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This study had as aims the extraction, purification and characterization of moringa oil for everyday applications with backing scientific. The average oil yield was of 23.92%, using the techniques: mechanical pressing (11.36%) and by with hexane extraction (35.48%). The oil extracted by pressing was analysed for gas chromatography, revealing a profile of 21.5% of saturated fatty acids and 78.5% of unsaturated fatty acids, having the oleic acid as the major component. The mixed crude oil was refined in four steps: degumming, neutralization, washing and drying. The crude and refined oils were characterised through their acidity index (8.8; 20.5 and 0.2 mgKOH g-1), peroxide index (3.3; 5.4 meqO2 kg-1 and not detected), water content (876.6; 632.0 and 630.2 mg kg-1), turbidity (64.1; 12.6 and 2.1 NTU), specific mass (909.5; 907.2 and 907.0 kg m3), kinematic viscosity (43.6; 39.1 and 41.7 mm2 s-1), high power calorific (39.7; 40. and 39.4 MJ kg-1) and calorific value lower (36.9; 36.9; 37.1 MJ kg-1), and ash content (0.05; 0.05 and 0.007%), respectively. The results show that moringa is a viable and sustainable plant in the use of its oil as raw material for several industries, especially in the food, cosmetic, pharmaceutical and biodiesel industry.

55 patients with advanced cutaneous squamous cell carcinoma (CSCC) of the trunk and extremities were studied. A Tissue Microarray was constructed using immunohistochemistry to quantify expression of the HER family, E-cadherins, and podoplanin. Clinical and histopathological factors related to lymph node metastasis and prognosis were also established. Primary tumor positivity was 25.5% for EGFR, 87.3% for HER-3, and 48.1% for HER-4. Metastases were positive for EGFR in 41.7%, for HER-3 in 83.3%, and HER-4 in 43.5%. HER-2 was negative in all samples. Membrane E-cadherin and cytoplasmic E-cadherin were positive in 47.3% and 30.2% of primary tumors and 45.5% and 27.3% of metastases, respectively. Podoplanin was positive in 41.8% of primary tumors and 41.7% of metastases. Intratumoral lymphocytic infiltrate was associated with lymph node metastasis. Patients with T3 tumors had better cancer-specific survival (CSS) than those with T4 tumors; patients with no lymph node involvement had better CSS than patients with N1 tumors. Undifferentiated tumors and hyperexpression of podoplanin were negative prognostic indicators on multivariate analysis.

Abstract Background Squamous cell carcinoma (SCC) of the skin of the trunk and extremities may present lymph node metastasis with difficult disease control and poor survival. The purpose of this study was to identify risk factors for lymph node metastasis and outcome. Patients/Methods Retrospective review of 57 patients with locally advanced SCC of the trunk and extremities was performed and several clinical variables including age, gender, ethnicity, previously injured skin (burns, scars, ulcers and others), patient origin (rural or urban), anatomic site and treatment were studied. Results Fifteen patients presented with previous skin lesions. Thirty-six were classified as T3 tumors and 21 as T4; 46 were N0, and 11, N1. Eleven N0 patients presented lymph node metastasis during follow up. Univariate analysis identified previous skin lesions (ulcers and scars) as risk factor for lymph node metastasis (p = 0.047). Better survival was demonstrated for T3 (p = 0.018) classification. N0 patients who presented lymph node metastasis during follow up (submitted to lymphadenectomy) had similar survival to patients without lymph node recurrence (p = 0.219). Conclusion Local advanced tumors are at risk of lymph node metastasis. Increased risk is associated to previous lesions at tumor site. T4 classification have worse prognosis. Lymph node recurrences in N0 patients, once treated, did not affect survival. For these patients, we propose close follow up and prompt treatment of lymph node metastasis. These results do not support indication for elective lymphadenectomy or sentinel node mapping. Further prospective studies must address this issue.

Background: SARS-CoV2 virus, responsible for the COVID-19 pandemic, has four structural proteins and 16 nonstructural proteins. S-protein is one of the structural proteins exposed on the virus surface and is the main target for producing neutralizing antibodies and vaccines. The S-protein forms a trimer that can bind the angiotensin-converting enzyme 2 (ACE2) through its receptor binding domain (RBD) for cell entry., Aims: The goal of this study was to express in HEK293 cells a new RBD recombinant protein in a constitutive and stable manner in order to use it as an alternative immunogen and diagnostic tool for COVID-19., Materials & Methods: The protein was designed to contain an immunoglobulin signal sequence, an explanded C-terminal section of the RBD, a region responsible for the bacteriophage T4 trimerization inducer, and six histidines in the pCDNA-3.1 plasmid. Following transformation, the cells were selected with geneticin-G418 and purified from serum-fre culture supernatants using Ni2+-agarand size exclusion chromatography. The protein was structurally identified by cross-linking and circular dichroism experiments, and utilized to immunize mice in conjuction with AS03 or alum adjuvants. The mice sera were examined for antibody recognition, receptor-binding inhibition, and virus neutralization, while spleens were evaluated for γ-interferon production in the presence of RBD., Results: The protein released in the culture supernatant of cells, and exhibited a molecular mass of 135 kDa with a secondary structure like the monomeric and trimeric RBD. After purification, it formed a multimeric structure comprising trimers and hexamers, which were able to bind the ACE2 receptor. It generated high antibody titers in mice when combined with AS03 adjuvant (up to 1:50,000). The sera were capable of inhibiting binding of biotin-labeled ACE2 to the virus S1 subunit and could neutralize the entry of the Wuhan virus strain into cells at dilutions up to 1:2000. It produced specific IFN-γ producing cells in immunized mouse splenocytes., Discussion: Our data describe a new RBD containing protein, forming trimers and hexamers, which are able to induce a protective humoral and cellular response against SARS-CoV2., Conclusion: These results add a new arsenal to combat COVID-19, as an alternative immunogen or antigen for diagnosis., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Bee pollen is considered an excellent dietary supplement with functional characteristics, and it has been employed in food and cosmetics formulations and in biomedical applications. Therefore, understanding its chemical composition, particularly crude protein contents, is essential to ensure its quality and industrial application. For the quantification of crude protein in bee pollen, this study explored the potential of combining digital image analysis and Random Forest algorithm for the development of a rapid, cost-effective, and environmentally friendly analytical methodology. Digital images of bee pollen samples (n = 244) were captured using a smartphone camera with controlled lighting. RGB channels intensities and color histograms were extracted using open source softwares. Crude protein contents were determined using the Kjeldahl method (reference) and in combination with RGB channels and color histograms data from digital images, they were used to generate a predictive model through the application of the Random Forest algorithm. The developed model exhibited good performance and predictive capability for crude protein analysis in bee pollen (R 2  = 80.93 %; RMSE = 1.49 %; MAE = 1.26 %). Thus, the developed analytical methodology can be considered environmentally friendly according to the AGREE metric, making it an excellent alternative to conventional analysis methods. It avoids the use of toxic reagents and solvents, demonstrates energy efficiency, utilizes low-cost instrumentation, and it is robust and precise. These characteristics indicate its potential for easy implementation in routine analysis of crude protein in bee pollen samples in quality control laboratories., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This paper provides the first description of the nesting biology of Ancistrocerus flavomarginatus (Brèthes) (Hymenoptera, Vespidae, Eumeninae), the only species of the genus found in Brazil. Our trap-nest experiments were conducted in two Mixed Ombrophilous Forest fragments and two adjacent matrices in Guarapuava (Paraná state, Brazil) from August 2017 to July 2018. In each area, we set 192 trap nests divided into six groups of 32 units, totalling 768 trap nests. We obtained a total of 47 nests of A. flavomarginatus, the vast majority of them (43, 91.5%) founded in the forest fragments. Most nests were built in wooden traps with a bore diameter of either 5 or 7 mm (19 nests in each type, 80.8%). Nests comprised 1-12 subcylindrical brood cells arranged linearly and separated from one another by transverse partitions of soil mastic. Larvae consumed 6-10 lepidopteran caterpillars before spinning the cocoon. Ancistrocerus flavomarginatus produced up to 6 annual generations (multivoltinism) and its immature forms were parasitized by chrysidid and ichneumonid wasps. The calculated sex ratio (1.78:1) was statistically biased towards males, but since they (21.3 ± 2.0 mg) were significantly lighter than females (50.9 ± 4.0 mg), the resulting investment ratio (1.34:1) was female biased. Males emerged from more external cells and developed significantly faster (27.2 ± 0.46 days) than females (30.1 ± 0.66 days), hence a case of protandry. We demonstrated that A. flavomarginatus is largely dependent on the Atlantic Rainforest and thus that deforestation poses a critical threat to this important species., (© 2022. Sociedade Entomológica do Brasil.)

Abstract: Rancid taste, pH, and TBARS are important quality parameters of food oxidation, analyzed in a time-consuming and destructive way. Non-destructive characterization of food can be achieved correlating this data with computational vision. Thus, the present study aimed to use RGB digital images to predict sensory rancid taste, pH, and TBARS results in fish burgers. A mobile obtained the digital images, in a controlled environment, and 768 grayscales were performed using RGB histograms. The pH, showed a peak at 21st day of storage, which PCA confirmed by isolating the 21st samples, corroborated by HCA grouping 21st day samples. PLS models from RGB digital images and sensory rancidity, pH and TBARS data, using mean center method and SIMPLS algorithm found models with > 0.97 R 2 . Thus, any digital image of this batch of burgers, inserted into the model to predict rancid taste, pH and TBARS has high confidence level of prediction., Competing Interests: Conflict of interestCaroline Marques declares that she has no conflict of interest. Carlos E. B. Toazza declares that he has no conflict of interest. Carla Cristina Lise declares that she has no conflict of interest Vanderlei A. de Lima declares that he no conflict of interest. Marina Leite Mitterer-Daltoé declares that she has no conflict of interest., (© Association of Food Scientists & Technologists (India) 2022.)

Objective: To estimate the rate of change during exercise and during recovery in moderate-continuous exercise (MCE) and high-intensity intermittent exercise (HIIE) in children and adolescents with type 1 diabetes (T1D)., Methods: Participants performed 2 sessions of exercise: thirty minutes of continuous activity on a cycle ergometer (60% of VO 2max ) and thirty minutes (60% VO 2max ) interspersed with five bouts of maximum intensity lasting ten seconds every five minutes. Capillary blood glucose was measured before and after each test. The glucose rate of change in exercise (RoC E ) was calculated (final blood glucose - onset blood glucose/exercise time), and the glucose rate of change in recovery (RoC R ) (blood glucose 30 minutes after exercise - end of exercise blood glucose/recovery time)., Results: The study included thirty-one participants (aged 13 ± 1.88 years). A lower blood glucose reduction was observed in the HIIE group, as well as better recovery values before, after, and thirty minutes after the test, respectively (333.14 ± 69.53, 226.19 ± 68.05 and 201.77 ± 66.84 versus 211.36 ± 91.03, 155.98 ± 82,68 and 165.76 ± 72.94). Covariance analyses showed a significant difference in glycemic variation between continuous and intermittent protocols immediately after exercise (-2.90 versus -2.08) and during the recovery period (-0.677 versus -0.389)., Conclusion: HIIE led to a lower glucose reduction rate per minute during exercise and better recovery in the first 30 minutes after exercise compared to MCE in children and adolescents with T1D.

It has been reported that patients diagnosed with COVID-19 become critically ill primarily around the time of activation of the adaptive immune response. However the role of antibodies in the worsening of disease is not obvious. Higher titers of anti-spike immunoglobulin IgG1 associated with low fucosylation of the antibody Fc tail have been associated to excessive inflammatory response. In contrast it has been also reported that NP-, S-, RBD- specific IgA, IgG, and IgM are not associated with SARS-CoV-2 viral load, indicating that there is no obvious correlation between antibody response and viral antigen detection. In the present work the micro-Fourier-transform infrared reflectance spectroscopy (micro-FTIR) was employed to investigate blood serum samples of healthy and COVID-19-ill (mild or oligosymptomatic) individuals (82 healthcare workers volunteers in "Instituto de Infectologia Emilio Ribas", São Paulo, Brazil). The molecular-level-sensitive, multiplexing quantitative and qualitative FTIR data probed on 1 µL of dried biofluid was compared to signal-to-cutoff index of chemiluminescent immunoassays CLIA and ELISA (IgG antibodies against SARS-CoV-2). Our main result indicated that 1702-1785 [Formula: see text] spectral window (carbonyl C=O vibration) is a spectral marker of the degree of IgG glycosylation, allowing to probe distinctive sub-populations of COVID-19 patients, depending on their degree of severity. The specificity was 87.5 % while the detection rate of true positive was 100%. The computed area under the receiver operating curve was equivalent to CLIA, ELISA and other ATR-FTIR methods ([Formula: see text]). In summary, overall discrimination of healthy and COVID-19 individuals and severity prediction as well could be potentially implemented using micro-FTIR reflectance spectroscopy on blood serum samples. Considering the minimal and reagent-free sample preparation procedures combined to fast (few minutes) outcome of FTIR we can state that this technology is suitable for fast screening of immune response of individuals with COVID-19. It would be an important tool in prospective studies, helping investigate the physiology of the asymptomatic, oligosymptomatic, or severe individuals and measure the extension of infection dissemination in patients., (© 2022. The Author(s).)

Purpose: The study analyzed the influence of exercise on hypoglycemia episodes postexercise and in the subsequent 24 hours in children and adolescents with type 1 diabetes., Methods: Thirty young people performed the same protocol of physical exercises for 1 hour (Ex1h) and 2 hours (Ex2h) after the administration of insulin. They performed 30 minutes of exercise on a cycle ergometer with a load of 60% of maximal oxygen uptake, interspersed with maximum intensity sprints lasting 10 seconds every 5 minutes., Results: Regarding the occurrence of hypoglycemia, in the 8 hours following the exercises, there was no occurrence in Ex1h (χ2 = 0.001; P = .0001) and a greater proportion for Ex2h (n = 71 episodes, 53.8%), while Ex1h had a higher number of nocturnal hypoglycemic episodes (n = 60, 71.4%) compared with Ex2h (n = 31, 23.1%, χ2 = 49.521, P = .0001), Ex1h triggered a lower number of hypoglycemia (n = 84) than Ex2h (n = 134, χ2 = 11.504, P = .001). There was a greater reduction in the average amount of fast-acting insulin administered the day after Ex1h compared with Ex2h (P = .031)., Conclusions: Intermittent exercise performed 1 hour after insulin administration shows a lower risk of hypoglycemia within 8 hours after exercise, as well as a reduction in insulin the following day.

Five new neocassane-like diterpenes ( 1 - 5 ) were isolated from the roots of Eragrostis plana . Their structures were elucidated by spectroscopic data, and the absolute configurations of the representative compounds neocassa-12(17),15-dien-3-one ( 2 ) and neocassa-12(13),15-diene-3,14-dione ( 5 ) were assigned by vibrational circular dichroism. The phytotoxic activity of compounds 3 , 4 , and 5 was evaluated against the germination and growth of Ipomoea grandifolia and Euphorbia heterophylla . Compound 4 exhibited the most potent activity for growth variables, resulting in the smallest radicle length of I. grandifolia and in the smallest aerial part length of E. heterophylla . Compound 5 reduced the germination speed index more effectively than the herbicide glyphosate (Roundup).

In this work the toxicity caused by explosive industries effluent (yellow water) at different levels of toxicity (genetic, cellular and organismal level) was evaluated by the Allium cepa test and the Sorghum sudanense germination. The results showed that the effluent paralyze the mitotic process, keeping the cells in the interphase, decreasing the mitotic index in A. cepa. Chromosomal abnormalities such as c-metaphases, adhesions, breaks, early ascending chromosomes and irregular nucleus were observed for this receptor species. The germination of S. sudanense was reduced, and the development of the radicles were affected, showing reduced tolerance index at the highest concentrations of the effluent. Thus, it is concluded that the effluent from the explosive industry is extremely toxic to the tested organisms, both in cellular and chromosomal level and also for seed germination.

The aim of this study was to evaluate the most effective extraction condition (temperature, solvent type and time) for recovery of high-value phytochemicals present in the Tabernaemontana catharinensis leaves (TC) and to assess their effect on biochemical parameters in streptozotocin-induced diabetic rats. The extraction of phenolic compounds from TC using a factorial design (FD) 2³, high performance liquid chromatography (HPLC), response surface methodology (RSM) and principal component analysis (PCA) were studied. It was found that the optimal conditions for extraction of phenolics were higher temperature (65 °C) and time (60 min) using ethanol as extractor solvent. In this condition of extraction (A8), total phenolic compounds (TPC) and antioxidant activity (AA) were determined. Additionally, this extract was used to evaluate their effect on antioxidant enzyme activities (superoxide dismutase (SOD) and catalase (CAT)) as well as lipid peroxidation (LP) and protein thiols level (PSH) in the liver and kidneys of normal and diabetic rats. As result, T. catharinensis extract presented TPC content of 23.34 mg EAG/g (equivalent gallic acid) and AA of 34.26 μmol Trolox/g. Phenolic acids (ferulic acid and coumaric acid) and flavonoids (quercetin, rutin and pinocembrin) could be recovered and identified by HPLC. This study indicated an important role of the T. catharinensis extract on free radical inactivation and on the antioxidant defense system in diabetic rats. In fact, the use of T. catharinensis extract restored the normal activity of SOD ( p < 0.05) and suppressed malondialdehyde levels in liver and kidney tissues. Thus, the T. catharinensis extract, rich in phenolic compounds, can be responsible for the recover the enzymatic changes in the liver and kidney tissues provoked by diabetes in rats. In addition, the lipid peroxidation rate decreased in the diabetic rats treated with T. catharinensis .

Although studies have focused on extracellular matrix (ECM) remodeling during the formation and functioning of adult ovaries, there is no comprehensive understanding of the mechanisms controlling preantral follicle development in fetal bovine ovaries during gestation. Thus, to gain insights into ECM remodeling during initial ovarian development, we used fetal ovaries to quantify the fractal dimension (FD), total collagen, and relative mRNA abundance of genes related to ECM remodeling (COL1A1, COL1A2, COL4A1, MMP2, MMP9, MMP14, TIMP1, and TIMP2). For this, pairs of fetal ovaries were obtained from cows in a local abattoir at days 60, 90, 120, and 150 of gestation; one of each pair was submitted to RNA extraction for target transcript analysis, and the other was used for total collagen and FD evaluation. From day 120 total collagen appeared to occupy a greater area in the fetal ovary. The fractal analysis with picrosirius red staining shows higher at day 150 when compared with that on day 60. On the contrary, we found an inverse pattern when we used the hematoxylin and eosin staining approach. Concerning target gene expression, the relative abundances of COL1A1, COL4A1, MMP2, MMP14, TIMP1, and TIMP2 mRNA were higher on day 150 when compared with that on day 60. We conclude that fractal analysis reflects the morphological changes occurring during structural organization of the fetal ovary and that the expression of genes related to ECM remodeling is modulated throughout gestation in bovine fetal ovaries., Competing Interests: Declaration of competing interest We declare that there is no conflict of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ipomoea species are troublesome weeds in crop systems through Brazil. Drought stress typically reduces glyphosate efficacy by reducing the foliar uptake of herbicides and their translocation. Using both glyphosate tolerant (GT) and sensitive (GS) plants from Ipomoea grandifolia , I. indivisa and I. purpurea species, this research aimed to (a) correlate amounts of epicuticular wax and tolerance to glyphosate in plants and (b) determine the effect of drought stress (DStress) on changes in the quantity and chemical composition of plant epicuticular waxes. The dose that causes 50% inhibition of growth (GR 50 ) of the biotypes varied between 62 and 1208 ( I. grandifolia ), 159 and 913 ( I. indivisa ), and 389 and 1925 g a.e. ha -1 of glyphosate ( I. purpurea ). There was low inverse correlation (-0.46) between the amount of epicuticular wax and the sensitivity to glyphosate. GT biotypes of the species presented greater plastic capacities than GS biotypes for increasing the amount of epicuticular wax under DStress. The three Ipomoea species exhibited different chemical profiles of waxes supported by IR spectra, which allows for their differentiation. For I. grandifolia and I. purpurea , there was an increase in the polar components in the state without DStress, while for the species I. indivisa , no differences in infrared spectra were detected between the two water conditions.

The aim of this study was to identify the influence of different catching practices during manual upright handling on broiler welfare and behavior. Catching was examined in a total of 4,595 Cobb broilers with average live weight of 3.2 kg and 42 days old. Six catching practices were evaluated: shed curtain position, loading time, catching method, catching team, height of the crates from the floor, and placement of the bird in the crate. Behavioral welfare indicators were defined as follows: 1) broiler agitation in the catcher's hands, measured when the birds flapped their wings, kicked, or wriggled in the hands; 2) broiler striking the crate entrance as it was being placed in the crate, measured when the birds get the head, wings, or legs, hit at the crate entrance; and 3) broiler agitation in the crate, measured when birds flapped the wings or jumped inside the crate for 3 s or more after placement in the crate. A logistic regression model was used to calculate the chance of occurrence of each behavioral welfare indicator due to the handling factors. All catching practices evaluated in the present study influenced the birds' welfare and behavior. Thus, some procedures during broiler catching potentially improved their behavior, making them less prone to accidents, and consequently improved their welfare. The catching process should be performed with the curtains in the closed position, carrying one broiler per catcher in an upright position while containing its wings, carefully placing the birds inside the crates, and with the crates being positioned at a height of at least 21 cm from the ground. Additionally, it was concluded that more attention should be given to the broiler catchers, since the position of the curtain, loading time, and position of the crate during handling can influence the work done by them, affecting the welfare and behavior of both humans and birds., (© The Author(s) 2019. Published by Oxford University Press on behalf of Poultry Science Association.)

To assist in evaluating and quantifying tissue changes, fractal dimension (FD) is a useful method for assessing the organization in an image from fractals that describes the amount of space and the self-similarity of the structure, once FD detects subtle morphological changes and performs functional quantitative measures. Here, we hypothesized that fractal analysis may be different in functional and regressing bovine corpus luteum (CL) and may be correlated with differential expression of genes involved in extracellular matrix remodeling. CL presents two developmental stages, the functional and regressing CL, according to progesterone levels and morphology. First, we found a lower FD in functional CL using HE staining and picrosirius red approach. Additionally, we found a great amount of total collagen in regressing CL. Regarding gene expression, we showed an up regulation of COL1A1, COL1A2, MMP2, and MMP14 and a down regulation of TIMP1 and TIMP2 in regressing CL compared to the functional one. Thus, we concluded that differential FD observed during luteal regression is an effective method to evaluate the tissue changes observed during luteal development in cattle and is related to differential quantity of genes involved in extracellular matrix remodeling., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the level of physical activity and cardiorespiratory fitness in teenagers with type 1 diabetes mellitus (T1D) in comparison with healthy scholar participants. Total of 154 teenagers (T1D = 45 and CON = 109). Height, weight, cardiorespiratory fitness (VO 2max ), and the level of physical activity by the Bouchard's Physical Activity Record were measured, and glycated hemoglobin (HbA1c) in T1D. The VO 2max was lower in the T1D (38.38 ± 7.54) in comparison with the CON (42.44 ± 4.65; p < .05). The VO 2max had correlation with the amount of time of moderate-to-vigorous physical activity (r = .63; p = .0001) and an inverse correlation with sedentary activities (r= -0.46; p = .006). In the T1D the levels of HbA1c had an inverse correlation with the amount of time of moderate-to-vigorous physical activity (r= -0.34; p = .041) and correlation with the BMI z-score (r = .43; p = .017). Only 37,8% of the participants in the T1D reached the adequate amount of daily moderate-to-vigorous intensity physical activity, in the CON 81,7% reached the WHO's recommendation., Conclusion: T1D had less cardiorespiratory capacity then healthy controls, the teenagers of T1D with lower BMI z-score and that dedicated a greater time in moderate-to-vigorous intensity physical activity demonstrated a better glycemic control.

Purpose: To evaluate, in a controlled prospective manner with double-blind read, whether there are differences in interpretations of PET/CT scans at our tertiary medical centre, Rigshospitalet, compared to the external hospitals., Methods: Ninety consecutive patients referred to our department who had an external F-18-FDG PET/CT scan were included. Only information that had been available at the time of the initial reading at the external hospital was available at re-interpretation. Teams with one radiologist and one nuclear medicine physician working side by side performed the re-interpretation in consensus. Two oncologists subsequently and independently compared the original reports with the re-interpretation reports. In case of 'major discordance', the oncologists assessed the respective reports validities., Results: The interpretations were graded as 'accordant' in 43 patients (48%), 'minor discordance' in 30 patients (33%) and 'major discordance' in 17 patients (19%). In 11 (65%) of the 17 cases graded as 'major discordance', it was possible to determine which report that was most correct. In 9 of these 11 cases (82%), the re-interpretation was most correct; in one case, the original report and in another case, both interpretations were incorrect., Conclusions: Major discordant interpretations were frequent [19% (17 of 90 cases)]. In those cases where follow-up could assess the validity, the re-interpretation at Rigshospitalet was most correct in 9 of 11 cases (82%), indicating that there is a difference in expertise in interpreting PET/CT at a tertiary referral hospital compared to primary local hospitals., (© 2015 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

There is no well-defined standard third-line chemotherapy for advanced malignant pleural mesothelioma (MPM). However, combination of carboplatin, liposomised doxorubicin (Caelyx) and gemcitabine (CCG regimen) has revealed noteworthy activity when used as first-line treatment. The aim of this study is to assess efficacy and toxicity profile for patients with MPM receiving CCG regimen as a third-line treatment. Carboplatin (AUC 5), Caelyx (30 mg/m(2)) and Gemcitabine (1,000 mg/m(2)) day 1, together with Gemcitabine (800 mg/m(2)) day 8, were given in up to six cycles. Patients were unresectable, PS 0-2, and had previously received a first-line platinum-based regimen and either vinorelbine or pemetrexed as second line. Response to treatment was assessed by CT scan using Modified RECIST criteria for mesothelioma. Forty-three patients were treated between 2010 and 2014. Median age was 67 years (47-82), 72 % males, and 79 % had previous asbestos exposure. Ninety per cent had PS 0-1, 58 % had epitheloid subtype and 63 % IMIG stage IV. First-line treatment was platinum and pemetrexed in 42 cases. Second-line treatment was vinorelbine in 42 cases and pemetrexed in one patient. Median lead time from cessation of second-line treatment to start of third CCG was 1 month. Twenty-eight per cent of the patients received six cycles, while treatment was postponed due to toxicities, mainly haematological, in 56 % of cases. No toxicity-related deaths occurred. Partial response (PR) occurred in 14 %, and disease control rate (DCR) was 60 %. Medians of overall survival (OS) from diagnosis and from start of CCG treatment were 25.2 months (18.4-31.5 months) and 6.8 months (5.4-8.4 months), respectively. Progression-free survival (PFS) was 4.1 months (1.7-4.5 months). Third-line CCG revealed a noteworthy efficacy with a DCR of 60.4 %. It was, however, associated with considerable haematological toxicity. Less toxic and more active treatment options are clearly needed.

Clavulanic acid (CA) is a powerful inhibitor of the beta-lactamases, enzymes produced by bacteria resistants to penicillin and cefalosporin. This molecule is produced industrially by strains of Streptomyces clavuligerus in complex media which carbon and nitrogen resources are supplied by inexpensive compounds still providing high productivity. The genetic production improvement using physical and chemical mutagenic agents is an important strategy in programs of industrial production development of bioactive metabolites. However, parental strains are susceptible to loss of their original productivity due genetic instability phenomenona. In this work, some S. clavuligerus mutant strains obtained by treatment with UV light and with MMS are compared with the wild type (Streptomyces clavuligerus ATCC 27064). The results indicated that the random mutations originated some strains with different phenotypes, most divergent demonstrated by the mutants strains named AC116, MMS 150 and MMS 54, that exhibited lack of pigmentation in their mature spores. Also, the strain MMS 150 presented a larger production of CA when cultivated in semi-synthetics media. Using other media, the wild type strain obtained a larger CA production. Besides, using the modifed complex media the MMS 150 strain showed changes in its lipolitic activity and a larger production of CA. The studies also allowed finding the best conditions for a lipase activity exhibited by wild type S. clavuligerus and the MMS150 mutant.