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1.
N Engl J Med ; 388(15): 1353-1364, 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-36876740

RESUMO

BACKGROUND: Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. RESULTS: A total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels. CONCLUSIONS: Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/cirurgia , Método Duplo-Cego , Ácidos Graxos/administração & dosagem , Ácidos Graxos/efeitos adversos , Ácidos Graxos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Revascularização Miocárdica , Hipolipemiantes/administração & dosagem , Hipolipemiantes/efeitos adversos , Hipolipemiantes/uso terapêutico
2.
Mol Psychiatry ; 28(7): 2674-2682, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37147390

RESUMO

Cross-sectional neuroimaging studies show that bipolar disorder is associated with structural brain abnormalities, predominantly observed in prefrontal and temporal cortex, cingulate gyrus, and subcortical regions. However, longitudinal studies are needed to elucidate whether these abnormalities presage disease onset or are consequences of disease processes, and to identify potential contributing factors. Here, we narratively review and summarize longitudinal structural magnetic resonance imaging studies that relate imaging outcomes to manic episodes. First, we conclude that longitudinal brain imaging studies suggest an association of bipolar disorder with aberrant brain changes, including both deviant decreases and increases in morphometric measures. Second, we conclude that manic episodes have been related to accelerated cortical volume and thickness decreases, with the most consistent findings occurring in prefrontal brain areas. Importantly, evidence also suggests that in contrast to healthy controls, who in general show age-related cortical decline, brain metrics remain stable or increase during euthymic periods in bipolar disorder patients, potentially reflecting structural recovering mechanisms. The findings stress the importance of preventing manic episodes. We further propose a model of prefrontal cortical trajectories in relation to the occurrence of manic episodes. Finally, we discuss potential mechanisms at play, remaining limitations, and future directions.


Assuntos
Transtorno Bipolar , Humanos , Mania , Estudos Transversais , Encéfalo , Córtex Pré-Frontal , Imageamento por Ressonância Magnética
3.
J Org Chem ; 89(5): 3226-3237, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38361498

RESUMO

Dehydrogenative aromatization (DA) of cyclic ketones is central to the development of functionalized aromatic precursors and hydrogen transfer-related technologies. Traditional DA strategies require precious metals with oxidants and are typically performed at high temperatures (100-150 °C) to overcome the high energy barrier of aliphatic C-H bond activation. Recently, a mild alternative approach based on I2 has been proposed to realize DA on substituted unsaturated cyclic ketones under ambient conditions. However, depending on the solvent, the product selectivity may vary between phenol ether and phenol, and the reaction mechanisms remain unclear. Herein, based on time-resolved proton nuclear magnetic resonance, DFT calculation, and mass spectrometric analyses, we established a unified mechanism to account for the product distribution. Through substrate scope and desorption electrospray ionization-mass spectrometry, we discovered the formation of a carbocation, which has been overlooked in previous studies. An expanded substrate scope study coupled with spectroscopic observation provided strong evidence to elucidate the formation mechanism and the location of the carbocation. With a renewed understanding of the mechanism, we achieved a phenolic product yield of 17-96% while controlling the selectivity. Moreover, some reactants could undergo DA in H2O, achieving 95-96% yield at below water-boiling temperature.

4.
J Sleep Res ; 32(4): e13815, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36579399

RESUMO

Fluid intelligence is seen as a beneficial attribute, protecting against stress and ill-health. Whether intelligence provides resilience to the cognitive effects of insufficient sleep was tested in the current pre-registered experimental study. Participants (N = 182) completed the Raven's test (measuring fluid intelligence) and a normal night of sleep or a night of total sleep deprivation. Sleepiness and four cognitive tests were completed at 22:30 hours (baseline), and the following day after sleep manipulation. At baseline, higher fluid intelligence was associated with faster and more accurate arithmetic calculations, and better episodic memory, but not with spatial working memory, simple attention or sleepiness. Those with higher fluid intelligence were more, not less, impacted by sleep deprivation, evident for arithmetic ability, episodic memory and spatial working memory. We need to establish a more nuanced picture of the benefits of intelligence, where intelligence is not related to cognitive advantages in all situations.


Assuntos
Cognição , Privação do Sono , Humanos , Privação do Sono/psicologia , Sonolência , Sono , Inteligência
5.
Inorg Chem ; 62(13): 5058-5066, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36946599

RESUMO

We present results for a series of complexes derived from a titanium complex capable of activating C-H bonds under mild conditions (PNP)Ti═CHtBu(CH2tBu), where PNP = N[2-PiPr2-4-methylphenyl]2-. In addition to the initial activation of methane, a tautomerization reaction to a terminal methylidene is also explored due to methylidene's potential use as a synthetic starting point. Analogous complexes with other low-cost 3d transition metals were studied, such as scandium, titanium, vanadium, and chromium as both isoelectronic and isocharged complexes. Our results predict that V(IV) and V(V) complexes are promising for methane C-H bond activation. The V(V) complex has a low rate-determining barrier for methane activation, specifically 16.6 kcal/mol, which is approximately 12 kcal/mol less than that for the Ti complex, as well as having a moderate tautomerization barrier of 29.8 kcal/mol, while the V(IV) complex has a methane activation barrier of 19.0 kcal/mol and a tautomerization barrier of 31.1 kcal/mol. Scandium and chromium complexes are much poorer for C-H bond activation; scandium has very high barriers, while chromium strongly overstabilizes the alkylidene intermediate, potentially stopping the further reaction. In addition to the original PNP ligand, some of the most promising ligands from a previous work were tested, although (as shown previously) modification of the ligand does not typically have large effects on the activity of the system. Our best ligand modification improves the performance of the V(V) complex via the substitution of the nitrogen in PNP by phosphorus, which reduces the tautomerization barrier by 5 to 24.4 kcal/mol.

6.
Environ Sci Technol ; 57(32): 11718-11730, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37527361

RESUMO

An expanding web of adverse impacts on people and the environment has been steadily linked to anthropogenic chemicals and their proliferation. Central to this web are the regulatory structures intended to protect human and environmental health through the control of new molecules. Through chronically insufficient and inefficient action, the current chemical-by-chemical regulatory approach, which considers regulation at the level of chemical identity, has enabled many adverse impacts to develop and persist. Recognizing the link between fundamental physicochemical properties and hazards, we describe a new paradigm─property-based regulation. By regulating physicochemical properties, we show how governments can delineate and enforce safe chemical spaces, increasing the scalability of chemical assessments, reducing the time and resources to regulate a substance, and providing transparency for chemical designers. We highlight sparse existing property-based approaches and demonstrate their applicability using bioaccumulation as an example. Finally, we present a path to implementation in the United States, prescribing roles and steps for government, nongovernmental organizations, and industry to accelerate this transition, to the benefit of all.

7.
BMC Psychiatry ; 23(1): 771, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872497

RESUMO

BACKGROUND: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture. METHODS: A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research. DISCUSSION: This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma. TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.


Assuntos
Doenças Autoimunes , Transtornos Psicóticos , Adulto , Humanos , Método Duplo-Cego , Inflamação , Transtornos Psicóticos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/uso terapêutico , Resultado do Tratamento
8.
Eur Child Adolesc Psychiatry ; 32(1): 75-86, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34223993

RESUMO

Despite poor treatment results, a family-oriented approach and the securing of residency have been deemed essential to recovery from resignation syndrome (RS). In a retrospective cohort study, we evaluated an alternative method involving environmental therapy, with patients separated from their parents, while actively abstaining from involving the asylum process in treatment. We examined medical records, social services acts, and residential care home acts from 13 individuals treated at Solsidan residential care home between 2005 and 2020. Severity and outcome were assessed with Clinical Global Impression, Severity and Improvement subscales. Thirteen participants were included and out of these nine (69%) recovered, i.e. they very much or much improved. Out of the eight that were separated, all recovered, also, one non-separated recovered. The difference in outcome between subjects separated and not was significant (p = 0.007). Moreover, out of the five which received a residency permit during treatment, one recovered whereas four did not. The difference in outcome between subjects granted residency and not was significant (p = 0.007). The data revealed three (23%) cases of simulation where parents were suspected to have instigated symptoms. Our evaluation suggests that separation from parents and abstaining from invoking residency permit could be essential components when treating RS. Relying on a family-oriented approach, and residency could even be detrimental to recovery. The examined intervention was successful also in cases of probable malingering by proxy.


Assuntos
Pais , Refugiados , Humanos , Estudos Retrospectivos , Estresse Psicológico
9.
Chem Biodivers ; 20(11): e202301044, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37772689

RESUMO

The composition and anticholinesterase activity of the dried MeOH extracts of Hieracium scheppigianum and H. naegelianum underground parts (rhizomes and roots), as well as the anticholinesterase activity of the dried, previously chemically characterised MeOH extracts of the flowering aerial parts of these two and 26 other Hieracium species in the strict sense (s. str.), were investigated. Furthermore, the anticholinesterase activity of 12 selected secondary metabolites of these extracts was evaluated. Using semi-preparative LC-MS, five caffeoylquinic acids and the sesquiterpene lactone crepiside E were isolated from H. scheppigianum underground parts extract. All these compounds were also identified in the underground parts extract of H. naegelianum. Quantitative LC-MS analysis showed that the analysed underground parts extracts were rich in both caffeoylquinic acids (139.77 and 156.62 mg/g of extract, respectively) and crepiside E (126.88 and 116.58 mg/g). In the Ellman method, the tested extracts showed an interesting anti-AChE and/or anti-BChE activity (IC50 =0.56-1.58 mg/mL), which can be explained, at least partially, by the presence of some of their constituents. Among the metabolites tested, the best activity was revealed for the flavonoids apigenin, luteolin and diosmetin, and the sesquiterpene lactone 8-epiixerisamine A (IC50 =68.09-299.37 µM).


Assuntos
Asteraceae , Sesquiterpenos , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Metanol/química , Antioxidantes/química , Extratos Vegetais/química , Componentes Aéreos da Planta/química , Flavonoides/análise , Asteraceae/química , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos/análise
10.
Brain Behav Immun ; 99: 9-16, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34547400

RESUMO

INTRODUCTION: The role of inflammation in common psychiatric diseases is now well acknowledged. However, the factors and mechanisms underlying inter-individual variability in the vulnerability to develop psychopathology-related symptoms in response to inflammation are not well characterized. Herein, we aimed at investigating morphological brain regions central for interoception and emotion regulation, and if these are associated with acute inflammation-induced sickness and anxiety responses. METHODS: Systemic inflammation was induced using an intravenous injection of lipopolysaccharide (LPS) at a dose of 0.6 ng/kg body weight in 28 healthy individuals, while 21 individuals received an injection of saline (placebo). Individuals' gray matter volume was investigated by automated voxel-based morphometry technique on T1-weighted anatomical images derived from magnetic resonance imaging (MRI). Plasma concentrations of TNF-α and IL-6, sickness symptoms (SicknessQ), and state anxiety (STAI-S) were measured before and after the injection. RESULTS: A stronger sickness response to LPS was significantly associated with a larger anterior insula gray matter volume, independently from increases in cytokine concentrations, age, sex and body mass index (R2 = 65.6%). Similarly, a greater LPS-induced state anxiety response was related to a larger anterior insula gray matter volume, and also by a stronger increase in plasma TNF-α concentrations (R2 = 40.4%). DISCUSSION: Anterior insula morphology appears central in the sensitivity to develop symptoms of sickness and anxiety in response to inflammation, and could thus be one risk factor in inflammation-related psychopathologies. Because of the limited sample size, the current results need to be replicated.


Assuntos
Lipopolissacarídeos , Transtornos Mentais , Encéfalo , Substância Cinzenta/diagnóstico por imagem , Humanos , Inflamação , Imageamento por Ressonância Magnética/métodos
11.
Mol Psychiatry ; 26(3): 999-1008, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160693

RESUMO

Family and twin studies of Borderline Personality Disorder (BPD) have found familial aggregation and genetic propensity for BPD, but estimates vary widely. Large-scale family studies of clinically diagnosed BPD are lacking. Therefore, we performed a total-population study estimating the familial aggregation and heritability of clinically diagnosed BPD. We followed 1,851,755 individuals born 1973-1993 in linked Swedish national registries. BPD-diagnosis was ascertained between 1997 and 2013, 11,665 received a BPD-diagnosis. We identified relatives and estimated sex and birth year adjusted hazard ratios, i.e., the rate of BPD-diagnoses in relatives to individuals with BPD-diagnosis compared to individuals with unaffected relatives, and used structural equation modeling to estimate heritability. The familial association decreased along with genetic relatedness. The hazard ratio was 11.5 (95% confidence interval (CI) = 1.6-83.8) for monozygotic twins; 7.4 (95% CI = 1.0-55.3) for dizygotic twins; 4.7 (95% CI = 3.9-5.6) for full siblings; 2.1 (95% CI = 1.5-3.0) for maternal half-siblings; 1.3 (95% CI = 0.9-2.1) for paternal half-siblings; 1.7 (95% CI = 1.4-2.0) for cousins whose parents were full siblings; 1.1 (95% CI = 0.7-1.8) for cousins whose parents were maternal half-siblings; and 1.9 (95% CI = 1.2-2.9) for cousins whose parents were paternal half-siblings. Heritability was estimated at 46% (95% CI = 39-53), and the remaining variance was explained by individually unique environmental factors. Our findings pave the way for further research into specific genetic variants, unique environmental factors implicated, and their interplay in risk for BPD.


Assuntos
Transtorno da Personalidade Borderline , Transtorno da Personalidade Borderline/genética , Predisposição Genética para Doença/genética , Humanos , Sistema de Registros , Fatores de Risco , Suécia , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética
12.
Mol Psychiatry ; 26(1): 341-349, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-30323291

RESUMO

Large-scale family studies on the co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of clinically ascertained ADHD and BPD diagnoses using the entire Swedish population. In a register-based cohort design we included individuals born in Sweden 1979-2001, and identified their diagnoses during 1997-2013; in total, 2,113,902 individuals were included in the analyses. We obtained clinical diagnoses of ADHD and BPD from inpatient and outpatient care. Individuals with an ADHD diagnosis had an adjusted (for birth year, sex, and birth order) odds ratio (aOR) of 19.4 (95% confidence interval [95% CI] = 18.6-20.4) of also having a BPD diagnosis, compared to individuals not diagnosed with ADHD. Having a sibling with ADHD also increased the risk for BPD (monozygotic twins, aOR = 11.2, 95% CI = 3.0-42.2; full siblings, aOR = 2.8, 95% CI = 2.6-3.1; maternal half-siblings, aOR = 1.4, 95% CI = 1.2-1.7; paternal half-siblings, aOR = 1.5, 95% CI = 1.3-1.7). Cousins also had an increased risk. The strength of the association between ADHD and BPD was similar in females and males, and full siblings showed similar increased risks regardless of sex. Among both males and females, ADHD and BPD co-occur within individuals and co-aggregate in relatives; the pattern suggests shared genetic factors and no robust evidence for etiologic sex differences was found. Clinicians should be aware of increased risks for BPD in individuals with ADHD and their relatives, and vice versa.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno da Personalidade Borderline/epidemiologia , Transtorno da Personalidade Borderline/genética , Irmãos , Adolescente , Criança , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/genética , Saúde da Família , Feminino , Humanos , Masculino , Sistema de Registros , Suécia/epidemiologia , Adulto Jovem
13.
Cereb Cortex ; 31(6): 2773-2786, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33454739

RESUMO

It is not known how specific the neural mechanisms underpinning empathy for different domains are. In the present study, we set out to test whether shared neural representations between first-hand pain and empathy for pain are pain-specific or extend to empathy for unpleasant affective touch as well. Using functional magnetic resonance imaging and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them with the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiates the role of shared representations in empathy.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Empatia/fisiologia , Antagonistas de Entorpecentes/farmacologia , Dor/diagnóstico por imagem , Tato/fisiologia , Adulto , Encéfalo/efeitos dos fármacos , Método Duplo-Cego , Empatia/efeitos dos fármacos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Dor/psicologia , Distribuição Aleatória , Tato/efeitos dos fármacos
14.
Eur Addict Res ; 28(3): 210-219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35026761

RESUMO

INTRODUCTION: Exposure to conditioned cues is a common trigger of relapse in addiction. It has been suggested that such cues can activate motivationally relevant neurocircuitry in individuals with substance use disorders even without being consciously perceived. We aimed to see if this could be replicated in a sample with severe amphetamine use disorder and a control group of healthy subjects. METHODS: We used fMRI to test the hypothesis that individuals with amphetamine use disorder, but not healthy controls, exhibit a specific neural reactivity to subliminally presented pictures related to amphetamine use. Twenty-four amphetamine users and 25 healthy controls were recruited and left data of sufficient quality to be included in the final analysis. All subjects were exposed to drug-related and neutral pictures of short duration (13.3 ms), followed by a backward visual mask image. The contrast of interest was drug versus neutral subliminal pictures. RESULTS: There were no statistically significant differences in BOLD signal between the drug and neutral cues, neither in the limbic regions of primary interest nor in exploratory whole-brain analyses. The same results were found both in amphetamine users and controls. DISCUSSION/CONCLUSION: We found no evidence of neural reactivity to subliminally presented drug cues in this sample of subjects with severe amphetamine dependence. These results are discussed in relation to the earlier literature, and the evidence for subliminal drug cue reactivity in substance use disorders is questioned.


Assuntos
Comportamento Aditivo , Transtornos Relacionados ao Uso de Substâncias , Anfetaminas , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Sinais (Psicologia) , Humanos , Imageamento por Ressonância Magnética/métodos
15.
Ann Diagn Pathol ; 59: 151977, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35609435

RESUMO

The paper presents a pathological-radiological correlation of the manifestation of mucosal cystadenoma with ovarian stroma of the liver with examination and correlation with the new stroma nomenclature and differential diagnostic dilemmas of radiologists and pathologists.


Assuntos
Cistadenoma Mucinoso , Cistadenoma , Neoplasias Ovarianas , Radiologia , Cistadenoma/diagnóstico por imagem , Cistadenoma Mucinoso/diagnóstico por imagem , Feminino , Humanos , Fígado/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Ovário
16.
Brain Behav Immun ; 93: 420-424, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33493626

RESUMO

Even though dysfunctional emotion regulation is prominent in depression and a link between depression and inflammation is well established, there is little knowledge about how inflammation affects the regulation of emotions. The aim of this pilot study was to explore the effect of experimentally induced inflammation on the cognitive reappraisal of emotions, and to assess domain specificity by comparing success in regulation of emotions towards two unpleasant stimuli classes (general negative stimuli and disgust stimuli). In a between-subject design, ten healthy participants were injected with an intravenous injection of lipopolysaccharide (2 ng/kg body weight) and eleven were injected with saline. Participants performed a cognitive reappraisal task, in which they had to down-regulate or up-regulate their emotions towards general negative stimuli and disgust stimuli, 5-6 h post-injection. Contrary to our hypotheses, participants injected with lipopolysaccharide reported greater success in down-regulating emotional responses towards unpleasant stimuli as compared to the saline group. In addition, both groups were poorer at down-regulating emotions towards disgust stimuli as compared to general negative stimuli. The current pilot study indicates that cognitive reappraisal of emotions is affected during experimental endotoxemia, and suggests that disgust stimuli might be difficult to reappraise.


Assuntos
Endotoxemia , Cognição , Emoções , Humanos , Projetos Piloto
17.
Mol Psychiatry ; 25(11): 3020-3033, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-30108313

RESUMO

Attention-Deficit/Hyperactivity Disorder (ADHD) and conduct disorder (CD) exemplify top-down dysregulation conditions that show a large comorbidity and shared genetics. At the same time, they entail two different types of symptomology involving mainly non-emotional or emotional dysregulation. Few studies have tried to separate the specific biology underlying these two dimensions. It has also been suggested that both types of conditions consist of extreme cases in the general population where the symptoms are widely distributed. Here we test whether brain structure is specifically associated to ADHD or CD symptoms in a general population of adolescents (n = 1093) being part of the IMAGEN project. Both ADHD symptoms and CD symptoms were related to similar and overlapping MRI findings of a smaller structure in prefrontal and anterior cingulate cortex. However, our regions of interest (ROI) approach indicated that gray matter volume (GMV) and surface area (SA) in dorsolateral/dorsomedial prefrontal cortex and caudal anterior cingulate cortex were negatively associated to ADHD symptoms when controlling for CD symptoms while rostral anterior cingulate cortex GMV was negatively associated to CD symptoms when controlling for ADHD symptoms. The structural findings were mirrored in performance of neuropsychological tests dependent on prefrontal and anterior cingulate regions, showing that while performance on the Stop Signal test was specifically related to the ADHD trait, delayed discounting and working memory were related to both ADHD and CD traits. These results point towards a partially domain specific and dimensional capacity in different top-down regulatory systems associated with ADHD and CD symptoms.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Encéfalo/patologia , Transtorno da Conduta/patologia , Transtorno da Conduta/psicologia , Adolescente , Feminino , Giro do Cíngulo/patologia , Humanos , Masculino , Córtex Pré-Frontal/patologia
18.
J Psychiatry Neurosci ; 46(4): E441-E450, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34291628

RESUMO

BACKGROUND: Bipolar disorder is highly heritable and polygenic. The polygenic risk for bipolar disorder overlaps with that of schizophrenia, and polygenic scores are normally distributed in the population. Bipolar disorder has been associated with structural brain abnormalities, but it is unknown how these are linked to genetic risk factors for psychotic disorders. METHODS: We tested whether polygenic risk scores for bipolar disorder and schizophrenia predict structural brain alterations in 98 patients with bipolar disorder and 81 healthy controls. We derived brain cortical thickness, surface area and volume from structural MRI scans. In post-hoc analyses, we correlated polygenic risk with functional hub strength, derived from resting-state functional MRI and brain connectomics. RESULTS: Higher polygenic risk scores for both bipolar disorder and schizophrenia were associated with a thinner ventromedial prefrontal cortex (vmPFC). We found these associations in the combined group, and separately in patients and drug-naive controls. Polygenic risk for bipolar disorder was correlated with the functional hub strength of the vmPFC within the default mode network. LIMITATIONS: Polygenic risk is a cumulative measure of genomic burden. Detailed genetic mechanisms underlying brain alterations and their cognitive consequences still need to be determined. CONCLUSION: Our multimodal neuroimaging study linked genomic burden and brain endophenotype by demonstrating an association between polygenic risk scores for bipolar disorder and schizophrenia and the structure and function of the vmPFC. Our findings suggest that genetic factors might confer risk for psychotic disorders by influencing the integrity of the vmPFC, a brain region involved in self-referential processes and emotional regulation. Our study may also provide an imaging-genetics vulnerability marker that can be used to help identify individuals at risk for developing bipolar disorder.


Assuntos
Transtorno Bipolar/genética , Predisposição Genética para Doença , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/genética , Envelhecimento/genética , Transtorno Bipolar/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Herança Multifatorial , Córtex Pré-Frontal/diagnóstico por imagem , Fatores de Risco , Esquizofrenia/diagnóstico por imagem
19.
Chem Eng J ; 4122021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37771372

RESUMO

The ability of transition metal chitosan complexes (TMCs) of varying valence and charge to selectively adsorb As(III) and As(V) over their strongest adsorptive competitor, phosphate is examined. Fe(III)-chitosan, Al(III)-chitosan, Ni(II)-chitosan, Cu(II)-chitosan, and Zn(II)-chitosan are synthesized, characterized via Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy (ATR-FTIR) and X-ray Diffractometry (XRD), and their selective sorption capabilities towards As(III) and As(V) in the presence of phosphate are evaluated. It was found that the stability of the metal-chitosan complexes varied, with Al(III)- and Zn(II)-chitosan forming very unstable complexes resulting in precipitation of gibbsite, and Wulfingite and Zincite, respectively. Cu(II)-, Ni(II)-, and Fe(III)-chitosan formed a mixture of monodentate and bidentate complexes. The TMCs which formed the bidentate complex (Cu(II)-, Ni(II)-, and Fe(III)-) showed greater adsorption capability for As(V) in the presence of phosphate. Using the binary separation factor ∝t/c, it can be shown that only Fe(III)-chitosan is selective for As(V) and As(III) over phosphate. Density Functional Theory (DFT) modeling and extended X-ray adsorption fine structure (EXAFS) determined that Fe(III)-chitosan and Ni(II)-chitosan adsorbed As(V) and As(III) via inner-sphere complexation, while Cu(II)-chitosan formed mainly outer-sphere complexes with As(V) and As(III). These differences in complexation likely result in the observed differences in selective adsorption capability towards As(V) and As(III) over phosphate. It is hypothesized that the greater affinity of Fe(III)- and Ni(II)-chitosan towards As(V) and As(III) compared to Cu(II)-chitosan is due to their forming less-stable, more reactive chitosan complexes as predicted by the Irving Williams Series.

20.
J Environ Manage ; 297: 113358, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34311248

RESUMO

The alkali treated subglebal tissue of the mosaic puffball (Handkea utriformis) (Sa) and Sa modified with hydroxyapatite (Sa-HAp), obtained by successive ionic layer adsorption and reaction (SILAR) method, were used for the removal of Pb2+, Cd2+ and Ni2+ from aqueous solution. The materials were characterized by FT-IR, Raman, SEM and EDS analysis and by determination of pHPZC. The adsorption performances of Sa and Sa-HAp were assessed in batch experiments at different pH, contact times, temperatures and mass of the adsorbent. Different models of adsorption isotherms were used, and the best fit was obtained with the Langmuir model. Maximum adsorption capacities of Sa towards Pb2+, Cd2+ and Ni2+ were 44.82, 15.54 and 17.21 mg g-1, while for Sa-HAp were 79.55, 52.59 and 45.01 mg g-1, respectively. Kinetic data were well fitted by a pseudo second-order model, while thermodynamic studies disclose spontaneous and endothermic adsorption process. The Sa-Hap was successfully regenerated with 1 M NaCl and after the fifth desorption cycle and 10 h achieved 82.9, 69.7 and 60.4 %, while for 0.5 M NaCl + 0.5 M NaOH and 1 h was 78.3, 64.1, 57.5 % of desorbed Pb2+, Cd2+ and Ni2+, respectively. The competitive study and results from a column system confirmed good applicability of Sa-HAp adsorbent.


Assuntos
Agaricales , Metais Pesados , Poluentes Químicos da Água , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica , Poluentes Químicos da Água/análise
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