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1.
Health Educ Behav ; : 10901981241240745, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38553981

RESUMO

Mental disorders constitute one of the population's principal health problems, especially among undergraduates. This quantitative study compared levels of depression, anxiety, and stress in a sample of emerging adult university undergraduates from a gender perspective (1) during the initial and intermediate years of emerging adulthood and (2) in two different cohorts. A total of 383 Spanish emerging adult university undergraduates were monitored longitudinally (2015-2018) and two cohorts were compared (2015-2020). Participants completed the validated Spanish version of the Depression Anxiety Stress Scale-21. Mean-level and rank-order stability was found across the two waves of the longitudinal study in relation to levels of depression, anxiety, and stress. Significant differences were found between the two cohorts, indicating higher levels of psychological distress in 2020 than in 2015. Women were found to have higher levels of psychological distress, particularly stress, than men in both waves and cohorts. Results are discussed in relation to the negative effects of the COVID-19 health crisis on the emotional health of emerging adults. The present study highlights the need to establish measures designed to improve the mental health of emerging adults, which was more severely affected by the COVID-19 crisis than by the aftermath of the 2008 financial crisis. It also underscores the need to develop interventions designed to alleviate the greater degree of stress suffered by women.

2.
J Med Chem ; 67(4): 2619-2630, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38294341

RESUMO

Targeting microtubules is the most effective wide-spectrum pharmacological strategy in antitumoral chemotherapy, and current research focuses on reducing main drawbacks: neurotoxicity and resistance. PM534 is a novel synthetic compound derived from the Structure-Activity-Relationship study on the natural molecule PM742, isolated from the sponge of the order Lithistida, family Theonellidae, genus Discodermia (du Bocage 1869). PM534 targets the entire colchicine binding domain of tubulin, covering four of the five centers of the pharmacophore model. Its nanomolar affinity and high retention time modulate a strikingly high antitumor activity that efficiently overrides two resistance mechanisms in cells (detoxification pumps and tubulin ßIII isotype overexpression). Furthermore, PM534 induces significant inhibition of tumor growth in mouse xenograft models of human non-small cell lung cancer. Our results present PM534, a highly effective new compound in the preclinical evaluation that is currently in its first human Phase I clinical trial.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Colchicina/metabolismo , Tubulina (Proteína)/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Microtúbulos , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/uso terapêutico , Moduladores de Tubulina/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células
3.
Br J Dev Psychol ; 42(2): 133-148, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38009815

RESUMO

Identity development is a key task during emerging adulthood. The goals of the present study are to validate the Spanish version of the Dimensions of Identity Development Scale (DIDS) and to explore the relationship between identity dimensions and adjustment (flourishing and distress), from a gender perspective. The sample comprised 1502 Spanish university students (60.1% women). The results reveal that the DIDS is valid in the Spanish context and that significant gender differences were observed in some dimensions of identity development, with men scoring higher for identification with commitment and women scoring higher for exploration in depth and ruminative exploration. Finally, both dimensions of commitment and ruminative exploration had a stronger effect on men's than on women's adjustment, suggesting that the integration of the self has more impact on men's outcomes than on women's. These findings highlight the need to include the gender perspective in all future research in order to gain deeper insight into the relationship between the identity development process and adjustment during emerging adulthood.


Assuntos
Identidade de Gênero , Identificação Social , Masculino , Humanos , Feminino , Adulto , Fatores Sexuais
4.
Cancers (Basel) ; 15(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38001682

RESUMO

Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies have increased the probability of remission, relapse rates remain high. Numerous studies have indicated the connection between cancer-initiating cells and slow cellular cycle cells, identified by their capacity to retain long labeling (LT+). In this study, we perform new assays showing how stem cell self-renewal modulating proteins, such as PEDF, can modify the properties, percentage of biomarker-expressing cells, and carcinogenicity of cancer stem cells. The PEDF signaling pathway could be a useful tool for controlling cancer stem cells' self-renewal and therefore control patient relapse, as PEDF enhances resistance in breast cancer patient cells' in vitro culture. We have designed a peptide consisting of the C-terminal part of this protein, which acts by blocking endogenous PEDF in cell culture assays. We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against docetaxel treatment in cancer patient cells in in vitro culture. We have also demonstrated that this modified PEDF protein produces a significant decrease in the percentage of expressed cancer stem cell markers.

5.
Int J Mol Sci ; 24(17)2023 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-37686114

RESUMO

Gold nanorods are the most commonly used nanoparticles in photothermal therapy for cancer treatment due to their high efficiency in converting light into heat. This study aimed to investigate the efficacy of gold nanorods of different sizes (large and small) in eliminating two types of cancer cell: melanoma and glioblastoma cells. After establishing the optimal concentration of nanoparticles and determining the appropriate time and power of laser irradiation, photothermal therapy was applied to melanoma and glioblastoma cells, resulting in the highly efficient elimination of both cell types. The efficiency of the PTT was evaluated using several methods, including biochemical analysis, fluorescence microscopy, and flow cytometry. The dehydrogenase activity, as well as calcein-propidium iodide and Annexin V staining, were employed to determine the cell viability and the type of cell death triggered by the PTT. The melanoma cells exhibited greater resistance to photothermal therapy, but this resistance was overcome by irradiating cells at physiological temperatures. Our findings revealed that the predominant cell-death pathway activated by the photothermal therapy mediated by gold nanorods was apoptosis. This is advantageous as the presence of apoptotic cells can stimulate antitumoral immunity in vivo. Considering the high efficacy of these gold nanorods in photothermal therapy, large nanoparticles could be useful for biofunctionalization purposes. Large nanorods offer a greater surface area for attaching biomolecules, thereby promoting high sensitivity and specificity in recognizing target cancer cells. Additionally, large nanoparticles could also be beneficial for theranostic applications, involving both therapy and diagnosis, due to their superior detection sensitivity.


Assuntos
Glioblastoma , Melanoma , Humanos , Glioblastoma/terapia , Terapia Fototérmica , Morte Celular , Ouro
6.
An. psicol ; 39(2): 265-272, May-Sep. 2023. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-219765

RESUMO

Los estilos de identidad buscan conocer cómo las personas se manejan diariamente en las situaciones buscando un compromiso identitario. En este trabajo se propone conocer si los estilos de identidad varían según la edad y el sexo, y analizar la relación entre estos y la fuerza del compromiso con variables de bienestar y malestar psicológico. Método: 278 participantes (M = 22.03; DT = 2.65) reclutados a través de un muestreo no probabilístico por bola de nieve cumplimentaron los cuestionarios. Resultados: Las mujeres puntuaron más alto en fuerza del compromiso y ellos adoptaron más un estilo difuso-evitativo. El estilo informacional correlacionó positivamente con las variables de bienestar (optimismo y florecimiento); el estilo normativo con depresión y ansiedad y el estilo difuso-evitativo correlacionó positivamente con las variables de malestar (depresión, ansiedad y estrés) y negativamente con las de bienestar. Finalmente, a mayor fuerza del compromiso más bienestar y menos malestar. La fuerza del compromiso media parcial o totalmente la relación entre estilos identitarios y las variables de bienestar/malestar. Conclusiones: Se deduce la importancia de la fuerza del compromiso en el bienestar personal y la necesidad de favorecer el desarrollo de la identidad de nuestros jóvenes.(AU)


Background:Identity styles seek to know how people handle themselves daily in situations looking for an identity commitment. This ar-ticle aims to find out whether identity styles vary according to age and sex, and to analyze the relation between these identity styles and the strength of commitment with variables of well-being and psychological distress. In ad-dition, it investigates whether commitment mediates between identity styles, well-being and psychological distress.Method:278 participants (M = 22.03; DT = 2.65), recruited through a non-probabilistic snowball sam-pling, completed the questionnaires. Results:Women scored higher in strength of commitment and men adopted a more diffusive-avoidant style. Age did not relate to identity style. The informational stylecorrelated posi-tively with well-being variables (flourishing and optimism); the normative style with depression and anxiety and the diffuse-avoidant style correlated positively with psychological distress (depression, anxiety and stress) and negatively with well-being. Finally, the greater the strength of commitment found, the more flourishing and optimism and the less psychological dis-tress there was. The strength of commitment partially or totally mediated the relationship between identity styles and thevariables of well-being / psychological distress. Conclusions:The importance of the strength of com-mitment in personal well-being and the necessity to favour the develop-ment of young people ́s identity is observed / deduced.(AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Identidade de Gênero , Otimismo , Estresse Psicológico , Saúde Mental , Psicologia , Psicologia do Adolescente
7.
Biol Sport ; 40(3): 723-730, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37398962

RESUMO

The present study presents a novel specific multi-joint isometric test to assess upper limb strength impairment for evidence-based classification in wheelchair sports. Sixteen wheelchair athletes participated in this study and were classified according to their type of physical impairment and health condition as follows: athletes with neurological impairment (ANI, n = 5) and athletes with impaired muscle power (IMP, n = 11). In addition, six non-disabled participants formed a control group (CG, n = 6). All the participants performed the isometric propulsion strength test (IPST), evaluating pushing and pulling actions, and two wheelchair performance tests. Excellent relative intra-session reliability scores were obtained for strength values for the ANI, IMP and CG groups (0.90 < ICC < 0.99) and absolute reproducibility showed acceptable scores of SEM (< 9.52%) for IPST pushing action. The ANI had significantly lower scores in strength and wheelchair performance than the IMP and the CG, while no differences were found between the IMP and the non-disabled participants. In addition, no correlations were found for wheelchair athletes between the isometric upper limb strength measure and wheelchair performance. Our findings suggest that the IPST is a valid test for strength measurement in upper limb impairment wheelchair athletes with different health conditions, which must be used in combination with a performance test to obtain a holistic assessment of this population.

8.
J Sch Psychol ; 99: 101222, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37507190

RESUMO

With concern growing about the increasing levels of school stress among secondary school students, examining its associations with students' perceptions of important elements in classroom climate can offer valuable scientific information. However, there is minimal research about the role of perceived classroom goal structures and teacher support in school stress. In addition, most research on classroom goal structure has not made a distinction between performance-approach structures and performance-avoidance structures, which may have different effects on school stress. The aim of the present study was to examine the role of classroom goal structures and teacher support in students' stress linked to school performance. We also examined the potential moderating effect of teacher support in the association between classroom goal structures and stress. Our sample consisted of 4768 secondary school students aged 11-17 years (Mage = 13.74; 47.9% boys) from 54 schools in Andalusia, Spain. Consistent with the study's aims, hierarchical multilevel multiple regression was used to examine the relationships between mastery goal structure, performance-approach goal structure, performance-avoidance goal structure, and teacher support on our stress of school performance outcome. After controlling for gender, age, and previous academic achievement, performance-avoidance goal structure was significantly associated with higher levels of stress of school performance (p < .01). Furthermore, perceived classroom goals and teacher support tended to work together, with the role of performance-approach goal structure being dependent on the levels of mastery goal structure and teacher support (p < .05). Practical implications from these findings and future research directions are discussed.


Assuntos
Objetivos , Motivação , Masculino , Humanos , Feminino , Estudantes , Escolaridade , Instituições Acadêmicas , Professores Escolares
9.
BJS Open ; 7(2)2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-37021546

RESUMO

BACKGROUND: The potential of haemostatic patches to reduce the rate of postoperative pancreatic fistula remains unclear. The aim of this trial was to evaluate the impact of a polyethylene glycol-coated haemostatic patch on the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy. METHODS: In this randomized, single-centre, clinical trial, patients undergoing pancreatoduodenectomy were randomized 1 : 1 to receive pancreatojejunostomy reinforced with two polyethylene glycol-coated haemostatic patches (patch group) or without any reinforcement (control group). The primary outcome was clinically relevant postoperative pancreatic fistula, defined as grade B/C according to International Study Group of Pancreatic Surgery criteria, within 90 days. Key secondary outcomes were length of hospital stay, total rate of postoperative pancreatic fistula, and overall complication rate. RESULTS: From 15 May 2018 to 22 June 2020, 72 patients were randomized, and 64 were included in the analyses (31 in the patch group and 33 in the control group). The risk of clinically relevant postoperative pancreatic fistula was reduced by 90 per cent (OR 0.10, 95 per cent c.i. 0.01 to 0.89, P = 0.039). Moreover, the use of the polyethylene glycol-coated patch retained its protective effect on clinically relevant postoperative pancreatic fistula in a multivariable regression model, significantly reducing the risk of clinically relevant postoperative pancreatic fistula by 93 per cent (OR 0.07, 95 per cent c.i. 0.01 to 0.67, P = 0.021), regardless of patient age, sex, or fistula risk score. The incidence of secondary outcomes did not significantly differ between the groups. One patient died within 90 days in the patch group versus three patients in the control group. CONCLUSIONS: A polyethylene glycol-coated haemostatic patch reduced the incidence of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy. REGISTRATION NUMBER: NCT03419676 (http://www.clinicaltrials.gov).


Assuntos
Hemostáticos , Fístula Pancreática , Humanos , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pâncreas , Pancreaticojejunostomia/efeitos adversos , Complicações Pós-Operatórias/etiologia
10.
Sports Biomech ; 22(7): 822-833, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32522109

RESUMO

There is a lack of evidence regarding the match demands encountered in elite Ultimate Frisbee (UF) overall and dependent upon opponent ranking. These data may be useful to elite UF coaches to implement optimal training loads and recovery strategies. Therefore, this study quantified the physical demands of elite UF match-play and analysed differences in demands according to opponent ranking. Twelve UF players from the same national team participated in the study. An observational design was used to compare the physical demands encountered by players between opponents carrying different rankings (1st, 3rd, 4th, and 5th) during four official matches in a 5-team competition. No significant differences (p > 0.05) in sprinting and repeated-sprinting activity were evident across UF matches between opponents. In contrast, a higher (moderate-large) quantity and greater intensities of body impacts were observed in UF matches played against higher-ranked (1st) compared to lower-ranked teams (3rd, 4th, and 5th). Additionally, greater (moderate-large) PL and metabolic power were observed in matches played against higher-ranked (1st) compared to lower-ranked teams (3rd and 4th). These findings suggest coaches may need to reduce the training loads in the next days after the matches played against higher-ranked opponents compared to when facing lower-ranked opponents.


Assuntos
Desempenho Atlético , Humanos , Fenômenos Biomecânicos
11.
BMC Public Health ; 22(1): 2425, 2022 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-36566192

RESUMO

BACKGROUND: The aim of this study is to evaluate the short- and long-term effects of the universal mental health literacy intervention "EspaiJove.net" in increasing mental health knowledge, help seeking and reducing stigma attitudes in the adolescent population. We also examine whether these effects depend on the intervention intensity.  METHODS: A clustered school-based randomised controlled trial (cRCT) design. SUBJECTS: 1,298 secondary pupils aged 13 and 14 were recruited from 18 schools in Barcelona (Spain) between September 2016 and January 2018. INTERVENTION: Three programmes were assessed: 1) Sensitivity Programme (SP; 1 h); 2) Mental Health Literacy (MHL; 6 h); 3) MHL plus a first-person Stigma Reduction Programme (MHL + SR; 7 h); 4) Control group (CG): waiting list. OUTCOME MEASURES: 1) MHL: EspaiJove.net EMHL Test (First part and Second Part); 2) Stigma: RIBS and CAMI; 3) Help-seeking and use of treatment: GHSQ. ANALYSIS: The data was collected at baseline, post-intervention and 6 and 12 months later. An intention-to-treat analysis and imputation method was used to analyse the missing data. Intervention effects were analysed using multilevel modelling. RESULTS: One thousand thirty-two students were included (SP = 225; MHL = 261; MHL + SR = 295 and CG = 251). The MHL and MHL + SR interventions showed short- and long-term an increase in knowledge compared to SP and CG, but no significant change post-intervention or over time (First part p = 0.52 and Second part p = 0.62) between intervention groups and CG. No significant changes were found in stigma scores post-intervention or over time (CAMI p = 0.61 and RIBS p = 0.98) or in help-seeking scores (parent p = 0.69; teacher p = 0.23 and healthcare professional p = 0.75). The MHL + SR intervention was the best valued and recommended (p < 0.005). CONCLUSIONS: The three interventions of the EspaiJove.net programme (SP, MHL and MHL + SR) seem not to be effective in terms MHL, Stigma and help-seeking behaviours. The contact with a person who has experimented mental illness first-hand did not reduce stigma attitudes. Further research should deal with the heterogeneity of MHL interventions (concept, duration and measures) and identify which components of stigma interventions are effective. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03215654 (registration date 12 July 2017).


Assuntos
Letramento em Saúde , Transtornos Mentais , Humanos , Adolescente , Saúde Mental , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Estigma Social , Letramento em Saúde/métodos , Instituições Acadêmicas
14.
Biomedicines ; 10(5)2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35625820

RESUMO

Protein expression profiles are directly related to the different properties of cells and are conditioned by the cellular niche. As an example, they are the cause of the characteristic cell plasticity, epithelium-mesenchymal transition (EMT), and drug resistance of cancer cells. This article characterizes ten biomarkers related to these features in three human colorectal cancer cell lines: SW-480, SW-620, and DLD-1, evaluated by flow cytometry; and in turn, resistance to oxaliplatin is studied through dose-response trials. The main biomarkers present in the three studied lines correspond to EpCAM, CD-133, and AC-133, with the latter two in low proportions in the DLD-1 line. The biomarker CD166 is present in greater amounts in SW-620 and DLD-1 compared to SW-480. Finally, DLD-1 shows high values of Trop2, which may explain the aggressiveness and resistance of these cells to oxaliplatin treatments, as EpCAM is also highly expressed. Exposure to oxaliplatin slows cell growth but also helps generate resistance to the treatment. In conclusion, the response of the cell lines is variable, due to their genetic variability, which will condition protein expression and cell growth. Further analyses in this area will provide important information for better understanding of patients' cellular response and how to prevent resistance.

15.
Front Oncol ; 12: 862321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372006

RESUMO

Ovarian cancer (OC) is a life-threatening tumor and the deadliest among gynecological cancers in developed countries. First line treatment with a carboplatin/paclitaxel regime is initially effective in the majority of patients, but most advanced OC will recur and develop drug resistance. Therefore, the identification of alternative therapies is needed. In this study, we employed a panel of high-grade serous ovarian cancer (HGSOC) cell lines, in monolayer and three-dimensional cell cultures. We evaluated the effects of a novel tubulin-binding agent, plocabulin, on proliferation, cell cycle, migration and invasion. We have also tested combinations of plocabulin with several drugs currently used in OC in clinical practice. Our results show a potent antitumor activity of plocabulin, inhibiting proliferation, disrupting microtubule network, and decreasing their migration and invasion capabilities. We did not observe any synergistic combination of plocabulin with cisplatin, doxorubicin, gemcitabine or trabectedin. In conclusion, plocabulin has a potent antitumoral effect in HGSOC cell lines that warrants further clinical investigation.

16.
Aust N Z J Public Health ; 46(5): 647-653, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35357742

RESUMO

OBJECTIVE: To understand the impact of family separation on refugees living in Australia. METHOD: Thirteen participants with a refugee background and experiencing separation from family participated in a semi-structured qualitative interview. Interviews were coded and a thematic analysis was conducted using NVivo software. RESULTS: Identified themes were organised under four domains. Domain 1 focused on the personal impact of family separation. Themes were the effects on mental health and functioning, driven by incessant worrying about the safety of family and the absence of key attachment figures, the specific effects of having missing family, alterations to self-identity and family dynamics. Domain 2 focused on themes relating to actions taken to find missing family, connect or reunite with separated family. Domain 3 highlighted the coping strategies, support mechanisms and protective factors used by participants. Domain 4 identified core beliefs about the importance of family unity, focusing on security, settlement and a happy future. CONCLUSIONS: Family separation has an enduring effect on the wellbeing of refugees, with key pathways being ongoing fear and insecurity, disrupted social attachments and identity shifts in relation to the future self. IMPLICATIONS FOR PUBLIC HEALTH: Refugees separated from or missing family struggle with ongoing stress and adjustment issues.


Assuntos
Refugiados , Adaptação Psicológica , Austrália , Humanos , Saúde Mental , Pesquisa Qualitativa , Refugiados/psicologia
17.
EMBO Mol Med ; 14(4): e14841, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35263037

RESUMO

Small-Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy with a poor prognosis. Here, we focus on the neuroendocrine SCLC subtypes, SCLC-A and SCLC-N, whose transcription addiction was driven by ASCL1 and NEUROD1 transcription factors which target E-box motifs to activate up to 40% of total genes, the promoters of which are maintained in a steadily open chromatin environment according to ATAC and H3K27Ac signatures. This leverage is used by the marine agent lurbinectedin, which preferentially targets the CpG islands located downstream of the transcription start site, thus arresting elongating RNAPII and promoting its degradation. This abrogates the expression of ASCL1 and NEUROD1 and of their dependent genes, such as BCL2, INSM1, MYC, and AURKA, which are responsible for relevant SCLC tumorigenic properties such as inhibition of apoptosis and cell survival, as well as for a part of its neuroendocrine features. In summary, we show how the transcription addiction of these cells becomes their Achilles's heel, and how this is effectively exploited by lurbinectedin as a novel SCLC therapeutic endeavor.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Carbolinas , Compostos Heterocíclicos de 4 ou mais Anéis , Neoplasias Pulmonares , Proteínas Repressoras , Carcinoma de Pequenas Células do Pulmão , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carbolinas/farmacologia , Linhagem Celular Tumoral , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos , Proteínas Repressoras/metabolismo , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo
18.
Health Sci Rep ; 5(2): e513, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35237730

RESUMO

BACKGROUND AND AIMS: During the first peak of the COVID-19 pandemic, the Preventive Medicine Department and the Occupational Health Department at Hospital Clinic de Barcelona (HCB), a large Spanish referral hospital, developed an innovative comprehensive SARS-CoV2 Surveillance and Control System (CoSy-19) in order to preserve patients' and health care workers' (HCWs) safety. We aim to describe the CoSy-19 and to assess the impact in the number of contacts that new cases generated along this time. METHODS: Observational descriptive study of the findings of the activity of contact tracing of all cases received at the HCB during the first peak of COVID-19 in Spain (February 25th-May 3rd, 2020). RESULTS: A team of 204 professionals and volunteers performed 384 in-hospital contact-tracing studies which generated contacts, detecting 298 transmission chains which suggested preventive measures, generated around 22 000 follow-ups and more than 30 000 days of work leave. The number of contacts that new cases generated decreased during the study period. CONCLUSION: Coordination between Preventive Medicine and Occupational Health departments and agile information systems were necessary to preserve non-COVID activity and workers safety.

19.
Cancer Discov ; 12(4): 1106-1127, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35046097

RESUMO

Remodeling of the microenvironment by tumor cells can activate pathways that favor cancer growth. Molecular delineation and targeting of such malignant-cell nonautonomous pathways may help overcome resistance to targeted therapies. Herein we leverage genetic mouse models, patient-derived xenografts, and patient samples to show that acute myeloid leukemia (AML) exploits peripheral serotonin signaling to remodel the endosteal niche to its advantage. AML progression requires the presence of serotonin receptor 1B (HTR1B) in osteoblasts and is driven by AML-secreted kynurenine, which acts as an oncometabolite and HTR1B ligand. AML cells utilize kynurenine to induce a proinflammatory state in osteoblasts that, through the acute-phase protein serum amyloid A (SAA), acts in a positive feedback loop on leukemia cells by increasing expression of IDO1-the rate-limiting enzyme for kynurenine synthesis-thereby enabling AML progression. This leukemia-osteoblast cross-talk, conferred by the kynurenine-HTR1B-SAA-IDO1 axis, could be exploited as a niche-focused therapeutic approach against AML, opening new avenues for cancer treatment. SIGNIFICANCE: AML remains recalcitrant to treatments due to the emergence of resistant clones. We show a leukemia-cell nonautonomous progression mechanism that involves activation of a kynurenine-HTR1B-SAA-IDO1 axis between AML cells and osteoblasts. Targeting the niche by interrupting this axis can be pharmacologically harnessed to hamper AML progression and overcome therapy resistance. This article is highlighted in the In This Issue feature, p. 873.


Assuntos
Cinurenina , Leucemia Mieloide Aguda , Animais , Humanos , Cinurenina/metabolismo , Cinurenina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Camundongos , Osteoblastos/metabolismo , Transdução de Sinais , Microambiente Tumoral
20.
Clin Nutr ESPEN ; 45: 433-441, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34620351

RESUMO

BACKGROUND AND AIMS: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. METHODS: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as <1, 1-2, 2-3 and >3 L/day. RESULTS: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn' disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. CONCLUSIONS: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.


Assuntos
Enteropatias , Síndrome do Intestino Curto , Adulto , Estudos Transversais , Feminino , Humanos , Enteropatias/epidemiologia , Enteropatias/terapia , Intestinos , Nutrição Parenteral , Síndrome do Intestino Curto/epidemiologia , Síndrome do Intestino Curto/terapia
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