COVID-19-related social restrictions resulted in more loneliness, but whether this had further effects on mental health remains unclear. This study aimed at examining the longitudinal effects of ...COVID-19-related loneliness on mental health among older adults (aged ≥60 years) in Austria.
Survey data were gathered from a longitudinal observational study among a random sample of older Austrian adults. The first survey wave was conducted in May 2020 (N1 = 557), and the second wave was conducted in March 2021 (N2 = 463).
Data collection was based on either computer-assisted web or telephone interviewing. For statistical analysis, we used a cross-lagged panel analysis.
The results showed the perceived COVID-19-related social restrictions to predict loneliness, which in turn predicted depressive and anxiety symptoms 10 months later.
COVID-19-related loneliness emerged as a risk factor for subsequent mental distress among older adults in Austria.
There is considerable heterogeneity within populations regarding the effects of the COVID-19 pandemic on mental health. This study aimed at identifying latent groups of individuals within the older ...Austrian population that differ in their mental health trajectories across three phases of the pandemic.
Data were gathered from a longitudinal survey study among a sample of older adults in Austria. The survey was carried out in May 2020 (N1 = 556), March 2021 (N2 = 462), and December 2021 (N3 = 370) via either computer-assisted web or telephone interviewing.
Latent class growth analysis was conducted to explore different homogenous groups in terms of non-linear trajectories of loneliness, depressive symptoms, and anxiety symptoms as well as potential correlates thereof.
We identified four latent classes. The vast majority of individuals belong to two classes that are either resilient (71%) or that have recovered relatively quickly from an initial COVID-19 shock (10.2%). Deterioration in mental health after the first phase of the pandemic (13.4%) or a generally high mental health burden (5.4%) characterizes the other two classes.
About 19% of individuals showed increasing or elevated levels in loneliness, depressive symptoms, and anxiety symptoms across the COVID-19 pandemic. The feeling of being socially supported and in control over one's own life emerged as potentially protective factors.
This study was conducted to describe how population-level subjective well-being (SWB) evolved throughout the pandemic.
Thirty waves of panel data representative of the Austrian population aged ≥14 ...years were collected between March 2020 and March 2022. Participants were quota sampled from a pre-existing online panel based on key demographics closely mirroring the Austrian resident population.
We present wave-specific means of SWB throughout 2 years of the COVID-19 pandemic next to the evolution of the pandemic (cases and deaths) and stringency of lockdown measures in Austria as well as estimate their bivariate correlations.
The analysed sample consisted of 3,293 participants contributing to a total of 46,168 observations. All components of SWB – negative affect, positive affect and life satisfaction – showed population-level fluctuation between March 2020 and March 2022. The magnitude of these changes was small. Population-level SWB correlated with the incidence rate of COVID-19 deaths (negative affect: r = 0.69, positive affect: r = −0.70, life satisfaction: r = −0.47), the Stringency Index (negative affect = 0.50, positive affect = −0.47, life satisfaction = −0.47) and less so with the incidence of COVID-19 cases (negative affect = 0.43, positive affect = −0.31, life satisfaction = −0.38).
Population-level SWB fluctuated in accordance with rises and falls in COVID-19 cases and deaths as well as with the stringency of lockdown measures. This connection suggests that incidence of COVID-19 cases and deaths, as well as public health measures to contain the pandemic affect population-level SWB and could thereby impact population health and productivity.
This study employed dominance analysis to assess the relative importance of maternal and paternal support, behavioral control, and psychological control in explaining depression, antisocial behavior, ...and social initiative within 644 adolescents. We noted the lack of replicated findings concerning differential effects of mothers and fathers and employed an approach that considered mothers' and fathers' overlapping predictive abilities in determining their relative importance. Results lend support to the overall parental framework and additionally suggest (a) mothers' behavioral control is relatively more important than fathers' in explaining sons' subsequent antisocial behavior, (b) fathers' support is relatively more important than mothers' support in explaining subsequent youth social initiative, and (c) mothering and fathering tend to have a cross-gendered effect on early adolescents' depression.
DX-2930 is a human monoclonal antibody inhibitor of plasma kallikrein under investigation for long-term prophylaxis of hereditary angioedema.
To assess the safety, tolerability, pharmacokinetics, and ...pharmacodynamics of DX-2930 in healthy subjects.
A single-center, double-blinded study was performed in 32 healthy subjects randomized 3:1 to receive a single subcutaneous administration of DX-2930 or placebo within 1 of 4 sequential, ascending dose cohorts (n = 8 each): 0.1, 0.3, 1.0, or 3.0 mg/kg.
No dose-limiting toxicity was observed. Headache was the most commonly reported treatment emergent adverse event (AE), occurring at a rate of 25% in the DX-2930- and placebo-treated groups; none were severe and all resolved. There were no serious AEs, discontinuations owing to an AE, or deaths. Two subjects had a severe AE reported as related to treatment by the blinded investigator; the 2 AEs were asymptomatic creatinine phosphokinase elevations of 902 U/L in 1 subject receiving 0.1 mg/kg DX-2930 and 1,967 U/L in 1 subject receiving placebo. For the 0.1-, 0.3-, 1.0-, and 3.0-mg/kg dose groups, respectively, mean maximum plasma concentrations were 0.6, 1.4, 5.6, and 14.5 μg/mL and mean elimination half-lives were 20.6, 16.8, 17.6, and 21.2 days. Exploratory biomarker assays, involving ex vivo activation of the kallikrein pathway, showed dose- and time-dependent inhibition of plasma kallikrein, with evidence of sustained bioactivity consistent with the pharmacokinetics profile.
A single administration of DX-2930 in healthy subjects up to doses of 3.0 mg/kg was well tolerated without dose-limiting toxicity. Pharmacokinetic and pharmacodynamic data provide evidence for a long-acting biological effect relevant to long-term prophylaxis for hereditary angioedema with C1-inhibitor deficiency.
ClinicalTrials.gov identifier: NCT01923207.
The use of thrombolytics is frequently considered in patients with cerebral venous and dural sinus thrombosis (CVT) who deteriorate despite anticoagulant therapy.
To collect all the published ...information about the use of systemic thrombolysis in CVT in order to assess its efficacy and safety.
We performed a PubMed search, checked all reference lists of studies found and used data from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Outcome was classified at the last available follow-up by the modified Rankin Scale (mRS). The cases were stratified according to variables that might influence outcome.
A total of 16 reports (26 patients, 2 from the ISCVT and 24 from the systematic review of the literature) were included. No randomized clinical trial was found. Seven patients presented with isolated intracranial hypertension syndrome (26.9%), 17 with encephalopathy (65.4%) and 2 were comatose (7.7%). The superior sagittal sinus was the one most often affected (n = 21; 80.8%), and there was thrombosis of the deep cerebral venous system in 5 patients (19.2%). Urokinase was the thrombolytic agent most frequently administered (n = 19; 73.1%), whereas streptokinase and recombinant tissue plasminogen activator were used in 2 cases each (7.7%). Intracranial hemorrhages occurred in 3 cases (11.5%). Extracranial hemorrhages occurred in 5 cases (19.2%), and overall there were 3 cases of serious bleeding (11.5%), including 2 deaths (7.7%). Partial or complete recanalization was verified in most patients (n = 16; 61.5%). The survival rate was 92.3% (24/26 patients). At the last available follow-up, 22/25 patients regained independency (mRS scores 0-2; 88%), 2/25 died (mRS score 6; 8%) and 1/25 was severely dependent (mRS scores 3-5; 4%).
In all, 88% of the CVT patients treated with systemic thrombolysis regained their independency, but 2 deaths associated with intracranial hemorrhage occurred. The mortality rate and disability at the last available follow-up were similar to those found in 2 previous systematic reviews concerning the use of thrombolytics in CVT. Due to the small sample size and lack of controls, the efficacy of systemic thrombolysis in acute CVT cannot be assessed from the published information. Concerning safety, a nonnegligible proportion of bleedings was reported.
Gene-editing technologies, which include the CRISPR-Cas nucleases
and CRISPR base editors
, have the potential to permanently modify disease-causing genes in patients
. The demonstration of durable ...editing in target organs of nonhuman primates is a key step before in vivo administration of gene editors to patients in clinical trials. Here we demonstrate that CRISPR base editors that are delivered in vivo using lipid nanoparticles can efficiently and precisely modify disease-related genes in living cynomolgus monkeys (Macaca fascicularis). We observed a near-complete knockdown of PCSK9 in the liver after a single infusion of lipid nanoparticles, with concomitant reductions in blood levels of PCSK9 and low-density lipoprotein cholesterol of approximately 90% and about 60%, respectively; all of these changes remained stable for at least 8 months after a single-dose treatment. In addition to supporting a 'once-and-done' approach to the reduction of low-density lipoprotein cholesterol and the treatment of atherosclerotic cardiovascular disease (the leading cause of death worldwide
), our results provide a proof-of-concept for how CRISPR base editors can be productively applied to make precise single-nucleotide changes in therapeutic target genes in the liver, and potentially in other organs.
Brain edema is a life-threatening consequence of stroke and leads to an extension of the affected tissue. The space-occupying effect due to brain edema can be quantified in rat stroke models with the ...use of MRI. The present study was performed to test 2 hypotheses: (1) Can quantification of the space-occupying effect due to brain edema serve as a noninvasive measure for brain water content? (2) Does morphometric assessment of brain swelling allow determination of true infarct size on MRI after correction for the space-occupying effect of edema?
Thirty rats were subjected to permanent suture middle cerebral artery occlusion. MRI was performed after 6 or 24 hours, and hemispheric swelling was assessed morphometrically. Interobserver and intraobserver agreements were determined for MRI measurements. In study I, the space-occupying effect due to brain edema was correlated with the absolute brain water content by the wet/dry method. In study II, lesion volumes corrected and uncorrected for edema were calculated on MRI and on TTC staining and compared.
Interobserver and intraobserver agreements for MRI measurements were excellent (r>or=0.97). Brain water content and hemispheric swelling correlated well after 6 and 24 hours (r>or=0.95). Corrected lesion volumes correlated with r=0.78 between TTC staining and MRI. Without edema correction, lesion volumes were overestimated by 20.3% after 6 hours and by 29.6% after 24 hours of ischemia.
Morphometric assessment of hemispheric swelling on MRI can determine the increase in absolute brain water content noninvasively and can also provide ischemic lesion volumes corrected for brain edema.
The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of ...circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases.
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