RESUMO
Bromodomain and extra-terminal (BET) proteins are relevant chromatin adaptors involved in the transcriptional control of thousands of genes. Two tandem N-terminal bromodomains are essential for chromatin attachment through acetyl-histone recognition. Recently, the BET proteins members BRD2 and BRD4 were found to interact with the SARS-CoV-2 envelope (E) protein, raising the question of whether the interaction constitutes a virus hijacking mechanism for transcription alteration in the host cell. To shed light on this question, we have compared the transcriptome of cells overexpressing E with that of cells treated with the BET inhibitor JQ1. Notably, E overexpression leads to a strong upregulation of natural immunity- and interferon response-related genes. However, BET inhibition results in the downregulation of most of these genes, indicating that these two conditions, far from causing a significant overlap of the altered transcriptomes, course with quite different outputs. Concerning the interaction of E protein with BET members, and differing from previous reports indicating that it occurs through BET bromodomains, we find that it relies on SEED and SEED-like domains, BET regions rich in Ser, Asp, and Glu residues. By taking advantage of this specific interaction, we have been able to direct selective degradation of E protein through a PROTAC system involving a dTAG-SEED fusion, highlighting the possible therapeutic use of this peptide for targeted degradation of a viral essential protein.
Assuntos
Proteínas de Ciclo Celular , SARS-CoV-2 , Fatores de Transcrição , Triazóis , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Triazóis/farmacologia , Azepinas/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Domínios Proteicos , Transcrição Gênica/efeitos dos fármacos , COVID-19/virologia , COVID-19/metabolismo , Células HEK293 , Ligação Proteica , Proteínas que Contêm BromodomínioRESUMO
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a harmful persistence of self-imposed starvation resulting in significant weight loss. Research suggests that alterations in the nucleus accumbens (NAcc) and circulating endocannabinoids (eCBs), such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may contribute to increased severity and maladaptive behaviors in AN, warranting an examination of the interplay between central reward circuitry and eCBs. For this purpose, we assessed NAcc functional connectivity and circulating AEA and 2-AG concentrations in 18 individuals with AN and 18 healthy controls (HC) to test associations between circulating eCBs, NAcc functional connectivity, and AN severity, as defined by body mass index (BMI). Decreased connectivity was observed between the NAcc and the right insula (NAcc-insula; pFWE < 0.001) and the left supplementary motor area (NAcc-SMA; pFWE < 0.001) in the AN group compared to HC. Reduced NAcc-insula functional connectivity mediated the association between AEA concentrations and BMI in the AN group. However, in HC, NAcc-SMA functional connectivity had a mediating role between AEA concentrations and BMI. Although no significant differences in eCBs concentrations were observed between the groups, our findings provide insights into how the interaction between eCBs and NAcc functional connectivity influences AN severity. Altered NAcc-insula and NAcc-SMA connectivity in AN may impair the integration of interoceptive, somatosensory, and motor planning information related to reward stimuli. Furthermore, the distinct associations between eCBs concentrations and NAcc functional connectivity in AN and HC could have clinical implications for weight maintenance, with eCBs being a potential target for AN treatment.
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Anorexia Nervosa , Núcleo Accumbens , Humanos , Endocanabinoides , Imageamento por Ressonância Magnética , RecompensaRESUMO
There is increasing recognition that respiratory viral infections such as influenza, respiratory syncytial virus, parainfluenza virus, adenovirus, and SARS-CoV-2 can promote the development of invasive fungal pulmonary coinfections, particularly invasive aspergillosis, both in immunocompetent and immunocompromised patients. To date, there are no case reports exploring the role of human metapneumovirus as a risk factor for fungal coinfection. Below, we describe the case of a 63-year-old woman who received a kidney transplant and developed invasive pulmonary aspergillosis after a human metapneumovirus infection and discuss the possible phenomena that could favor this association.
Assuntos
Aspergilose Pulmonar Invasiva , Metapneumovirus , Transplante de Órgãos , Infecções por Paramyxoviridae , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Feminino , Humanos , Pessoa de Meia-Idade , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , TransplantadosRESUMO
Histoplasmosis is an expected endemic mycosis in solid organ transplant recipients and occurs as a primary infection, reactivation, or, rarely, acquired from an infected allograft. Reactivation is favored by maintenance immunosuppression or anti-rejection therapy, which facilitates the appearance of disseminated forms as well as unusual presentations. We present the case of a 66-year-old woman with isolated tenosynovitis due to Histoplasma capsulatum 25 years after a kidney transplant.
Assuntos
Histoplasma , Histoplasmose , Transplante de Rim , Tenossinovite , Humanos , Transplante de Rim/efeitos adversos , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Histoplasmose/microbiologia , Histoplasma/isolamento & purificação , Feminino , Idoso , Tenossinovite/microbiologia , Tenossinovite/tratamento farmacológico , Antifúngicos/uso terapêutico , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , TransplantadosRESUMO
Climate change has intensified the effects of habitat fragmentation in many ecosystems, particularly exacerbated in riparian habitats. Therefore, there is an urgent need to identify keystone connectivity spots to ensure long-term conservation and sustainable management of riparian systems as they play a crucial role for landscape connectivity. This paper aims to identify critical areas for connectivity under two contrasting climate change scenarios (RCP 4.5 and RCP 8.5 models) for the years 2030, 2050 and 2100 and to group these critical areas by similar connectivity in keystone spots for sustainable management. A set of analyses comprising climate analysis, drainage network analysis, configuration of potential riparian habitats, riparian habitat connectivity, data clustering, and statistical analysis within a Spanish river basin (NW Spain) were applied. The node and link connectivity would be reduced under the two climate change scenarios (≈2.5 % and 4.4 % reduction, respectively), intensifying riparian habitat fragmentation. Furthermore, 51 different clusters (critical areas) were obtained and classified in five classes (keystone spots) with similar connectivity across the different scenarios of climate change. Each keystone spot obtained by hierarchical classification was associated with one or more climate scenarios. One of these keystone spots was especially susceptible to the worst climate change scenario. Key riparian connectivity spots will be crucial for the management and restoration of highly threatened riparian systems and to ensure long-term biodiversity conservation.
Assuntos
Mudança Climática , Ecossistema , Biodiversidade , Rios , Espanha , Conservação dos Recursos NaturaisRESUMO
Cancer is one of the leading causes of death worldwide, with breast cancer being the second cause of cancer-related mortality among women. Natural Products (NPs) are one of the main sources for drug discovery. During a screening campaign focused on the identification of extracts from Fundación MEDINA's library inhibiting the proliferation of cancer cell lines, a significant bioactivity was observed in extracts from cultures of the fungus Angustimassarina populi CF-097565. Bioassay-guided fractionation of this extract led to the identification and isolation of herbarin (1), 1-hydroxydehydroherbarin (4) plus other three naphthoquinone derivatives of which 3 and 5 are new natural products and 2 is herein described from a natural source for the first time. Four of these compounds (1, 3, 4 and 5) confirmed a specific cytotoxic effect against the human breast cancer cell line MCF-7. To evaluate the therapeutic potential of the compounds isolated, their efficacy was validated in 3D cultures, a cancer model of higher functionality. Additionally, an in-depth study was carried out to test the effect of the compounds in terms of cell mortality, sphere disaggregation, shrinkage, and morphology. The cell profile of the compounds was also compared to that of known cytotoxic compounds with the aim to distinguish the drug mode of action (MoA). The profiles of 1, 3 and 4 showed more biosimilarity between them, different to 5, and even more different to other known cytotoxic agents, suggesting an alternative MoA responsible for their cytotoxicity in 3D cultures.
Assuntos
Ascomicetos , Medicamentos Biossimilares , Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , BioensaioRESUMO
OBJECTIVES: To validate and test the reliability of the 10-Item Unilateral Vocal Fold Paralysis-Voice Handicap Index (UVFP-HI-10) quality of life (QoL) questionnaire for patients with UVFP. DESIGN: Prospective describe study based on perceptive surveys. PARTICIPANTS: We recruited 61 patients with UVFP and 53 healthy individuals comprised the control group. MAIN OUTCOME MEASURES: Both the patients and controls completed the UVFP-HI-10 questionnaire. A statistical analysis was performed to assess the internal consistency and validity of the survey. In addition, maximum phonation time (MPT) was used to objectively measure patient QoL. RESULTS: Internal consistency was high (α = .914) and the correlation with MPT was significant (rs = -0.722). The estimated marginal mean in the discriminant validity study was around seven times higher in the UVFP group compared to the controls. The UVFP-HI-10 cut-off value was more than 0.9 and the sensitivity and specificity were more than 0.8. CONCLUSIONS: The UVFP-HI-10 is a self-administered patient-reported outcome questionnaire with a high reliability and excellent criterion-based validity. This questionnaire can be used to evaluate specific clinical complaints (e.g., vocalisation, swallowing, and breathing) in terms of their impact on QoL in patients with UVFP. Thus, its use is appropriate as a basic assessment tool as part of a specific UVFP treatment protocol.
Assuntos
Paralisia das Pregas Vocais , Prega Vocal , Humanos , Qualidade de Vida , Estudos Prospectivos , Reprodutibilidade dos Testes , Paralisia das Pregas Vocais/cirurgia , Inquéritos e QuestionáriosRESUMO
Using a male eating disorder (ED) sample, this study assessed the clinical utility of the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) severity indices for males with anorexia nervosa (AN) and bulimia nervosa (BN) and compared it to an alternative transdiagnostic severity categorisation based on drive for thinness (DT). The participants included 143 males with an ED (60 [42.0%] AN and 83 [58.0%] BN) diagnosis, who were classified using these two severity classifications. The different severity categories were then compared based on ED symptoms, general psychopathology, and personality traits. Our results revealed that the DSM-5 "mild" and DT "low" severity categories were most prevalent in the AN and BN male patients. Clinically significant findings were strongest for the DT categorisation for both AN and BN. The current findings provide initial support for an alternative transdiagnostic DT severity classification for males that may be more clinically meaningful than the DSM-5 severity indices.
Assuntos
Anorexia Nervosa , Bulimia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Masculino , Magreza , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Bulimia Nervosa/diagnóstico , Anorexia Nervosa/diagnóstico , Psicopatologia , Manual Diagnóstico e Estatístico de Transtornos MentaisRESUMO
BACKGROUND: Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. METHODS: We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. RESULTS: Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. CONCLUSIONS: We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.
Assuntos
Criptococose , Cryptococcus neoformans , Meningite Criptocócica , Adulto , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Meningite Criptocócica/diagnóstico , Autoanticorpos , Colômbia , Criptococose/diagnósticoRESUMO
Joubert syndrome (JS) is a clinically and genetically heterogeneous genetic disorder. To date, 40 JS-causing genes have been reported and CPLANE1 is one of the most frequently mutated, with biallelic pathogenic missense and truncating variants explaining up to 14% of JS cases. We present a case of JS diagnosed after the identification of a novel biallelic intragenic duplication of exons 20-46 of CPLANE1. The quadruplication was identified by short-read sequencing and copy number variant analysis and confirmed in tandem by long PCR with the breakpoints defined by a nanopore-based long-read sequencing approach. Based on the genetic findings and the clinical presentation of the patient, a brain MRI was ordered, evidencing the molar tooth sign, which confirmed the diagnosis of JS in the patient. This is, to the best of our knowledge, the first report of an intragenic duplication in this gene as the potential molecular mechanism of JS.
Assuntos
Anormalidades Múltiplas , Anormalidades do Olho , Doenças Renais Císticas , Humanos , Retina/patologia , Cerebelo , Anormalidades Múltiplas/genética , Doenças Renais Císticas/diagnóstico , Anormalidades do Olho/genéticaRESUMO
BACKGROUND: Hemovigilance (HV) is usually based on voluntary reports (passive HV). Our aim is to ascertain credible incidence, severity, and mortality of transfusion-associated adverse events (TAAEs) using an active HV program. STUDY DESIGN AND METHODS: Prospective cohort study to estimate transfusion risk after 46,488 transfusions in 5830 patients, using an active HV program with follow-up within the first 24 h after transfusion. We compared these results to those with the previously established passive HV program during the same 30 months of the study. We explored factors associated with the occurrence of TAAEs using generalized estimating equations models. RESULTS: With the active HV program TAAEs incidence was 57.3 (95% CI, 50.5-64.2) and mortality 1.1 (95% CI, 0.13-2.01) per 10,000 transfusions. Incidence with the new surveillance model was 14.0 times higher than with the passive. Most events occurred when transfusions had already finished (60.2%); especially pulmonary events (80.4%). Three out of five deaths and 50.3% of severe TAAEs were pulmonary. In the multivariate analysis surgical patients had half TAAEs risk when compared to medical patients (OR, 0.53; 95% CI, 0.34-0.78) and women had nearly twice the risk of a pulmonary event compared to men (OR, 1.84; 95% CI, 1.03-3.32). Patient's age, blood component type, or blood component shelf-life were unrelated to TAAEs risk. DISCUSSION: Active hemovigilance programs provide additional data which may lead to better recognition and understanding of TAAEs and their frequency and severity.
Assuntos
Segurança do Sangue , Transfusão de Sangue , Masculino , Humanos , Feminino , Incidência , Estudos Prospectivos , SeguimentosRESUMO
OBJECTIVE: The aim of this study was to evaluate the risk factors associated with xerostomia and hyposalivation in a group of hypertensive patients. SUBJECTS AND METHODS: A cross-sectional study was conducted. Hypertensive patients belonged to two healthcare centers were included. Xerostomia was assessed by asking a question and using the Xerostomia Inventory. Unstimulated salivary flow was collected. Different epidemiological variables were analyzed such as age, sex, habits, diseases, drugs, and blood pressure. RESULTS: 221 individuals were included. Xerostomia was reported in 51.13% of patients. Patients with xerostomia suffered more from osteoarthritis and diaphragmatic hernia. These patients took more anticoagulants (acenocoumarol), antiarrhythmics (amiodarone), analgesics (paracetamol) and epilepsy drugs (pregabalin) and less platelet aggregation inhibitors and angiotensin II receptor blockers (losartan). Unstimulated flow was reduced in 37.56% of patients. Patients suffering hyposalivation presented more diseases such as anxiety, infectious or parasitic diseases, hepatitis C, diaphragmatic hernia, and osteoarthritis. These patients took more repaglinide, thiazides, anti-inflammatories, anti-rheumatics, glucosamine, diazepam, and selective beta-2-adrenoreceptor agonists and less combinations of candesartan and diuretics. CONCLUSIONS: Xerostomia and hyposalivation are frequent in hypertensive patients. It is advisable to take into consideration the comorbidities and the drugs they receive, since they can increase the risk of these salivary disorders.
Assuntos
Hérnia Diafragmática , Xerostomia , Humanos , Saliva , Estudos Transversais , Xerostomia/complicações , Fatores de Risco , Hérnia Diafragmática/complicaçõesRESUMO
Human mitoribosomes are macromolecular complexes essential for translation of 11 mitochondrial mRNAs. The large and the small mitoribosomal subunits undergo a multistep maturation process that requires the involvement of several factors. Among these factors, GTP-binding proteins (GTPBPs) play an important role as GTP hydrolysis can provide energy throughout the assembly stages. In bacteria, many GTPBPs are needed for the maturation of ribosome subunits and, of particular interest for this study, ObgE has been shown to assist in the 50S subunit assembly. Here, we characterize the role of a related human Obg-family member, GTPBP5. We show that GTPBP5 interacts specifically with the large mitoribosomal subunit (mt-LSU) proteins and several late-stage mitoribosome assembly factors, including MTERF4:NSUN4 complex, MRM2 methyltransferase, MALSU1 and MTG1. Interestingly, we find that interaction of GTPBP5 with the mt-LSU is compromised in the presence of a non-hydrolysable analogue of GTP, implying a different mechanism of action of this protein in contrast to that of other Obg-family GTPBPs. GTPBP5 ablation leads to severe impairment in the oxidative phosphorylation system, concurrent with a decrease in mitochondrial translation and reduced monosome formation. Overall, our data indicate an important role of GTPBP5 in mitochondrial function and suggest its involvement in the late-stage of mt-LSU maturation.
Assuntos
Proteínas Mitocondriais/metabolismo , Ribossomos Mitocondriais/metabolismo , Proteínas Monoméricas de Ligação ao GTP/fisiologia , Proteínas Ribossômicas/metabolismo , Subunidades Ribossômicas Maiores de Eucariotos/metabolismo , Neoplasias Ósseas/patologia , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Técnicas de Inativação de Genes , Guanosina Trifosfato/metabolismo , Células HEK293 , Humanos , Osteossarcoma/patologia , Fosforilação Oxidativa , Mapeamento de Interação de ProteínasRESUMO
This paper aims to study the determinants of the governance model of water resources in the agriculture of the Hermosillo-Coast (Mexico). To achieve this objective, a literature review, in-depth interviews and a workshop were carried out. The results show that the main threats to the system come from the model of granting concessions for access to water resources, the lack of supervision by the competent authority and the control of a group of stakeholders over water in relation to the rest of the interested parties. Finally, measures aimed at improving the sustainability of agricultural activity in the area are proposed.
Assuntos
Países em Desenvolvimento , Água , México , Agricultura/métodos , Abastecimento de ÁguaRESUMO
Breakthrough invasive infections occurs during the use of antifungals both in prophylaxis and therapy, it favors the emergence of new pathogens in the fungal landscape. Hormographiella aspergillata is considered a rare but emerging pathogen in the era of broad-spectrum antifungal use in patients with hematological malignancies. Here, we present a case report of invasive sinusitis due to Hormographiella aspergillata, manifesting as a breakthrough infection in a patient with severe aplastic anemia under treatment with voriconazole for invasive pulmonary aspergilosis. Also, we make a review of H. aspergillata breakthrough infections published in the literature.
Assuntos
Agaricales , Pneumopatias Fúngicas , Humanos , Voriconazol/uso terapêutico , Pneumopatias Fúngicas/tratamento farmacológico , Antifúngicos/uso terapêuticoRESUMO
BACKGROUND: Post-psychotic depression (PPD) after a FEP (first-episode psychosis) differs from other depressive symptoms in chronic schizophrenia in its aetiology, symptomatology, and prognostic implications. The objective was to search if any pharmacological or non-pharmacological interventions have proven to be effective on depressive symptoms after a FEP. METHODS: for this systematic review we systematically searched and screened PubMed for articles published from August 1975 to October 15, 2020, with the terms: treatment AND first-episode psychosis OR post-psychotic OR post-schizophrenic AND depression. RESULTS: we identified 139 articles of which 20 met the inclusion criteria. These interventions were then categorized into four subgroups (antipsychotics, antidepressants, psychological and miscellaneous). LIMITATIONS: this review has several limitations. The reviewed studies were heterogeneous as to assessments, interventions, and samples; furthermore, only one study had PPD in FEP as its primary outcome. CONCLUSIONS: to our knowledge, this is the first review of PPD in a FEP's treatment. PPD continues to be a diagnostic and therapeutic challenge. The available evidence for the use of treatment whether pharmacological or non-pharmacological is limited. However, certain approaches such as online therapy and treatment with n-3 polyunsaturated fatty acids (PUFA) show promising results. It could be of interest for future studies to focus not only on the treatment of PPD but also on the diagnostic heterogeneity of the sample and the adaptation of the content of the intervention to the individual.
Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Depressão , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Antidepressivos/uso terapêuticoRESUMO
OBJECTIVE: This study assessed gender-related differences in executive functions (decision-making, inhibitory control and cognitive flexibility), personality traits and psychopathological symptoms in binge-spectrum eating disorders (EDs). Secondly, we aimed to separately explore the predictive value of gender and executive functions in treatment outcome. METHOD: A battery of self-reported and neurocognitive measures were answered by a sample of 85 patients (64 females) diagnosed with a binge-spectrum ED (41 BN; 44 binge eating disorder). RESULTS: Data showed gender-related differences in executive functioning, displaying women lower inhibitory control and lower cognitive flexibility than men. Regarding personality traits and psychopathology symptoms, women presented higher reward dependence and cooperativeness, as well as more drive for thinness, body dissatisfaction, bulimia, and somatisation symptoms than men. Finally, worse executive functioning, particularly having lower ability in concept formation seems to predict worse treatment outcomes and dropout in these patients. CONCLUSIONS: We described gender specific neuropsychological, personality and psychopathological impairments in patients with binge-spectrum EDs. Moreover, difficulties in executive functioning might have an impact on treatment response, since patients with a lower ability in concept formation are less likely to benefit from treatment. The present results can help improving current treatment approaches by tackling gender and individual differences.
Assuntos
Transtorno da Compulsão Alimentar , Bulimia Nervosa , Bulimia , Transtornos da Alimentação e da Ingestão de Alimentos , Masculino , Humanos , Feminino , Transtorno da Compulsão Alimentar/terapia , Transtorno da Compulsão Alimentar/psicologia , Bulimia Nervosa/psicologia , Bulimia/terapia , Bulimia/psicologia , Função Executiva/fisiologia , Cognição , Transtornos da Alimentação e da Ingestão de Alimentos/terapiaRESUMO
OBJECTIVE: The aim of the present study was to test the usefulness of an add-on serious video game approach (i.e., Playmancer) to treatment as usual (TAU) on reducing impulsive behaviours and psychopathology in individuals diagnosed with an eating disorder (ED). METHOD: Thirty-seven patients diagnosed with an ED according to the DSM-5 were included in the present randomized clinical trial (RCT; study record 35,405 in ClinicalTrials.gov) and were randomly assigned to either the TAU or TAU + Playmancer group. All participants completed a clinical interview. Impulsivity (UPPS-P self reported questionnaire and Stroop task) and general psychopathology (SCL-90-R) measures were assessed at: baseline, 4 weeks into treatment, at the end of TAU (after 16 weeks), and follow-up (2 years). In addition, patients in the experimental group underwent a total of nine sessions with Playmancer over the span of 3 weeks. RESULTS: Patients in both treatment groups (TAU + Playmancer or TAU) improved on Stroop task performance and psychological distress. Additionally, patients in TAU-Playmancer improved on the impulsive trait domain of lack of perseverance. No statistical differences were found regarding treatment outcomes (i.e., treatment adherence and remission of eating symptomatology) when comparing the two treatment groups. CONCLUSION: Our results suggest that the impulsivity associated with EDs should be addressed and could be modified, as some facets of trait impulsivity improved after Playmancer add-on treatment. Yet, there were no significant differences in treatment outcomes when comparing the two groups and further research needs to be conducted.
Assuntos
Terapia Cognitivo-Comportamental , Transtornos da Alimentação e da Ingestão de Alimentos , Jogos de Vídeo , Humanos , Projetos Piloto , Terapia Cognitivo-Comportamental/métodos , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Comportamento ImpulsivoRESUMO
OBJECTIVES: To evaluate whether the severity of xerostomia in older polymedicated patients impacts oral health-related quality of life (OHRQoL). BACKGROUND: Medication-associated xerostomia is common in older people. Xerostomia may impair OHRQoL. MATERIALS AND METHODS: This cross-sectional study included older hypertensive patients from two health centres. We assessed the severity of xerostomia and OHRQoL using the Xerostomia Inventory (XI) tool, and the Oral Health Impact Profile-14 (OHIP-14) instrument, respectively. We measured unstimulated (UWS) and stimulated (SWS) salivary flows. Univariate and multiple linear regression analyses evaluated the associations of XI and OHIP-14 and different explanatory variables. RESULTS: Of the 218 patients enrolled, 51.8% had xerostomia, and 38.1% and 27.5% suffered from UWS and SWS hyposalivation, respectively. Patients with xerostomia, UWS, and SWS hyposalivation scored significantly higher on the XI. However, only those with xerostomia or UWS hyposalivation had significantly higher OHIP-14 scores. A moderate correlation was observed between XI and OHIP-14 scores. The multiple regression model showed that factors with the greatest impact on XI were the patient's complaint of xerostomia, UWS flow rate, age and sex. However, only the XI score was significantly associated with the OHIP-14 score. CONCLUSION: Xerostomia has a negative impact on OHRQoL in older polymedicated patients, but this impact is less than in other types of xerostomia. Longitudinal studies are needed to determine whether changes in the detected explanatory variables influence XI and OHIP scores in these patients.
RESUMO
BACKGROUND: Voriconazole has been recommended as primary treatment for patients with invasive aspergillosis. Intravenous and tablet formulations of posaconazole that have improved systemic absorption could be an effective alternative to voriconazole. We aimed to assess non-inferiority of posaconazole to voriconazole for the primary treatment of invasive aspergillosis. METHODS: We did a randomised, prospective, double-blind, double-dummy, controlled trial comparing posaconazole (intravenous or oral posaconazole 300 mg twice on day 1, followed by 300 mg once a day for days 2-84) with voriconazole (6 mg/kg intravenous or 300 mg oral twice on day 1 followed by 4 mg/kg intravenously or 200 mg orally twice a day for days 2-84) for 12 weeks or less in the primary treatment of invasive aspergillosis. Participants were from 91 study sites in 26 countries, were aged 13 years or older, weighed at least 40 kg, and met criteria for proven, probable, or possible fungal disease. Participants were randomly assigned (1:1) via a computer-generated randomisation schedule with stratification by risk status. The primary endpoint was cumulative all-cause mortality up until day 42 in the intention-to-treat (ITT) population (defined as randomly assigned participants who received ≥1 dose of study drug), with a 10% non-inferiority margin. The ITT population was also evaluated for safety. This study is registered with ClinicalTrials.gov, NCT01782131, and EudraCT, 2011-003938-14. FINDINGS: Between Oct 25, 2013, and Sept 10, 2019, of 653 individuals assessed for eligibility, 575 ITT participants were randomly assigned and received one or more doses of study drug (n=288 [50%] posaconazole, n=287 [50%] voriconazole). Mortality up until day 42 was 15% (44 of 288) in the posaconazole group and 21% (59 of 287) in the voriconazole group (treatment difference -5·3% [95% CI -11·6 to 1·0]; p<0·0001). Mortality up until day 42 in the full-analysis-set subpopulation (ITT participants with proven or probable invasive aspergillosis) supported this conclusion: 31 (19%) of 163 participants in the posaconazole group and 32 (19%) of 171 participants in the voriconazole group (treatment difference 0·3% [95% CI -8·2 to 8·8]). The most frequently reported treatment-related adverse events (incidence >3%) were increased aspartate aminotransferase (AST) or alanine aminotransferase (ALT), nausea, hypokalaemia, and vomiting in the posaconazole group and increased ALT, AST, or alkaline phosphatase, hallucination, increased γ-glutamyltransferase peptidase, nausea, and blurred vision in the voriconazole group. The overall incidence of treatment-related adverse event rates in the ITT population was 30% for posaconazole and 40% for voriconazole (treatment difference -10·2% [95% CI -17·9 to -2·4]). INTERPRETATION: Posaconazole was non-inferior to voriconazole for all-cause mortality up until day 42 in participants with invasive aspergillosis. Posaconazole was well tolerated, and participants had fewer treatment-related adverse events than in the voriconazole group. This study supports the use of posaconazole as a first-line treatment for the condition. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.