period); II) 48 days after the training (transition period); III) 96 days after the training (rainy period). In the first stage, a diagnosis of the situation was performed with raw milk samplings for laboratory analysis, and training for implementation of good milking practices. In stages II and II, the checklist and laboratory analysis were also performed. The rainfall and high temperatures were found to represent the main factors affecting the milk composition and production, and TBC. The composition and physical properties of raw milk, and the TBC and SCC parameters can be controlled or minimized by applying proper milking management practices and constant monitoring.(AU)

Avaliou-se a influência das condições climáticas em regiões tropicais, bem como do treinamento e da implementação de boas práticas de manejo na produção e qualidade do leite em distintos períodos em fazendas leiteiras no estado de Minas Gerais, Brasil. No presente estudo, as características físico-químicas do leite, a contagem bacteriana total (CBT) e a contagem de células somáticas (CCS) foram determinadas em 3.096 amostras de tanques de leite proveniente de 43 fazendas leiteiras, durante um período de três anos, e correlacionadas com os principais fatores climáticos (temperatura diária do ar mínima, média e máxima; pluviosidade e umidade relativa). Foram avaliados os resultados obtidos nas análises das amostras de leite cru coletadas no ano anterior (2009/2010) e também no posterior (2011/2012) àquele em que foi realizado o treinamento para implementação das boas práticas de manejo de ordenha (2010/2011), compreendendo três etapas: antes do treinamento (período seco - tempo 0, etapa I), 48 dias após o treinamento (período de transição - etapa II) e 96 dias após o treinamento (período chuvoso - etapa III). Na etapa I foi realizado um diagnóstico de situação com coleta de amostras para análises laboratoriais, aplicação da lista de verificação padronizada e treinamento para a implementação das boas práticas de manejo de ordenha; na etapa II foram realizadas novas análises laboratoriais e reaplicação da lista de verificação para avaliar a eficiência do treinamento; e na etapa III foi realizada a repetição da etapa II. Com base no histórico dos três anos, observou-se que condições climáticas de alta temperatura e pluviosidade representam importantes fatores que afetam a composição do leite e o volume produzido, assim como parâmetros higiênico-sanitários do leite. Ademais, as boas condições de manejo são ferramentas úteis, eficazes, práticas e essenciais para a maior produção de leite com qualidade, desde que constantemente monitoradas.(AU)

Mechanical Property of Hydrogels and the Presence of Adipose Stem Cells in Tumor Stroma Affect Spheroid Formation in the 3D Osteosarcoma Model.

Osteosarcoma is one of the most common metastatic bone cancers, which results in significant morbidity and mortality. Unfolding of effectual therapeutic strategies against osteosarcoma is impeded because of the absence of adequate animal models, which can truly recapitulate disease biology of humans. Tissue engineering provides an opportunity to develop physiologically relevant, reproducible, and tunable in vitro platforms to investigate the interactions of osteosarcoma cells with its microenvironment. Adipose-derived stem cells (ASCs) are detected adjacent to osteosarcoma masses and are considered to have protumor effects. Hence, the present study focuses on investigating the role of reactive ASCs in formation of spheroids of osteosarcoma cells (Saos 2) within a three-dimensional (3D) niche, which is created using gellan gum (GG)-silk fibroin. By modifying the blending ratio of GG-silk, the optimum stiffness of the resultant hydrogels such as GG and GG75: S25 is obtained for cancer spheroid formation. This work indicates that the co-existence of cancer and stem cells can form a spheroid, the hallmark of cancer, only in particular microenvironment stiffness. The incorporation of fibrillar silk fibroin within the hydrophilic network of GG in GG75: S25 spongy-like hydrogels closely mimics the stiffness of commercially established cancer biomaterials (e.g., Matrigel, HyStem). The GG75: S25 hydrogel maintains the metabolically active construct for a longer time with elevated expression of osteopontin, osteocalcin, RUNX 2, and bone sialoprotein genes, the biomarkers of osteosarcoma, compared to GG. The GG75: S25 construct also exhibits intense alkaline phosphatase expression in immunohistochemistry compared to GG, indicating itspotentiality to serve as biomimetic niche to model osteosarcoma. Taken together, the GG-silk fibroin-blended spongy-like hydrogel is envisioned as an alternative low-cost platform for 3D cancer modeling.

Comparison of soybean hull pre-treatments to obtain cellulose and chemical derivatives: Physical chemistry characterization.

The cellulose from soybean hull, a waste without value from the argentine agriculture, was successfully obtained by using two different treatments: the traditional alkaline-bleaching pathway and from a simple pre-alkaline treatment at low temperatures. The comparison of both methods yielded similar results regarding its ability to open the lignin cellulosic structure of the hull and the total elimination of the lignin content. Fourier Transform Infrared spectroscopy (FT-IR), Thermogravimetric analysis (TGA), Scanning electron microscopy (SEM), 13C nuclear magnetic resonance (13C-RMN) and Raman spectroscopy were used to characterize the structures and the properties of cellulose. The results showed that cellulose can be easily obtained with just an alkaline pre-treatment of 5% (w/v) NaOH during 40 h at 50 °C and free of any lignin content. The attachment of different functional groups, such as -COOH and (CH3)3N+, changed the physicochemical properties of the obtained cellulose, showing mayor crystalline structure, and consequently modifying the swelling capacity and its ability to adsorb model proteins.