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1.
Proc Natl Acad Sci U S A ; 120(18): e2204621120, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37098055

RESUMO

The unique cancer-associated immunosuppression in brain, combined with a paucity of infiltrating T cells, contributes to the low response rate and poor treatment outcomes of T cell-based immunotherapy for patients diagnosed with glioblastoma multiforme (GBM). Here, we report on a self-assembling paclitaxel (PTX) filament (PF) hydrogel that stimulates macrophage-mediated immune response for local treatment of recurrent glioblastoma. Our results suggest that aqueous PF solutions containing aCD47 can be directly deposited into the tumor resection cavity, enabling seamless hydrogel filling of the cavity and long-term release of both therapeutics. The PTX PFs elicit an immune-stimulating tumor microenvironment (TME) and thus sensitizes tumor to the aCD47-mediated blockade of the antiphagocytic "don't eat me" signal, which subsequently promotes tumor cell phagocytosis by macrophages and also triggers an antitumor T cell response. As adjuvant therapy after surgery, this aCD47/PF supramolecular hydrogel effectively suppresses primary brain tumor recurrence and prolongs overall survivals with minimal off-target side effects.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Paclitaxel , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Macrófagos Associados a Tumor/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Hidrogéis/uso terapêutico , Imunoterapia/métodos , Microambiente Tumoral , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico
2.
Br J Neurosurg ; : 1-8, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651499

RESUMO

INTRODUCTION: Decompressive craniectomy and craniotomy are among the most common procedures in Neurosurgery. In recent years, increased attention has focused on the relationships between incision type, extent of decompression, vascular supply to the scalp, cosmetic outcomes, and complications. Here, we review the current literature on scalp incisions for large unilateral front-temporo-parietal craniotomies and craniectomies. METHODS: Publications in the past 50 years on scalp incisions used for front-temporo-parietal craniectomies/craniotomies were reviewed. Only full texts were considered in the final analysis. A total of 27 studies that met the criteria were considered for the final manuscript. PRISMA guidelines were adopted for this study. RESULTS: Five main incision types have been described. In addition to the question mark incision, other common incisions include the T-Kempe, developed to obtain wide access to the skull, the retroauricular incision, designed to spare the occipital branch, as well as the N-shaped and cloverleaf incisions which integrate with pterional approaches. Advantages and drawbacks, integration with existing incisions, relationships with the main arteries, cosmetic outcomes, and risks of wound complications including dehiscence, necrosis, and infection were assessed. DISCUSSION: The reverse-question mark incision, despite being a mainstay of trauma neurosurgery, can place the vascular supply to the scalp at risk and favor wound dehiscence and infection. Several incisions, such as the T-Kempe, retroauricular, N-shaped, and cloverleaf approaches have been developed to preserve the main vessels supplying the scalp. Incision choice needs to be carefully weighted based on the patient's anatomy, position and size of main vessels, risk of wound dehiscence, and desired volume of decompression.

3.
BMC Pregnancy Childbirth ; 23(1): 382, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37231375

RESUMO

BACKGROUND: Pregnancy is a crucial transition moment exposing women to potential mental health problems, especially depressive disturbances. Sociodemographic, pregnancy-related, and psychological factors have been related to depressive symptoms in the perinatal period. This study aims at (1) exploring personality and individual factors related with perinatal depressive symptoms, and (2) testing the mediating role of personality in the relation between characteristics of the woman's family of origin and depressive symptoms. METHODS: Women in the perinatal period admitted to the gynecology unit for motherhood-related routine assessments (n = 241) were included in the study. A survey on individual sociodemographic, clinical, and pregnancy-related factors was administered, also including the Edinburgh Postnatal Depression Scale (EPDS) and the BIG-5 personality test. RESULTS: Couple conflict and neuroticism were independent and directly correlated with EPDS total score (respectively: B = 2.337; p = .017; B = 0.303; p < .001). Neuroticism was a significant mediator of the relation between the presence of a psychiatric disorder diagnosis in participant's parents and the EPDS total score (indirect b = 0.969; BCCI95%=0.366-1.607). CONCLUSIONS: Couple relation and neuroticism traits are individual factors related to depressive symptoms in the perinatal period. The family of origin also plays an indirect role on perinatal depressive symptoms. Screening of these factors could lead to early recognition and more tailored treatments, ultimately leading to better outcome for the entire family.


Assuntos
Depressão Pós-Parto , Ginecologia , Gravidez , Feminino , Humanos , Depressão/psicologia , Depressão Pós-Parto/psicologia , Estudos Transversais , Personalidade , Escalas de Graduação Psiquiátrica
4.
Eat Weight Disord ; 27(3): 857-865, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34091875

RESUMO

Numerous studies addressed the topic of behavioral and symptomatic changes in eating disorders. Rates of transition vary widely across studies, ranging from 0 to 70.8%, depending on the diagnoses taken into account and the study design. Evidence shows that the specific transition from restrictive-type anorexia nervosa (AN-R) to disorders involving binging and purging behaviors (BPB) is related to a worsening of the clinical picture and worse long-term outcomes. The aim of this systematic review and meta-analysis is to focus on this specific transition, review existing literature, and summarize related risk factors. Medline and PsycINFO databases were searched, including prospective and retrospective studies on individuals with AN-R. The primary outcome considered was the rate of onset of BPB. Twelve studies (N = 725 patients) were included in the qualitative and quantitative analysis. A total of 41.84% (95% CI 33.58-50.11) of patients with AN-R manifested BPB at some point during follow-up. Risk factors for the onset of BPB included potentially treatable and untreatable factors such as the family environment, unipolar depression and higher premorbid BMI. These findings highlight that patients with AN-R frequently transition to BPB over time, with a worsening of the clinical picture. Existing studies in this field are still insufficient and heterogeneous, and further research is needed. Mental health professionals should be aware of the frequent onset of BPB in AN-R and its risk factors and take this information into account in the treatment of AN-R. LEVEL OF EVIDENCE: Evidence obtained from a systematic review and meta-analysis, Level I.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Anorexia Nervosa/psicologia , Transtorno da Compulsão Alimentar/psicologia , Humanos , Estudos Prospectivos , Estudos Retrospectivos
5.
J Gen Intern Med ; 36(6): 1702-1707, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33782888

RESUMO

BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe but treatable mental disorder that develops after a life-threatening traumatic event. Coronavirus disease 19 (COVID-19) hospitalisation is a potentially traumatic experience, especially in severe cases. Furthermore, the unprecedented context of the severe acute respiratory syndrome coronavirus 2 pandemic, with daily media bombardment about COVID-19 mortality, may have amplified life-threatening perception also in patients with moderate infection. The aim of this study was to assess the prevalence and risk factors of PTSD at 3-month follow-up in patients hospitalised for COVID-19 infection. DESIGN: In this cohort follow-up study conducted in a large Italian academic COVID-19 hospital, 115 recruited survivors were contacted by telephone 3 months after discharge to home care. The Posttraumatic Stress Disorder Checklist for DSM-5 was administered. Multivariate logistic regression models were used to analyse risk factors for the development of PTSD. KEY RESULTS: A total of 10.4% of the sample received a PCL-5-based diagnosis of PTSD. Other 8.6% of the sample received a diagnosis of subthreshold PTSD, which leads to significant levels of distress and impairment. Multivariate regression analysis indicated that previous psychiatric diagnosis (odds ratio (OR) = 6.3, 95% confidence interval (CI): 3.7-78.6, p < 0.001) and obesity (OR = 3.51, 95% CI: 1.4-857.9, p = 0.03) were risk factors for developing PTSD. Chronic pulmonary diseases approached significance as a risk factor (OR = 6.03, 95% CI: 1.0-37.1, p = 0.053). Male sex was a protective factor (OR=0.04, 95% CI: 0.0-0.041, p = 0.007). CONCLUSIONS: PTSD and subthreshold PTSD rates in patients hospitalised for COVID-19 are worrying. Female sex and pre-existing mental disorders are established risk factors for PTSD, while the prospective association with obesity needs further investigation. Clinicians treating COVID-19 should consider screening for PTSD at follow-up assessments in patients discharged from the hospital.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , Feminino , Seguimentos , Hospitais , Humanos , Masculino , Alta do Paciente , Estudos Prospectivos , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Sobreviventes
6.
Childs Nerv Syst ; 37(3): 779-788, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33409616

RESUMO

Quantitative mass spectrometry (MS)-based approaches have allowed further characterization of medulloblastoma (MB) classification and clinical/biological behavior. By investigating protein expression, as well as the role of post-translational modifications in shaping cellular activity, novel avenues of research will clarify the current subgrouping, providing elements for tumor treatment-new molecular targets and signaling cascades-and introducing serum, urinary, and CSF markers of tumor growth and recurrence. We systematically searched and reviewed original research articles treating MB proteomics on PubMed. Reviews, opinion papers, and abstracts were excluded from the final work. A total of 30 novel articles treating the proteomic characterization of MB were included in our review. Research conducted on tissue samples, cell lines, CSF, and urine, as well as exosome and medullospheres, was considered, to picture a broad view of the different directions MS-based proteomic analysis is moving toward. In this review, we collect, summarize, and interpret the current literature on this topic. Significant progress has been achieved in the last decade in MB characterization, paving the way for further exploration of large biobanks of MB and other tissues that will allow a more systematic understanding of MB functioning and clinical progression.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Biomarcadores , Criança , Humanos , Recidiva Local de Neoplasia , Proteômica
7.
Eat Weight Disord ; 26(2): 475-481, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32080821

RESUMO

INTRODUCTION: Epidemiologic information on sociodemographic and clinical characteristics in eating disorders in Western European countries are scarce. PURPOSE: In this study, we report demographic and clinical characteristics of eating disorder (ED) patients undergoing treatment in five specialized ED centers in Flanders (Belgium). METHOD: Data from 642 ED patients were collected by means of a structured questionnaire. RESULTS: Data show that 93.8% of patients are female, with an average age of 22.6 years. The largest subgroup in our sample suffers from anorexia nervosa, namely 52.8%. Bulimia nervosa (BN), binge eating disorder (BED) and eating disorder not otherwise specified (EDNOS) account for 17.7%, 10.7% and 18.8% of the sample, respectively. Mean age of onset was 17 years. Mean duration of illness was 5.6 years, but 20.2% of patients had their illness for over 8 years. Anorexia nervosa patients of the restricting type (AN-R) have the shortest duration of illness. BED patients stood out because they were older on average, more often in a relationship and more often in ambulatory treatment. 70% of patients over 20 years old completed higher education, but one-third of this group was unemployed and/or disabled. Remarkably, ED patients grow more up in intact families compared to the general population. CONCLUSIONS: Epidemiology of ED patients in treatment in Flanders (Belgium) seems to resemble worldwide findings. The long duration of illness, the common evolution towards chronicity and the early work impairment underline the severe personal and societal impact of ED and call to the need for early detection and treatment of these patients. LEVEL OF EVIDENCE: Level V: cross-sectional descriptive study.


Assuntos
Anorexia Nervosa , Transtorno da Compulsão Alimentar , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Adolescente , Adulto , Bélgica/epidemiologia , Estudos Transversais , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Feminino , Humanos , Masculino , Adulto Jovem
8.
Int J Eat Disord ; 53(3): 339-348, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31868255

RESUMO

BACKGROUND: Binge eating and purging behaviors (BPB) are common among college students, but evidence is scant on prevalence and associations of BPB with mental health problems and objective academic performance. This study aims to investigate: (a) 12-month prevalence of BPB among college first-year students, (b) comorbidity patterns of BPB with various mental health problems, and (c) the association of BPB with objective academic functioning. METHODS: Using data from the Leuven College Surveys (Belgium), as part of the World Mental Health Surveys International College Student initiative, we cross-sectionally assessed 12-month BPB and mental health problems among college first-year students (n = 4,889; response rate = 73.2%) at the beginning of the academic year. Objective measures of academic functioning (final grades, expressed in academic year percentage "AYP" [0-100%] and academic failure) were obtained from administrative records at the end of the academic year. RESULTS: Twelve-month prevalence of BPB was 7.6% (7.3%binge eating and 1.0%purging), with higher rates among females than males. Bivariate models showed an association between BPB and numerous mental health problems (ORs = 3.4-18.4). Multivariate models showed associations with non-suicidal self-injury, post-traumatic stress, internalizing/externalizing problems and suicidal ideation. After controlling for sociodemographic characteristics and comorbid mental health problems, BPB were still associated with lower AYP (-4.1 to -11.2% range) and elevated odds of academic year failure (ORs = 1.4-4.2). CONCLUSIONS: BPB (especially binge eating) are relatively common and associated with mental health problems, comparatively low academic performance, and higher risk of academic failure among college first-year students. Further study is needed to examine the causal dynamics underlying these associations.


Assuntos
Desempenho Acadêmico/psicologia , Transtorno da Compulsão Alimentar/epidemiologia , Estudantes/psicologia , Adolescente , Adulto , Transtorno da Compulsão Alimentar/psicologia , Comorbidade , Feminino , Humanos , Masculino , Prevalência , Inquéritos e Questionários , Universidades , Adulto Jovem
9.
Eur Eat Disord Rev ; 28(3): 309-317, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32080958

RESUMO

BACKGROUND: Binge eating disorder (BED) is commonly associated with a history of trauma. Yet, there is little insight into the potential effect that trauma, dissociation, and depressive symptoms may have on the outcome of treatment interventions. METHODS: A total of 142 treatment-seeking patients admitted with a diagnosis of DSM-5 BED (88% female; mean age = 38.7; SD = 10.8) took part in a 6-month, protocolized, group cognitive behavioural therapy (CBT). Self-report questionnaires were administered to assess lifetime traumatic experiences, dissociation, and depression. Body mass index and the number of binges per week (BPW) were measured throughout treatment. The main outcomes were the percentage reduction in BPW and remission (i.e., less than one BPW; cf. DSM-5). RESULTS: Most BED patients (91.5%) reported a history of trauma, with two in three patients reporting three or more traumatic experiences. Whereas the number of traumatic experiences was not significantly associated with a reduction in BPW or remission, a higher traumatic impact score significantly decreased the likelihood of obtaining remission at the end of treatment (OR = 0.96; 95% CI [0.92, 0.99]). Higher levels of dissociative symptoms partially mediated this prospective association. CONCLUSIONS: The impact of traumatic experiences, as opposed to the number of traumatic experiences experienced, negatively predicts remission after 6 months of CBT. These findings highlight the importance of addressing trauma and dissociative features in the CBT treatment of BED.


Assuntos
Transtorno da Compulsão Alimentar/psicologia , Transtorno da Compulsão Alimentar/terapia , Terapia Cognitivo-Comportamental , Transtornos Dissociativos/psicologia , Trauma Psicológico/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psicoterapia de Grupo , Autorrelato , Resultado do Tratamento
11.
J Neurotrauma ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38308472

RESUMO

In previous studies, the incidence of traumatic intracranial aneurysms (TICAs) after civilian gunshot wound to the head (cGSWH) was ∼3%. Given the use of delayed vessel imaging, we hypothesize that a significant fraction of TICAs is missed on initial non-contrasted scans. This study was designed to characterize acute TICAs using admission computed tomographic angiography (aCTA) in cGSWH. Over the period from 2017 to 2022, 341 patients were admitted to R. Adams Cowley Shock Trauma Center with cGSWH; 136 subjects had aCTA ∼3 (standard deviation [SD] 3.5) h post-injury. Demographics, clinical findings, imaging techniques, endovascular/surgical interventions, and outcomes were analyzed. Mean age was 34.7 (SD 13.1), male:female ratio was 120:16. Average admission Glasgow Coma Scale (GCS) score was 6 (SD 3.9). Entry site was frontal in 41, temporal in 55, parietal in 18, occipital in 6, suboccipital in 9, temporo-parietal in 1, and frontobasal-temporal in 6. Projectiles crossed multiple dural compartments in 76 (55%) patients. 35 TICAs were diagnosed in 28 subject: 24 were located along the middle cerebral artery (MCA), 6 in the anterior cerebral artery (ACA), 3 in the internal carotid artery (ICA), 1 in the posterior cerebral artery (PCA), and 1 in the middle meningeal artery (MMA). Eleven TICAs resolved spontaneously in nine patients. Eight aneurysms were treated by endovascular means, two via combined endovascular/open approaches. Forty-nine patients died, 10 of whom had 15 TICAs. Eighty patients developed intracerebral hematoma s (ICHs). Regression models showed that the presence of an ICH was the main predictor of TICA in cGSWH. Larger ICHs (average 22.3 cc vs. 9.4 cc in patients with and without aneurysms, respectively) in patients with cGSWH suggest hidden TICAs. Nearly 30% of patients had spontaneous resolution within 1 week. When CTA was performed acutely, TICAs were 10 times more frequent in cGSWH than in previous literature, and those patients were more likely to proceed to surgery. Almost one third of patients in this series died from the devastating effects of cGSWH.

12.
World Neurosurg ; 182: e611-e623, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38061544

RESUMO

OBJECTIVE: External ventricular drain (EVD) placement is a common neurosurgical procedure that can be performed at bedside. A frequent complication following EVD placement is catheter-associated hemorrhage (CAH). The hemorrhage itself is rarely clinically significant but may be complicated in patients taking anticoagulant or antiplatelet (AC/AP) medications. METHODS: A total of 757 patients were who underwent EVD placement at bedside were included as part of a retrospective study at a large academic medical center. Demographic factors, use of AC/AP therapies, and several other clinical variables were recorded and assessed in univariate and multivariate regression analysis for association with CAH and mortality. RESULTS: One hundred (13.2%) patients experienced CAH within 24 hours of the procedure. After univariate analysis, in 2 tandem-run multivariate regression analyses after stepwise variable selection, use of 2 or more AC/AP agents (odds ratio [OR] = 2.362, P = 0.020) and dual antiplatelet therapy with aspirin and clopidogrel (OR = 3.72, P = 0.009) were significantly associated with CAH. Use of noncoated catheters was a protective factor against CAH compared to use of antibiotic-coated catheters (OR = 0.55, P = 0.019). Multivariate analysis showed age, multiagent therapy, and thrombocytopenia were significantly associated with increased mortality. CONCLUSIONS: There was increased risk of CAH after EVD placement in patients taking more than one AC/AP agent regardless of presenting pathology. In particular, use of aspirin and clopidogrel combined was associated with significantly higher odds of CAH, although it was not associated with higher mortality. In addition, there appears to be an association between use of antibiotic-coated catheters and CAH across univariate and multivariate analysis.


Assuntos
Anticoagulantes , Inibidores da Agregação Plaquetária , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Anticoagulantes/efeitos adversos , Estudos Retrospectivos , Clopidogrel , Neurocirurgiões , Drenagem/efeitos adversos , Drenagem/métodos , Hemorragia/etiologia , Aspirina , Catéteres/efeitos adversos , Ventriculostomia/efeitos adversos , Antibacterianos/uso terapêutico
13.
Brain Sci ; 14(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38539619

RESUMO

In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling.

14.
Eur J Psychotraumatol ; 15(1): 2355828, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828909

RESUMO

Background: Scalable psychological interventions such as the WHO's Self-Help Plus (SH+) have been developed for clinical and non-clinical populations in need of psychological support. SH+ has been successfully implemented to prevent common mental disorders among asylum seekers and refugees who are growing in number due to increasing levels of forced migration. These populations are often exposed to multiple, severe sources of traumatisation, and evidence of the effect of such events on treatment is insufficient, especially for non-clinical populations.Objective: We aim to study the effect of potentially traumatic experiences (PTEs) and the mediating role of symptoms of posttraumatic stress disorder (PTSD) on the improvement following SH+.Method: Participants allocated to SH+ who received at least three sessions (N = 345) were extracted from two large, randomised, European prevention trials involving asylum seekers and refugees. Measures of distress, depression, functional impairment, and post-traumatic stress symptoms were administered at baseline and 6 months post-intervention, together with measures of well-being and quality of life. Adjusted models were constructed to examine the effect of PTEs on post-intervention improvement. The possible mediating role of PTSD symptoms in this relationship was then tested.Results: Increasing numbers of PTEs decreased the beneficial effect of SH+ for all measures. This relationship was mediated by symptoms of PTSD when analysing measures of well-being and quality of life. However, this did not apply for measures of mental health problems.Conclusions: Exposure to PTEs may largely reduce benefits from SH+. PTSD symptomatology plays a specific, mediating role on psychological well-being and quality of life of participants who experienced PTE. Healthcare professionals and researchers should consider the role of PTEs and PTSD symptoms in the treatment of migrants and refugees and explore possible feasible add-on solutions for cases exposed to multiple PTEs.


Increasing numbers of potentially traumatic experiences can decrease the beneficial effect of a manualized group psychotherapeutic intervention in migrants and refugees across multiple countries.In absence of a full threshold diagnosis of post-traumatic stress disorder, post-traumatic stress symptoms still mediate the relation between potentially traumatic experiences and some outcome improvements at follow-up.While the moderating role of number of potentially traumatic experiences applies to all outcomes (depression symptoms, psychological distress, functional impairment, well-being, and quality of life), the mediating role of post-traumatic stress symptoms in this relation only applies to well-being and quality of life.


Assuntos
Refugiados , Transtornos de Estresse Pós-Traumáticos , Humanos , Refugiados/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/psicologia , Masculino , Feminino , Adulto , Intervenção Psicossocial , Qualidade de Vida/psicologia
15.
Front Neurol ; 14: 1092205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37034077

RESUMO

Introduction: The movement of fluids and solutes across the ependymal barrier, and their changes in physiologic and disease states are poorly understood. This gap in knowledge contributes strongly to treatment failures and complications in various neurological disorders. Methods: We systematically searched and reviewed original research articles treating ependymal intercellular junctions on PubMed. Reviews, opinion papers, and abstracts were excluded. Research conducted on tissue samples, cell lines, CSF, and animal models was considered. Results: A total of 45 novel articles treating tight, adherens and gap junctions of the ependyma were included in our review, spanning from 1960 to 2022. The findings of this review point toward a central and not yet fully characterized role of the ependymal lining ultrastructure in fluid flow interactions in the brain. In particular, tight junctions circumferentially line the apical equator of ependymal cells, changing between embryonal and adult life in several rodent models, shaping fluid and solute transit in this location. Further, adherens and gap junctions appear to have a pivotal role in several forms of congenital hydrocephalus. Conclusions: These findings may provide an opportunity for medical management of CSF disorders, potentially allowing for tuning of CSF secretion and absorption. Beyond hydrocephalus, stroke, trauma, this information has relevance for metabolite clearance and drug delivery, with potential to affect many patients with a variety of neurological disorders. This critical look at intercellular junctions in ependyma and the surrounding interstitial spaces is meant to inspire future research on a central and rather unknown component of the CSF-brain interface.

16.
Front Public Health ; 11: 1215617, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37655280

RESUMO

Background: The identification of interventions for rehabilitation and related evidence is a crucial step in the development of World Health Organization's (WHO) Package of Interventions for Rehabilitation (PIR). Interventions for rehabilitation may be particularly relevant in schizophrenia, as this condition is associated with a high risk of disability, poor functioning, and lack of autonomy. Aiming to collect evidence for the WHO PIR, we conducted a systematic review of Clinical Practice Guidelines (CPG) on interventions for rehabilitation of schizophrenia. Methods: Methods for the systematic identification and critical appraisal of CPG were developed by WHO Rehabilitation Programme and Cochrane Rehabilitation under the guidance of WHO's guideline review committee secretariat. The Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II) was used to evaluate the methodological quality of identified CPG. Results: After full text screening, nine CPG were identified, for a total of 130 recommendations. Three were excluded because their total AGREE-II scores were below cut-off. Six CPG were approved by the Technical Working Group and included for data extraction. Only one CPG with specific focus on rehabilitation of schizophrenia was retrieved. Other CPG were general, including some recommendations on rehabilitation. Some CPG gave no indications on the assessment of rehabilitation needs. Discrepancies were detectable, with different CPG emphasizing different domains. Most recommendations addressed "symptoms of schizophrenia," while "community and social life" was targeted by few recommendations. International CPG were often conceptualized for high-income countries, and CPG accounting for their implementation in lower income contexts were scarce. Quality of evidence was high/moderate for 41.54% (n = 54) of the recommendations, and very low only in two cases (1.52%). N = 45 (34.62%) were based on experts' opinion. Conclusions: The concepts of recovery and rehabilitation in schizophrenia are relatively new in medical sciences and somewhat ill-defined. An unbalanced distribution in the domains addressed by available CPG is therefore understandable. However, the need for more focus in some areas of rehabilitation is obvious. More clarity is also required regarding which interventions should be prioritized and which are more feasible for global implementation in the rehabilitation of schizophrenia.


Assuntos
Esquizofrenia , Humanos , Renda , Organização Mundial da Saúde
17.
Neurosurgery ; 93(6): 1346-1352, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37530524

RESUMO

BACKGROUND AND OBJECTIVES: Intracranial meningiomas are a diverse group of tumors, which vary by grade, genetic composition, location, and vasculature. Expanding the understanding of the supply of skull base (SBMs) and non-skull base meningiomas (NSBMs) will serve to further inform resection strategies. We sought to delineate the vascular supply of a series of intracranial meningiomas by tumor location. METHODS: A retrospective study of intracranial meningiomas that were studied using preoperative digital subtraction angiograms before surgical resection at a tertiary referral center was performed. Patient, tumor, radiologic, and treatment data were collected, and regression models were developed. RESULTS: One hundred sixty-five patients met inclusion criteria. The mean age was 57.1 years (SD: 12.6). The mean tumor diameter was 4.9 cm (SD: 1.5). One hundred twenty-six were World Health Organization Grade I, 37 Grade II, and 2 Grade III. Arterial feeders were tabulated by Al-Mefty's anatomic designations. SBMs were more likely to derive arterial supply from the anterior circulation, whereas NSBMs were supplied by external carotid branches. NSBMs were larger (5.61 cm vs 4.45 cm, P = <.001), were more often presented with seizure (20% vs 8%, P = .03), were higher grade ( P = <.001) had more frequent peritumoral brain edema (84.6% vs 66%, P = .04), and had more bilateral feeders (47.7% vs 28%, P = .01) compared with SBMs. More arterial feeders were significantly associated with lower tumor grade ( P = .023, OR = 0.59). Higher tumor grade (Grade II/III) was associated with fewer arterial feeders ( P = .017, RR = 0.74). CONCLUSION: Meningioma location is associated with specific vascular supply patterns, grade, and patient outcomes. This information suggests that grade I tumors, especially larger tumors, are more likely to have diverse vascular supply patterns, including internal carotid branches. This study may inform preoperative embolization and surgical considerations, particularly for large skull base tumors.


Assuntos
Neoplasias Meníngeas , Meningioma , Neoplasias da Base do Crânio , Humanos , Pessoa de Meia-Idade , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Meningioma/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Neoplasias Meníngeas/patologia , Estudos Retrospectivos , Base do Crânio/diagnóstico por imagem , Base do Crânio/patologia , Neoplasias da Base do Crânio/diagnóstico por imagem , Neoplasias da Base do Crânio/cirurgia , Neoplasias da Base do Crânio/patologia
18.
Front Public Health ; 11: 1100546, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761135

RESUMO

Introduction: Migrant populations, including workers, undocumented migrants, asylum seekers, refugees, internationally displaced persons, and other populations on the move, are exposed to a variety of stressors and potentially traumatic events before, during, and after the migration process. In recent years, the COVID-19 pandemic has represented an additional stressor, especially for migrants on the move. As a consequence, migration may increase vulnerability of individuals toward a worsening of subjective wellbeing, quality of life, and mental health, which, in turn, may increase the risk of developing mental health conditions. Against this background, we designed a stepped-care programme consisting of two scalable psychological interventions developed by the World Health Organization and locally adapted for migrant populations. The effectiveness and cost-effectiveness of this stepped-care programme will be assessed in terms of mental health outcomes, resilience, wellbeing, and costs to healthcare systems. Methods and analysis: We present the study protocol for a pragmatic randomized study with a parallel-group design that will enroll participants with a migrant background and elevated level of psychological distress. Participants will be randomized to care as usual only or to care a usual plus a guided self-help stress management guide (Doing What Matters in Times of Stress, DWM) and a five-session cognitive behavioral intervention (Problem Management Plus, PM+). Participants will self-report all measures at baseline before random allocation, 2 weeks after DWM delivery, 1 week after PM+ delivery and 2 months after PM+ delivery. All participants will receive a single-session of a support intervention, namely Psychological First Aid. We will include 212 participants. An intention-to-treat analysis using linear mixed models will be conducted to explore the programme's effect on anxiety and depression symptoms, as measured by the Patient Health Questionnaire-Anxiety and Depression Scale summary score 2 months after PM+ delivery. Secondary outcomes include post-traumatic stress disorder symptoms, resilience, quality of life, resource utilization, cost, and cost-effectiveness. Discussion: This study is the first randomized controlled trial that combines two World Health Organization psychological interventions tailored for migrant populations with an elevated level of psychological distress. The present study will make available DWM/PM+ packages adapted for remote delivery following a task-shifting approach, and will generate evidence to inform policy responses based on a more efficient use of resources for improving resilience, wellbeing and mental health. Clinical trial registration: ClinicalTrials.gov, identifier: NCT04993534.


Assuntos
COVID-19 , Migrantes , Humanos , Intervenção Psicossocial , Pandemias , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Eur J Pharm Biopharm ; 170: 179-186, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34968646

RESUMO

Glioblastomas have been historically difficult to treat with poor long-term survival. With novel strategies focused on targeting hypoxia-inducible factor (HIF) regulatory pathways, recent evidence has shown that Acriflavine (ACF) can effectively target glioma invasiveness and recurrence. However, local delivery of ACF and its combinatory effects with Temozolomide (TMZ) and radiation therapy (XRT) have not yet been optimized. In this study we test a novel polymeric matrix that can gradually release ACF at the tumor bed site in combination with systemic TMZ and XRT. In vitro cytotoxicity assays of ACF in combination with TMZ and XRT were performed on rodent and human cell lines with CCK-8 and flow cytometry. In vitro drug release was measured and intracranial safety was assessed in tumor-free animals. Finally, efficacy was assessed in an intracranial gliosarcoma model and combination therapy with TMZ and XRT evaluated. Combination therapy of ACF, TMZ, and XRT was able to reduce cell viability and induce apoptosis in glioma cells. In vitro and in vivo release of ACF was measured in benchtop and animal models. Efficacy was established in an in vivo gliosarcoma model in which intracranial ACF (p < 0.01) significantly improved median survival and the combination therapy of ACF, TMZ and XRT (p < 0.01) significantly improved median survival and led to long-term survival (LTS). We provide evidence that ACF, combined with TMZ and XRT, led to LTS in an intracranial model of rat gliosarcoma. These findings, in combination with the use of a novel polymeric matrix that allows more gradual drug delivery, constitute a first step in the translation of this novel strategy to human use.


Assuntos
Acriflavina/administração & dosagem , Neoplasias Encefálicas/terapia , Implantes de Medicamento , Glioma/terapia , Dosagem Radioterapêutica , Temozolomida/administração & dosagem , Implantes Absorvíveis , Acriflavina/farmacologia , Animais , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Terapia Combinada , Polímeros/química , Ratos , Ratos Endogâmicos F344 , Taxa de Sobrevida , Temozolomida/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Artigo em Inglês | MEDLINE | ID: mdl-35886306

RESUMO

Background: Coronavirus disease (COVID-19) hospitalization has been related to Post-Traumatic Stress Disorder (PTSD). Available information is limited by insufficient follow-up and lack of longitudinal studies. Baseline factors (e.g., sex; obesity) have been related to PTSD, but post-hospitalization factors have not been studied. Objective: This study aimed to analyse prevalence, baseline, post-discharge factors and possible clinical courses of PTSD after hospitalization for COVID-19. Method: 109 patients (94.7% of the original sample) completed a programme of three follow-up telephone assessments during the year following hospitalization. Data included clinical and sociodemographic factors as well as psychometric tools assessing PTSD, social support, and perception of threat to life (PTL). Mixture model analysis was performed to study the longitudinal course of PTSD symptoms. Chronic (>6 months) PTSD predictors were also analysed. Results: 1-year PTSD period prevalence was 23.9%, peaking at six months; 11% of the patients suffered chronic PTSD. Pre- and post-hospitalization factors influenced the onset and course of PTSD over time. These included working status, PTL, and lack of social support. Interestingly, obesity, pulmonary diseases and family cluster infection seem specifically related to PTSD following COVID-19. Inversely, clinical interventions, older age and male gender were protective. Conclusions: PTSD following COVID-19 hospitalization is common. The analysed demographic, social, clinical, and psychological factors predict PTSD symptomatology over time and can modify odds of a chronic course. Clinicians could better identify cases at risk of a chronic PTSD course. Finally, treatment as usual appeared related to a better outcome and should be proposed to patients with PTSD.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , Assistência ao Convalescente , COVID-19/epidemiologia , Hospitalização , Humanos , Masculino , Obesidade , Alta do Paciente , Transtornos de Estresse Pós-Traumáticos/psicologia
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