Label-free quantification of imaging features in the extracellular matrix of left and right-sided colon cancer tissues.

The molecular pathogenesis of colorectal cancer is known to differ between the right and left side of the colon. Several previous studies have focussed on the differences in clinicopathological features, proteomic and genetic biomarkers, the composition of gut microbiota, response to therapy, and the characteristics of the tumour microenvironment. However, the morphology and density of collagen in the extracellular matrix (ECM) have not been studied intensively. In this study, we employed 2-photon laser scanning microscopy (2PLSM) to visualise the intrinsic second-harmonic generation (SHG) signal emitted by collagen fibres in the heterogeneous ECM of human colon tumour tissues. Through texture analysis of the SHG signal, we quantitatively distinguished the imaging features generated by structural differences of collagen fibres in healthy colon and cancers and found marked differences. The fibres inside of tumours exhibited a loss of organisation, particularly pronounced in right-sided colon cancer (RSCC), where the chaotic regions were significantly increased. In addition, a higher collagen content was found in left-sided colon cancer (LSCC). In future, this might aid in subclassification and therapeutic decisions or even in designing new therapy regimens by taking into account the differences between collagen fibres features between colon tumours located at different sides.

A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver.

Primaquine is the mainstream antimalarial drug to prevent Plasmodium vivax relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks. Nanoemulsion (NE-Pq) and nanochitosan (NQ-Pq) formulations of primaquine diphosphate containing D-galactose were prepared and characterized by their physicochemistry properties. Pharmacokinetic and biodistribution studies were conducted using Swiss Webster mice. A single dose of 10 mg/kg of each nanoformulation or free primaquine solution was administered by gavage to the animals, which were killed at 0.5, 1, 2, 4, 8, and 24 hours. Blood samples and tissues were collected, processed, and analyzed by high-performance liquid chromatography. The nanoformulation showed sizes around 200 nm (NE-Pq) and 400 nm (NQ-Pq) and physicochemical stability for over 30 days. Free primaquine solution achieved higher primaquine Cmax in the liver than NE-Pq or NQ-Pq at 0.5 hours. However, the half-life and mean residence time (MRT) of primaquine in the liver were three times higher with the NQ-Pq formulation than with free primaquine, and the volume distribution was four times higher. Conversely, primaquine's half-life, MRT, and volume distribution in the plasma were lower for NQ-Pq than for free primaquine. NE-Pq, on the other hand, accumulated more in the lungs but not in the liver. Galactose-coated primaquine nanochitosan formulation showed increased drug targeting to the liver compared to free primaquine and may represent a promising strategy for a more efficient and safer radical cure for vivax malaria.

Exogenous application of salicylic acid induces salinity tolerance in eggplant seedlings

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.

Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.

Exogenous application of salicylic acid induces salinity tolerance in eggplant seedlings / Aplicação exógena de ácido salicílico induz tolerância à salinidade em mudas de berinjela

Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.

Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.

Definition of protocols for cryopreservation and three-dimensional in vitro culture of prepubertal goat testicular tissue after histomorphological, ultrastructural, and functional analysis.

This study aims to define the best method (slow freezing or vitrification) and fragment size (1, 5, or 9 mm³) for prepubertal goat testis cryopreservation, as well as to evaluate testicular morphological integrity after cryopreservation and in vitro culture (IVC). Initially (experiment I), 1, 5, or 9 mm³ testis fragments were cryopreserved by slow freezing using a Mr. Frosty container with 20% Dimethylsulfoxide (DMSO) or vitrified using the Ovarian Tissue Cryosystem (OTC) device, (Equilibration solution - ES: 10% DMSO and 10% ethylene glycol - EG; Vitrification solution - VS: 20% DMSO and 20% EG) and then subjected to morphological analysis, type I and III collagen quantification and gene expression (Oct4, C-kit, Bax, and Bcl-2). Subsequently, (experiment II), fresh or cryopreserved by slow freezing testis fragments were cultured in vitro and submitted to morphological analysis by scanning electron microscopy. The data from the experiment I revealed fewer morphological alterations in 1 and 5 mm³ fragments after vitrification and slow freezing, respectively. The percentage of type I collagen fibers in 5 and 9 mm³ frozen was higher than in fresh or vitrified fragments. For type III collagen, fresh or frozen fragments of 1 and 5 mm3 showed a higher percentage than fragments of 9 mm3. Gene expression for Oct4 and C-kit after slow freezing or vitrification in the 5 mm3 fragments was lower than that observed in the fresh fragments. The Bax:Bcl-2 ratio in the 1 and 9 mm³ fragments was lower than in the 5 mm³ fragments for fresh fragments or after freezing. In experiment II, fragments cultured in vitro, previously frozen or not, showed more morphological alterations than fresh or frozen fragments. We concluded that slow freezing of 5 mm³ fragments was the best protocol for cryopreserving prepubertal goat testis and although the results of IVC are encouraging, it still needs improvement to restore testicular function after cryopreservation.

Exogenous application of salicylic acid induces salinity tolerance in eggplant seedlings.

Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.

Lipopolysaccharide Regulates Pro- and Anti-Inflammatory Cytokines, Corticosterone, and Melatonin in Toads.

Glucocorticoids and melatonin (MEL) show integrated and complex immunomodulatory effects, mostly described for endotherms, yet underexplored in amphibians. In this context, the RT-qPCR of molecules mediating inflammatory processes in amphibians is a valuable tool to explore the relationships among molecular biology, endocrine mediators, and immune response in these animals. In this study, toads (Rhinella diptycha) received an intraperitoneal saline injection or lipopolysaccharide (LPS; 2 mg/kg). Six hours post-injection, we analyzed plasma corticosterone (CORT) and MEL levels and pro- and anti-inflammatory molecules (IL-1ß, IL-6, IL-10, IFN-γ, and C1s). We found increased CORT and decreased MEL levels in response to LPS. Also, IL-1ß, IL-6, and IL-10 were upregulated in LPS-injected toads compared with saline-injected toads. Overall, our results demonstrate an LPS-induced inflammatory response with endocrine and immune modulation in R. diptycha toads, exhibiting expected patterns for an inflammatory stimulus within this time frame (6 h post-injection). Toads were responsive to LPS by secreting different cytokines, such as proinflammatory cytokines IL-1ß and IL-6, related to immune cell attraction to inflammatory sites and the anti-inflammatory cytokine IL-10, which limits the rate of leukocyte infiltration, inflammation, and downregulates the expression of proinflammatory cytokines. Increased circulating CORT levels are probably associated with the activation of the hypothalamus-pituitary-interrenal axis by the LPS and the endocrine actions of IL-6. Furthermore, decreased circulating MEL levels are likely due to inhibited MEL secretion by the pineal gland by inflammatory stimuli, indicating the activation/existence of the immune-pineal axis in amphibians.

Os glicocorticoides e a melatonina (MEL) apresentam efeitos imunomoduladores integrados e complexos, principalmente descritos para endotérmicos, porém pouco explorados em anfíbios. Nesse contexto, o RT-qPCR de moléculas mediadoras de processos inflamatórios em anfíbios é uma ferramenta valiosa para explorar as relações entre biologia molecular, mediadores endócrinos e resposta imune nesses animais. Neste estudo, sapos (Rhinella diptycha) receberam uma injeção intraperitoneal de solução salina ou lipopolissacarídeo (LPS; 2 mg/kg). Seis horas após a injeção, analisamos as concentrações plasmáticas de corticosterona (CORT) e MEL e moléculas pró e anti-inflamatórias (IL-1ß, IL-6, IL-10, IFN-γ e C1s). Encontramos aumento de CORT e diminuição da concentração de MEL em resposta ao LPS. Além disso, IL-1ß, IL-6 e IL-10 foram reguladas positivamente em sapos injetados com LPS em comparação com os sapos injetados com solução salina. No geral, nossos resultados demonstram uma resposta inflamatória induzida por LPS com modulação endócrina e imunológica em sapos R. diptycha, exibindo padrões esperados para um estímulo inflamatório dentro deste período (6 h pós-injeção). Os sapos foram responsivos ao LPS secretando diferentes citocinas, como as citocinas pró-inflamatórias IL-1ß e IL-6, relacionadas à atração de células imunes para os sítios inflamatórios e a citocina anti-inflamatória IL-10, que limita a taxa de infiltração leucocitária, inflamação, e diminui a expressão de citocinas pró-inflamatórias. As concentrações elevadas de CORT circulante estão provavelmente associados à ativação do eixo hipotálamo-hipófise-interrenal pelo LPS e às ações endócrinas da IL-6. Além disso, a diminuição da concentração circulante de MEL é provavelmente devida à inibição da secreção de MEL pela glândula pineal por estímulos inflamatórios, indicando a ativação/existência do eixo imune-pineal em anfíbios.

Nutritional support during the hospital stay reduces mortality in patients with different types of cancers: secondary analysis of a prospective randomized trial.

BACKGROUND: Nutritional support in patients with cancer aims at improving quality of life. Whether use of nutritional support is also effective in improving clinical outcomes requires further study. PATIENTS AND METHODS: In this preplanned secondary analysis of patients with cancer included in a prospective, randomized-controlled, Swiss, multicenter trial (EFFORT), we compared protocol-guided individualized nutritional support (intervention group) to standard hospital food (control group) regarding mortality at 30-day (primary endpoint) and other clinical outcomes. RESULTS: We analyzed 506 patients with a main admission diagnosis of cancer, including lung cancer (n = 113), gastrointestinal tumors (n = 84), hematological malignancies (n = 108) and other types of cancer (n = 201). Nutritional risk based on Nutritional Risk Screening (NRS 2002) was an independent predictor for mortality over 180 days with an (age-, sex-, center-, type of cancer-, tumor activity- and treatment-) adjusted hazard ratio of 1.29 (95% CI 1.09-1.54; P = 0.004) per point increase in NRS. In the 30-day follow-up period, 50 patients (19.9%) died in the control group compared to 36 (14.1%) in the intervention group resulting in an adjusted odds ratio of 0.57 (95% CI 0.35-0.94; P = 0.027). Interaction tests did not show significant differences in mortality across the cancer type subgroups. Nutritional support also significantly improved functional outcomes and quality of life measures. CONCLUSIONS: Compared to usual hospital nutrition without nutrition support, individualized nutritional support reduced the risk of mortality and improved functional and quality of life outcomes in cancer patients with increased nutritional risk. These data further support the inclusion of nutritional care in cancer management guidelines.

Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications.

Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model.

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

A prospective cohort study on the safety of checkpoint inhibitors in older cancer patients - the ELDERS study.

OBJECTIVE: Older cancer patients are underrepresented in the pivotal trials of checkpoint inhibitors (CPIs). This study aimed to investigate the impact of an ageing immune system on CPI-related toxicity and provide evidence for the role of geriatric assessments with CPI. METHODS: The ELDERS study is a prospective observational study with two cohorts: older (70+ years of age) and younger (<70 years of age). Patients with advanced/metastatic non-small-cell lung cancer or melanoma starting single-agent CPI were eligible. The older cohort was assessed for frailty with Geriatric-8 (G8) screening, which when positive (<15 points) was followed by a holistic set of geriatric assessments. Primary endpoint was the incidence of grade 3-5 immune-related adverse events (irAEs). RESULTS: One hundred and forty patients were enrolled with 43% being pretreated and pembrolizumab represented 92% of treatments on study. The older cohort had a significantly higher comorbidity burden (P < 0.001) and polypharmacy (P = 0.004). While 50% of older patients had a positive G8 screening, 60% on this frail subgroup had a performance status score of 0 or 1. There was no significant difference in the incidence of irAEs grade 3-5 between older and younger cohorts (18.6% versus 12.9%; odds ratio 1.55, confidence interval 95% 0.61-3.89; P = 0.353). Exposure to systemic steroids due to irAEs was numerically longer for older patients (22 versus 8 weeks; P = 0.208). A positive G8 screening predicted hospital admissions (P = 0.031) and risk of death (P = 0.01). CONCLUSIONS: The use of CPI in older patients was not associated with more high-grade toxicity. The G8 screening identified a subgroup with higher risk of AEs and its implementation should be considered in the context of CPI.

Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications

Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model.

Comparison of powdered and fresh jambu (Acmella oleracea).

Jambu, Acmella oleracea (L.), is a low-growing herb plant, with cylindrical, fleshy, decumbent and branched stem varying from 20 to 30 cm in height. It is an abundantly cultivated and consumed vegetable in the northern region of Brazil and usually consumed in preparations of typical foods of the Amazon region. So, this work aimed to compare the chemical composition and physical chemistry of powdered and jambu leaf mass. Acmella oleracea plants were selected, sanitized and their leaves were crushed (without adding water). The mass was dried in an oven with forced air circulation under different conditions of temperature (60, 70 and 80 °C) and relative humidity (13.09, 8.14 and 5.45%, respectively), in two layer thicknesses (0.5 and 1.0 cm). The physical, chemical, physicochemical parameters moisture content, water activity, ash, protein, lipids, pH, total titratable acidity and color were analyzed in powdered and fresh leaves. Contrast test was used to evaluate the interaction between the layer thicknesses at 5% level of significance. Considering the contrasts, the parameters total soluble solids, ash, protein and lipids do not differ from those in the fresh sample, demonstrating that these parameters are not modified or degraded with the drying conditions. The pH and color parameters differed from those of the fresh material, due to degradation, which can be linked to the rise in temperature sensitivity. The moisture content and water activity also differed and were reduced, contributing to conservation of the material. Contrast analysis made it possible to conclude that the physicochemical composition did not undergo modifications through the use of drying. In addition, a powdered material with reduced water activity was obtained.

Trends and predictions for survival and mortality in individuals with Down syndrome in Brazil: A 21-year analysis.

BACKGROUND: Regional heterogeneities and sociodemographic characteristics affect mortality and population survival in Brazil. However, for individuals with Down syndrome (DS) this information remains unknown. In this study, we analysed survival and mortality rates among DS individuals in the five Brazilian geographic regions. In addition, we investigated whether there is an association between mortality and sociodemographic factors across administrative regions. METHODS: Data between 1996 and 2016, comprising 10 028 records of deaths of individuals with DS, were collected from database records of the Department of Informatics of the Unified Health System. Data on race/ethnicity, sex, age and years of schooling were defined for the association analyses. Survival data were analysed according to the Kaplan-Meier method and Cox regression model. RESULTS: The number of deaths among people with DS has increased in recent years. Children are more susceptible to death, especially in the first years of life. Individuals living in the northern region, Indigenous women and people with no years of schooling have higher mortality. In the Southeast and South region, for White and Yellow, survival is related to a higher level of education. Ethnic factors and years of schooling influence risk for mortality across the administrative regions. CONCLUSIONS: These findings show that sociodemographic characteristics affect survival and are associated with the risk of mortality for people with DS. In addition, this suggests that differences in access to health services among Brazilian regions, especially in the first years of life, may affect the survival of individuals with DS.

No man is an island: spatial clustering and access to primary care as possible targets for the development of new community mental health approaches.

BACKGROUND: to understand if patients seen at Centro Hospitalar Psiquiátrico de Lisboa (CHPL) live in geographical clusters or randomly throughout the city, as well as determine their access to the psychiatric hospital and primary care facilities (PCF). METHODS: spatial autocorrelation statistics were performed (queen criterion of contiguity), regarding all patients observed at CHPL in 2017 (at the census subsection level), and considering not only their overall number but also main diagnosis, and admission to the psychiatric ward - voluntary or compulsory. Distance to the hospital and to the closest PCF was measured (for each patient and the variables cited above), and the mean values were compared. Finally, the total number of patients around each PCF was counted, considering specified radius sizes of 656 and 1000 m. RESULTS: All 5161 patients (509 psychiatric admissions) were geolocated, and statistical significance regarding patient clustering was found for the total number (p-0.0001) and specific group of disorders, namely Schizophrenia and related disorders (p-0.007) and depressive disorders (p-0.0002). Patients who were admitted in a psychiatric ward live farther away from the hospital (p-0.002), with the compulsory admissions (versus voluntary ones) living even farther (p-0.004). Furthermore, defining a radius of 1000 m for each PCF allowed the identification of two PCF with more than 1000 patients, and two others with more than 800. CONCLUSIONS: as patients seem to live in geographical clusters (and considering PCFs with the highest number of them), possible locations for the development of programs regarding mental health treatment and prevention can now be identified.

Severe acute pancreatitis: eight fundamental steps revised according to the 'PANCREAS' acronym.

Severe acute pancreatitis remains a life-threatening condition, responsible for many disorders of homeostasis and organ dysfunction. By means of a mnemonic 'PANCREAS', eight important steps in the management of severe acute pancreatitis are highlighted. These steps follow the principle of goal-directed therapy and should be borne in mind after diagnosis and during clinical treatment. The first step is perfusion: the goal is to reach a central venous pressure of 12-15mmHg, urinary output 0.5-1ml/kg/hour and inferior vena cava collapse index greater than 48%. Next is analgesia: multimodal, systemic and combined pharmacological agent and epidural block are possibilities. Third is nutrition: precocity, enteral feeding in gastric or post-pyloric position. Parenteral nutrition works best in difficult cases to achieve the individual total caloric value. Fourth is clinical: mild, moderate or severe pancreatitis according to the Atlanta criteria. Radiology is fifth: abdominal computed tomography on the fourth day for prognosis or to modify management. Endoscopy is sixth: endoscopic retrograde cholangiopancreatography (cholangitis, unpredicted clinical course and ascending jaundice); management of pancreatic fluid collection and 'walled-off necrosis'. Antibiotics come next: infectious complications are common causes of morbidity. The only rational indication for antibiotics is documented pancreatic infection. The last step is surgery: the dogma is represented by the 'three Ds' (delay, drain, debride). The preferred method is a minimally invasive step-up approach, which allows for gradually more invasive procedures when the previous treatment fails.

Nandrolone decanoate and resistance exercise affect prostate morphology and hormone receptor interface in adult rats with implications for the aging process.

BACKGROUND: Nandrolone decanoate (ND) is an anabolic-androgenic steroid, and its indiscriminate use leads to subclinical alterations in the hypothalamic-pituitary-gonadal axis and androgen-dependent organs. OBJECTIVES: To evaluate the effects of ND, either alone or in combination with resistance exercise (RE), on the levels of sex hormones, converting enzymes, and steroid receptors and the morphology of the ventral prostate (VP) in adult and aged rats. METHODS: Forty Sprague-Dawley adult and aged rats were divided into four groups each, sedentary and trained with and without ND. The groups received treatments over 8 weeks. Adult animals were sacrificed immediately following treatment completion, while the aged groups were left untreated until 300 days of age. RESULTS: Adult and aged animals showed reductions in testosterone levels following the different treatments, and 17ß-estradiol levels were decreased in the ND-treated groups. The level of 5α-reductase type 2 (5αR2) and aromatase was increased significantly in the prostates of adult animals that performed RE. However, aromatase levels were decreased in the prostates of aged animals that performed RE and were treated with ND, while 5αR2 levels were reduced in aged animals that performed RE without ND treatment. When sex receptors levels were examined, the aged and trained animals presented low androgen receptor (AR) levels. Estrogen receptors (ERs) levels were increased in the prostates of adult animals that received ND. ERß levels were reduced after treatments in aged animals. The heights of the prostatic epithelium were reduced in all adult treated animals, coinciding with increases in PCNA and PAR4 levels. DISCUSSION: ND and RE alter the levels of hormone, converting enzymes, and sex steroid receptors and the morphology of the VP. These effects were observed in both adult and aged rats. CONCLUSION: ND, either with or without RE, during post-puberty stage is able to interfere with the morphophysiology of the prostate.