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Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Laccase is a versatile enzyme with low specificity and exhibits the ability to oxidize both phenolic and non-phenolic compounds, utilizing a broad range of substrates. These unique characteristics make laccase suitable for diverse applications, including bioremediation, food processing, and pharmaceutical industries. In this study, we focused on the production of laccase using Penicillium brevicompactum CCDCA 11400 through solid-state fermentation, employing sugarcane bagasse and atrazine as carbon sources. The efficiency of laccase in degrading the solid substrate was also investigated. Three sources of laccase, namely crude laccase extract, commercial laccase, and the inoculum, were compared to identify the most effective in promoting substrate degradation, both with and without the addition of atrazine. Results revealed that the highest enzymatic activity (6 U/g) were achieved in Erlenmeyer flask at pH 4 and 19 °C. A bioreactor under the same conditions also exhibited the highest laccase level (3.2 U/g). The presence of atrazine led to an even higher laccase production when applied to the sugarcane bagasse, indicating its potential to enhance enzyme synthesis. The combined effect of enzymatic activity and atrazine facilitated the degradation of approximately 40% of the substrate, further underscoring the positive impact of atrazine. Overall, the successful production and application of laccase from Penicillium brevicompactum CCDCA 11400 demonstrates the biotechnological potential of this species, providing an economically and environmentally friendly method for enzyme production. [ABSTRACT FROM AUTHOR]

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPβ1, a surface receptor that triggers amyloid-β(Aβ) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPβ1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPβ1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPβ1 protein isoform landscape compromising its ability to bind oligomeric Aβ and its affinity for TYROBP. SIRPβ1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aβ ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPβ1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPβ1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aβ. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPβ1 structural variant might be considered as a potential modulator of this causative pathway. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment of metastatic urothelial carcinoma (mUC) upon platinum-based chemotherapy according to the positive results of large clinical trials. Nevertheless, results from unselected populations reflecting real-world data (RWD) are highly informative to the clinician. We reviewed daily clinical practice outcomes in patients with mUC who received atezolizumab in our institution. Methods: Here we evaluated the clinical activity and safety of atezolizumab in an unselected population of mUC patients who received atezolizumab between 2018 and 2022 reflecting RWD. Efficacy and safety information were retrospectively collected. Results: A total of 63 patients were included. The mean age was 68 years and the objective response rate was 14.3%. The median progression-free survival was 3 months and the median overall survival 6 months. At 1 year, 42% of the patients were alive. ECOG (0 vs 1) and neutrophil–lymphocytes ratio < 2 at the start of ICI were positive prognostic factors that discriminated between long vs short survivors. Overall tolerance was good with no new safety signals. Five patients (17%) had treatment-related adverse events grade ≥ 2 that required corticosteroids. Conclusion: In this retrospective study, atezolizumab was an effective and tolerable treatment option for patients with mUC after progression to platinum-based chemotherapy. Yet, patient selection remains critical to improve outcomes. [ABSTRACT FROM AUTHOR]

Reactive astrogliosis accompanies the two neuropathological hallmarks of Alzheimer’s disease (AD)—Aβ plaques and neurofibrillary tangles—and parallels neurodegeneration in AD and AD-related dementias (ADRD). Thus, there is growing interest in developing imaging and fluid biomarkers of reactive astrogliosis for AD/ADRD diagnosis and prognostication. Monoamine oxidase-B (MAO-B) is emerging as a target for PET imaging radiotracers of reactive astrogliosis. However, a thorough characterization of MAO-B expression in postmortem control and AD/ADRD brains is lacking. We sought to: (1) identify the primary cell type(s) expressing MAO-B in control and AD brains; (2) quantify MAO-B immunoreactivity in multiple brain regions of control and AD donors as a proxy for PET radiotracer uptake; (3) correlate MAO-B level with local AD neuropathological changes, reactive glia, and cortical atrophy; (4) determine whether the MAOB rs1799836 SNP genotype impacts MAO-B expression level; (5) compare MAO-B immunoreactivity across AD/ADRD, including Lewy body diseases (LBD) and frontotemporal lobar degenerations with tau (FTLD-Tau) and TDP-43 (FTLD-TDP). We found that MAO-B is mainly expressed by subpial and perivascular cortical astrocytes as well as by fibrous white matter astrocytes in control brains, whereas in AD brains, MAO-B is significantly upregulated by both cortical reactive astrocytes and white matter astrocytes across temporal, frontal, and occipital lobes. By contrast, MAO-B expression level was unchanged and lowest in cerebellum. Cortical MAO-B expression was independently associated with cortical atrophy and local measures of reactive astrocytes and microglia, and significantly increased in reactive astrocytes surrounding Thioflavin-S+ dense-core Aβ plaques. MAO-B expression was not affected by the MAOB rs1799836 SNP genotype. MAO-B expression was also significantly increased in the frontal cortex and white matter of donors with corticobasal degeneration, Pick’s disease, and FTLD-TDP, but not in LBD or progressive supranuclear palsy. These findings support ongoing efforts to develop MAO-B-based PET radiotracers to image reactive astrogliosis in AD/ADRD. [ABSTRACT FROM AUTHOR]

Copyright of DoisPontos is the property of Universidade Federal do Parana, Departamento de Filosofia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: In 2020, there were 880,000 new cases and 440,000 deaths attributed to head and neck cancer worldwide. Nivolumab was approved in 2016 in the United States, and 2017 in the European Union and Canada, for use in patients with recurrent/metastatic squamous cell carcinoma of the head and neck with progressive disease at or within 6 months after platinum-based therapy. This study was conducted to capture the real-world utilization of nivolumab and to assess the impact of treatment on quality of life among affected patients. The retrospective protocol (VOLUME) described the effectiveness of treatment with nivolumab in terms of survival times and response on imaging, while the prospective protocol (VOLUME-PRO) described the health-related quality of life (HRQoL) among patients treated with nivolumab. This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and patient-reported symptoms. There were 447 and 51 patients in VOLUME and VOLUME-PRO, respectively. Across both studies, the median age was 64.0 years, 80.9% were male, and 52.6% were former smokers. Clinical outcomes of interest included real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). The median rwOS was 9.2 months. Among patients with at least one assessment, 21.7% reported their best response as 'partial response', with 3.9% reporting 'complete response'. The median duration of response (DoR) and median rwPFS were 11.0 months and 3.9 months, respectively. At baseline, VOLUME-PRO patients reported difficulties relating to fatigue, physical and sexual functioning, dyspnea, nausea, sticky saliva, dry mouth, pain/discomfort, mobility, and financial difficulties. There were improvements in social functioning and financial difficulties throughout the study; however, no other clinically meaningful changes were noted. No new safety concerns were identified. This real-world, multinational, multicenter, retrospective and prospective study supports the effectiveness and safety of nivolumab for R/M SCCHN patients. [ABSTRACT FROM AUTHOR]

Microglia are brain-resident myeloid cells and play a major role in the innate immune responses of the CNS and the pathogenesis of Alzheimer's disease (AD). However, the contribution of nonparenchymal or brain-infiltrated myeloid cells to disease progression remains to be demonstrated. Here, we show that monocyte-derived cells (MDC) invade brain parenchyma in advanced stages of AD continuum using transcriptional analysis and immunohistochemical characterization in post-mortem human hippocampus. Our findings demonstrated that a high proportion (60%) of demented Braak V–VI individuals was associated with up-regulation of genes rarely expressed by microglial cells and abundant in monocytes, among which stands the membrane-bound scavenger receptor for haptoglobin/hemoglobin complexes or Cd163. These Cd163-positive MDC invaded the hippocampal parenchyma, acquired a microglial-like morphology, and were located in close proximity to blood vessels. Moreover, and most interesting, these invading monocytes infiltrated the nearby amyloid plaques contributing to plaque-associated myeloid cell heterogeneity. However, in aged-matched control individuals with hippocampal amyloid pathology, no signs of MDC brain infiltration or plaque invasion were found. The previously reported microglial degeneration/dysfunction in AD hippocampus could be a key pathological factor inducing MDC recruitment. Our data suggest a clear association between MDC infiltration and endothelial activation which in turn may contribute to damage of the blood brain barrier integrity. The recruitment of monocytes could be a consequence rather than the cause of the severity of the disease. Whether monocyte infiltration is beneficial or detrimental to AD pathology remains to be fully elucidated. These findings open the opportunity to design targeted therapies, not only for microglia but also for the peripheral immune cell population to modulate amyloid pathology and provide a better understanding of the immunological mechanisms underlying the progression of AD. [ABSTRACT FROM AUTHOR]

Cylindrospermopsin (CYN) is a cyanotoxin whose incidence has been increasing in the last decades. Due to its capacity to exert damage at different levels of the organism, it is considered a cytotoxin. Although the main target organ is the liver, recent studies indicate that CYN has potential toxic effects on the nervous system, both in vitro and in vivo. Thus, the aim of the present work was to study the effects of this cyanotoxin on neuronal viability and synaptic integrity in murine primary cultures of neurons exposed to environmentally relevant concentrations (0–1 µg/mL CYN) for 12, 24, and 48 h. The results demonstrate a concentration- and time-dependent decrease in cell viability; no cytotoxicity was detected after exposure to the cyanotoxin for 12 h, while all of the concentrations assayed decreased this parameter after 48 h. Furthermore, CYN was also demonstrated to exert damage at the synaptic level in a murine primary neuronal culture in a concentration- and time-dependent manner. These data highlight the importance of studying the neurotoxic properties of this cyanotoxin in different experimental models. [ABSTRACT FROM AUTHOR]

Background: Astrocytes and microglia react to Aβ plaques, neurofibrillary tangles, and neurodegeneration in the Alzheimer's disease (AD) brain. Single-nuclei and single-cell RNA-seq have revealed multiple states or subpopulations of these glial cells but lack spatial information. We have developed a methodology of cyclic multiplex fluorescent immunohistochemistry on human postmortem brains and image analysis that enables a comprehensive morphological quantitative characterization of astrocytes and microglia in the context of their spatial relationships with plaques and tangles.Methods: Single FFPE sections from the temporal association cortex of control and AD subjects were subjected to 8 cycles of multiplex fluorescent immunohistochemistry, including 7 astroglial, 6 microglial, 1 neuronal, Aβ, and phospho-tau markers. Our analysis pipeline consisted of: (1) image alignment across cycles; (2) background subtraction; (3) manual annotation of 5172 ALDH1L1+ astrocytic and 6226 IBA1+ microglial profiles; (4) local thresholding and segmentation of profiles; (5) machine learning on marker intensity data; and (6) deep learning on image features.Results: Spectral clustering identified three phenotypes of astrocytes and microglia, which we termed "homeostatic," "intermediate," and "reactive." Reactive and, to a lesser extent, intermediate astrocytes and microglia were closely associated with AD pathology (≤ 50 µm). Compared to homeostatic, reactive astrocytes contained substantially higher GFAP and YKL-40, modestly elevated vimentin and TSPO as well as EAAT1, and reduced GS. Intermediate astrocytes had markedly increased EAAT2, moderately increased GS, and intermediate GFAP and YKL-40 levels. Relative to homeostatic, reactive microglia showed increased expression of all markers (CD68, ferritin, MHC2, TMEM119, TSPO), whereas intermediate microglia exhibited increased ferritin and TMEM119 as well as intermediate CD68 levels. Machine learning models applied on either high-plex signal intensity data (gradient boosting machines) or directly on image features (convolutional neural networks) accurately discriminated control vs. AD diagnoses at the single-cell level.Conclusions: Cyclic multiplex fluorescent immunohistochemistry combined with machine learning models holds promise to advance our understanding of the complexity and heterogeneity of glial responses as well as inform transcriptomics studies. Three distinct phenotypes emerged with our combination of markers, thus expanding the classic binary "homeostatic vs. reactive" classification to a third state, which could represent "transitional" or "resilient" glia. [ABSTRACT FROM AUTHOR]

Investigar el valor pronóstico de la tomografía por emisión de positrones (PET) interim (PETi) en pacientes adultos con linfoma de Hodgkin (LH), comparando el análisis visual con el semicuantitativo. Análisis retrospectivo de pacientes con LH diagnosticados entre 2012 y 2016 en el Departamento de Oncología del Instituto Portugués de Oncología - Oporto (mediana de seguimiento: 46,5 meses [2,6-66,4]). Se incluyeron 58 pacientes con PET disponible en el momento del diagnóstico (PET0) y datos de PETi. Las exploraciones de PETi se analizaron de acuerdo con la escala de puntuación de 5 puntos de Deauville (5-DS), y los valores de corte para los cambios en el valor máximo de captación estandarizada (SUV máx), el SUV máximo (SUV peak), el volumen tumoral metabólico (MTV) y el índice de glicólisis de la lesión total (TLG) entre el PETi y el PET0 se calcularon mediante el análisis ROC. Los datos visuales y semicuantitativos se compararon entre sí en la predicción de los resultados de los pacientes. El análisis semicuantitativo obtuvo una mayor sensibilidad para la enfermedad persistente/recidivante en comparación con el 5-DS (70 vs. 10%, respectivamente), pero una menor especificidad. También demostró un mejor rendimiento predictivo para la respuesta a la terapia de primera línea (valor predictivo negativo > 92%). El valor predictivo positivo fue similar en las cinco mediciones. A los 60 meses de seguimiento, hubo una diferencia significativa entre las curvas de supervivencia libre de progresión (PFS) de los pacientes con PETi positivo y negativo según SUV máx (56,9 vs. 88,0%, p < 0,05), ΔSUV peak (55,9 vs. 88,1%, p < 0,05), ΔMTV (35,3 vs. 88,7%, p < 0,05), y ΔTLG (42,4 vs. 88,1%, p < 0,05). No se alcanzó la significación estadística al considerar los resultados de la 5-DS. La interpretación del PETi según un enfoque semicuantitativo parece discriminar mejor a los pacientes de LH que el análisis visual de 5-DS. Esto podría permitir una mejor detección de la enfermedad persistente o de la recaída temprana, mientras que un resultado negativo de PETi podría apoyar la disminución de la intensidad de la terapia. To investigate the prognostic value of interim PET (PETi) in adult HL patients, comparing visual with semiquantitative analysis. Retrospective analysis of Hodgkin's Lymphoma (HL) patients diagnosed between 2012 and 2016 in the Onco-Hematology Department of Instituto Português de Oncologia – Porto (median follow-up: 46.5 months [2,6-66,4]). Fifty-eight patients with available PET at diagnosis (PET0) and PETi data were included. PETi scans were analysed according to Deauville 5-point scale (5-PS), and cut-off values for changes in maximum standardized uptake value [SUVmax], peak SUV [SUVpeak], metabolic tumour volume [MTV] and total lesion glycolysis index [TLG] between PETi and PET0 were computed using ROC analysis. Visual and semiquantitative data were compared with each other in the prediction of patient outcomes. Semiquantitative analysis obtained a higher sensitivity for persistent/relapsed disease compared to the 5-PS (70% vs. 10%, respectively), but lower specificity. It also demonstrated better predictive performance for response to first-line therapy (negative predictive value > 92%). The positive predictive value was similar for all five measurements. At 60 months of follow-up, there was a significant difference between the progression free survival (PFS) curves of patients with positive and negative PETi according to ΔSUVmax (56.9% vs. 88.0%, p < 0.05), ΔSUVpeak (55.9% vs 88.1%, p< 0.05), ΔMTV (35.3% vs. 88.7%, p< 0.05), and ΔTLG (42.4% vs. 88.1%, p< 0.05). Statistical significance wasn't reached when considering 5-PS results. PETi interpretation according to a semiquantitative approach appears to discriminate HL patients better than the visual 5-PS analysis. This could allow better detection of persistent or early relapsed disease, while a negative PETi result could support de-escalating therapy intensity. [ABSTRACT FROM AUTHOR]

Background: Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Despite successful local treatment, approximately 50% of these patients develop lethal metastatic disease. BRCA1-associated protein 1 (BAP1) encodes BAP1, which functions as a tumor suppressor. Inactivation by a somatic mutation in BAP1 results in a loss of protein expression, which is associated with increased risk of metastasis. Aim: To analyze the expression of BAP1 protein in primary uveal tumors and their corresponding metastasis in an animal model of UM and to determine whether BAP1 expression is lost during the metastatic process. Subjects and Methods: Postmortem eyes and lungs with metastasis from nine rabbits previously inoculated with human UM cells expressing BAP1 (92.1 strain) were analyzed. Immunohistochemistry was performed on formalin-fixed paraffin-embedded samples using a monoclonal BAP1 (C-4) antibody. Expression was evaluated by the extent and intensity of staining. All primary tumors and metastasis were positive for BAP1. Results: The staining was diffuse and intense in the primary tumors of four rabbits (67%), focal-intense in one rabbit and focal-mild in one rabbit. All lung metastasis showed focal staining. All animals with intense BAP1 staining in the primary tumor showed mild BAP1 in the metastasis. Discussion: A predominant pattern observed between primary and metastatic lesion shows a transition from moderate into mild intensity and diffuse into the focal extent, suggesting a decrease in BAP1 expression. Future studies, including the human tissue of primary UM and their corresponding metastasis, should be performed to corroborate these findings. [ABSTRACT FROM AUTHOR]

Background: Visceral pain conducted by sympathetic fibers with pelvic and perineal origin can be treated using ganglion impar (GIB) or Walters' block in a simple and effective manner. This article aims to evaluate the effectiveness, security, and performance difficulty of GIB in patients with pelvic and perineal oncological pain.Methods: A retrospective study between January 2016 and August 2017. Patients with poorly controlled pelvic oncological pain and patients experimenting opioid side effects in which GIB was performed ambulatory were included. Prognostic GIB was performed, under echographic and fluoroscopic control, with local anesthetic and corticoid. The neurolytic block was performed under fluoroscopic guidance. The technique was performed by the same anesthetist with pain management competence. For statistical analysis, Microsoft Excel 2013® and IBM SPSS Statistics version 22.0 were used.Results: Fifteen patients were included. One patient was excluded. A statistical significant basal pain score reduction was observed ((median of the verbal numerical scale (VNS) 7 (p25 = 7; p75 = 8)) compared with 72 h median VNS 4 ((p25 = 3; p75 = 5.3) p = 0.001, and 3 months (median VNS 4 (p25 = 3, p75 = 7)) p = 0.003 after the procedure. Regarding morphine consumption, a statistically significant reduction was observed 3 months after GIB performance (p = 0.012).Discussion/conclusion: GIB is a safe and easy-to-perform technique achieving satisfactory and statistically significant results, regarding pain control improvement and opioid consumption reduction in patients which meet selection criteria. Prospective, randomized studies with more patients are needed for further conclusions. [ABSTRACT FROM AUTHOR]

Survival for breast cancer (BC) is lower in eastern than northern/central Europe, and in older than younger women. We analysed how comorbidities at diagnosis affected whether selected standard treatments (STs) were given, across Europe and over time, also assessing consequences for survival/relapse. We analysed 7581 stage I/IIA cases diagnosed in 9 European countries in 2009–2013, and 4 STs: surgery; breast‐conserving surgery plus radiotherapy (BCS + RT); reconstruction after mastectomy; and prompt treatment (≤6 weeks after diagnosis). Covariate‐adjusted models estimated odds of receiving STs and risks of death/relapse, according to comorbidities. Pearson's R assessed correlations between odds and risks. The z‐test assessed the significance of time‐trends. Most women received surgery: 72% BCS; 24% mastectomy. Mastectomied patients were older with more comorbidities than BCS patients (p < 0.001). Women given breast reconstruction (25% of mastectomies) were younger with fewer comorbidities than those without reconstruction (p < 0.001). Women treated promptly (45%) were younger than those treated later (p = 0.001), and more often without comorbidities (p < 0.001). Receiving surgery/BCS + RT correlated strongly (R = −0.9), but prompt treatment weakly (R = −0.01/−0.02), with reduced death/relapse risks. The proportion receiving BCS + RT increased significantly (p < 0.001) with time in most countries. This appears to be the first analysis of the influence of comorbidities on receiving STs, and of consequences for outcomes. Increase in BCS + RT with time is encouraging. Although women without comorbidities usually received STs, elderly patients often received non‐standard less prompt treatments, irrespective of comorbidities, with increased risk of mortality/relapse. All women, particularly the elderly, should receive ST wherever possible to maximise the benefits of modern evidence‐based treatments. What's new?: This is the first Europe‐wide study (37 cancer registries, 9 countries) analysing the effect of comorbidities on whether women with early breast cancer (diagnosed 2009–13) receive standard treatments. Women with no comorbidities usually received standard treatments, but elderly women often received less prompt and non‐standard treatments, irrespective of comorbidities, with increased probability of relapse and mortality. All women, particularly the elderly, should receive standard treatments wherever possible to maximize the benefits of modern evidence‐based approaches. [ABSTRACT FROM AUTHOR]

Microglial cells are crucial players in the pathological process of neurodegenerative diseases, such as Alzheimer's disease (AD). Microglial response in AD has been principally studied in relation to amyloid-beta pathology but, comparatively, little is known about inflammatory processes associated to tau pathology. In the hippocampus of AD patients, where tau pathology is more prominent than amyloid-beta pathology, a microglial degenerative process has been reported. In this work, we have directly compared the microglial response in two different transgenic tau mouse models: ThyTau22 and P301S. Surprisingly, these two models showed important differences in the microglial profile and tau pathology. Where ThyTau22 hippocampus manifested mild microglial activation, P301S mice exhibited a strong microglial response in parallel with high phospho-tau accumulation. This differential phospho-tau expression could account for the different microglial response in these two tau strains. However, soluble (S1) fractions from ThyTau22 hippocampus presented relatively high content of soluble phospho-tau (AT8-positive) and were highly toxic for microglial cells in vitro , whereas the correspondent S1 fractions from P301S mice displayed low soluble phospho-tau levels and were not toxic for microglial cells. Therefore, not only the expression levels but the aggregation of phospho-tau should differ between both models. In fact, most of tau forms in the P301S mice were aggregated and, in consequence, forming insoluble tau species. We conclude that different factors as tau mutations, accumulation, phosphorylation, and/or aggregation could account for the distinct microglial responses observed in these two tau models. For this reason, deciphering the molecular nature of toxic tau species for microglial cells might be a promising therapeutic approach in order to restore the deficient immunological protection observed in AD hippocampus. [ABSTRACT FROM AUTHOR]

Purpose: Eastern Africa was recently described as a high-incidence geographic area for esophageal cancer. Mozambique is included in this region. This study aimed to characterize this malignant disease at Maputo Central Hospital (MCH) to develop a global program for esophageal cancer management in Mozambique. Methods: MCH records from between 2012 and 2016 were used to assess the clinical, pathologic, and outcome profiles of esophageal tumors. A descriptive analysis of data collected was performed. Overall survival was evaluated using Kaplan-Meier curves. Results: In the study, 522 consecutive patient cases of esophageal cancer were recorded. The median patient age was 56.1 years (range, 27 to 97 years); 291 (55.7%) patients were women, and 230 (44.1%) were men. Regarding tumor site, 113 patients (21.6%) had a tumor in the lower third, 154 (29.5%) in the middle, and 50 (9.6%) in the upper third of the esophagus; in the remaining 196 (37.5%), tumor site was unknown. Squamous cell carcinoma comprised 94.4% of cases with documented histopathology (74.9% of the sample). Surgical treatment was possible in 32 patients (6.1%). Disease stage was documented only in these 32 surgical patients; 28.1%, 53.1%, and 18.8% had stage I, II, and III disease, respectively. The remaining patient cases seemed to involve clinically advanced tumors. The median follow-up time was of 1.6 months. The median survival time was of 3.5 months for all patients; for patients treated with curative intent, it was of 8.7 months. Conclusion: Esophageal carcinoma is a common malignant tumor at MCH and is diagnosed in the advanced stages resulting in poor prognosis. Therefore, implementation of an Esophageal Cancer Program in Mozambique is essential. [ABSTRACT FROM AUTHOR]

Microglial activation has been considered a crucial player in the pathological process of multiple human neurodegenerative diseases. In some of these pathologies, such as Amyotrophic Lateral Sclerosis or Multiple Sclerosis, the immune system and microglial cells (as part of the cerebral immunity) play a central role. In other degenerative processes, such as Alzheimer's disease (AD), the role of microglia is far to be elucidated. In this "mini-review" article, we briefly highlight our recent data comparing the microglial response between amyloidogenic transgenic models, such as APP/PS1 and AD patients. Since the AD pathology could display regional heterogeneity, we focus our work at the hippocampal formation. In APP based models a prominent microglial response is triggered around amyloid-beta (Ab) plaques. These strongly activated microglial cells could drive the AD pathology and, in consequence, could be implicated in the neurodegenerative process observed in models. On the contrary, the microglial response in human samples is, at least, partial or attenuated. This patent difference could simply reflect the lower and probably slower Ab production observed in human hippocampal samples, in comparison with models, or could reflect the consequence of a chronic long-standing microglial activation. Beside this differential response, we also observed microglial degeneration in Braak V-VI individuals that, indeed, could compromise their normal role of surveying the brain environment and respond to the damage. This microglial degeneration, particularly relevant at the dentate gyrus, might be mediated by the accumulation of toxic soluble phospho-tau species. The consequences of this probably deficient immunological protection, observed in AD patients, are unknown. [ABSTRACT FROM AUTHOR]

There are marked differences in the etiology of the major histological types of esophageal cancer (EC)-squamous cell carcinomas (ESCC) and adenocarcinomas (EAC). This study aimed to summarize the current scientific knowledge on modifiable risk factors for EC, by histological type, through a systematic review of meta-analyses referenced in PubMed and ISI Web of Knowledge. We identified 100 meta-analyses on risk factors for ESCC (n = 54), EAC (n = 43), or EC (n = 51). ESCC risk significantly increased with alcohol and maté drinking, smoking, red and processed meat consumption and human papillomavirus infection, while it was negatively associated with body mass index and consumption of fruit, vegetables, white meat, folate, and some carotenoids. Cessation of drinking and smoking significantly reduced ESCC risk. For EAC, an increased risk was reported for smoking, body mass index, and red and processed meat consumption, while risk decreased with Helicobacter pylori infection, low/moderate alcohol drinking, physical activity, and consumption of fruit, vegetables, folate, fiber, beta-carotene, and vitamin C. Differences in results between meta-analyses and mechanisms underlying some of the associations found are discussed. This work reinforces the importance of a separate assessment of EC subtypes to allow for a proper evaluation of incidence trends and planning of prevention/control interventions. [ABSTRACT FROM AUTHOR]

Copyright of DoisPontos is the property of Universidade Federal do Parana, Departamento de Filosofia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Educación y Ciudad is the property of Instituto para la Investigacion Educativa y Desarrollo Pedagogico and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: Eastern Africa was recently described as a high-incidence geographic area for esophageal cancer. Mozambique is included in this region. This study aimed to characterize this malignant disease at Maputo Central Hospital (MCH) to develop a global program for esophageal cancer management in Mozambique. Methods: MCH records from between 2012 and 2016 were used to assess the clinical, pathologic, and outcome profiles of esophageal tumors. A descriptive analysis of data collected was performed. Overall survival was evaluated using Kaplan-Meier curves. Results: In the study, 522 consecutive patient cases of esophageal cancer were recorded. The median patient age was 56.1 years (range, 27 to 97 years); 291 (55.7%) patients were women, and 230 (44.1%) were men. Regarding tumor site, 113 patients (21.6%) had a tumor in the lower third, 154 (29.5%) in the middle, and 50 (9.6%) in the upper third of the esophagus; in the remaining 196 (37.5%), tumor site was unknown. Squamous cell carcinoma comprised 94.4% of cases with documented histopathology (74.9% of the sample). Surgical treatment was possible in 32 patients (6.1%). Disease stage was documented only in these 32 surgical patients; 28.1%, 53.1%, and 18.8% had stage I, II, and III disease, respectively. The remaining patient cases seemed to involve clinically advanced tumors. The median follow-up time was of 1.6 months. The median survival time was of 3.5 months for all patients; for patients treated with curative intent, it was of 8.7 months. Conclusion: Esophageal carcinoma is a common malignant tumor at MCH and is diagnosed in the advanced stages resulting in poor prognosis. Therefore, implementation of an Esophageal Cancer Program in Mozambique is essential. [ABSTRACT FROM AUTHOR]

Copyright of Colombian Journal of Anesthesiology / Revista Colombiana de Anestesiología is the property of Sociedad Colombiana de Anestesiologia y Reanimacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Assessing the impact that patterns of Na intake may have on gastric cancer will provide a more comprehensive estimation of Na reduction as a primary prevention approach. We aimed to estimate the proportion of gastric cancer cases that are attributable to Na intake above the recommendation by the WHO (≤2 g/d) throughout the world in 2010, as well as expected values for 2030. Population attributable fractions (PAF) were computed for 187 countries, using Na intakes in 1990 and 2010 and estimates of the association between Na intake and gastric cancer, assuming a time lag of 20 years. Median PAF ranged from 10·1% in low to 22·5 % in very high Human Development Index (HDI) countries in men (P<0·001) and from 7·2 to 16·6 %, respectively, among women (P<0·001). An increase in median PAF until 2030 is expected in most settings, except for countries classified as low HDI, in both sexes. High Na intakes account for a large proportion of gastric cancer cases, and proportions are expected to increase in almost all of the countries. Intensified efforts to diminish Na intake in virtually all populations are needed to further reduce gastric cancer burden. [ABSTRACT FROM PUBLISHER]

The regional and temporal variation in patterns of fruit and vegetable intake contributes to differences in the impact on gastric cancer burden across regions and over the years. We aimed to estimate the proportion and absolute number of gastric cancer cases that could have been prevented in 2012 with an increase in fruit and vegetable intake up to the levels defined by the Global Burden of Disease as the theoretical minimum-risk exposure distribution (300 and 400 g/d, respectively), as well as the corresponding figures expected for 2025. Preventable fractions (PF) were computed for 161 countries, using data on fruit and vegetable availability in 1997 and 2010 and published estimates of the magnitude of the association between fruit and vegetable intake and gastric cancer, assuming a time lag of approximately 15 years. Countries classified as very high Human Development Index (HDI) presented median PF in 2012 much lower than low-HDI countries for both fruits (3·0 v. 10·2%, P<0·001) and vegetables (6·0 v. 11·9%, P<0·001). For vegetables only, PF significantly decreased until 2025 in most settings; however, this corresponded to a reduction in the absolute number of preventable gastric cancer cases in less than half of the countries. Increasing fruit and vegetable intake would allow preventing a relatively high proportion of gastric cancer cases, mostly in developing countries. Although declines in PF are predicted in the near future, changes in order to achieve healthier lifestyles may be insufficient to overcome the load of demographic variation to further reduce the gastric cancer burden. [ABSTRACT FROM AUTHOR]

Background: It is expected that, by 2020, 15 million new cases of cancer will occur every year in the world, one million of them in Africa. Knowledge of cancer trends in African countries is far from adequate, and improvements in cancer prevention efforts are urgently needed. The aim of this study was to characterize breast cancer clinically and pathologically at presentation in Luanda, Angola; we additionally provide quality information that will be useful for breast cancer care planning in the country.Methods: Data on breast cancer cases were retrieved from the Angolan Institute of Cancer Control, from 2006 to 2014. For women diagnosed in 2009 (5-years of follow-up), demographic, clinical and pathological information, at presentation, was collected, namely age at diagnosis, parity, methods used for pathological diagnoses, tumor pathological characteristics, stage of disease and treatment. Descriptive statistics were performed.Results: The median age of women diagnosed with breast cancer in 2009 was 47 years old (range 25-89). The most frequent clinical presentation was breast swelling with axillary lymph nodes metastasis (44.9 %), followed by a mass larger than 5 cm (14.2 %) and lump (12.9 %). Invasive ductal carcinoma was the main histologic type (81.8 %). Only 10.1 % of cancer cases had a well differentiated histological grade. Cancers were diagnosed mostly at advanced stages (66.7 % in stage III and 11.1 % in stage IV).Discussion: In this study, breast cancer was diagnosed at a very advanced stage. Although it reports data from a single cancer center in Luanda, Angola it reinforces the need for early diagnosis and increasing awareness. According to the main challenges related to breast cancer diagnosis and treatment herein presented, we propose a realistic framework that would allow for the implementation of a breast cancer care program, built under a strong network based on cooperation, teaching, audit, good practices and the organization of health services.Conclusion: Angola needs urgently a program for early diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

Background: The heterogeneous patterns and trends in tobacco consumption contribute to regional and gender differences in the burden of gastric cancer attributable to smoking. Aims: To estimate the proportion and absolute number of gastric cancer cases that can be attributed to smoking in different countries, in 2012 and 2020. Methods: Population attributable fractions (PAFs) were computed for 118 countries, using data of smoking prevalence in 2002 and 2011 and published estimates of the magnitude of the association between smoking and gastric cancer, assuming a time lag of ≈10 years. Results: For men, the highest PAF estimates in 2012 were observed in Eastern Asia and the lowest in North America, whereas for women the highest were in Western Europe and the lowest in Africa. Very high Human Development Index (HDI) countries presented the lowest median PAF in men (very high vs. high, medium, and low HDI: 17.2 vs. 20.8 %, p = 0.014) and the highest median PAF in women (very high vs. high, medium, and low HDI: 4.3 vs. 1.8 %, p < 0.001). Estimates for 2020 show a decrease in median PAFs, but the estimated absolute number of cases attributable to smoking in the countries analyzed increased for men (≈154,000 vs. ≈160,000) and decreased for women (≈6200 vs. ≈5600). Conclusions: Smoking accounts for a larger number of gastric cancer cases among men, and gender differences are expected to increase in the next decade, despite the decrease in PAFs. Intensified efforts to control smoking are needed to further reduce the burden of gastric cancer. [ABSTRACT FROM AUTHOR]

Drosophila serves as a playground for examining the effects of genetic mutations on development, physiological function and behavior. Many physiological measures that address the effects of mutations require semi-intact or cultured preparations. To obtain consistent physiological recordings, cellular function needs to remain viable. Numerous physiological salines have been developed for fly preparations, with emphasis on nervous system viability. The commonly used saline drifts in pH and will cause an alteration in the heart rate. We identify a saline that maintains a stable pH and physiological function in the larval heart, skeletal neuromuscular junction, and ventral nerve cord preparations. Using these common assays, we screened various pH buffers of differing concentrations to identify optimum conditions. Buffers at 25 mM produce a stable heart rate with minimal variation in pH. Excitatory junction potentials evoked directly on larval muscles or through sensory-CNS-motor circuits were unaffected by at buffers at 25 mM. The salines examined did not impede the modulatory effect of serotonin on heart rate or neural activity. Together, our results indicate that the higher buffer concentrations needed to stabilize pH in HL3 hemolymph-like saline do not interfere with the acute function of neurons or cardiac myocytes. [ABSTRACT FROM AUTHOR]

Cancer is the first cause of natural death among young subjects. Population-based statistics are important to evaluate the burden of disease and the effectiveness of healthcare provision. We aimed to describe cancer incidence and survival among adolescents (15-19 years) and young adults (20-24 years) in the north of Portugal. Data on the cancers diagnosed between 1997 and 2006 were obtained from the Portuguese North Region Cancer Registry, and incidence rates were computed. Vital status was determined until December 2010. Survival was estimated using the Kaplan-Meier survival function. Trends on cancer incidence were assessed using the Joinpoint regression analysis. A total of 1223 cases were diagnosed: 441 among adolescents and 782 among young adults. Overall incidence rate was 198.3 per million adolescents [95% confidence interval (95% CI): 135.7-260.9] and 306.2 per million young adults (95% CI: 262.3-350.0). The most frequent tumors were Hodgkin lymphoma (adolescents: 21.0%; young adults: 14.8%), thyroid carcinoma (adolescents: 11.5%; young adults: 16.2%), and germ cell tumors (adolescents: 11.1%; young adults: 16.3%). Cancer incidence significantly increased among young adults [annual average percent change: 3.6%, (95% CI: 1.7-5.4)], while appears to vary randomly among adolescents. Overall five-year observed survival was 77.2% (95% CI: 72.9%-80.8%) among adolescents and 81.3% (95% CI: 78.4%-83.9%) among young adults, lower in males. In conclusion, cancer incidence among adolescents and young adults is higher in the north of Portugal than in other European countries, especially of thyroid tumors. Between 1997 and 2006, the incidence increased significantly in young adults. [ABSTRACT FROM AUTHOR]

Microglia play a critical role in both homeostasis and disease, displaying a wide variety in terms of density, functional markers and transcriptomic profiles along the different brain regions as well as under injury or pathological conditions, such as Alzheimer's disease (AD). The generation of reliable models to study into a dysfunctional microglia context could provide new knowledge towards the contribution of these cells in AD. In this work, we included an overview of different microglial depletion approaches. We also reported unpublished data from our genetic microglial depletion model, Cx3cr1CreER/Csf1rflx/flx, in which we temporally controlled microglia depletion by either intraperitoneal (acute model) or oral (chronic model) tamoxifen administration. Our results reported a clear microglial repopulation, then pointing out that our model would mimic a context of microglial replacement instead of microglial dysfunction. Next, we evaluated the origin and pattern of microglial repopulation. Additionally, we also reviewed previous works assessing the effects of microglial depletion in the progression of Aβ and Tau pathologies, where controversial data are found, probably due to the heterogeneous and time-varying microglial phenotypes observed in AD. Despite that, microglial depletion represents a promising tool to assess microglial role in AD and design therapeutic strategies. [ABSTRACT FROM AUTHOR]

In Alzheimer's disease (AD), and other tauopathies, microtubule destabilization compromises axonal and synaptic integrity contributing to neurodegeneration. These diseases are characterized by the intracellular accumulation of hyperphosphorylated tau leading to neurofibrillary pathology. AD brains also accumulate amyloid-beta (Aβ) deposits. However, the effect of microtubule stabilizing agents on Aβ pathology has not been assessed so far. Here we have evaluated the impact of the brain-penetrant microtubule-stabilizing agent Epothilone D (EpoD) in an amyloidogenic model of AD. Three-month-old APP/PS1 mice, before the pathology onset, were weekly injected with EpoD for 3 months. Treated mice showed significant decrease in the phospho-tau levels and, more interesting, in the intracellular and extracellular hippocampal Aβ accumulation, including the soluble oligomeric forms. Moreover, a significant cognitive improvement and amelioration of the synaptic and neuritic pathology was found. Remarkably, EpoD exerted a neuroprotective effect on SOM-interneurons, a highly AD-vulnerable GABAergic subpopulation. Therefore, our results suggested that EpoD improved microtubule dynamics and axonal transport in an AD-like context, reducing tau and Aβ levels and promoting neuronal and cognitive protection. These results underline the existence of a crosstalk between cytoskeleton pathology and the two major AD protein lesions. Therefore, microtubule stabilizers could be considered therapeutic agents to slow the progression of both tau and Aβ pathology. [ABSTRACT FROM AUTHOR]