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1.
Int J Mol Sci ; 22(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202550

RESUMO

In this study, we determined the potential of polyethylene glycol-encapsulated iron oxide nanoparticles (IONPCO) for the intracellular delivery of the chemotherapeutic doxorubicin (IONPDOX) to enhance the cytotoxic effects of ionizing radiation. The biological effects of IONP and X-ray irradiation (50 kV and 6 MV) were determined in HeLa cells using the colony formation assay (CFA) and detection of γH2AX foci. Data are presented as mean ± SEM. IONP were efficiently internalized by HeLa cells. IONPCO radiomodulating effect was dependent on nanoparticle concentration and photon energy. IONPCO did not radiosensitize HeLa cells with 6 MV X-rays, yet moderately enhanced cellular radiosensitivity to 50 kV X-rays (DMFSF0.1 = 1.13 ± 0.05 (p = 0.01)). IONPDOX did enhance the cytotoxicity of 6 MV X-rays (DMFSF0.1 = 1.3 ± 0.1; p = 0.0005). IONP treatment significantly increased γH2AX foci induction without irradiation. Treatment of HeLa cells with IONPCO resulted in a radiosensitizing effect for low-energy X-rays, while exposure to IONPDOX induced radiosensitization compared to IONPCO in cells irradiated with 6 MV X-rays. The effect did not correlate with the induction of γH2AX foci. Given these results, IONP are promising candidates for the controlled delivery of DOX to enhance the cytotoxic effects of ionizing radiation.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Compostos Férricos , Nanopartículas Metálicas , Tolerância a Radiação/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Portadores de Fármacos/química , Compostos Férricos/química , Células HeLa/efeitos dos fármacos , Células HeLa/patologia , Células HeLa/efeitos da radiação , Células HeLa/ultraestrutura , Humanos , Nanopartículas Metálicas/química , Radiação Ionizante
3.
PLoS One ; 16(6): e0242456, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34111143

RESUMO

Since May 2020, several COVID-19 outbreaks have occurred in the German meat industry despite various protective measures, and temperature and ventilation conditions were considered as possible high-risk factors. This cross-sectional study examined meat and poultry plants to assess possible risk factors. Companies completed a self-administered questionnaire on the work environment and protective measures taken to prevent SARS-CoV-2 infection. Multivariable logistic regression analysis adjusted for the possibility to distance at least 1.5 meters, break rules, and employment status was performed to identify risk factors associated with COVID-19 cases. Twenty-two meat and poultry plants with 19,072 employees participated. The prevalence of COVID-19 in the seven plants with more than 10 cases was 12.1% and was highest in the deboning and meat cutting area with 16.1%. A subsample analysis where information on maximal ventilation rate per employee was available revealed an association with the ventilation rate (adjusted odds ratio (AOR) 0.996, 95% CI 0.993-0.999). When including temperature as an interaction term in the working area, the association with the ventilation rate did not change. When room temperatures increased, the chance of testing positive for COVID-19 (AOR 0.90 95% CI 0.82-0.99) decreased, and the chance for testing positive for COVID-19for the interaction term (AOR 1.001, 95% CI 1.000-1.003) increased. Employees who work where a minimum distance of less than 1.5 m between workers was the norm had a higher chance of testing positive (AOR 3.61; 95% CI 2.83-4.6). Our results further indicate that climate conditions and low outdoor air flow are factors that can promote the spread of SARS-CoV-2 aerosols. A possible requirement for pandemic mitigation strategies in industrial workplace settings is to increase the ventilation rate.


Assuntos
COVID-19/transmissão , Indústria Alimentícia , Local de Trabalho , COVID-19/epidemiologia , Estudos Transversais , Surtos de Doenças , Emprego , Indústria Alimentícia/organização & administração , Alemanha/epidemiologia , Humanos , Produtos da Carne/provisão & distribuição , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Temperatura , Ventilação , Local de Trabalho/organização & administração
4.
Cell Rep Med ; 2(6): 100321, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34075365

RESUMO

The pathogenesis of severe coronavirus disease 2019 (COVID-19) remains poorly understood. While several studies suggest that immune dysregulation plays a central role, the key mediators of this process are yet to be defined. Here, we demonstrate that plasma from a high proportion (93%) of critically ill COVID-19 patients, but not healthy controls, contains broadly auto-reactive immunoglobulin M (IgM) and less frequently auto-reactive IgG or IgA. Importantly, these auto-IgMs preferentially recognize primary human lung cells in vitro, including pulmonary endothelial and epithelial cells. By using a combination of flow cytometry, analytical proteome microarray technology, and lactose dehydrogenase (LDH)-release cytotoxicity assays, we identify high-affinity, complement-fixing, auto-reactive IgM directed against 260 candidate autoantigens, including numerous molecules preferentially expressed on the cellular membranes of pulmonary, vascular, gastrointestinal, and renal tissues. These findings suggest that broad IgM-mediated autoimmune reactivity may be involved in the pathogenesis of severe COVID-19, thereby identifying a potential target for therapeutic interventions.

6.
Cyberpsychol Behav Soc Netw ; 24(10): 648-653, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33535010

RESUMO

Research on parasocial interaction (PSI) has a long tradition in noninteractive environments such as watching TV or listening to radio speakers. In the past years, researchers have started to apply PSI on videogame streaming environments, where the audience can interact with the observed media persona and get immediate feedback on their messages and requests. In a 3 × 2 online experiment (N = 251), we manipulated how a streamer addressed participants (individual vs. collective vs. no addressing) and whether he paid attention to and answered messages in the chat (attention vs. no attention to the chat). Findings show that the more individually participants were addressed and whether the streamer reacted to messages in the chat affected experiences of PSI. Furthermore, alongside their overall enjoyment, PSI predicted viewers' commitment to social norms. We discuss these findings regarding their implications for the conceptualization of PSI in light of interactive novel technologies.


Assuntos
Jogos de Vídeo , Humanos , Masculino
7.
Eur Arch Psychiatry Clin Neurosci ; 271(2): 315-324, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32748261

RESUMO

Even today, patients with schizophrenia often have an unfavorable outcome. Negative symptoms and cognitive deficits are common features in many patients and prevent recovery. In recent years, aerobic endurance training has emerged as a therapeutic approach with positive effects on several domains of patients' health. However, appropriately sized, multicenter randomized controlled trials that would allow better generalization of results are lacking. The exercise study presented here is a multicenter, rater-blind, two-armed, parallel-group randomized clinical trial in patients with clinically stable schizophrenia being conducted at five German tertiary hospitals. The intervention group performs aerobic endurance training on bicycle ergometers three times per week for 40-50 min/session (depending on the intervention week) for a total of 26 weeks, and the control group performs balance and tone training for the same amount of time. Participants are subsequently followed up for 26 weeks. The primary endpoint is all-cause discontinuation; secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and explorative biological measures regarding the underlying mechanisms of exercise. A total of 180 patients will be randomized. With currently 162 randomized participants, our study is the largest trial to date to investigate endurance training in patients with schizophrenia. We hypothesize that aerobic endurance training has beneficial effects on patients' mental and physical health, leading to lower treatment discontinuation rates and improving disease outcomes. The study results will provide a basis for recommending exercise interventions as an add-on therapy in patients with schizophrenia.The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).


Assuntos
Treino Aeróbico , Reabilitação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Esquizofrenia/reabilitação , Adolescente , Adulto , Idoso , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Método Simples-Cego , Adulto Jovem
8.
Clin Pharmacol Drug Dev ; 10(6): 647-659, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33038289

RESUMO

Deutetrabenazine (Austedo, Teva), an approved treatment of chorea in Huntington's disease and tardive dyskinesia in adult patients, is a rationally designed deuterated form of tetrabenazine. Two studies assessed the pharmacokinetics and safety of deutetrabenazine compared with tetrabenazine, and the effects of food on absorption of the deuterated active metabolites, α-dihydrotetrabenazine (α-HTBZ) and ß-dihydrotetrabenazine (ß-HTBZ). One study was an open-label 2-part study in healthy volunteers; the first part included a crossover single dose of two 15 mg candidate deutetrabenazine formulations in fed and fasted states compared with tetrabenazine 25 mg in the fasted state, and the second part included single and repeated dosing of the commercial formulation of deutetrabenazine (7.5, 15, and 22.5 mg) compared with tetrabenazine 25 mg. The second study was an open-label 5-way crossover study in healthy volunteers (n = 32) to evaluate relative bioavailability of 4 dose levels of the commercial formulation of deutetrabenazine (6, 12, 18, and 24 mg) with a standard meal and 18 mg with a high-fat meal. Both studies confirmed longer half-lives for active metabolites and lower peak-to-trough fluctuations for the sum of the metabolites (total [α+ß]-HTBZ) following deutetrabenazine compared with tetrabenazine (3- to 4-fold and 11-fold, respectively) in steady-state conditions. Deutetrabenazine doses estimated to provide total (α+ß)-HTBZ exposure comparable to tetrabenazine 25 mg were 11.4-13.2 mg. Food had no effect on exposure to total (α+ß)-HTBZ, as measured by AUC. Although the total (α+ß)-HTBZ Cmax of deutetrabenazine was increased by ≈50% in the presence of food, it remained lower than that of tetrabenazine.

9.
J Contemp Brachytherapy ; 12(5): 480-486, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33299437

RESUMO

Purpose: Radiotherapy is the mainstay in the treatment of locally inoperable tumors. Interstitial electronic needle-based kilovoltage brachytherapy (EBT) could be an economic alternative to high-dose-rate (HDR) brachytherapy or permanent seed implantation (PSI). In this work, we evaluated if locally inoperable tumors treated with PSI at our institution may be suitable for EBT. Material and methods: A total of 10 post-interventional computed tomography (CT) scans of patients, who received PSI and simulated stepping-source EBT applied with Intrabeam system and needle applicator were used. EBT treatment planning software with 3-dimensional image and projection of applicator were applied for designing trajectories and establishing dwell positions. Dwell position doses were summarized, and doses covering 90% of the target volume (D90) achieved with stepping-source EBT were compared to those of PSI. Additionally, conformality of dose distributions and total irradiation time were assessed using conformation number (CN) or conformal index (COIN). Results: In all patients, D90 of EBT exceeded the prescribed dose or D90 of PSI on average by 4.7% or 21.3% relative to the prescribed dose, respectively. Mean number of trajectories was 5.0 for EBT and 6.9 for PSI. Average CN/COIN for EBT was 0.69, with a mean irradiation time of 27.8 minutes for standardized dose of 13 Gy. Conclusions: Stepping-source EBT allowed for a conformal treatment of inoperable interstitial tumors with similar D90. Fewer trajectories were required for EBT in majority of cases.

10.
Radiat Oncol ; 15(1): 263, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183307

RESUMO

INTRODUCTION: The spine represents the site which is most frequently affected by bone metastases in patients with systemic cancer. Of all local treatment options, combined kyphoplasty and intraoperative radiotherapy (Kypho-IORT) provides both, instantaneous stabilization and immediate pain relief. We here report on the long-term outcomes of the largest cohort treated with Kypho-IORT to date. METHODS: Between 2009 and 2019 a total of 104 patients underwent Kypho-IORT to vertebral tumors in the thoracic, lumbar, or sacral spine with transpedicular kyphoplasty and intraoperative irradiation with a needle-shaped electronic brachytherapy source at our center. Patients were treated either on trial, within the prospective Kypho-IORT studies (NCT01280032 and NCT02773966), or, after completion of the study, off trial but compliant with the study protocol. Follow-up and imaging with computed tomography (CT) or magnetic resonance imaging was scheduled after 3 and 6 months and then bi-annually. RESULTS: A total of 143 vertebrae (89 thoracic spine, 53 lumbar spine, and 1 sacral spine) were treated in 104 patients. The median follow-up was 14.5 months (range 0.4-109). Local progression occurred in 10 patients (10 vertebrae) after a median time of 22.3 months (range 1.5-73) resulting in local control rates of 97.1, 95.9, and 94.2% at 6, 12, and 24 months, respectively. Overall survival was 74.6, 61.7, and 50.3% at 6, 12, and 24 months, respectively. A single serious adverse event was reported. CONCLUSION: In addition to immediate pain reduction and stabilization, Kypho-IORT shows excellent long-term local control with minimal side effects.


Assuntos
Cifoplastia/métodos , Neoplasias da Coluna Vertebral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Cifoplastia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Dosagem Radioterapêutica , Neoplasias da Coluna Vertebral/mortalidade
11.
Circ Arrhythm Electrophysiol ; 13(11): e008753, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33031001

RESUMO

BACKGROUND: Stereotactic body radiation therapy (SBRT) is a novel treatment for refractory ventricular tachycardia (VT). While outcomes have been described in small studies, histological findings after SBRT for VT are unknown. METHODS: We identified 4 explanted hearts in the context of transplant that received prior SBRT as part of an 11-patient compassionate use series at our institution. Clinical VTs and computed tomography-defined target volume areas of SBRT were correlated to the anatomic specimens. Gross pathological, histological, and ultrastructural examination of tissue in the target area of SBRT was performed. RESULTS: All 4 patients had nonischemic cardiomyopathy, and 3 had left ventricular assist devices. In all cases, patients had recurrent sustained VT and had failed multiple antiarrhythmics and radiofrequency ablations. Four patients underwent 5 total SBRT therapy sessions with 25-Gy single-fraction dose delivered to the area of culprit scar. The time from SBRT to explant ranged from 12 to 250 days. Histopathologic features following radiation were comparable in all patients and were characterized by areas of subendocardial necrosis surrounded by a rim of fibrosis. In 1 patient, the surrounding myocardium showed cytoplasmic vacuolization in myocytes and in another patchy interstitial fibrosis. Vascular changes consisted of myointimal thickening with prominence of endothelial cells. Electron microscopy of myocardium showed irregular, convoluted intercalated disc regions, loss of contractile elements with disrupted and haphazardly arranged myofibrils, and edematous mitochondria with loss of cisternae. CONCLUSIONS: Here, we report the first series of findings in human tissue in 4 patients after SBRT. Histopathologic features were consistent across all 4 patients and were indicative of cell injury, death, and to a lesser extent, fibrosis. Electron microscopy demonstrated features consistent with acute injury. These specimens provide radiobiological mechanisms of acute cellular injury during SBRT for VT, which may have an antiarrhythmic effect before the onset of fibrosis.


Assuntos
Miocárdio/ultraestrutura , Radiocirurgia , Taquicardia Ventricular/radioterapia , Idoso , Ensaios de Uso Compassivo , Feminino , Fibrose , Transplante de Coração , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Doses de Radiação , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Resultado do Tratamento
12.
Brachytherapy ; 19(5): 635-641, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32651094

RESUMO

PURPOSE: The purpose of the study was to report the outcomes of a single-center adjuvant electronic brachytherapy (e-BT) experience for patients with endometrial carcinoma. METHODS AND MATERIALS: Patients were retrospectively assessed. Intracavitary e-BT was applied through a cylindrical applicator (diameters 2.5-3.5 cm). e-BT single doses ranged between 4 and 7 Gy (EQD2 ∼ 6-12, α/ß of 10 Gy and an relative biological effectiveness of 1.3) at 5-mm depth. Adverse events are reported at first week, 1-3 months, 3-12 months, 12-24 months, and >24 months. The overall survival, disease-free survival, distant disease control rate, and local control rate were estimated using the Kaplan-Meier method. RESULTS: Twenty-nine patients were assessed. The median age was 68 [48-86] years. External beam radiotherapy was added in n = 8 (27.6%) patients. Staging was 13.8% for T1a, 51.7% for T1b, 24.1% for T2, 6.9% for T3a, and 3.4% for T3b. Grading was G3 in 51.7% (n = 15), G2 in 20.7% (n = 6), and G1 in 27.6% (n = 8). Median followup was 47 months [5-88]. Overall Grade 1, 2, and 3 toxicity was 89.7% (n = 26), 17.2% (n = 5), and 6.9% (n = 2), respectively. No Grade 3 cystitis or proctitis or any Grade 4 or 5 toxicity occurred during followup. No local recurrences were detected. Estimated distant disease control rate was 92.1% (n = 2, distant metastasis at 7 and 11 months). Estimated 4-year overall survival was 84.8% (n = 4 events, two unrelated to disease) and disease-free survival was 84.6%. CONCLUSIONS: Our data suggest that e-BT resembles a very-low-toxicity profile and a high local control rate in the adjuvant scenario for patients with endometrial carcinoma.


Assuntos
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias do Endométrio/radioterapia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Cistite/epidemiologia , Intervalo Livre de Doença , Eletrônica , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Dor Pélvica/epidemiologia , Proctite/epidemiologia , Lesões por Radiação/epidemiologia , Radioterapia , Estudos Retrospectivos , Taxa de Sobrevida , Doenças Vaginais/epidemiologia
14.
Clin Transl Sci ; 13(4): 707-717, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32155315

RESUMO

Deutetrabenazine (Austedo, Teva Pharmaceuticals) is a deuterated form of tetrabenazine. It is the first deuterated drug to receive US regulatory approval and is approved for treatment of chorea in Huntington's disease and tardive dyskinesia. Two oral single dose studies comparing deutetrabenazine (25 mg) with tetrabenazine (25 mg) in healthy volunteers evaluated the impact of deuteration on pharmacokinetics of the active metabolites, alpha-dihydrotetrabenazine (α-HTBZ) and beta-dihydrotetrabenazine (ß-HTBZ), metabolite profile, safety, and tolerability. In the two-way, cross-over study, the mean elimination half-life of deuterated total (α + ß)-HTBZ was doubled compared with nondeuterated total (α + ß)-HTBZ, with a twofold increase in overall mean exposure (area under the concentration-time curve from zero to infinity (AUC0-inf )) and a marginal increase in mean peak plasma concentration (Cmax ). In the mass balance and metabolite profiling study, there were no novel plasma or urinary metabolites of [14 C]-deutetrabenazine relative to [14 C]-tetrabenazine. Specific deuteration in deutetrabenazine resulted in a superior pharmacokinetic profile and an increased ratio of active-to-inactive metabolites, attributes considered to provide significant benefits to patients.


Assuntos
Inibidores da Captação Adrenérgica/farmacocinética , Doença de Huntington/tratamento farmacológico , Discinesia Tardia/tratamento farmacológico , Tetrabenazina/análogos & derivados , Administração Oral , Adolescente , Inibidores da Captação Adrenérgica/administração & dosagem , Adulto , Área Sob a Curva , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Masculino , Tetrabenazina/administração & dosagem , Tetrabenazina/farmacocinética , Adulto Jovem
15.
Brain Lang ; 205: 104772, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32126372

RESUMO

This paper presents an fMRI study on healthy adult understanding of metaphors in multimodal communication. We investigated metaphors expressed either only in coverbal gestures ("monomodal metaphors") or in speech with accompanying gestures ("multimodal metaphors"). Monomodal metaphoric gestures convey metaphoric information not expressed in the accompanying speech (e.g. saying the non-metaphoric utterance, "She felt bad" while dropping down the hand with palm facing up; here, the gesture alone indicates metaphoricity), whereas coverbal gestures in multimodal metaphors indicate metaphoricity redundant to the speech (e.g. saying the metaphoric utterance, "Her spirits fell" while dropping the hand with palm facing up). In other words, in monomodal metaphors, gestures add information not spoken, whereas the gestures in multimodal metaphors can be redundant to the spoken content. Understanding and integrating the information in each modality, here spoken and visual, is important in multimodal communication, but most prior studies have only considered multimodal metaphors where the gesture is redundant to what is spoken. Our participants watched audiovisual clips of an actor speaking while gesturing. We found that abstract metaphor comprehension recruited the lateral superior/middle temporal cortices, regardless of the modality in which the conceptual metaphor is expressed. These results suggest that abstract metaphors, regardless of modality, involve resources implicated in general semantic processing and are consistent with the role of these areas in supramodal semantic processing as well as the theory of embodied cognition.


Assuntos
Comunicação , Gestos , Metáfora , Tempo de Reação/fisiologia , Semântica , Lobo Temporal/diagnóstico por imagem , Adolescente , Adulto , Cognição/fisiologia , Compreensão/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Estimulação Luminosa/métodos , Fala/fisiologia , Lobo Temporal/fisiologia , Adulto Jovem
16.
Psychophysiology ; 57(5): e13540, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32011003

RESUMO

Elevated levels of risk-taking behavior as well as affective instability are both cardinal features of Borderline Personality Disorder (BPD). To our knowledge, there are no studies which directly investigate underlying affective processes of risk-taking behavior in BPD, despite the centrality of affect in BPD symptomatology, and indications of affective dysregulation contributing to increased risk-taking behavior in BPD. Here, we examined risk-taking behavior in BPD and its underlying affective processes, using skin conductance responses (SCRs) as a proxy. Twenty-three individuals with BPD and 24 healthy controls performed a modified version of the Balloon Analogue Risk Task, where decisions take place over a time scale of several seconds, enabling us to investigate a continuous integral of SCRs in anticipation of decisions. We used trial-by-trial mixed model analyses to account for within- and between-participant effects, as well as large variability that are often observed in SCRs. In contrast to healthy controls, who showed elevated SCRs in response to high risk, individuals with BPD did not show differential physiological sensitivity towards different risk levels. In addition, increased SCRs--under low risk--were related to more cautious risk-taking behavior in HCs. However, increased SCRs under low risk in BPD were related to greater risk-taking behavior. Alterations in the processing of affective signals, such as SCRs in the context of risk, may impair adaptation to environmental demands and may lead to increased risk-taking behavior in BPD.


Assuntos
Sintomas Afetivos/fisiopatologia , Nível de Alerta/fisiologia , Transtorno da Personalidade Borderline/fisiopatologia , Resposta Galvânica da Pele/fisiologia , Assunção de Riscos , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
17.
Surg Pathol Clin ; 13(1): 57-71, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32005435

RESUMO

Lung cancer staging is a foundation of patient care, informing management decisions and prognosis. This comprehensive overview of the current 8th edition American Joint Committee on Cancer Cancer Staging Manual addresses common difficulties in staging, such as measuring the invasive component of adenocarcinomas and staging multiple lung nodules.


Assuntos
Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Humanos , Neoplasias Pulmonares/diagnóstico , Estadiamento de Neoplasias/métodos , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/patologia
18.
Fortschr Neurol Psychiatr ; 88(2): 82-88, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-32102099

RESUMO

STUDY GOAL: This article presents the results of a pilot project to support mentally affected refugees by trained peer helpers. The evaluation aims to assess the necessity, usefulness and effectiveness of the project. METHODS: External agents as well as those involved in this project were interviewed with the help of validated and self-designed instruments and the results subjected to statistical analysis. The sample consisted of 197 refugees living in camps, 18 peer helpers participating in the project, as well as 16 social workers and administrators of twelve refugee shelters. RESULTS: More than half of the refugee sample reported having psychological problems. Peer-help, which consisted primarily of individual consultations, was rated positively by the refugees. 58.5 % severely affected refugees were reassigned to standard health care. Trained peer helpers rated peer training, coordination and supervision as good. The psychological burden of peer helpers did not change during the project. Social workers and administrators of the refugee shelters evaluated the peer-helper project as helpful. CONCLUSION: The pilot project appears to be necessary and useful. Mentally affected refugees benefit from the low-level help offer with trained peers providing valuable, native-speaker assistance. Good training, coordination and supervision as framework conditions allow the successful use of peer helpers to support mentally affected refugees effectively.


Assuntos
Serviços de Saúde Mental , Grupo Associado , Refugiados/psicologia , Apoio Social , Humanos , Projetos Piloto
19.
Cereb Cortex ; 30(5): 2755-2765, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31999324

RESUMO

The exact neurobiological underpinnings of gender identity (i.e., the subjective perception of oneself belonging to a certain gender) still remain unknown. Combining both resting-state functional connectivity and behavioral data, we examined gender identity in cisgender and transgender persons using a data-driven machine learning strategy. Intrinsic functional connectivity and questionnaire data were obtained from cisgender (men/women) and transgender (trans men/trans women) individuals. Machine learning algorithms reliably detected gender identity with high prediction accuracy in each of the four groups based on connectivity signatures alone. The four normative gender groups were classified with accuracies ranging from 48% to 62% (exceeding chance level at 25%). These connectivity-based classification accuracies exceeded those obtained from a widely established behavioral instrument for gender identity. Using canonical correlation analyses, functional brain measurements and questionnaire data were then integrated to delineate nine canonical vectors (i.e., brain-gender axes), providing a multilevel window into the conventional sex dichotomy. Our dimensional gender perspective captures four distinguishable brain phenotypes for gender identity, advocating a biologically grounded reconceptualization of gender dimorphism. We hope to pave the way towards objective, data-driven diagnostic markers for gender identity and transgender, taking into account neurobiological and behavioral differences in an integrative modeling approach.


Assuntos
Encéfalo/diagnóstico por imagem , Identidade de Gênero , Aprendizado de Máquina/classificação , Imageamento por Ressonância Magnética/classificação , Imageamento por Ressonância Magnética/métodos , Pessoas Transgênero/psicologia , Adolescente , Adulto , Encéfalo/fisiologia , Feminino , Previsões , Humanos , Masculino , Neuroimagem/métodos , Inquéritos e Questionários , Adulto Jovem
20.
Brain Imaging Behav ; 14(2): 485-495, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30847803

RESUMO

Recent resting-state functional connectivity studies have shown significant group differences in several networks between patients suffering from borderline personality disorder (BPD) and healthy controls. However, reliable and consistent findings have not been reported yet. Several methodological factors might be responsible for the discrepant findings, including the heterogeneity of patient samples in terms of symptom severity. In the current study, we combined investigations of the whole-brain resting-state functional connectivity patterns of BPD patients with seed-based connectivity measures and then computed the correlation of connectivity measures with borderline symptom severity. Correlation-based connectivity analysis was performed on resting-state functional magnetic resonance imaging (fMRI) data from 26 female BPD patients and 26 healthy controls. Increased intrinsic connectivity was found in clusters involving part of the caudate nucleus and the left insula in the patient group, indicating greater integration of each region. Further seed-based connectivity analyses revealed that with the caudate seed, the patient data exhibited an increased resting-state functional connectivity in the bilateral ventral striatum and the midline prefrontal regions extending to the ACC, a network associated with reward processing. The left insula seed showed significantly increased connectivity with the bilateral fronto-orbital/insula, the inferior parietal lobule and the mid-cingulate cortex, a network involved in attention and salience encoding, in the patient population. Moreover, symptom severity, as assessed with the BSL-95 outside the scanner, was negatively correlated with the coupling of the insula and the striatum in the BPD group. Overall, an increased functional connectivity within two large-scale circuitries underlying reward and salience processing was evident in patients, as compared to healthy participants. When correlated with borderline symptom severity, a reduced connectivity between key regions belonging to the reward system and salience network was observed in the patients. These findings may be helpful for facilitating further understanding of the potential mechanisms underlying the BPD pathophysiology and thereby delineate potential treatment targets.


Assuntos
Transtorno da Personalidade Borderline/fisiopatologia , Núcleo Caudado/fisiopatologia , Córtex Cerebral/fisiopatologia , Adulto , Encéfalo/fisiopatologia , Mapeamento Encefálico , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Sistema Límbico/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiopatologia , Pacientes/psicologia , Descanso/fisiologia , Recompensa , Estriado Ventral/fisiopatologia
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