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1.
bioRxiv ; 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38585830

ABSTRACT

A lack of empathy, and particularly its affective components, is a core symptom of behavioural variant frontotemporal dementia (bvFTD). Visual exposure to images of a needle pricking a hand (pain condition) and Q-tips touching a hand (control condition) is an established functional magnetic resonance imaging (fMRI) paradigm used to investigate empathy for pain (EFP; pain condition minus control condition). EFP has been associated with increased blood oxygen level dependent (BOLD) signal in regions known to become atrophic in the early stages in bvFTD, including the anterior insula and the anterior cingulate. We therefore hypothesized that patients with bvFTD would display altered empathy processing in the EFP paradigm. Here we examined empathy processing using the EFP paradigm in 28 patients with bvFTD and 28 sex and age matched controls. Participants underwent structural MRI, task-based and resting-state fMRI. The Interpersonal Reactivity Index (IRI) was used as a measure of different facets of empathic function outside the scanner. The EFP paradigm was analysed at a whole brain level and using two regions-of-interest approaches, one based on a metanalysis of affective perceptual empathy versus cognitive evaluative empathy and one based on the controls activation pattern. In controls, EFP was linked to an expected increase of BOLD signal that displayed an overlap with the pattern of atrophy in the bvFTD patients (insula and anterior cingulate). Additional regions with increased signal were the supramarginal gyrus and the occipital cortex. These latter regions were the only ones that displayed increased BOLD signal in bvFTD patients. BOLD signal increase under the affective perceptual empathy but not the cognitive evaluative empathy region of interest was significantly greater in controls than in bvFTD patients. The controls rating on their empathic concern subscale of the IRI was significantly correlated with the BOLD signal in the EFP paradigm, as were an informants ratings of the patients empathic concern subscale. This correlation was not observed on other subscales of the IRI or when using the patient's self-ratings. Finally, controls and patients showed different connectivity patterns in empathy related networks during resting-state fMRI, mainly in nodes overlapping the ventral attention network. Our results indicate that reduced neural activity in regions typically affected by pathology in bvFTD is associated with reduced empathy processing, and a predictor of patients capacity to experience affective empathy.

2.
PLoS One ; 19(4): e0301268, 2024.
Article in English | MEDLINE | ID: mdl-38573928

ABSTRACT

Nitric oxide (NO) is involved in a variety of biological functions including blood vessel dilation and neurotransmitter release. In animals, NO has been demonstrated to affect multiple behavioral outcomes, such as memory performance and arousal, whereas this link is less explored in humans. NO is created in the paranasal sinuses and studies show that humming releases paranasal NO to the nasal tract and that NO can then cross the blood brain barrier. Akin to animal models, we hypothesized that this NO may traverse into the brain and positively affect information processing. In contrast to our hypothesis, an articulatory suppression memory paradigm and a speeded detection task found deleterious effects of humming while performing the task. Likewise, we found no effect of humming on emotional processing of photos. In a fourth experiment, participants hummed before each trial in a speeded detection task, but we again found no effect on response time. In conclusion, either nasal NO does not travel to the brain, or NO in the brain does not have the expected impact on cognitive performance and emotional processing in humans. It remains possible that NO influences other cognitive processes not tested for here.


Subject(s)
Nitric Oxide , Paranasal Sinuses , Humans , Nose , Emotions , Cognition
3.
Foods ; 13(3)2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38338507

ABSTRACT

In this study, spray drying was used as a technological solution for the valorization of Teucrium montanum extract into carboxymethyl cellulose-based delivery systems (CMC), individually or in combination with collagen, guar gum, gum arabic, and kappa-carrageenan. The results showed that the process yield and morphological properties were positively influenced by the introduction of CMC binary blends. The employment of CMC resulted in a high encapsulation efficiency (77-96%) for all phenylethanoid glycosides (PGs) analyzed. Due to the low wettability of the microparticles, a relatively gradual in vitro release of the PGs was achieved. Infusion of the filling with hydrophilic T. montanum extract encapsulated in microparticles with high hydrophobic surface area proved to be a practical route for significant confectionery fortification (5-9 mg PGs per dw serving), ensuring prolonged interaction between the food matrix used and the extract under simulated gastrointestinal conditions. Based on sensory evaluation, the introduction of kudzu starch into the jelly matrix has shown a texture-modifying potential.

4.
J Affect Disord ; 351: 765-773, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38331048

ABSTRACT

The high prevalence of stress-related disorders and depression underscores the urgent need to unravel their impact on individual well-being. This study aim to investigate common psychiatric and stress-related diagnoses, along with postviral fatigue, in individuals with prior stress-induced exhaustion disorder (SED) and prior depression compared to those without prior SED or depression, and to study whether the psychiatric comorbidity patterns differ. The study includes individuals in Region Stockholm who, in 2011, did not have a diagnosis of SED or depression. ICD-10 diagnosis of SED, depression, or both, recorded in 2012-2013, were compared to individuals without prior SED or depression in a cohort (n = 1,362,886), aged 18 to 65. Odds ratios (OR) with 99 % confidence intervals, adjusted for age and neighborhood socioeconomic status, were calculated for psychiatric disorders and post-viral fatigue in 2014-2022. Patients with prior SED showed associations primarily with stress related diagnoses, including acute stress reaction, reaction to severe stress, as well as post-COVID-19 and post-viral fatigue syndrome. These ORs were all larger for SED than depression. Depression was primarily associated with post-traumatic stress disorder (PTSD), alcohol related and substance use disorders, schizophrenia, schizotypal disorders, delusional disorders, manic episode, bipolar affective disorder, persistent mood disorder, neurotic disorder, borderline personality disorder, autistic disorder, Asperger's syndrome, attention -deficit hyperactivity disorder, attention-deficit disorders ADHD/ADD), and suicide attempt. These ORs were all higher for depression, although autistic disorders, ADHD/ADD and PTSD were also highly associated with prior SED (OR > 3.5). The divergent psychiatric comorbidity patterns suggest different underlying mechanisms and clinical prognosis.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Fatigue Syndrome, Chronic , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/psychology , Cohort Studies , Depression/epidemiology , Comorbidity , Attention Deficit Disorder with Hyperactivity/epidemiology , Fatigue/epidemiology
5.
J Org Chem ; 89(5): 3226-3237, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38361498

ABSTRACT

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.

6.
J Affect Disord ; 351: 194-201, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38280572

ABSTRACT

It has long been speculated that psychedelic use could provoke the onset of psychosis, but there is little evidence to support this conjecture. Using a longitudinal research design with samples representative of the US and UK adult populations with regard to sex, age, and ethnicity (n = 9732), we investigated associations between psychedelic use and change in the number of psychotic symptoms during the two-month study period. In covariate-adjusted regression models, psychedelic use during the study period was not associated with a change in the number of psychotic symptoms unless it interacted with a personal or family history of bipolar disorder, in which case the number of symptoms increased, or with a personal (but not family) history of psychotic disorders, in which case the number of symptoms decreased. Taken together, these findings indicate that psychedelic use may affect psychotic symptoms in individuals with a personal or family history of certain disorders characterized by psychotic symptomatology.


Subject(s)
Bipolar Disorder , Hallucinogens , Psychotic Disorders , Adult , Humans , United States/epidemiology , Hallucinogens/adverse effects , Psychotic Disorders/drug therapy , Psychotic Disorders/epidemiology , Psychotic Disorders/complications , Bipolar Disorder/drug therapy , Bipolar Disorder/epidemiology , Bipolar Disorder/complications , United Kingdom/epidemiology
7.
Environ Sci Pollut Res Int ; 30(54): 116376-116396, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37910357

ABSTRACT

The objective of this study is to uncover the nature and strength of the effect that innovations have on CO2 emissions. The main motivation of this research is to offer reliable and credible findings by eliminating some methodical and conceptual shortcomings of the existing papers. The scope of the analysis is examining the innovations-CO2 emissions relationship in a sample of 43 countries in the period from 1991 to 2018. The research is based on the application of hidden panel cointegration theory and the concept of a partially asymmetric cointegration equation. The main findings of the study demonstrate that when innovations grow by 1%, the pattern of their change leads to an increase in CO2 emissions by an average of 0.006%. At the same time, when innovations decline by 1%, their change leads to a reduction in CO2 emissions by an average of 0.001%. Strictly speaking, in the phase of innovations growth, they have environmentally hostile average influence, while in the phase of innovations reduction, their impact is on average environmentally friendly. The average effect of innovations is very asymmetric, because negative environmental impact is about six times stronger than the positive one. Analysis by countries demonstrates that innovations influence varies significantly from country to country. The impact is environmentally friendly in only 32.6% of countries, regardless of whether innovations increase or decrease. In the remaining cases, the influence on the environment is hostile either when innovations grow, when they decline, or in both situations. The main conclusion of this study is that nature of the impact of innovations on CO2 emissions is quite unfavorable, which points to the need for much greater support for green innovations.


Subject(s)
Carbon Dioxide , Economic Development , Carbon Dioxide/analysis
8.
Alzheimers Res Ther ; 15(1): 161, 2023 10 02.
Article in English | MEDLINE | ID: mdl-37779209

ABSTRACT

BACKGROUND: Chronic stress and depression are potential risk factors for mild cognitive impairment and dementia, including Alzheimer disease. The aim was to investigate whether any such risk is additive. METHODS: Cohort study including 1 362 548 people (665 997 women, 696 551 men) with records in the Region Stockholm administrative healthcare database (VAL). Exposure was a recorded ICD-10 diagnosis of chronic stress, depression, or both, recorded in 2012 or 2013. Outcome was a diagnosis of Alzheimer disease, other dementia, or mild cognitive impairment recorded from 2014 through 2022. Odds ratios with 99% confidence intervals (CI) adjusted for age, sex, neighborhood socioeconomic status, diabetes, and cardiovascular disorders were calculated. RESULTS: During the exposure period, 4 346 patients were diagnosed with chronic stress, 40 101 with depression, and 1 898 with both. The average age at baseline was around 40 years in all groups. In the fully adjusted model, the odds ratio of Alzheimer disease was 2.45 (99% CI 1.22-4.91) in patients with chronic stress, 2.32 (99% CI 1.85-2.90) in patients with depression, and 4.00 (99% CI 1.67-9.58) in patients with chronic stress and depression. The odds ratio of mild cognitive impairment was 1.87 (99% CI 1.20-2.91) in patients with chronic stress, 2.85 (99% CI 2.53-3.22) in patients with depression, and 3.87 (99% CI 2.39-6.27) in patients with both. When other dementia was analyzed, the odds ratio was significant only in patients with depression, 2.39 (99% CI 1.92-2.96). CONCLUSIONS: Documented chronic stress increased the risk of mild cognitive impairment and Alzheimer disease. The same was seen with depression. The novel finding is the potential additive effect of chronic stress to depression, on risk of MCI and AD.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Male , Humans , Female , Adult , Adolescent , Young Adult , Middle Aged , Aged , Cohort Studies , Alzheimer Disease/diagnosis , Depression/epidemiology , Cognitive Dysfunction/diagnosis , Risk Factors
9.
BMC Psychiatry ; 23(1): 771, 2023 10 23.
Article in English | MEDLINE | ID: mdl-37872497

ABSTRACT

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.


Subject(s)
Autoimmune Diseases , Psychotic Disorders , Adult , Humans , Double-Blind Method , Inflammation , Psychotic Disorders/drug therapy , Randomized Controlled Trials as Topic , Rituximab/therapeutic use , Treatment Outcome
10.
Chem Biodivers ; 20(11): e202301044, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37772689

ABSTRACT

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).


Subject(s)
Asteraceae , Sesquiterpenes , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Methanol/chemistry , Antioxidants/chemistry , Plant Extracts/chemistry , Plant Components, Aerial/chemistry , Flavonoids/analysis , Asteraceae/chemistry , Lactones/pharmacology , Sesquiterpenes/pharmacology , Sesquiterpenes/analysis
11.
Sci Rep ; 13(1): 16432, 2023 09 30.
Article in English | MEDLINE | ID: mdl-37777572

ABSTRACT

Previous research has suggested that classical psychedelics can foster significant and enduring changes in personality traits and subjective wellbeing. Despite the lack of evidence for adverse effects on mental health stemming from psychedelic use, concerns persist regarding the capacity of these substances to modulate information processing and attitudes towards factual data. The aim of the present study was to investigate the propensity for accepting alternative facts and the general treatment of knowledge within a sample of 392 participants, 233 of whom reported at least a single incidence of psychedelic use in their lifetime. To do this, we leveraged step-wise methods of linear modelling investigating effects of demographics, psychiatric conditions and concomitant drug use. Our findings revealed a moderate positive association between psychedelic use and beliefs in alternative facts, as well as the specific belief that facts are politically influenced. However, no links were found for favouring intuition over evidence when confirming facts. Among other investigated drugs, only alcohol was negatively associated with beliefs in alternative facts. Taken together, our results support the link between psychedelic use and non-conformist thinking styles, which can be attributed to the psychological effects of the drugs themselves, but may also mirror a common trait related to unconventional beliefs and illicit substance use.


Subject(s)
Drug Users , Hallucinogens , Substance-Related Disorders , Humans , Hallucinogens/adverse effects , Substance-Related Disorders/psychology , Attitude , Mental Health
12.
Environ Sci Technol ; 57(32): 11718-11730, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37527361

ABSTRACT

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.

13.
Schizophr Bull ; 49(6): 1425-1436, 2023 11 29.
Article in English | MEDLINE | ID: mdl-37478890

ABSTRACT

BACKGROUND AND HYPOTHESIS: The neurocomputational framework of predictive processing (PP) provides a promising approach to explaining delusions, a key symptom of psychotic disorders. According to PP, the brain makes inferences about the world by weighing prior beliefs against the available sensory data. Mismatches between prior beliefs and sensory data result in prediction errors that may update the brain's model of the world. Psychosis has been associated with reduced weighting of priors relative to the sensory data. However, delusional beliefs are highly resistant to change, suggesting increased rather than decreased weighting of priors. We propose that this "delusion paradox" can be resolved within a hierarchical PP model: Reduced weighting of prior beliefs at low hierarchical levels may be compensated by an increased influence of higher-order beliefs represented at high hierarchical levels, including delusional beliefs. This may sculpt perceptual processing into conformity with delusions and foster their resistance to contradictory evidence. STUDY DESIGN: We review several lines of experimental evidence on low- and high-level processes, and their neurocognitive underpinnings in delusion-related phenotypes and link them to predicted processing. STUDY RESULTS: The reviewed evidence supports the notion of decreased weighting of low-level priors and increased weighting of high-level priors, in both delusional and delusion-prone individuals. Moreover, we highlight the role of prefrontal cortex as a neural basis for the increased weighting of high-level prior beliefs and discuss possible clinical implications of the proposed hierarchical predictive-processing model. CONCLUSIONS: Our review suggests the delusion paradox can be resolved within a hierarchical PP model.


Subject(s)
Delusions , Psychotic Disorders , Humans , Delusions/diagnosis , Psychotic Disorders/psychology , Brain , Prefrontal Cortex
14.
Mol Psychiatry ; 28(7): 2674-2682, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37147390

ABSTRACT

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.


Subject(s)
Bipolar Disorder , Humans , Mania , Cross-Sectional Studies , Brain , Prefrontal Cortex , Magnetic Resonance Imaging
15.
N Engl J Med ; 388(15): 1353-1364, 2023 Apr 13.
Article in English | MEDLINE | ID: mdl-36876740

ABSTRACT

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.).


Subject(s)
Cardiovascular Diseases , Humans , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/surgery , Double-Blind Method , Fatty Acids/administration & dosage , Fatty Acids/adverse effects , Fatty Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocardial Infarction/epidemiology , Myocardial Infarction/prevention & control , Stroke/epidemiology , Stroke/prevention & control , Administration, Oral , Myocardial Revascularization , Hypolipidemic Agents/administration & dosage , Hypolipidemic Agents/adverse effects , Hypolipidemic Agents/therapeutic use
16.
Inorg Chem ; 62(13): 5058-5066, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-36946599

ABSTRACT

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.

17.
Eur Child Adolesc Psychiatry ; 32(1): 75-86, 2023 Jan.
Article in English | MEDLINE | ID: mdl-34223993

ABSTRACT

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.


Subject(s)
Parents , Refugees , Humans , Retrospective Studies , Stress, Psychological
18.
J Sleep Res ; 32(4): e13815, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36579399

ABSTRACT

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.


Subject(s)
Cognition , Sleep Deprivation , Humans , Sleep Deprivation/psychology , Sleepiness , Sleep , Intelligence
19.
Brain Sci ; 12(10)2022 Oct 03.
Article in English | MEDLINE | ID: mdl-36291272

ABSTRACT

Psychotic disorders as well as psychosis proneness in the general population have been associated with perceptual instability, suggesting weakened predictive processing. Sleep disturbances play a prominent role in psychosis and schizophrenia, but it is unclear whether perceptual stability diminishes with sleep deprivation, and whether the effects of sleep deprivation differ as a function of psychosis proneness. In the current study, we aimed to clarify this matter. In this preregistered study, 146 participants successfully completed an intermittent version of the random dot kinematogram (RDK) task and the 21-item Peters Delusion Inventory (PDI-21) to assess perceptual stability and psychosis proneness, respectively. Participants were randomized to sleep either as normal (8 to 9 h in bed) (n = 72; Mage = 24.7, SD = 6.2, 41 women) or to stay awake through the night (n = 74; Mage = 24.8, SD = 5.1, 44 women). Sleep deprivation resulted in diminished perceptual stability, as well as in decreases in perceptual stability over the course of the task. However, we did not observe any association between perceptual stability and PDI-21 scores, nor a tendency for individuals with higher PDI-21 scores to be more vulnerable to sleep-deprivation-induced decreases in perceptual stability. The present study suggests a compromised predictive processing system in the brain after sleep deprivation, but variation in psychosis trait is not related to greater vulnerability to sleep deprivation in our dataset. Further studies in risk groups and patients with psychosis are needed to evaluate whether sleep loss plays a role in the occurrence of objectively measured perceptual-related clinical symptoms.

20.
Foods ; 11(12)2022 Jun 20.
Article in English | MEDLINE | ID: mdl-35742016

ABSTRACT

Ground ivy (Glechoma hederacea L.) has been known as a medicinal plant in folk medicine for generations and, as a member of the Lamiaceae family, is characterized with a high content of rosmarinic acid. The aim of the present study was to formulate delivery systems containing bioactive compounds from ground ivy in encapsulated form and incorporated into candies. Liposomes were examined as the encapsulation systems that were additionally coated with an alginate-plant protein gel to reduce leakage of the incorporated material. Bioactive characterization of the ground ivy extract showed a high content of total phenolics (1186.20 mg GAE/L) and rosmarinic acid (46.04 mg/L). The formulation of liposomes with the high encapsulation efficiency of rosmarinic acid (97.64%), with at least a double bilayer and with polydisperse particle size distribution was achieved. Alginate microparticles reinforced with rice proteins provided the highest encapsulation efficiency for rosmarinic acid (78.16%) and were therefore used for the successful coating of liposomes, as confirmed by FT-IR analysis. Coating liposomes with alginate-rice protein gel provided prolonged controlled release of rosmarinic acid during simulated gastro-intestinal digestion, and the same was noted when they were incorporated into candies.

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