Effect of Agaricus blazei Murill on exploratory behavior of mice-model

Abstract Increased anxiety and depressive symptoms have reported to be its association with long term illness. Because of having unwanted effects of newly available drugs, patients administering anxiolytic drugs usually discontinue the treatment before they are completely recovered. Therefore, there is a serious need to develop new anxiolytic drugs. The anxiolytic effect of hydro-alcoholic extract of Agaricus blazei in animal models was assessed. 24 male mice (Mus musculus genus) were included in the study. Four groups were prepared and each group contained six animals. The groups were vehicle control, positive control (diazepam 1.0 mg/kg, i.p.) as well as two treatment groups receiving Agaricus blazei hydro-alcoholic extract at a dose of 136.50 mg/kg and 273.0 mg/kg orally. The Marble burying test, Nestlet shredding test and Light and Dark box test used to assess anxiolytic activity. Mice administered with diazepam 1.0 mg/kg, i.p. while hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) was administered via oral route which exhibited marked reduction in number of marbles-burying as compared to vehicle control group. Mice administered with diazepam 1.0 mg/kg, i.p. and Oral administration of hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) exhibited significant decrease in nestlet shredding in comparison to vehicle control group. The oral administration of hydro-alcoholic extract at a dose of 136.5mg/kg and 273mg/kg showed elevation in time spent in light box and was comparable to standard treated group while time spent by mice following oral administration of hydro-alcoholic extract of Agaricus blazei at a dose of 273.0 mg/kg also showed elevation and was found to be more near to standard treated group (diazepam 1 mg/kg, i.p.).

Resumo O aumento da ansiedade e dos sintomas depressivos têm relatado sua associação com doenças de longa duração. Por causa dos efeitos indesejáveis dos novos medicamentos disponíveis, os pacientes que administram medicamentos ansiolíticos geralmente interrompem o tratamento antes de estarem completamente recuperados. Portanto, há uma necessidade séria de desenvolver novos medicamentos ansiolíticos. Foi avaliado o efeito ansiolítico do extrato hidroalcoólico de Agaricus blazei em modelos animais. Vinte e quatro camundongos machos (gênero Mus musculus) foram incluídos no estudo. Quatro grupos foram preparados, e cada grupo continha seis animais. Os grupos foram controle de veículo, controle positivo (diazepam 1,0 mg/kg, i.p.), bem como dois grupos de tratamento recebendo extrato hidroalcoólico de Agaricus blazei na dose de 136,50 mg/kg e 273,0 mg/kg por via oral. O teste de enterrar Marble, o teste de retalhamento Nestlet e o teste de caixa clara e escura são usados para avaliar a atividade ansiolítica. Camundongos foram administrados com diazepam 1,0 mg/kg, i.p., enquanto o extrato hidroalcoólico de AbM (136,50 e 273,0 mg/kg, respectivamente) foi administrado por via oral, que exibiu redução acentuada no número de mármores enterrados em comparação com o grupo de controle de veículo. Camundongos administrados com diazepam 1,0 mg/kg, i.p. e a administração oral de extrato hidroalcoólico de AbM (136,50 e 273,0 mg/kg, respectivamente) exibiu diminuição significativa na trituração de ninhos em comparação ao grupo de controle de veículo. A administração oral de extrato hidroalcoólico na dose de 136,5mg/kg e 273mg/kg mostrou elevação no tempo gasto na caixa de luz e foi comparável ao grupo tratado padrão, enquanto o tempo gasto por camundongos após a administração oral de extrato hidroalcoólico de Agaricus blazei na dose de 273,0 mg/kg também mostrou elevação e foi mais próximo do grupo tratado padrão (diazepam 1 mg/kg, ip).

Effect of Agaricus blazei Murill on exploratory behavior of mice-model / Efeito de Agaricus blazei Murill no comportamento exploratório de modelo de camundongo

Abstract Increased anxiety and depressive symptoms have reported to be its association with long term illness. Because of having unwanted effects of newly available drugs, patients administering anxiolytic drugs usually discontinue the treatment before they are completely recovered. Therefore, there is a serious need to develop new anxiolytic drugs. The anxiolytic effect of hydro-alcoholic extract of Agaricus blazei in animal models was assessed. 24 male mice (Mus musculus genus) were included in the study. Four groups were prepared and each group contained six animals. The groups were vehicle control, positive control (diazepam 1.0 mg/kg, i.p.) as well as two treatment groups receiving Agaricus blazei hydro-alcoholic extract at a dose of 136.50 mg/kg and 273.0 mg/kg orally. The Marble burying test, Nestlet shredding test and Light and Dark box test used to assess anxiolytic activity. Mice administered with diazepam 1.0 mg/kg, i.p. while hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) was administered via oral route which exhibited marked reduction in number of marbles-burying as compared to vehicle control group. Mice administered with diazepam 1.0 mg/kg, i.p. and Oral administration of hydro-alcoholic extract of AbM (136.50 and 273.0 mg/kg, respectively) exhibited significant decrease in nestlet shredding in comparison to vehicle control group. The oral administration of hydro-alcoholic extract at a dose of 136.5mg/kg and 273mg/kg showed elevation in time spent in light box and was comparable to standard treated group while time spent by mice following oral administration of hydro-alcoholic extract of Agaricus blazei at a dose of 273.0 mg/kg also showed elevation and was found to be more near to standard treated group (diazepam 1 mg/kg, i.p.).

Resumo O aumento da ansiedade e dos sintomas depressivos têm relatado sua associação com doenças de longa duração. Por causa dos efeitos indesejáveis dos novos medicamentos disponíveis, os pacientes que administram medicamentos ansiolíticos geralmente interrompem o tratamento antes de estarem completamente recuperados. Portanto, há uma necessidade séria de desenvolver novos medicamentos ansiolíticos. Foi avaliado o efeito ansiolítico do extrato hidroalcoólico de Agaricus blazei em modelos animais. Vinte e quatro camundongos machos (gênero Mus musculus) foram incluídos no estudo. Quatro grupos foram preparados, e cada grupo continha seis animais. Os grupos foram controle de veículo, controle positivo (diazepam 1,0 mg/kg, i.p.), bem como dois grupos de tratamento recebendo extrato hidroalcoólico de Agaricus blazei na dose de 136,50 mg/kg e 273,0 mg/kg por via oral. O teste de enterrar Marble, o teste de retalhamento Nestlet e o teste de caixa clara e escura são usados ​​para avaliar a atividade ansiolítica. Camundongos foram administrados com diazepam 1,0 mg/kg, i.p., enquanto o extrato hidroalcoólico de AbM (136,50 e 273,0 mg/kg, respectivamente) foi administrado por via oral, que exibiu redução acentuada no número de mármores enterrados em comparação com o grupo de controle de veículo. Camundongos administrados com diazepam 1,0 mg/kg, i.p. e a administração oral de extrato hidroalcoólico de AbM (136,50 e 273,0 mg/kg, respectivamente) exibiu diminuição significativa na trituração de ninhos em comparação ao grupo de controle de veículo. A administração oral de extrato hidroalcoólico na dose de 136,5mg/kg e 273mg/kg mostrou elevação no tempo gasto na caixa de luz e foi comparável ao grupo tratado padrão, enquanto o tempo gasto por camundongos após a administração oral de extrato hidroalcoólico de Agaricus blazei na dose de 273,0 mg/kg também mostrou elevação e foi mais próximo do grupo tratado padrão (diazepam 1 mg/kg, ip).

Salicylic acid does not relieve salt stress on gas exchange, chlorophyll fluorescence, and hydroponic melon growth.

The objective of this study was to evaluate the salicylic acid applications in attenuating the harmful effects of saline nutrient solution on the physiology and growth of 'Gaúcho' melon cultivated in the NFT hydroponic system. The experiment was conducted in a greenhouse, in Pombal-PB, Brazil. The cultivation system used was the Nutrient Film Technique - NFT hydroponics. A completely randomized split-plot design was used, with the plot referring to four levels of salinity in the nutrient solution - ECns (2.1 control, 3.2, 4.3, and 5.4 dS m-1) and the sub-plot four concentrations of salicylic acid (SA) (0, 1.5, 3.0, and 4.5 mM), applied via foliar spray, with six replications. Nutrient solution of 4.3 and 5.4 dS m-1 electrical conductivity promotes higher maximum and variable fluorescence, respectively. The stomatal conductance, transpiration, stem diameter, main branch length, leaf dry mass, and stem dry mass of 'Gaúcho' melon plants decrease with the increase in salinity of the nutrient solution. Salicylic acid increases the initial fluorescence and the main branch length of 'Gaúcho' melon plants in hydroponic cultivation. Salicylic acid at a concentration of 1.5 to 4.5 mM did not attenuate the effects of salt stress on the internal CO2 concentration, CO2 assimilation rate, and root dry mass of 'Gaúcho' melon plants.

Utility of Prophylactic Percutaneous Gastrostomy in Patients With Head and Neck Cancer Receiving Concurrent Chemoradiotherapy: A Multicenter Analysis.

INTRODUCTION: Patients with head and neck cancer (HNC) have an elevated incidence of cachexia and malnutrition due to the tumor's location interfering with oral feeding. Concurrent chemoradiation (CCRT) can have an emetic effect and cause dysphagia and oral mucositis. Adequate nutrition improves immunity, raises the response to therapy, reduces adverse effects, and improves survival. Numerous studies have suggested the utility of nutritional support from percutaneous endoscopic gastrostomy (PEG) in HNC patients. Although PEG is usually considered a safe procedure, it has a mortality rate of 0-2.2% and a risk of other procedure-related complications of 17-40%. Our work intends to evaluate the utility of PEG in patients with locally advanced HNC who underwent CCRT. METHODS: We performed a cohort study at three institutions. We included patients with HNC who underwent definitive CCRT treatment from January 2013 to December 2022. The study consisted of an observational, descriptive, retrospective analysis of prespecified clinical data. Descriptive statistics were used to compare the data between the PEG group and the non-PEG group. Analysis of covariance (ANCOVA) was used for covariance analysis. Fisher's exact test was used to compare proportional data and Student's t-test was used to assess the differences in continuous data. Survival analysis was performed using the Kaplan-Meier estimator. P-values of <0.05 were considered to be indicative of statistical significance. The SPSS Statistics version 28.0 (Armonk, NY: IBM Corp.) was used to perform all statistical evaluations. RESULTS:  We identified 90 eligible patients diagnosed with local advanced HNC who had received definitive CCRT with three weekly cycles of cisplatin as follows: 44 with a prophylactic PEG tube and 46 without a prophylactic PEG tube. Most patients were male (84.4%) and 50% of patients were diagnosed with stage IVa HNC at the time of diagnosis. There wasn't an effect of PEG placement on BMI at the end of CCRT after controlling for the effect of baseline BMI (F {1.84}=0.065 {p=0.799}). In the study population, BMI was significantly lower after CCRT (21.30 kg/m2 vs. 23.97 kg/m2), t (86)=12.389, p<0.001. In the subgroup with baseline BMI <18.5 kg/m2 (15 patients), 90% of patients with prophylactic PEG were able to complete the three planned cycles of chemotherapy vs. 66.7% in the non-PEG group. Ten patients in the PEG group (22.7%) referred feeding tube dependency. Patients with dysphagia were 3.2 times more likely to have placed prophylactic PEG (p=0.007). The difference in overall survival and progression-free survival between the two groups was not statistically significant (p=0.57 and p=0.497, respectively). CONCLUSION: In this study using real-world data, we found a potentially protective effect of PEG in underweight patients with locally advanced HNC performing CCRT in order to complete three cycles of treatment.

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates.

Introduction. One third of people with CF in the UK are co-infected by both Staphylococcus aureus and Pseudomonas aeruginosa. Chronic bacterial infection in CF contributes to the gradual destruction of lung tissue, and eventually respiratory failure in this group.Gap Statement. The contribution of S. aureus to cystic fibrosis (CF) lung decline in the presence or absence of P. aeruginosa is unclear. Defining the molecular and phenotypic characteristics of a range of S. aureus clinical isolates will help further understand its pathogenic capabilities.Aim. Our objective was to use molecular and phenotypic tools to characterise twenty-five clinical S. aureus isolates collected from mono- and coinfection with P. aeruginosa from people with CF at the Royal Victoria Infirmary, Newcastle upon Tyne.Methodology. Genomic DNA was extracted and sequenced. Multilocus sequence typing was used to construct phylogeny from the seven housekeeping genes. A pangenome was calculated using Roary, and cluster of Orthologous groups were assigned using eggNOG-mapper which were used to determine differences within core, accessory, and unique genomes. Characterisation of sequence type, clonal complex, agr and spa types was carried out using PubMLST, eBURST, AgrVATE and spaTyper, respectively. Antibiotic resistance was determined using Kirby-Bauer disc diffusion tests. Phenotypic testing of haemolysis was carried out using ovine red blood cell agar plates and mucoid phenotypes visualised using Congo red agar.Results. Clinical strains clustered closely based on agr type, sequence type and clonal complex. COG analysis revealed statistically significant enrichment of COG families between core, accessory and unique pangenome groups. The unique genome was significantly enriched for replication, recombination and repair, and defence mechanisms. The presence of known virulence genes and toxins were high within this group, and unique genes were identified in 11 strains. Strains which were isolated from the same patient all surpassed average nucleotide identity thresholds, however, differed in phenotypic traits. Antimicrobial resistance to macrolides was significantly higher in the coinfection group.Conclusion. There is huge variation in genetic and phenotypic capabilities of S. aureus strains. Further studies on how these may differ in relation to other species in the CF lung may give insight into inter-species interactions.

Study of human knowledge and attitude toward urban birds in Faisalabad city, Pakistan / Estudo do conhecimento humano e da atitude em relação às aves urbanas na cidade de Faisalabad, Paquistão

Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.

Os pássaros são indicadores muito valiosos da riqueza de espécies e padrões endêmicos em um determinado ecossistema, o que acaba ajudando o cientista a medir a degradação ambiental. O objetivo do presente estudo foi conhecer o conhecimento humano e a atitude em relação às aves urbanas na cidade de Faisalabad, Paquistão. O estudo foi conduzido em quatro meses consecutivos: novembro de 2019 a fevereiro de 2020. A população de pássaros foi observada em oito cidades residenciais da cidade de Faisalabad, os dados foram coletados por meio de questionário. Faisalabad tem uma população razoavelmente grande de pássaros, e os dados atuais mostram que há uma diferença significativa entre as aves favoritas de áreas residenciais e instituições. O pombo recebeu mais semelhanças na população de pássaros entre os residentes de áreas residenciais, enquanto o myna recebeu menos. A ave mais popular nas instituições de Faisalabad era o pardal, enquanto a ave menos popular era o myna comum. A porcentagem de adaptação de pássaros em áreas residenciais e institucionais de Faisalabad foi a mais alta para papagaios e pardais, respectivamente. As pessoas em áreas residenciais e instituições, por outro lado, se adaptaram menos ao myna comum. Conclui-se que pessoas da área de estudo como pássaros e alimentos oferecidos e alta população de pássaros estão presentes na área de estudo.

Study of human knowledge and attitude toward urban birds in Faisalabad city, Pakistan

Abstract Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.

Resumo Os pássaros são indicadores muito valiosos da riqueza de espécies e padrões endêmicos em um determinado ecossistema, o que acaba ajudando o cientista a medir a degradação ambiental. O objetivo do presente estudo foi conhecer o conhecimento humano e a atitude em relação às aves urbanas na cidade de Faisalabad, Paquistão. O estudo foi conduzido em quatro meses consecutivos: novembro de 2019 a fevereiro de 2020. A população de pássaros foi observada em oito cidades residenciais da cidade de Faisalabad, os dados foram coletados por meio de questionário. Faisalabad tem uma população razoavelmente grande de pássaros, e os dados atuais mostram que há uma diferença significativa entre as aves favoritas de áreas residenciais e instituições. O pombo recebeu mais semelhanças na população de pássaros entre os residentes de áreas residenciais, enquanto o myna recebeu menos. A ave mais popular nas instituições de Faisalabad era o pardal, enquanto a ave menos popular era o myna comum. A porcentagem de adaptação de pássaros em áreas residenciais e institucionais de Faisalabad foi a mais alta para papagaios e pardais, respectivamente. As pessoas em áreas residenciais e instituições, por outro lado, se adaptaram menos ao myna comum. Conclui-se que pessoas da área de estudo como pássaros e alimentos oferecidos e alta população de pássaros estão presentes na área de estudo.

Study of human knowledge and attitude toward urban birds in Faisalabad city, Pakistan / Estudo do conhecimento humano e da atitude em relação às aves urbanas na cidade de Faisalabad, Paquistão

Abstract Birds are very valuable indicators of species richness and endemic patterns in a specified ecosystem, which eventually help the scientist to measure the environmental degradation. The aim of present study was to know human knowledge and attitude toward urban birds in Faisalabad city, Pakistan. The study conducted in four consecutive months: November 2019 to February 2020. Population of birds was noted from eight residential towns of Faisalabad city, data were collected through questionnaire. Faisalabad has a reasonably large population of birds and present data show that, there is a significant difference between favorite bird of residential areas and institutions. The pigeon received the most likeness in bird population among residential area residents, while the myna received the least. The most popular bird in Faisalabad institutions was the sparrow, while the least popular bird was the common myna. Bird adaptation percentage of residential areas and institutional areas of Faisalabad was the highest for parrot and sparrow respectively. People in residential areas and institutions, on the other hand, adapted least to common myna. It is concluded that people of the study area like birds and offered food and high population of birds are present in study area.

Resumo Os pássaros são indicadores muito valiosos da riqueza de espécies e padrões endêmicos em um determinado ecossistema, o que acaba ajudando o cientista a medir a degradação ambiental. O objetivo do presente estudo foi conhecer o conhecimento humano e a atitude em relação às aves urbanas na cidade de Faisalabad, Paquistão. O estudo foi conduzido em quatro meses consecutivos: novembro de 2019 a fevereiro de 2020. A população de pássaros foi observada em oito cidades residenciais da cidade de Faisalabad, os dados foram coletados por meio de questionário. Faisalabad tem uma população razoavelmente grande de pássaros, e os dados atuais mostram que há uma diferença significativa entre as aves favoritas de áreas residenciais e instituições. O pombo recebeu mais semelhanças na população de pássaros entre os residentes de áreas residenciais, enquanto o myna recebeu menos. A ave mais popular nas instituições de Faisalabad era o pardal, enquanto a ave menos popular era o myna comum. A porcentagem de adaptação de pássaros em áreas residenciais e institucionais de Faisalabad foi a mais alta para papagaios e pardais, respectivamente. As pessoas em áreas residenciais e instituições, por outro lado, se adaptaram menos ao myna comum. Conclui-se que pessoas da área de estudo como pássaros e alimentos oferecidos e alta população de pássaros estão presentes na área de estudo.

Chronic Cadmium Exposure and Genetic Polymorphisms of MMP-2 and MMP-9 in a Population Exposed to Steel Slag in the State of Rio de Janeiro, Brazil: A Cross-Sectional Study.

Genetic polymorphisms in the matrix metalloproteinases (MMPs) family genes may be associated with cadmium (Cd) levels and its adverse effects. This study investigated the impact of MMP-2 and MMP-9 polymorphisms on Cd levels in 238 residents of a condominium in Rio de Janeiro, Brazil, built over an industrial steel slag waste. Polymorphisms were genotyped using TaqMan validated assays, and the Cd levels were measured in blood (BCd) and urine (UCd) samples by atomic absorption spectrometry. Associations were evaluated by linear correlation coefficients and multiple logistic regression, using odds ratios (OR) and 95% confidence intervals (CI). Mean age was 50 ± 15 years; 58% were female, 69% non-smokers. Mean concentrations for BCd and UCd were 0.70 ± 0.2 µg L-1 and 0.56 ± 0.55 µg L-1, respectively. Smoking status was associated with BCd ≥ 0.70 µg L-1 (OR = 2.9; 95% CI = 1.6-5.9). MMP-9 rs17576 A > G was associated with BCd ≥ 0.70 µg L-1 (OR = 2.11; 95% CI = 1.10-4.05) and UCd ≥ 0.56 µg L-1 (OR = 3.38; 95% CI = 1.82-7.65). Knowing possible individual predisposing factors is essential to understand Cd toxicity, and to improve the monitoring of high-risk populations.

Use of paclitaxel carried in lipid core nanoparticles in patients with late-stage solid cancers with bone metastases: Lack of toxicity and therapeutic benefits.

Patients with heavily pretreated, late-stage cancer and bone metastasis are usually poor candidates for further chemotherapy. Previously, we showed that association to lipid nanoparticles (LDE) drastically decreases the toxicity of anti-cancer drugs. Here, we tested the hypothesis that paclitaxel (PTX) carried in LDE could benefit end-of-life patients with painful bone metastases that had been previously treated with conventional PTX. Methods: Eighteen consecutive patients with late-stage cancer, 8 with breast, 5 with prostate and 5 with lung carcinoma, aged 59±9 years, were included in this study. All were receiving opioid medication. LDE-PTX was administered at 175 mg/m 2 every 3 weeks until disease progression. Clinical imaging examinations and serum biochemistry determinations were performed to monitor disease progression. Intensity of bone pain, use of opioid medications and occurrence of pathological bone fractures were also evaluated. Results: In total, 104 chemotherapy cycles were performed and none of the patients showed clinical and laboratorial toxicities or pathological bone fractures. In all patients, pain was reduced so as to allow substitution of non-opioid for opioid medication. Median progression-free survival (PFS) was four months (95% CI 2.4-5.5), but in five patients PFS was longer than 6 months. Conclusions: Absence of observable clinical and laboratorial toxicities from LDE-PTX treatment, improvement of bone pain and the possible effect on PFS in some patients, despite previous use of conventional PTX, suggest that LDEPTX merits further clinical investigation .

Impact of Human Epidermal Growth Factor Receptor 2 (HER2) Low Status in Response to Neoadjuvant Chemotherapy in Early Breast Cancer.

Introduction In clinical practice, there is a binary distinction between human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative (HER2-) breast cancer (BC). However, within HER2- disease, there is significant heterogeneity. Particularly, HER2- tumors that express some level of HER2 by immunohistochemistry (IHC) score 1+ or 2+/in situ hybridization (ISH) non-amplified are currently defined as HER2-low. This subgroup has shown distinct biological features compared to HER2-zero (HER2-0) BC and additionally novel antibody-drug conjugate therapies have demonstrated a potential and promising activity in HER2-low BC population. This study aims to evaluate the impact of HER2-low status in response to neoadjuvant chemotherapy (NACT) in HER2- BC being HER2-low and HER2-0 status. Materials and methods In a single institution, we retrospectively reviewed clinical and pathological data of HER2 early-stage BC patients treated with NACT following definitive surgery from January 2015 to December 2020. Tumors with HER2 IHC 0 were classified as HER2-0 and IHC score 1+ and 2+/ISH non-amplified as HER2-low. The primary objective was to evaluate the rate of pathological complete response (pCR) using the definition of ypT0/Tis ypN0 according to HER2-low and HER2-0 subgroups. Secondary objectives were to evaluate biological features between the two subgroups, disease-free survival (DFS), and overall survival (OS). Pearson chi-square, Fisher's exact, and Mann-Whitney tests were performed. The Kaplan-Meier method was used to plot DFS and OS curves. A p-value of <0.05 was considered statistically significant. Results A total of 72 patients with HER2 BC were included with a median age at diagnosis of 52.5 years and a median follow-up time of 35.5 months. Of patients, 56.9% had HER2-low disease and 43.1% had HER2-0 disease. Significant differences between the two subgroups were detected regarding hormonal receptor status and proliferation grade (Ki67). In the HER2-low subgroup, 70% of tumors were luminal-like and 64.5% of HER2-0 patients had triple-negative BC (p = 0.03). There were statistically significant differences regarding estrogen (p = 0.00) and progesterone (p = 0.02) receptors. The median Ki67 rate was higher in the HER2-0 subset (mean rank = 43.9) compared to HER2-low (mean rank = 30.9) and this difference was statistically significant (p = 0.00). HER2-low patients presented more stage III tumors (65.9%) and HER2-0 patients were mainly stage II (61.3%), and this was statistically relevant (p = 0.03). The prevalence of other clinical and pathological features was comparable between both groups. HER2-low subgroup achieved lower pCR rates (14.6% vs. 29.0%) but this difference was not statistically significant (p = 0.15). Similarly, there was no difference between the two subgroups regarding DFS (p = 0.97) and OS (p = 0.35), although the data were immature. Conclusion As in prior studies, this study did not support a significant impact of HER2-low status on response to NACT in HER2- patients with early-stage BC. HER2-low patients had a lower pCR, which may suggest a worse response to classic chemotherapy regimen and may have clinical implications that should be further exploited. The prevalence of hormonal receptors in HER2-low tumors was consistent with previous data in the literature. Although retrospective, the data suggest that HER2-low tumors should be regarded as a distinct biological subtype and more research is warranted.

Prognostic Impact of Baseline Neutrophil-to-Eosinophil Ratio in Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Therapy in Second or Later Lines.

Background Inflammation is a crucial component in carcinogenesis. The neutrophil-to-eosinophil ratio (NER) has been studied as a biomarker of prognosis and predictive of response in metastatic renal cell carcinoma (mRCC). In the present study, we evaluated the relevance of baseline NER on the progression-free survival (PFS) and overall survival (OS) outcomes in real-world patients with mRCC treated with nivolumab in second or subsequent lines. We also assessed the association of baseline NER with objective response, as well as with toxicity and histology. Methods In this multicenter retrospective analysis of patients with mRCC treated with nivolumab, the last systemic absolute neutrophil and eosinophil count before treatment with nivolumab was used to calculate the NER. An additive Cox proportional hazards model was used to identify the cut-off point for NER considering PFS and the patients were allocated into low and high NER groups. Median OS and median PFS were estimated using the Kaplan-Meier estimator, and survival curves of groups were compared using the log-rank test. Univariable and multivariable Cox regression models were used to study OS and PFS and Fisher's exact test was performed to evaluate the association of NER with the response, toxicity, and histology. Results The 49 analyzed patients had a median follow-up of nine months. The NER cut-off was established at 48, locating 29 patients in the low NER group (NER < 48) and 20 in the high NER group (NER ≥ 48). Median PFS and median OS were significantly shorter in patients with high NER versus low NER (3 vs. 30 months (p < 0.001) and 6 vs. 24 months (p = 0.002), respectively). Multivariable analyses showed that NER (HR 3.92 (95% CI: 1.66-9.23), p = 0.002) was an independent factor for PFS and that NER (HR 3.85 (95% CI: 1.33-11.17), p = 0.013) and progressive disease (HR 5.62 (95% CI: 1.88-16.83), p = 0.002) were independent factors for OS. NER was significantly associated with objective response rate (ORR) (NER ≥ 48-12.5% vs. NER < 48-87.5%, p = 0.003), immune-related adverse events (irAEs) (NER ≥ 48-10.0% vs. NER < 48-42.9%, p = 0.014), and tumor's histology as patients of high NER group had more non-clear cell carcinoma than low NER group (35.0% vs. 7.4%, p = 0.017). Conclusion Our real-world data analysis of NER in patients with mRCC confirmed the prognostic value of this biomarker, supporting clinical utility in predicting survival. Results also suggested an association between lower NER and better ORR, and that irAEs occur more frequently in patients with a lower NER. However, further large-scale prospective studies are needed to confirm these findings and to validate this biomarker.

Cutaneous and Cerebral Metastases From Primary Peritoneal Clear Cell Carcinoma.

Peritoneal tumors are very uncommon and among them, primary peritoneal clear cell carcinoma is extremely rare and often misdiagnosed as others subtypes. There are only 13 cases of primary peritoneal clear cell carcinoma previously reported in the literature and there are no reports about cutaneous metastasis in this setting and only brain metastases were described to be associated with other primary peritoneal carcinoma subtypes. More information about this topic is needed and so we are presenting a new case of primary peritoneal clear cell carcinoma with cutaneous and cerebral metastases in a 34-year-old female.

HALOBACTERIAS PROMOTORAS DE CRECIMIENTO VEGETAL ASOCIADAS A Lippia palmer! (VERBENACEAE) EN LA ZONA ÁRIDA DEL NOROESTE DE MÉXICO / Plant growth promoting halobacteria associated to plant growth promoting halobacteria associated to Lippia palmeri (Verbenaceae) in the arid zone of northwestern Mexico

RESUMEN La producción de orégano es de relevancia económica en el noroeste de México. Sin embargo, los productores para obtener altos rendimientos recurren a la fertilización química, pero su mal uso, agudiza la salinidad. Lippia palmeri crece de manera natural en suelos áridos, pobres en materia orgánica, alta salinidad y temperatura en el noroeste de México. En el contexto de una agricultura sustentable, los microorganismos mantienen la fertilidad del suelo e incrementan la productividad de la planta. Actualmente existe interés en proponer biofertilizantes en la agricultura de alta intrusión salina y elevadas temperaturas para el cultivo de orégano. Las Halobacterias Promotoras del Crecimiento de Plantas (HPCP), se han destacado por beneficiar a los cultivos nutrimentalmente y mitigar el efecto de la salinidad. El objetivo del presente trabajo consistió en identificar termo- y halo-tolerantes HPCP asociadas a la rizosfera de L. palmeri; se evaluó la actividad solubilizadora de fosfatos, producción de ácidos orgánicos, sideróforos y fijación de nitrógeno; se identificaron mediante el gen ARNr-16S aquellas con alta actividad evaluándose su efecto en la germinación y longitud radicular. Quince diferentes colonias sobresalieron al crecer en NaCl (0.25, 0.50 y 0.75 M) a 35 y 45 °C, destacando tres bacterias identificadas: Bacillus amyloliquefaciens, Bacillus subtilis y Bacillus licheniformis. El efecto en la longitud radicular es significativo por la aplicación de B. amyloliquefaciens. Estudios relacionados con la promoción vegetal deben ser considerados en posteriores estudios. Este es el primer informe de B. amyloliquefaciens como una bacteria fijadora de nitrógeno asociada a L. palmeri.

ABSTRACT The production of oregano is of economic relevance in northwestern Mexico. However, to obtain high yields, producers resort to chemical fertilization, but its misuse increases salinity. Lippia palmeri Watts is a species of oregano that naturally grows in arid soils with poor organic matter, high salinity and temperature in the northwestern Mexico. In the context of sustainable agriculture, microorganisms activate soil fertility and increase plant productivity. Currently there is interest in proposing biofertilizers in the agriculture with high saline intrusion and temperatures for the cultivation of oregano. The Plant Growth Promoting Halobacteria (HPCP) have stood out by the beneficiary of the nutritious crops and mitigate the effect of the salinity. The goal of this work was to identify HPCP associated to the rhizosphere of L. palmeri, thermo and halotolerant; phosphate solubilizing activity, organic acid production, siderophores and nitrogen fixation were evaluated; the highest activity colonies were identified by the rRNA-16S gene and the effect on germination and root length was evaluated. Fifteen different colonies stood out when growing in NaCl (G.25, G.5G and G.75 M) at 35 and 45 °C, from which three bacteria were identified: Bacillus amyloliquefaciens, Bacillus subtilis and Bacillus licheniformis. The effect on root length was significant for B. amyloliquefaciens. Studies related to plant promotion should be involved in subsequent studies. This is the first report of Bacillus amyloliquefaciens as a nitrogen fixing bacteria associated with Lipia palmeri.

Phylogeny of Lantana, Lippia, and related genera (Lantaneae: Verbenaceae).

PREMISE: Lantana and Lippia (Verbenaceae) are two large Linnean genera whose classification has been based on associated fruit traits: fleshy vs. dry fruits and one vs. two seed-bearing units. We reconstruct evolutionary relationships and the evolution of the two fruit traits to test the validity of these traits for classification. METHODS: Previous studies of plastid DNA sequences provided limited resolution for this group. Consequently, seven nuclear loci, including ITS, ETS, and five PPR loci, were sequenced for 88 accessions of the Lantana/Lippia clade and three outgroups. RESULTS: Neither Lantana nor Lippia is monophyletic. Burroughsia, Nashia, Phyla, and several Aloysia species are included within the clade comprising Lantana and Lippia. We provide a hypothesis for fruit evolution and biogeographic history in the group and their relevance for classification. CONCLUSIONS: Fleshy fruits evolved multiple times in the Lantana/Lippia clade and thus are not suitable taxonomic characters. Several sections of Lantana and Lippia and the small genera are monophyletic, but Lippia section Zappania is broadly paraphyletic, making circumscription of genera difficult. Lippia sect. Rhodolippia is a polyphyletic group characterized by convergence in showy bracts. Species of Lantana sect. Sarcolippia, previously transferred to Lippia, are not monophyletic. The clade originated and diversified in South America, with at least four expansions into both Central America and the Caribbean and two to Africa. The types species of Lantana and Lippia occur in small sister clades, rendering any taxonomy that retains either genus similar to its current circumscription impossible.

Ganoderma sessile is a fast polysaccharide producer among Ganoderma species.

The selection of fast-growing and high-yield-producing strains is required to satisfy the market demand on fungal food supplements. To that aim, three strains deposited in our collection as G. lucidum and G. oregonense were screened for polysaccharide production and biomass yield. Ganoderma strains deposited as G. lucidum were identified as G. sessile and G. lingzhi by nuc rDNA internal transcribed spacer ITS1-5.8S-ITS2 (ITS) and translation elongation factor 1-α (TEF1-α) phylogenies. The identity of G. oregonense was confirmed by molecular phylogeny and biogeography. Additionally, mycelial antagonism confirmed species differentiation, and strains were further distinguished by morphology and protein profiles. Biomass and polysaccharide yields of G. sessile were clearly different from those of G. lingzhi and G. oregonense in both liquid culture and solid-state fermentation. The maximum polysaccharide yield (4.52 ± 0.83 g L-1) for G. sessile was obtained from submerged cultures at day 9. G. sessile also achieved the highest linear growth in lignocellulosic solid substrates. Consequently, basidiomata were successfully obtained by solid-state fermentation in polypropylene bags, whereas G. lingzhi and G. oregonense mushrooms were not produced in artificial solid substrates. G. sessile, a species frequently collected in America, showed to be a promising polysaccharide producer for the manufacture of dietary supplements.

Wooden breast and white striping: comparative occurrence in three poultry companies

ABSTRACT: To increase the amount of meat produced, researchers have promoted intensive genetic selection for growth rate and muscling and have improved nutrition and management conditions. However, there has been an increase in the number of reports of breast muscle myopathies observed in poultry processing plants, including white striping (WS) and wooden breast (WB). This study aimed to evaluate and to compare the occurrence of WS and WB myopathies in three poultry processing plants and to perform an anatomopathological characterization, including macroscopic and microscopic analyses. A total of 408,334 carcasses were condemned or downgraded due to the presence of WB or WS, which represents 0.73% of the total number of slaughtered animals during the evaluated period. WB was more frequent than WS, but the occurrence of each myopathy varied significantly according to each establishment. WB was more frequent in the establishment which includes only male flocks, an average age of 45 days, and an average live weight of 2775g (B). WS was more frequent in establishment with male, female and mixed flocks, average ages ranging from 41 to 44 days, and average live weight 1731g-2830g (A). It is probably related with specific condition of each poultry company, including genetics, age, nutrition and management conditions. Macroscopically, WB and WS lesions are characterized by hypertrophy and stiffness of the pectoralis major muscle. Under microscopy, the myopathies showed similarities regarding the detected histological abnormalities, characterized by a process of myodegeneration, although the connective tissue infiltrate was more severe in the breasts with WB than in those with WS myopathy. The results found in this study demonstrate that the rates of condemnation for these myopathies are high, vary significantly among the analyzed companies and may cause major economic losses for the productive sector in the region.

RESUMO: Para melhorar a quantidade de carne produzida, os pesquisadores têm promovido ao longo dos anos uma seleção genética intensiva para a taxa de crescimento e desenvolvimento de músculos, além de melhorias nas condições nutricionais, sanitárias e de manejo. No entanto, houve um aumento no número de relatos de miopatias dos músculos do peito observados em abatedouros-frigoríficos de aves, incluindo white striping (WS) e wooden breast (WB). O objetivo deste estudo foi avaliar a ocorrência de WB e WS em três abatedouros-frigoríficos de aves e realizar uma caracterização anatomopatológica, incluindo análises macroscópicas e microscópicas. Um total de 408.334 carcaças foi condenado (total ou parcialmente) devido à presença WB ou WS, o que representou 0,73% do número total de animais abatidos durante o período avaliado. Apesar de a ocorrência de WB ter sido maior do que a de WS, a frequência de cada uma variou significativamente de acordo com o estabelecimento. WB foi mais frequente no estabelecimento que incluía apenas lotes de machos, com média de 45 dias de idade e peso médio ao abate de 2775g (B). WS foi mais frequente no estabelecimento com lotes de machos, fêmeas e mistos, com idade entre 41 e 44 dias e peso médio ao abate entre 1731g-2830g (A). Isto pode ser justificado por condições específicas de cada empresa, incluindo genética, idade das aves, nutrição e condições de manejo. Macroscopicamente, as lesões de WB e de WS foram caracterizadas principalmente por hipertrofia e rigidez do músculo pectoralis major. À microscopia, ambas as miopatias mostraram semelhanças em relação às anormalidades histológicas detectadas, caracterizadas principalmente por um processo de miodegeneração. Nos músculos apresentando WB, o infiltrado de tecido conjuntivo foi mais intenso quando comparado àqueles com WS. Os resultados encontrados neste trabalho demonstram que os índices de condenação por essas miopatias são altos, variam significativamente entre as empresas analisadas e podem causar grandes perdas econômicas para o setor produtivo da região.

Wooden breast and white striping: comparative occurrence in three poultry companies / Wooden breast e white striping: ocorrência em três empresas avícolas

To increase the amount of meat produced, researchers have promoted intensive genetic selection for growth rate and muscling and have improved nutrition and management conditions. However, there has been an increase in the number of reports of breast muscle myopathies observed in poultry processing plants, including white striping (WS) and wooden breast (WB). This study aimed to evaluate and to compare the occurrence of WS and WB myopathies in three poultry processing plants and to perform an anatomopathological characterization, including macroscopic and microscopic analyses. A total of 408,334 carcasses were condemned or downgraded due to the presence of WB or WS, which represents 0.73% of the total number of slaughtered animals during the evaluated period. WB was more frequent than WS, but the occurrence of each myopathy varied significantly according to each establishment. WB was more frequent in the establishment which includes only male flocks, an average age of 45 days, and an average live weight of 2775g (B). WS was more frequent in establishment with male, female and mixed flocks, average ages ranging from 41 to 44 days, and average live weight 1731g-2830g (A). It is probably related with specific condition of each poultry company, including genetics, age, nutrition and management conditions. Macroscopically, WB and WS lesions are characterized by hypertrophy and stiffness of the pectoralis major muscle. Under microscopy, the myopathies showed similarities regarding the detected histological abnormalities, characterized by a process of myodegeneration, although the connective tissue infiltrate was more severe in the breasts with WB than in those with WS myopathy. The results found in this study demonstrate that the rates of condemnation for these myopathies are high, vary significantly among the analyzed companies and may cause major economic losses for the productive sector in the region.(AU)

Para melhorar a quantidade de carne produzida, os pesquisadores têm promovido ao longo dos anos uma seleção genética intensiva para a taxa de crescimento e desenvolvimento de músculos, além de melhorias nas condições nutricionais, sanitárias e de manejo. No entanto, houve um aumento no número de relatos de miopatias dos músculos do peito observados em abatedouros-frigoríficos de aves, incluindo white striping (WS) e wooden breast (WB). O objetivo deste estudo foi avaliar a ocorrência de WB e WS em três abatedouros-frigoríficos de aves e realizar uma caracterização anatomopatológica, incluindo análises macroscópicas e microscópicas. Um total de 408.334 carcaças foi condenado (total ou parcialmente) devido à presença WB ou WS, o que representou 0,73% do número total de animais abatidos durante o período avaliado. Apesar de a ocorrência de WB ter sido maior do que a de WS, a frequência de cada uma variou significativamente de acordo com o estabelecimento. WB foi mais frequente no estabelecimento que incluía apenas lotes de machos, com média de 45 dias de idade e peso médio ao abate de 2775g (B). WS foi mais frequente no estabelecimento com lotes de machos, fêmeas e mistos, com idade entre 41 e 44 dias e peso médio ao abate entre 1731g-2830g (A). Isto pode ser justificado por condições específicas de cada empresa, incluindo genética, idade das aves, nutrição e condições de manejo. Macroscopicamente, as lesões de WB e de WS foram caracterizadas principalmente por hipertrofia e rigidez do músculo pectoralis major. À microscopia, ambas as miopatias mostraram semelhanças em relação às anormalidades histológicas detectadas, caracterizadas principalmente por um processo de miodegeneração. Nos músculos apresentando WB, o infiltrado de tecido conjuntivo foi mais intenso quando comparado àqueles com WS. Os resultados encontrados neste trabalho demonstram que os índices de condenação por essas miopatias são altos, variam significativamente entre as empresas analisadas e podem causar grandes perdas econômicas para o setor produtivo da região.(AU)

Androgen deprivation therapy improves the in vitro capacity of high-density lipoprotein (HDL) to receive cholesterol and other lipids in patients with prostate carcinoma.

BACKGROUND: Androgen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. ADT often increases plasma LDL and HDL cholesterol and triglycerides. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters. METHODS: Sixteen volunteers with advanced prostate carcinoma submitted to pharmacological ADT or orchiectomy had plasma collected shortly before and after 6 months of ADT. In vitro transfer of lipids to HDL was performed by incubating plasma with donor emulsion containing radioactive lipids by 1 h at 37 °C. After chemical precipitation of apolipoprotein B-containing lipoprotein, the radioactivity of HDL fraction was counted. RESULTS: ADT reduced testosterone to nearly undetectable levels and markedly diminished PSA. ADT increased the body weight but glycemia, triglycerides, LDL and HDL cholesterol, HDL lipid composition and CETP concentration were unchanged. However, ADT increased the plasma unesterified cholesterol concentration (48 ± 12 vs 56 ± 12 mg/dL, p = 0.019) and LCAT concentration (7.15 ± 1.81 vs 8.01 ± 1.55µg/mL, p = 0.020). Transfer of unesterified (7.32 ± 1.09 vs 8.18 ± 1.52%, p < 0.05) and esterified cholesterol (6.15 ± 0.69 vs 6.94 ± 1.29%, p < 0.01) and of triglycerides (6.37 ± 0.43 vs 7.18 ± 0.91%, p < 0.001) to HDL were increased after ADT. Phospholipid transfer was unchanged. CONCLUSION: Increase in transfer of unesterified and esterified cholesterol protects against cardiovascular disease, as shown previously, and increased LCAT favors cholesterol esterification and facilitates the reverse cholesterol transport. Thus, our results suggest that ADT may offer anti-atherosclerosis protection by improving HDL functional properties. This could counteract, at least partially, the eventual worse effects on plasma lipids.

Targeting ROS overgeneration by N-benzyl-2-nitro-1-imidazole-acetamide as a potential therapeutic reposition approach for cancer therapy.

BackgroundWe investigated the role of reactive oxygen species (ROS) in the anticancer mechanism of N-benzyl-2-nitro-1-imidazole-acetamide (BZN), a drug used in Chagas' disease treatment. MethodsBALB/c mice, inoculated with Ehrlich ascites carcinoma (EAC), were treated with BZN or BZN + Nacylcysteine (NAC) or NAC for 9 days. Subsequently, the inhibition of tumor growth and angiogenesis as well as animal survival were evaluated. Apoptosis and the cell cycle were evaluated using fluorescence microscopy and flow cytometry, while oxidative stress was evaluated by measuring TBARS content, DNA damage, calcium influx and ROS generation and antioxidant defenses (CAT, SOD, GPx, GST and GR). Immunoblotting was used to evaluate key death and cell cycle proteins. Results BZN treatment inhibited tumor progression (79%), angiogenesis (2.8-fold) and increased animal survival (29%). Moreover, BZN increased ROS levels (42%), calcium influx (55%), TBARS contents (1.9-fold), SOD (4.4-fold), GPx (17.5-fold) and GST (3-fold) activities and GSH depletion (2.5-fold) also caused DNA fragmentation (7.6-fold), increased cleaved PARP and promoted the trapping of cells in the G1 phase, as corroborated by the reduction in cyclin A and increased CDK2 protein levels. In silico DNA and molecular dynamic simulations showed H-bonds and hydrophobic interactions that were confirmed by circular dichroism. Increased apoptosis (232%), induced by treatment with BZN, was demonstrated by apoptotic cell staining and p53 level. Conclusion The current findings indicate that BZN acts as a tumor growth inhibitor and anti-angiogenic agent by ROS overgeneration, which interact with DNA causing damage and triggering apoptosis.