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BACKGROUND: Allergy to lipid transfer proteins (LPT) is common in Mediterranean Europe, and it causes severe reactions in patients and affects multiple foods, impairing the quality of life. OBJECTIVE: This study aimed to describe the clinical and sensitization profile of patients with LTP syndrome and to determine a clinical pattern of severity. Molecular diagnosis is shown in a broad population through microarrays. MATERIAL AND METHODS: This study was performed at the LTP Allergy Consultation of the Reina Sofia Hospital in Murcia, Spain. We analyzed the patients' characteristics, reactions, cofactors, food implicated, quality of life, skin prick test to food and aeroallergens, and serologic parameters, such as total immunoglobulin E, peach LTP (Pru p 3 IgE) and immunoglobulin G4, and microarray Immuno Solid-phase Allergen Chip (ISAC). We related the severity of the reactions with other variables. RESULTS: We presented a series of 236 patients diagnosed with LTP allergy, 54.66% suffering from anaphylaxis, 36.02% from urticaria angioedema, and 9.32% from oral allergy syndrome. The most frequently implicated food was peach, producing symptoms in 70% of patients, followed by walnut in 55%, peanut in 45%, hazelnut in 44%, and apple in 38% patients. Regarding the food that provoked anaphylaxis, walnut was the most frequent instigator, along with peach, peanut, hazelnut, almond, sunflower seed, and apple. According to the severity of LPT reaction, we did not discover significant differences in gender, age, food group involved, and serologic parameters. We found differences in the presence of cofactors, with 48.84% of cofactors in patients with anaphylaxis, compared to 27.1% in patients without anaphylaxis and in family allergy background (P < 0.0001). CONCLUSION: In our series of patients, 54% presented anaphylaxis, and the foods that most frequently produced symptoms were peaches, apples, and nuts. Cofactors and family allergy backgrounds were associated with the severity of LPT reaction.
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Alérgenos , Antígenos de Plantas , Hipersensibilidade Alimentar , Imunoglobulina E , Testes Cutâneos , Humanos , Masculino , Feminino , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Adulto , Pessoa de Meia-Idade , Antígenos de Plantas/imunologia , Alérgenos/imunologia , Espanha/epidemiologia , Adolescente , Proteínas de Plantas/imunologia , Adulto Jovem , Proteínas de Transporte/imunologia , Criança , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Idoso , Qualidade de Vida , Anafilaxia/imunologia , Anafilaxia/diagnóstico , Anafilaxia/etiologia , Pré-EscolarRESUMO
BACKGROUND: Patient heterogeneity poses significant challenges for managing individuals and designing clinical trials, especially in complex diseases. Existing classifications rely on outcome-predicting scores, potentially overlooking crucial elements contributing to heterogeneity without necessarily impacting prognosis. METHODS: To address patient heterogeneity, we developed ClustALL, a computational pipeline that simultaneously faces diverse clinical data challenges like mixed types, missing values, and collinearity. ClustALL enables the unsupervised identification of patient stratifications while filtering for stratifications that are robust against minor variations in the population (population-based) and against limited adjustments in the algorithm's parameters (parameter-based). RESULTS: Applied to a European cohort of patients with acutely decompensated cirrhosis (n = 766), ClustALL identified five robust stratifications, using only data at hospital admission. All stratifications included markers of impaired liver function and number of organ dysfunction or failure, and most included precipitating events. When focusing on one of these stratifications, patients were categorized into three clusters characterized by typical clinical features; notably, the 3-cluster stratification showed a prognostic value. Re-assessment of patient stratification during follow-up delineated patients' outcomes, with further improvement of the prognostic value of the stratification. We validated these findings in an independent prospective multicentre cohort of patients from Latin America (n = 580). CONCLUSIONS: By applying ClustALL to patients with acutely decompensated cirrhosis, we identified three patient clusters. Following these clusters over time offers insights that could guide future clinical trial design. ClustALL is a novel and robust stratification method capable of addressing the multiple challenges of patient stratification in most complex diseases.
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Cirrose Hepática , Humanos , Masculino , Feminino , Análise por Conglomerados , Pessoa de Meia-Idade , Prognóstico , Doença Aguda , Algoritmos , Idoso , Estudos de CoortesRESUMO
Introduction: Digital health interventions, particularly mobile health platforms, have shown promise in supporting patients with respiratory conditions, but their application in pulmonary arterial hypertension (PAH) remains limited. We aimed to assess the feasibility, acceptability, and potential clinical benefit of the novel PAHcare™ digital platform as a patient-centred intervention for PAH management through a prospective, single-arm, multicenter pilot study conducted on 53 patients diagnosed with PAH who used the platform for 6 months. Methods: The primary objective was to assess the impact on Health-Related Quality of Life (HRQoL) through questionnaires. Secondary objectives included evaluating clinical outcomes, including disease progression, PAH signs and symptoms, the 6-min walking test, and the patient's symptom perception. Additionally, we assessed patient satisfaction and engagement with the PAHcare™ platform, interaction with health coaches, retention, costs and healthcare resource utilisation (HCRU), and safety through monitoring device incidents. Results: Minimal changes in HRQoL and clinical outcomes were observed over 6 months. A noteworthy 92.4% of patients actively used the platform in the first month, maintaining high usage throughout the study. Patient satisfaction was substantial, with more than half of the patients expressing excellence in service quality, willingness to reuse the platform, and fulfilment of their needs. Health coach interaction was high, with 76% of patients initiating contact within the first week. User retention rates were 70%, with prevalent ongoing usage and interaction with healthcare professionals even after the study. In terms of HCRU and costs, the study showed no significant changes in PAH-related hospital admissions, clinical visits, or tests. Finally, the low number of device-related incidents indicated platform safety. Conclusion: This pilot study provides compelling evidence supporting the feasibility and acceptability of the PAHcare™ digital platform to empower patients to manage their disease and significantly enhance their overall experience with PAH.
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Hipertensão Arterial Pulmonar , Humanos , Hipertensão Arterial Pulmonar/terapia , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Medidas de Resultados Relatados pelo PacienteRESUMO
Two severe cases of hemolytic anemia are described in different pediatric age groups, both linked to severe cobalamin deficiency from distinct causes. The first case refers to an exclusively breastfed infant with vitamin deficit secondary to maternal impaired absorption. Apart from the neurological deficits present at diagnosis, he also presented with infantile epileptic spasms syndrome a few months after treatment while having normal cobalamin serum levels. The second case refers to an adolescent with long-term inadequate intake. The occurrence of severe hemolytic anemia in cobalamin deficiency is exceptionally rare.
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Deficiência de Vitamina B 12 , Adolescente , Feminino , Humanos , Lactente , Masculino , Aleitamento Materno , Vitamina B 12 , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/diagnóstico , VitaminasRESUMO
Adrenoleukodystrophy, a rare genetic disease associated with the X chromosome (X-ALD - X-linked adrenoleukodystrophy), predominantly affects males and stems from mutations in the ABCD1 gene, responsible for transporting very long chain fatty acids (VLCFA) into peroxisomes. It leads to adrenal insufficiency (AI) and axonal demyelination. In males, the phenotype varies from isolated adrenocortical insufficiency and progressive myelopathy to cerebral adrenoleukodystrophy (CALD). The aim of this case series is to characterize patients with different clinical presentations of X-ALD with follow-up at a tertiary Portuguese hospital. All four patients were males, and the median age at the diagnosis was 5 years. Three patients were diagnosed through family screening, with the oldest already displaying hyperpigmentation. Two distinct forms were identified: adolescent CALD (25%) and isolated primary adrenal insufficiency (75%). Analytical studies revealed elevated plasma VLCFA levels in all cases, and genetic analysis demonstrated two different mutations in the ABCD1 gene. This disorder requires early diagnosis for improved prognosis. Screening male children with primary AIfor X-ALD using a VLCFA panel should be considered, particularly after ruling out the most common causes or when learning difficulties are evident. Genetic confirmation of the diagnosis is essential, enabling genetic counseling, family planning, and preimplantation genetic diagnosis.
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BACKGROUND: Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by the expansion of a noncoding triplet repeat. METHODS: A cross-sectional study was performed to characterize pediatric patients with DM1 followed in a tertiary hospital over the last 29 years, comparing the congenital and the childhood/juvenile-onset forms. RESULTS: Thirty-seven patients (59.5 % male) were included, with a median age at the latest assessment of 16.8 years and a median follow-up of 7.7 years. Eleven patients were lost to follow-up, and two died. Twenty-five had congenital DM1 (CDM1), and this form had significantly higher triplet repeat length, history of polyhydramnios, lower median age at diagnosis, and first and last assessment. Common symptoms included distal skeletal muscle weakness (75.7 %) and facial involvement (94.6 %), along with dysphonia/dysarthria (73.0 %) and myotonia (73.0 %). Delayed independent ambulation frequency was significantly higher for CDM1 cases. Skeletal deformities affected 54.1 %, with talipes equinovarus and scoliosis occurring exclusively in CDM1 patients. Cognitive deficit was present in 75.7 % of cases. Polysomnograms revealed seven cases of obstructive sleep apnea and two of hypoventilation. Noninvasive ventilation was used in nine cases, and three had recurrent respiratory infections. The cardiovascular system was affected in 21.6 % of cases. Gastrointestinal issues included constipation (24.3 %), feeding difficulties (16.2 %), and cholelithiasis (5.4 %). Cataracts, epilepsy, and diabetes mellitus were reported in two cases each. CONCLUSION: Our study highlights the diverse spectrum of severity and multiorgan involvement of DM1 in pediatric patients. It underscores the importance of establishing a pediatric-specific standard of care to enhance health outcomes through comprehensive multidisciplinary management.
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Disfunção Cognitiva , Distrofia Miotônica , Gravidez , Feminino , Humanos , Criança , Masculino , Distrofia Miotônica/complicações , Distrofia Miotônica/epidemiologia , Distrofia Miotônica/diagnóstico , Estudos Transversais , Hospitais Pediátricos , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Glycogen storage disease type V (GSDV) is an autosomal recessive metabolic condition caused by pathogenic PYGM variants. This is an underdiagnosed condition as it presents with exercise intolerance in children. We reviewed the GSDV cases of a tertiary hospital center to assess diagnostic timing/accuracy, as well as potential clinical/analytical predictors of such factors. METHODS: We retrospectively reviewed all GSDV cases with follow-up in both Pediatric and Adult Metabolic Diseases consultations. We included 28 cases and assessed their hospital record for clinical information. RESULTS: Over 90% of our cases had late diagnoses, with more than 50% being diagnosed in adulthood despite symptom onset in preschool (very late diagnosis). Diagnostic age was lower in patients exhibiting myoglobinuria. Interestingly, patients with a positive family history of GSDV had similar rates of very late diagnoses, likely since the index case was already detected very late in life. Finally, we observe that the R50* variant is associated with increased myoglobinuria and CK elevation, in a dosage-dependent manner. CONCLUSION: We concluded that GSDV is severely underdiagnosed, and that some clinical and analytical aspects of the condition can be more indicative of this diagnosis. Furthermore, we propose for the first time a genotype-phenotype correlation in GSDV. IMPACT: GSDV is a pediatric-onset metabolic disorder that is mostly diagnosed late in the adult age and commonly misdiagnosed. We observed the first genotype-phenotype correlation in GSDV, regarding the common R50* variant. Awareness of GSDV for pediatricians and the overall medical community is vital.
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Purpose: the aim of this paper is to analyze the evolution of understanding of hybrid telework, especially after the boom experienced in the global pandemic of COVID-19, which has given rise to new ways of working. Design: /methodology/approach: in this study, bibliometrics and scientific mapping were used to analyze the conceptual structure of hybrid telework based on 104 documents extracted from the Web of Science (WoS) database. Thanks to the co-word analysis performed with SciMAT, the main themes were mapped, and the evolution, importance and relevance of terms related to hybrid telework were identified. Findings: the body of research literature about hybrid telework is underdeveloped even though it is the most valued option of telework, both by organizations and employees. There is a lack of published studies in the public sphere and in such relevant fields as occupational health. Practical implications: this study is the first bibliometric analysis conducted for hybrid telework and demonstrates how hybrid telework is key for organizations to manage the emerging challenges in this field: new preferences from employment candidates, occupational health, etc, and how important it is to have a proper management of hybrid telework in organizations. Originality/value: this study explores in detail the evolution of hybrid telework, an underexplored telework modality, given its growth as a mode of work as a consequence of the COVID-19 pandemic. It reveals critical points, dilemmas, paradoxes, and research gaps.
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Acute fulminant cerebral edema (AFCE) is a recently identified encephalitis type associated with significant morbimortality. Described as rare, limited data exists on its early detection and treatment. This paper describes a case of AFCE that progressed to unresponsive intracranial hypertension. A previously healthy four-year-old boy presented with fever, myalgias, and neurological symptoms. Diagnostic assessments showed cerebrospinal fluid abnormalities, and despite medical interventions, his condition deteriorated rapidly and developed severe cerebral edema and herniation within 24 hours. A decompressive craniectomy was attempted to decrease intracranial pressure, without success. This case emphasizes the urgency of early AFCE recognition and effective management strategies given its severe prognosis, aiming to improve understanding and spur further research.
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Introduction - Glycogen storage disease type V (GSDV, MIM #232600) is an autosomal recessive metabolic myopathy caused by pathogenic variants in the PYGM gene. The characteristic symptoms of exercise intolerance, myalgia, and cramps, which improve after a few minutes of rest, are frequently unrecognized in affected children. When there is clinical suspicion, the initial approach with a forearm exercise test has diagnostic value by detecting low post-exercise plasma lactate-to-ammonia ratio values. The diagnostic algorithm is followed by genetic testing if the results suggest myophosphorylase deficiency. Methods - This was a retrospective observational study conducted based on reviewing medical records of patients with GSDV in a tertiary hospital. We assessed demographic variables, including the timing of onset and diagnosis, relevant clinical characteristics, and whether genetic testing was performed, including its results. Results/Case Report - Our goal was to review the GSDV cases in our center to assess our cohort's diagnostic timing and clinical and genetic characteristics. We identified 28 patients from 24 families, three with consanguinity. The mean age at the time of the study was 43 years. While most (26/28; 93%) recalled their first symptoms in childhood/adolescence, only 25% (7/28) were diagnosed then. All patients had exercise intolerance and CK elevation, while about half reported the second wind phenomenon. Genetic testing was performed in 22 patients, revealing biallelic PYGM variants (9 homozygous, 13 compound heterozygous) as the most common (p.R50*). Conclusion - GSDV is rare and presents in the pediatric age, with subtle manifestations often underestimated for decades. A late diagnosis may negatively impact the psychosocial development of affected children. It is essential to recognize some unique features that facilitate diagnosis: history of exercise intolerance, the second wind sign, and high resting serum CK levels. Identifying the disease-causing variants in PYGM is currently the gold standard for diagnosis as it is less invasive than performing a muscle biopsy, and may promptly diagnose the condition and avoid wrongful labelling of patients.
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Reading acquisition is a complex process that can be predicted by several components which, in turn, can be affected by the orthography depth. This study aims to explore the early predictors of (un)success in reading acquisition within an intermediate transparent orthography. At the beginning of the school year, 119 European Portuguese-speaking first graders were assessed regarding (i) sociodemographic variables: mothers' education and socioeconomic status (SES); (ii) cognitive variables: phonological working memory and vocabulary; (iii) reading-related variables: letter-sound knowledge, phonemic awareness, and rapid naming. Results of the three variable clusters were correlated with the final classification obtained in the Portuguese discipline. Specifically, there was a correlation between the Portuguese discipline classification with all reading and cognitive-related variables, with the highest correlations occurring with mother education and letter spelling. A regression analysis was conducted to assess the predictor impact of mother education and letter spelling (variables that correlated stronger with the Portuguese classification) on Portuguese classifications. Letter spelling was the sole significant predictor of the Portuguese classification. Based on these results, a path analysis was run to test whether letter spelling is a mediator of the relationship between the mother's education and the Portuguese classification. The results of the model test yielded a reasonable fit, indicating a relationship between the mother's education and letter spelling, which in turn, relates to the Portuguese classification. The identification of reading predictors in an intermediate-depth orthography such as European Portuguese contributes to more accurate identification of at-risk children.
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The advance and stability of replication forks rely on a tight co-regulation of DNA synthesis and nucleosome assembly. We show that mutants affected in parental histone recycling are impaired in the recombinational repair of the single-stranded DNA gaps generated in response to DNA adducts that hamper replication, which are then filled in by translesion synthesis. These recombination defects are in part due to an excess of parental nucleosomes at the invaded strand that destabilizes the sister chromatid junction formed after strand invasion through a Srs2-dependent mechanism. In addition, we show that a dCas9∗/R-loop is more recombinogenic when the dCas9∗/DNA-RNA hybrid interferes with the lagging than with the leading strand, and this recombination is particularly sensitive to problems in the deposition of parental histones at the strand that contains the hindrance. Therefore, parental histone distribution and location of the replication obstacle at the lagging or leading strand regulate homologous recombination.
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Replicação do DNA , Histonas , Histonas/metabolismo , Recombinação Homóloga , Nucleossomos , Reparo do DNA , DNARESUMO
The diagnosis of early infantile epileptic encephalopathy (EIEE) remains challenging, and next-generation sequencing (NGS) techniques have played a key role in identifying genetic causes. Recent studies have shown an association between mutations in the CYFIP2 gene and EIEE, with 20 deleterious variants reported so far and a de novo mutational hotspot at codon 87. A male infant presented with seizures since the age of four months as well as significant developmental delay and microcephaly. The seizures were of different types, frequent and refractory to treatment, including different anticonvulsant drugs. Metabolic studies showed no significant changes. The initial electroencephalogram revealed bilateral paroxysmal activity with hemispherical diffusion. Brain MRI showed no pathological changes. Analysis of a whole exome sequencing (WES) based multigene panel for epilepsy disclosed a heterozygous CYFIP2 gene variant [c.258_266del; p.(Trp86_Ser88del)] established as de novo. We describe the case of an infant with EIEE due to a de novo heterozygous in-frame deletion of three amino acids in CYFIP2: c.258_266del; p.(Trp86_Ser88del). This in-frame deletion eliminates codon 87, a mutational hotspot associated with a particularly severe EIEE phenotype. All previous reports had missense variants with a presumably gain-of-function mechanism. The clinical picture of our patient is very similar to the ones with deleterious variants affecting codon 87 reported in the literature. Our case report is the first to describe a disease-causing in-frame deletion in CYFIP2 and reiterates a consistent genotype-phenotype correlation.
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BACKGROUND AND AIMS: Current prognostic scores of patients with acutely decompensated cirrhosis (AD), particularly those with acute-on-chronic liver failure (ACLF), underestimate the risk of mortality. This is probably because systemic inflammation (SI), the major driver of AD/ACLF, is not reflected in the scores. SI induces metabolic changes, which impair delivery of the necessary energy for the immune reaction. This investigation aimed to identify metabolites associated with short-term (28-day) death and to design metabolomic prognostic models. METHODS: Two prospective multicentre large cohorts from Europe for investigating ACLF and development of ACLF, CANONIC (discovery, n=831) and PREDICT (validation, n=851), were explored by untargeted serum metabolomics to identify and validate metabolites which could allow improved prognostic modelling. RESULTS: Three prognostic metabolites strongly associated with death were selected to build the models. 4-Hydroxy-3-methoxyphenylglycol sulfate is a norepinephrine derivative, which may be derived from the brainstem response to SI. Additionally, galacturonic acid and hexanoylcarnitine are associated with mitochondrial dysfunction. Model 1 included only these three prognostic metabolites and age. Model 2 was built around 4-hydroxy-3-methoxyphenylglycol sulfate, hexanoylcarnitine, bilirubin, international normalised ratio (INR) and age. In the discovery cohort, both models were more accurate in predicting death within 7, 14 and 28 days after admission compared with MELDNa score (C-index: 0.9267, 0.9002 and 0.8424, and 0.9369, 0.9206 and 0.8529, with model 1 and model 2, respectively). Similar results were found in the validation cohort (C-index: 0.940, 0.834 and 0.791, and 0.947, 0.857 and 0.810, with model 1 and model 2, respectively). Also, in ACLF, model 1 and model 2 outperformed MELDNa 7, 14 and 28 days after admission for prediction of mortality. CONCLUSIONS: Models including metabolites (CLIF-C MET) reflecting SI, mitochondrial dysfunction and sympathetic system activation are better predictors of short-term mortality than scores based only on organ dysfunction (eg, MELDNa), especially in patients with ACLF.
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Insuficiência Hepática Crônica Agudizada , Metoxi-Hidroxifenilglicol , Humanos , Prognóstico , Estudos Prospectivos , Cirrose Hepática/complicações , Inflamação/complicações , Metabolômica , MitocôndriasRESUMO
Cdc7 and its regulator Dbf4 (Dbf4-dependent kinase; DDK) form an essential complex due to its function in replication initiation, which is carried out by phosphorylating different residues at the helicase MCM during the G1/S transition. In response to replication stress, late origins are inhibited to prevent cell cycle progression until the problems are resolved. In yeast, this inhibition is partially achieved by attenuating DDK activity. In addition, evidence from yeast to human shows that Cdc7 is required for a successful DNA damage response by coordinating multiple processes dealing with replication stress (replication checkpoint, DNA damage tolerance and break-induced replication) through mechanisms that go beyond its role in origin activation. These studies reveal the importance of getting a better understanding of the spatiotemporal regulation of DDK. Here, we will discuss how DDK operates in these processes and its putative role in controlling the activity of replication and repair factors at specific nuclease-resistant nucleoprotein scaffolds.
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Proteínas Serina-Treonina Quinases , Proteínas de Saccharomyces cerevisiae , Humanos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Replicação do DNA , FosforilaçãoRESUMO
Posterior reversible encephalopathy syndrome (PRES) is a reversible clinical-radiographic abnormality. It is characterized by headache, altered consciousness, seizures, and visual disruption, in addition to characteristic white matter edema lesions in the parieto-occipital areas of the brain. Early detection and treatment are crucial to prevent irreversible damage. This paper presents the cases of three patients with PRES with concurrent diagnoses of glomerulonephritis, Guillain-Barré syndrome, and sickle cell disease. All patients experienced systemic hypertension, seizures, and altered consciousness. All patients were admitted to intensive care for decreased level of awareness or status epilepticus requiring invasive mechanical ventilation. Anticonvulsants and antihypertensive therapy were essential. No chronic complications were recorded.
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Introduction: Pulmonary arterial hypertension (PAH) is a rare, multifactorial, chronic condition that requires ongoing monitoring and assessment. PAHcare™ is a novel, patient-centered digital platform that provides software intended for use on patients' mobile phones (downloadable application) and web-based dashboards for use by physicians and health coaches (HC). We describe herein the protocol of a clinical study aimed at evaluating the clinical benefit and safety of PAHcare™ for the routine management of patients with PAH. Methods and analysis: In this prospective, single cohort, multicenter study, 50 patients with PAH will be recruited at six specialized PAH units from reference hospitals of the public Spanish healthcare system. The PAHcare™ digital health platform allows patients to log health and lifestyle information while also providing structured content for patient education, medication reminders, and behavioral and lifestyle coaching from a remote HC. Evaluation will be primarily focused on the impact of the platform use on the patient's health-related quality of life (HRQoL) via questionnaires completion through electronic patient-reported outcomes. Moreover, the analysis of the impact on the patient's functional status, signs and symptoms of PAH, patient costs and healthcare resource utilization, satisfaction, knowledge of the disease and its management, and adherence to and safety of the platform will be secondary outcomes. The clinical investigation started in July 2021 and is expected to end by September 2022. Discussion: The PAHcare™ platform is anticipated to provide direct benefits to healthcare professionals, patients, and caregivers. These include the simplification of the multidisciplinary approach needed to tailor routine PAH management, enhancement of the patient/healthcare professional interaction, patient's empowerment to become more actively involved in the management and treatment of the disease, and increase of the patient's and caregiver's knowledge on PAH.
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Hipertensão Arterial Pulmonar , Humanos , Hipertensão Arterial Pulmonar/terapia , Qualidade de Vida , Estudos Prospectivos , Doença Crônica , Pacientes , Estudos Multicêntricos como AssuntoRESUMO
PURPOSE OF REVIEW: To review the evidence about video game-based therapeutic intervention for people diagnosed with depressive disorders. RECENT FINDINGS: Psychotherapy has been proved to reduce depressive symptoms and is a key element in the treatment of depressive disorders. However, geographical, economical and stigmatized concerns are barriers to access to psychotherapy. New technologies and videos games can overcome some of these barriers by providing teleconferencing evidence-based therapy as time as they may offer an interactive entertainment. Overall, video game-based interventions were useful and effective in reducing symptoms of depressive disorders. Seven of the studies were published in the last 5 years, which reflects the increased research interest in video game-based interventions for depression. Overall, when adherence was reported, rates of acceptability and feasibility were high.
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Transtorno Depressivo , Jogos de Vídeo , Depressão/terapia , Transtorno Depressivo/terapia , Humanos , PsicoterapiaRESUMO
The role played by certain domestic species such as dogs as a translational model in comparative oncology shows great interest to develop new therapeutic strategies in brain tumors. Gliomas are a therapeutic challenge that represents the most common form of malignant primary brain tumors in humans and the second most common form in dogs. Gene-directed enzyme/prodrug therapy using adipose mesenchymal stem cells (Ad-MSCs) expressing the herpes simplex virus thymidine kinase (TK) has proven to be a promising alternative in glioblastoma therapy, through its capacity to migrate and home to the tumor and delivering local cytotoxicity avoiding other systemic administration. In this study, we demonstrate the possibility for canine Ad-MSCs (cAd-MSCs) to be genetically engineered efficiently with a lentiviral vector to express TK (TK-cAd-MSCs) and in combination with ganciclovir (GCV) prodrug demonstrated its potential antitumor efficacy in vitro and in vivo in a mice model with the human glioblastoma cell line U87. TK-cAd-MSCs maintained cell proliferation, karyotype stability, and MSCs phenotype. Genetic modification significantly affects its secretory profile, both the analyzed soluble factors and exosomes. TK-cAd-MSCs showed a high secretory profile of some active antitumor immune response cytokines and a threefold increase in the amount of secreted exosomes, with changes in their protein cargo. We also found that the prodrug protein is not released directly into the culture medium by TK-cAd-MSCs. We believe that our work provides new perspectives for glioblastoma gene therapy in dogs and a better understanding of this therapy in view of its possible implantation in humans.