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The textile industry generates highly contaminated wastewater. It severely threatens local ecosystems without proper treatment, significantly diminishing biodiversity near the discharge point. With rapid growth rates, microalgae offer an effective solution to mitigate the environmental impact of textile wastewater, and the generated biomass can be valorised. This study sets out to achieve two primary objectives: (i) to assess the removal of pollutants by Chlorella vulgaris from two distinct real textile wastewaters (without dilution) and (ii) to evaluate microalgal biomass composition for further valorisation (in a circular economy approach). Microalgae grew successfully with growth rates ranging from 0.234 ± 0.005 to 0.290 ± 0.003 d-1 and average productivities ranging from 78 ± 3 to 112.39 ± 0.07 mgDW L-1 d-1. All cultures demonstrated a significant reduction in nutrient concentrations for values below the legal limits for discharge, except for COD in effluent 2. Furthermore, the pigment concentration in the culture increased during textile effluent treatment, presenting a distinct advantage over conventional ones due to the economic value of produced biomass and pigments. This study underscores the promise of microalgae in textile wastewater treatment and provides valuable insights into their role in addressing the environmental challenges the textile industry poses.
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Introduction: The optimal rectal cancer care is achieved by a multidisciplinary approach, with a high-quality surgical resection, with complete mesorectal excision and adequate margins. New approaches like the transanal total mesorectal excision (TaTME) aim to achieve these goals, maximizing the sphincter preservation ratio, with good oncologic and functional results. This report describes a way to implement TaTME without a proctor, presents the first case series of this approach in a center experienced in rectal cancer, and compares the results with those of the international literature. Methods: We performed a retrospective study of the first 10 consecutive patients submitted to TaTME for rectal cancer at our institution. The primary outcomes were postoperative complications, pathological specimen quality and local recurrence rate. The results and performance were compared with the outcomes of a known structured program with proctorship and with the largest meta-analysis on this topic. Results: All patients had locally advanced cancer; therefore, all underwent neoadjuvant therapy. A total of 30% had postoperative complications, without mortality or re-admissions. In comparison with the structured training program referred, no differences were found in postoperative complications and reintervention rates, resulting in a similar quality of resection. Comparing these results with those of the largest meta-analysis on the subject, no differences in the postoperative complication rates were found, and very similar outcomes regarding anastomotic leaks and oncological quality of resection were registered. Conclusion: The results of this study validate the safety and effectiveness of our pathway regarding the implementation of the TaTME approach, highlighting the fact that it should be done in a center with proficiency in minimally invasive rectal surgery. (AU)
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Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias del Recto/cirugía , Cirugía Endoscópica Transanal/métodos , Periodo Posoperatorio , Recurrencia , Resultado del Tratamiento , Tempo Operativo , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Recently, artificial intelligence-powered devices have been put forward as potentially powerful tools for the improvement of mental healthcare. An important question is how these devices impact the physician-patient interaction. AIMS: Aifred is an artificial intelligence-powered clinical decision support system (CDSS) for the treatment of major depression. Here, we explore the use of a simulation centre environment in evaluating the usability of Aifred, particularly its impact on the physician-patient interaction. METHOD: Twenty psychiatry and family medicine attending staff and residents were recruited to complete a 2.5-h study at a clinical interaction simulation centre with standardised patients. Each physician had the option of using the CDSS to inform their treatment choice in three 10-min clinical scenarios with standardised patients portraying mild, moderate and severe episodes of major depression. Feasibility and acceptability data were collected through self-report questionnaires, scenario observations, interviews and standardised patient feedback. RESULTS: All 20 participants completed the study. Initial results indicate that the tool was acceptable to clinicians and feasible for use during clinical encounters. Clinicians indicated a willingness to use the tool in real clinical practice, a significant degree of trust in the system's predictions to assist with treatment selection, and reported that the tool helped increase patient understanding of and trust in treatment. The simulation environment allowed for the evaluation of the tool's impact on the physician-patient interaction. CONCLUSIONS: The simulation centre allowed for direct observations of clinician use and impact of the tool on the clinician-patient interaction before clinical studies. It may therefore offer a useful and important environment in the early testing of new technological tools. The present results will inform further tool development and clinician training materials.
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Theta burst stimulation (TBS) has been proposed as a novel treatment for major depression (MD). However, randomized and sham-controlled trials (RCTs) published to date have yielded heterogeneous clinical results and we have thus carried out the present systematic review and exploratory meta-analysis of RCTs to evaluate this issue. We searched the literature for RCTs on TBS for MD from January 2001 through September 2016 using MEDLINE, EMBASE, PsycINFO, and CENTRAL. We then performed a random-effects meta-analysis with the main outcome measures including pre-post score changes in the Hamilton Depression Rating Scale (HAM-D) as well as rates of response, remission and dropout. Data were obtained from 5 RCTs, totalling 221 subjects with MD. The pooled Hedges' g for pre-post change in HAM-D scores was 1.0 (p = 0.003), indicating a significant and large-sized difference in outcome favouring active TBS. Furthermore, active TBS was associated with significantly higher response rates when compared to sham TBS (35.6% vs. 17.5%, respectively; p = 0.005), although the groups did not differ in terms of rates of remission (18.6% vs. 10.7%, respectively; p = 0.1) and dropout (4.2% vs. 7.8%, respectively; p = 0.5). Finally, subgroup analyses indicated that bilateral TBS and unilateral intermittent TBS seem to be the most promising protocols. In conclusion, although TBS is a promising novel therapeutic intervention for MD, future studies should identify more clinically-relevant stimulation parameters as well as neurobiological predictors of treatment outcome, and include larger sample sizes, active comparators and longer follow-up periods.
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Trastorno Depresivo Mayor/terapia , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Estimulación Magnética Transcraneal/métodos , Resultado del Tratamiento , Bases de Datos Bibliográficas/estadística & datos numéricos , Femenino , Humanos , MasculinoRESUMEN
As the passage of time structurally alters one's brain, cognition does not have to suffer the same faith, at least not to the same extent. Indeed, the existence of age-related compensatory mechanisms allow for some cognitive preservation. This paper attempts to coherently review the existing concepts of neurofunctional compensation when applied to two different cognitive domains, namely executive function and language processing. More precisely, we explore the Cognitive reserve (CR) model in healthy aging as well as its two underlying mechanisms: neural reserve and neural compensation. Furthermore, we review the Compensation-Related Utilization of Neural Circuits Hypothesis as well as the Growing Of Life Differences Explains Normal Aging model. Finally, we propose, based on some functional neuroimaging studies, the existence of another compensatory mechanism characterized by age-related delayed cerebral activation allowing for cognitive performance to be preserved at the expense of speed processing: the Temporal Hypothesis for Compensation.
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It is widely believed that language function tends to show little age-related performance decline. Indeed, some older individuals seem to use compensatory mechanisms to maintain a high level of performance when submitted to lexical tasks. However, how these mechanisms affect cortical and subcortical activity during semantic and phonological processing has not been extensively explored. The purpose of this study was to look at the effect of healthy aging on cortico-subcortical routes related to semantic and phonological processing using a lexical analogue of the Wisconsin Cart-Sorting Task. Our results indicate that while young adults tend to show increased activity in the ventrolateral prefrontal cortex, the dorsolateral prefrontal cortex, the fusiform gyrus, the ventral temporal lobe and the caudate nucleus during semantic decisions and in the posterior Broca's area (area 44), the temporal lobe (area 37), the temporoparietal junction (area 40) and the motor cortical regions during phonological decisions, older individuals showed increased activity in the dorsolateral prefrontal cortex and motor cortical regions during both semantic and phonological decisions. Furthermore, when semantic and phonological decisions were contrasted with each other, younger individuals showed significant brain activity differences in several regions while older individuals did not. Therefore, in older individuals, the semantic and phonological routes seem to merge into a single pathway. These findings represent most probably neural reserve/compensation mechanisms, characterized by a decrease in specificity, on which the elderly rely to maintain an adequate level of performance.
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Envejecimiento/fisiología , Encéfalo/fisiología , Fonética , Semántica , Adulto , Anciano , Encéfalo/crecimiento & desarrollo , Mapeo Encefálico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In C4-HD murine mammary carcinomas and in human breast cancer T47D cells, we showed that medroxyprogesterone acetate (MPA) induces a nuclear physical association between estrogen receptor alpha (ERa) and progesterone receptors (PR). The blockade of ERa inhibits cell proliferation mediated by progestins. We hypothesized that this nuclear association between ERa/PR is necessary to trigger progestin-induced cell proliferation and tumor growth. We demonstrated that fulvestrant (FUL, ICI182.780) induced complete regression of C4-HD tumors growing with progestins. MPA treatment induced an early increase in both CCND1 and MYC expression in T47D cells. The blockade of ERa prevented the MPA-dependent transcription of both genes. Specific binding of PR/ERa was observed at the same MPA-sensitive regions at the CCND1 and MYC gene promoters after chromatin immunoprecipitation (ChIP) analysis. ICI inhibited binding of ERa to both gene regulatory sequences while PR binding was unaffected. The nuclear colocalization between both receptors in T47D cells was confirmed by: confocal microscopy, Duolink assays and co-immunoprecipitation assays. In breast cancer samples we also observed a nuclear interaction between both steroid receptors. Our results indicate that the presence of ERa interacting with activated PR at the CCND1 and MYC promoters is required to trigger progestin-induced gene transcription and cell proliferation in breast cancer cells.
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Carcinoma/patología , Estradiol/análogos & derivados , Receptor alfa de Estrógeno/fisiología , Neoplasias Mamarias Experimentales/patología , Receptores de Progesterona/fisiología , Animales , Antineoplásicos Hormonales/farmacología , Neoplasias de la Mama/genética , Carcinoma/inducido químicamente , Carcinoma/tratamiento farmacológico , Proliferación Celular , Inmunoprecipitación de Cromatina , Ciclina D1/metabolismo , Estradiol/administración & dosificación , Receptor alfa de Estrógeno/efectos de los fármacos , Femenino , Fulvestrant , Genes myc , Humanos , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Acetato de Medroxiprogesterona/farmacología , Murinae , Progestinas/metabolismo , Receptores de Progesterona/efectos de los fármacos , Transcripción GenéticaRESUMEN
Synthetic progesterone used in contraception drugs (progestins) can promote breast cancer growth, but the mechanisms involved are unknown. Moreover, it remains unclear whether cytoplasmic interactions between the progesterone receptor (PR) and estrogen receptor alpha (ERα) are required for PR activation. In this study, we used a murine progestin-dependent tumor to investigate the role of ERα in progestin-induced tumor cell proliferation. We found that treatment with the progestin medroxyprogesterone acetate (MPA) induced the expression and activation of ERα, as well as rapid nuclear colocalization of activated ERα with PR. Treatment with the pure antiestrogen fulvestrant to block ERα disrupted the interaction of ERα and PR in vitro and induced the regression of MPA-dependent tumor growth in vivo. ERα blockade also prevented an MPA-induced increase in CYCLIN D1 (CCND1) and MYC expression. Chromatin immunoprecipitation studies showed that MPA triggered binding of ERα and PR to the CCND1 and MYC promoters. Interestingly, blockade or RNAi-mediated silencing of ERα inhibited ERα, but not PR binding to both regulatory sequences, indicating that an interaction between ERα and PR at these sites is necessary for MPA-induced gene expression and cell proliferation. We confirmed that nuclear colocalization of both receptors also occurred in human breast cancer samples. Together, our findings argued that ERα-PR association on target gene promoters is essential for progestin-induced cell proliferation.
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Neoplasias de la Mama/patología , Ciclina D1/genética , Receptor alfa de Estrógeno/metabolismo , Genes myc , Neoplasias Mamarias Experimentales/patología , Receptores de Progesterona/metabolismo , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Procesos de Crecimiento Celular/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Estradiol/análogos & derivados , Estradiol/farmacología , Receptor alfa de Estrógeno/antagonistas & inhibidores , Receptor alfa de Estrógeno/genética , Femenino , Fulvestrant , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Genes Reporteros , Humanos , Neoplasias Mamarias Experimentales/genética , Neoplasias Mamarias Experimentales/metabolismo , Acetato de Medroxiprogesterona/farmacología , Ratones , Ratones Endogámicos BALB C , Neoplasias Hormono-Dependientes/genética , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias Hormono-Dependientes/patología , Regiones Promotoras Genéticas , Receptores de Progesterona/genéticaRESUMEN
Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-ß-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P < 0.01; Spearman correlation) between FGFR-2 and -3 expressions and a weaker correlation of each receptor with estrogen receptor expression. FGFR-4 correlated with c-erbB2 over expression. We conclude that FGFR-2 and -3 may be mechanistically linked and can be potential targets for treatment of estrogen receptor-positive breast cancer patients.
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Neoplasias de la Mama/metabolismo , Glándulas Mamarias Animales/fisiología , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/metabolismo , Adulto , Anciano , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Análisis por Conglomerados , Femenino , Perfilación de la Expresión Génica , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Ratones Desnudos , Ratones SCID , Persona de Mediana Edad , Embarazo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Trasplante HeterólogoRESUMEN
Some older individuals seem to use compensatory mechanisms to maintain high-level performance when submitted to cognitive tasks. However, whether and how these mechanisms affect fronto-striatal activity has never been explored. The purpose of this study was to investigate how aging affects brain patterns during the performance of a lexical analog of the Wisconsin Card Sorting Task, which has been shown to strongly depend on fronto-striatal activity. In the present study, both younger and older individuals revealed significant fronto-striatal loop activity associated with planning and execution of set-shifts, though age-related striatal activity reduction was observed. Most importantly, while the younger group showed the involvement of a "cognitive loop" during the receiving negative feedback period (which indicates that a set-shift will be required to perform the following trial) and the involvement of a "motor loop" during the matching after negative feedback period (when the set-shift must be performed), older participants showed significant activation of both loops during the matching after negative feedback period only. These findings are in agreement with the "load-shift" model postulated by Velanova et al. (Velanova K, Lustig C, Jacoby LL, Buckner RL. 2007. Evidence for frontally mediated controlled processing differences in older adults. Cereb Cortex. 17:1033-1046.) and indicate that the model is not limited to memory retrieval but also applies to executive processes relying on fronto-striatal regions.
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Envejecimiento/fisiología , Cognición/fisiología , Cuerpo Estriado/fisiología , Lóbulo Frontal/fisiología , Estimulación Luminosa/métodos , Lectura , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiología , Tiempo de Reacción/fisiología , Factores de Tiempo , Adulto JovenRESUMEN
Fibroblast growth factor (FGF) receptor 2 (FGFR-2) polymorphisms have been associated with an increase in estrogen receptor and progesterone receptor (PR)-positive breast cancer risk; however, a clear mechanistic association between FGFR-2 and steroid hormone receptors remains elusive. In previous works, we have shown a cross talk between FGF2 and progestins in mouse mammary carcinomas. To investigate the mechanisms underlying these interactions and to validate our findings in a human setting, we have used T47D human breast cancer cells and human cancer tissue samples. We showed that medroxyprogesterone acetate (MPA) and FGF2 induced cell proliferation and activation of ERK, AKT, and STAT5 in T47D and in murine C4-HI cells. Nuclear interaction between PR, FGFR-2, and STAT5 after MPA and FGF2 treatment was also showed by confocal microscopy and immunoprecipitation. This effect was associated with increased transcription of PRE and/or GAS reporter genes, and of PR/STAT5-regulated genes and proteins. Two antiprogestins and the FGFR inhibitor PD173074, specifically blocked the effects induced by FGF2 or MPA respectively. The presence of PR/FGFR-2/STAT5 complexes bound to the PRE probe was corroborated by using NoShift transcription and chromatin immunoprecipitation of the MYC promoter. Additionally, we showed that T47D cells stably transfected with constitutively active FGFR-2 gave rise to invasive carcinomas when transplanted into NOD/SCID mice. Nuclear colocalization between PR and FGFR-2/STAT5 was also observed in human breast cancer tissues. This study represents the first demonstration of a nuclear interaction between FGFR-2 and STAT5, as PR coactivators at the DNA progesterone responsive elements, suggesting that FGFRs are valid therapeutic targets for human breast cancer treatment.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptores de Progesterona/metabolismo , Factor de Transcripción STAT5/metabolismo , Animales , Antineoplásicos Hormonales/farmacología , Línea Celular Tumoral , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Humanos , Acetato de Medroxiprogesterona/farmacología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Ratones SCID , Trasplante de NeoplasiasRESUMEN
We studied frequency sensitivity of flight-capable and flight-incapable forms of the wing-dimorphic cricket Gryllus texensis, using both behavioral and neurophysiological measurements. Behavioral thresholds for negative phonotaxis in response to ultrasound stimuli are lower for long-winged (i.e. flight-capable) crickets than for short-winged (flight-incapable) individuals, whereas thresholds for positive phonotaxis in response to a calling-song model do not differ. Similarly, thresholds of the identified interneurons ON1 and AN2 differ between flight morphs for high sound frequencies but not for the frequency of calling song. Our results show that sensitivity to ultrasound is closely linked to flight ability, and thus to the risk of predation from aerially hawking bats. We suggest that sensitivity to ultrasound is one of a suite of flight-associated characteristics, the development of which may be under common hormonal regulation.
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Vuelo Animal/fisiología , Gryllidae/fisiología , Audición/fisiología , Ultrasonido , Estimulación Acústica , Animales , Conducta Animal , Femenino , Masculino , Discriminación de la Altura Tonal , Localización de Sonidos , Alas de AnimalesRESUMEN
Se presenta el cuarto caso mundial y el primero nacional de leiomioma del duodeno. Se trata de un hombre de 78 años de edad cuyo síntoma fundamental fue una hemorragia digestiva alta. Se describen los métodos diagnósticos y terapéuticos utilizados, enfatizando el papel decisivo de la biopsia por inclusión