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A Corrigendum on "SARS-CoV-2 Omicron variants: burden of disease, impact on vaccine effectiveness and need for variant-adapted vaccines" by Pather S, Madhi SA, Cowling BJ, Moss P, Kamil JP, Ciesek S, Muik A and Türeci Ö (2023). . 14:1130539. doi: 10.3389/fimmu.2023.1130539
Objectives: Patient-level factors that influence compliance with a recommendation for CBT in nursing home residents diagnosed with depression were identified.
Methods: Within a cluster-randomized trial on stepped care for depression in nursing homes (DAVOS-study, Trial registration: DRKS00015686), participants received an intake interview administered by a licensed psychotherapist. If psychotherapy was required, patients were offered a referral for CBT. Sociodemographic characteristics, severity of depression, loneliness, physical health, antidepressant medication, prior experience with psychotherapy, and attitudes towards own aging were assessed. A binary regression determined predictors of compliance with referral.
Results: Of 123 residents receiving an intake interview, 80 were recommended a CBT. Forty-seven patients (58.8 %) followed the recommendation. The binary logistic regression model on compliance with recommended CBT was significant, χ2(9) = 21.64, p = .010. Significant predictors were age (Odds Ratio (OR) = 0.9; 95 % Confidence Interval (CI) = 0.82, 0.99; p = .024) and depression (OR = 1.33; 95 % CI = 1.08, 1.65; p = .008).
Conclusion: Within the implemented setting compliance rate was comparable to other age groups. Future interventions should include detailed psychoeducation on the benefits of psychotherapy on mild depressive symptoms in older age and evidence-based interventions to address the stigma of depression. Interventions such as reminiscence-based methods or problem-solving could be useful to increase compliance with referral, especially in very old patients (80+). Language barriers and a culturally sensitive approach should be considered when screening residents.
In a recent discussion on how to deal with data analysis issues initiated by reviewers of pain-related scientific manuscripts in the European Journal of Pain, a seemingly simple statistical issue was raised: two subsets of data in a paper had the same mean and standard deviation. A reviewer asked for a statistical test for or against the identity of the subset distributions. The authors insisted that if the mean and standard deviation were the same, this was sufficient evidence that the subsets of data were not significantly different.
This prompted a discussion among pain researchers, who are not necessarily primarily from the field of data science, a discussion of the importance of carefully examining the distribution of pain-related data in a journal whose primary audience is pain researchers seems warranted...
Treatment of patients with recent-onset type 1 diabetes with an anti-CD3 antibody leads to the transient stabilization of C-peptide levels in responder patients. Partial efficacy may be explained by the entry of islet-reactive T-cells spared by and/or regenerated after the anti-CD3 therapy. The CXCR3/CXCL10 axis has been proposed as a key player in the infiltration of autoreactive T cells into the pancreatic islets followed by the destruction of β cells. Combining the blockade of this axis using ACT-777991, a novel small-molecule CXCR3 antagonist, with anti-CD3 treatment may prevent further infiltration and β-cell damage and thus, preserve insulin production. The effect of anti-CD3 treatment on circulating T-cell subsets, including CXCR3 expression, in mice was evaluated by flow cytometry. Anti-CD3/ACT-777991 combination treatment was assessed in the virally induced RIP-LCMV-GP and NOD diabetes mouse models. Treatments started at disease onset. The effects on remission rate, blood glucose concentrations, insulitis, and plasma C-peptide were evaluated for the combination treatment and the respective monotherapies. Anti-CD3 treatment induced transient lymphopenia but spared circulating CXCR3+ T cells. Combination therapy in both mouse models synergistically and persistently reduced blood glucose concentrations, resulting in increased disease remission rates compared to each monotherapy. At the study end, mice in disease remission demonstrated reduced insulitis and detectable plasma C-peptide levels. When treatments were initiated in non-severely hyperglycemic NOD mice at diabetes onset, the combination treatment led to persistent disease remission in all mice. These results provide preclinical validation and rationale to investigate the combination of ACT-777991 with anti-CD3 for the treatment of patients with recent-onset diabetes.
Assessment of the acute effects of 2C-B vs. psilocybin on subjective experience, mood, and cognition
(2023)
2,5-dimethoxy-4-bromophenethylamine (2C-B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it's acute effects and distinctions from classical progenitors have yet to be characterized in a controlled study. We assessed for the first time the immediate acute subjective, cognitive, and cardiovascular effects of 2C-B (20 mg) in comparison to psilocybin (15 mg) and placebo in a within-subjects, double-blind, placebo-controlled study of 22 healthy psychedelic-experienced participants. 2C-B elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution largest under psilocybin. Participants demonstrated equivalent psychomotor slowing and spatial memory impairments under either compound compared with placebo, as indexed by the Digit Symbol Substitution Test, Tower of London, and Spatial Memory Task. Neither compound produced empathogenic effects on the Multifaceted Empathy Test. 2C-B induced transient pressor effects to a similar degree as psilocybin. The duration of self-reported effects of 2C-B was shorter than that of psilocybin, largely resolving within 6 hours. Present findings support the categorization of 2C-B as a psychedelic of moderate experiential depth at doses given. Tailored dose-effect studies are needed to discern the pharmacokinetic dependency of 2C-B's experiential overlaps.
Anti-inflammatory response of Vitamin D on extracranial vessels after subarachnoid hemorrhage
(2023)
Oral e-Poster Presentations - Booth 1: Vascular A (Aneurysms), September 25, 2023, 1:00 PM - 2:30 PM
Background: Vitamin D has been promoted to vascular regeneration in non-cerebral arteries because of its anti-inflammatory properties. Systematic inflammatory reaction as a multifactorial complication after subarachnoid hemorrhage (SAH), correlated with higher mortality and poor outcome, is the result of a multifactorial mechanism with vasoactive inflammation on extracranial vessels. We therefore hypothesized that vitamin D attenuates the systemic vascular inflammatory reaction.
Methods: We investigated the effect of vitamin D pretreatment (100 ng/kg/d; 5 days) in a blood injection SAH model in adult male C57BL6 mice. Vasomotor function (via wire myograph) of carotid and femoral artery and neurological deficits were measured. Different inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM), were also tested.
Results: A significantly enhanced vasorelaxation was identified in Vitamin D pretreated mice (SAH-VitD versus SAH-control: p<0,001; n=10). Missing a relevant difference in vasocontraction of carotid and femoral artery comparing SAH mice with and without vitamin D treatment, there was a significantly higher endothelial related vasorelaxing effect in treated SAH mice (p<0,01, n=5). Neurological deficits in vitamin D pre-treated SAH mice were significantly decreased (p<0,05; n=10). All tested inflammatory factors were down-regulated in vitamin D pre-treated mice (SAH-VitD versus SAH-control: p<0,0001; n=10).
Conclusions: Extracranial vascular Inflammation after SAH, as one of the influencing components in the follow-up after SAH onset, was significantly attenuated by Vitamin D pretreatment. Furthermore, anti-inflammatory effect of vitamin D resulted in a decrease of extracranial vasoconstriction and neurological deficits. Further research should be focused on vitamin D to optimize therapeutic strategies for SAH patients in critical care units.
Abnormal venous atrial (VA) connections present a congenital heart disease (CHD) challenge for pediatric cardiologists. Fully anatomical evaluation is very difficult in prenatal and perinatal follow-up, but it has a profound impact on surgical correction and outcome. The echocardiogram is first-line imaging and represents the gold standard tool for simple abnormal VA connection. CT and MRI are mandatory for more complex heart disease and “nightmare cases”. 3D post-processing of volumetric CT and MRI acquisition helps to clarify anatomical relationships and allows for the creation of 3D printing models that can become crucial in customizing surgical strategy.
Highlights
• Up-to-date overview on developing new medications including candidates with novel bioloigical targets for the treatment of anxiety disorders and PTSD.
• Targeting glutamatergic, cholinergic and neurosteroid mechanisms can produce acute anxiolytic effects.
• Drugs, including psychedelics, are hypothesized to produce neuroplasticity to cause enduring clinical effects.
• Combining medication with psychological approaches may augment therapeutic efficacy.
• Advances in circuit neuroscience can be leveraged to inform the design of rationale drug targets.
Abstract
Psychiatric disorders associated with psychological trauma, stress and anxiety are a highly prevalent and increasing cause of morbidity worldwide. Current therapeutic approaches, including medication, are effective in alleviating symptoms of anxiety disorders and posttraumatic stress disorder (PTSD), at least in some individuals, but have unwanted side-effects and do not resolve underlying pathophysiology. After a period of stagnation, there is renewed enthusiasm from public, academic and commercial parties in designing and developing drug treatments for these disorders. Here, we aim to provide a snapshot of the current state of this field that is written for neuropharmacologists, but also practicing clinicians and the interested lay-reader. After introducing currently available drug treatments, we summarize recent/ongoing clinical assessment of novel medicines for anxiety and PTSD, grouped according to primary neurochemical targets and their potential to produce acute and/or enduring therapeutic effects. The evaluation of putative treatments targeting monoamine (including psychedelics), GABA, glutamate, cannabinoid, cholinergic and neuropeptide systems, amongst others, are discussed. We emphasize the importance of designing and clinically assessing new medications based on a firm understanding of the underlying neurobiology stemming from the rapid advances being made in neuroscience. This includes harnessing neuroplasticity to bring about lasting beneficial changes in the brain rather than – as many current medications do – produce a transient attenuation of symptoms, as exemplified by combining psychotropic/cognitive enhancing drugs with psychotherapeutic approaches. We conclude by noting some of the other emerging trends in this promising new phase of drug development.
Adhesion of human pathogenic bacteria to endothelial cells is facilitated by fibronectin interaction
(2023)
Human pathogenic bacteria circulating in the bloodstream need to find a way to interact with endothelial cells (ECs) lining the blood vessels to infect and colonise the host. The extracellular matrix (ECM) of ECs might represent an attractive initial target for bacterial interaction, as many bacterial adhesins have reported affinities to ECM proteins, in particular to fibronectin (Fn). Here, we analysed the general role of EC-expressed Fn for bacterial adhesion. For this, we evaluated the expression levels of ECM coding genes in different ECs, revealing that Fn is the highest expressed gene and thereby, it is highly abundant in the ECM environment of ECs. The role of Fn as a mediator in bacterial cell-host adhesion was evaluated in adhesion assays of Acinetobacter baumannii, Bartonella henselae, Borrelia burgdorferi, and Staphylococcus aureus to ECs. The assays demonstrated that bacteria colocalised with Fn fibres, as observed by confocal laser scanning microscopy. Fn removal from the ECM environment (FN1 knockout ECs) diminished bacterial adherence to ECs in both static and dynamic adhesion assays to varying extents, as evaluated via absolute quantification using qPCR. Interactions between adhesins and Fn might represent the crucial step for the adhesion of human-pathogenic Gram-negative and Gram-positive bacteria targeting the ECs as a niche of infection.