The state of protein phosphorylation can be a key determinant of cellular physiology such as early-stage cancer, but the development of phosphoproteins in biofluids for disease diagnosis remains ...elusive. Here we demonstrate a strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs isolated from small volumes of plasma samples. Using label-free quantitative phosphoproteomics, we identified 144 phosphoproteins in plasma EVs that are significantly higher in patients diagnosed with breast cancer compared with healthy controls. Several biomarkers were validated in individual patients using paralleled reaction monitoring for targeted quantitation. This study demonstrates that the development of phosphoproteins in plasma EV as disease biomarkers is highly feasible and may transform cancer screening and monitoring.
People with dementia die prematurely. Identifying differences in mortality rates between different types of dementia might aid in the development of preventive interventions for the most vulnerable ...populations. The aim of this study was to compare the difference in mortality rates between individuals without dementia and individuals with various types of dementia.
For this systematic review and meta-analysis, we did a systematic search of MEDLINE, PubMed, Embase, and Cochrane Library from inception to July 11, 2020, for cross-sectional or cohort studies that assessed mortality and survival-related outcomes among people with different types of dementia compared with people without dementia. Single-arm studies without comparison groups and autopsy studies or family studies that used a selected sample were excluded. The Newcastle-Ottawa Scale was used by two authors (D-JL and C-SC) independently to measure the methodological quality of included studies, and two authors (F-CY and P-TT) independently extracted data. We assessed differences in all-cause mortality rate and survival time from dementia diagnosis between individuals without dementia, individuals with Alzheimer's disease, and individuals with non-Alzheimer's disease dementias. The secondary outcomes were age at death and survival time from disease onset. Random-effects meta-analyses were done. Effect sizes included hazard ratios (HRs) and mean differences (MDs) with 95% CIs. Potential moderators, including age-associated moderators, were identified through meta-regression and subgroup analyses. This study is registered with PROSPERO, CRD42020198786.
Our database search identified 11 973 records, and we included 78 eligible studies in our analyses, encompassing 63 125 individuals with dementia and 152 353 controls. Individuals with any type of dementia had a higher mortality rate than individuals without dementia (HR 5·90, 95% CI 3·53 to 9·86), and the HR for all-cause mortality was highest for Lewy body dementia (17·88, 5·87 to 54·46). After diagnosis, the mean survival time for people with Alzheimer's disease was 5·8 years (SD 2·0). Compared with people with Alzheimer's disease, a diagnosis of any non-Alzheimer's disease dementia was associated with a higher risk of all-cause mortality (HR 1·33, 1·21 to 1·46), a shorter survival time from diagnosis (MD −1·12 years, 95% CI −1·52 to −0·72), and a younger age at death (−1·76 years, −2·66 to −0·85). Survival time from disease onset was also shorter in people with non-Alzheimer's dementia, across types, compared with people with Alzheimer's disease, but the subgroup analysis revealed that this difference was only significant for vascular dementia (MD −1·27 years, −1·90 to −0·65) and dementia with Lewy bodies (MD −1·06 years, −1·68 to −0·44). The interactions between age and several survival-related outcomes were significant. 39 (50%) of the 78 included studies were rated as good quality, and large heterogeneity (I2>75%) was observed for most of the study outcomes.
Alzheimer's disease is the most common type of dementia and one of the major causes of mortality worldwide. However, the findings from the current study suggest that non-Alzheimer's disease dementias were associated with higher morality rates and shorter life expectancy than Alzheimer's disease. Developing tailored treatment and rehabilitation programmes for different types of dementia is important for mental health providers, patients, and their families.
None.
•Serotonergic antidepressants improved overall NPS, agitation, depressive symptom, cognition, and care burden.•Both SSRIs and non-SSRIs significantly reduced agitation and depressive symptoms.•SSRIs, ...but not SSRIs reduced overall NPS and care burden.•Serotonergic antidepressants improved overall NPS among patients with not pure AD compared those with pure AD.
Serotonergic dysfunction may be involved in the etiology of overall neuropsychiatric symptoms (NPS) and agitation in patients with dementia; therefore, we aim to perform a systematic review and meta-analysis to investigate the efficacy of serotonergic antidepressants in such populations.
We systematically searched PubMed, Medline, Embase, and Cochrane Library to obtain randomized controlled trials (RCTs) from the date of their inception until December 11, 2020 to examine the effect of serotonergic antidepressants on the outcomes of interest in patients with dementia. Data were pooled using a random-effects model. Co-primary outcomes were mean changes in overall NPS and agitation as a specific symptom of NPS. Secondary outcomes were mean changes in depressive symptoms, cognition, and care burden.
Fourteen randomized controlled trials were eligible (n = 1,374; mean age = 76.8 years; mean proportion of female = 61.9 %). Serotonergic antidepressants significantly reduced the overall NPS (k = 12, n = 1276, Hedges’ g = −0.49, 95 % confidence intervals CIs = -0.74 to -0.24, p < 0.001) and agitation severity (k = 9, n = 749, Hedges’ g = −0.28, 95 % CIs = −0.43 to −0.14, p < 0.001), both with small effect size in patients with dementia. For secondary outcome, serotonergic antidepressants also significantly improved depressive symptoms, cognition, and care burden with small to very small effect sizes (depressive symptoms, k = 8, n = 938, Hedges’ g = −0.32, 95 % CIs = −0.49 to −0.15, p < 0.001;cognition, k = 6, n = 983, Hedges’ g = 0.15, 95 % CIs = 0.002 to 0.29, p = 0.046; care burden, k = 7, n = 961, Hedges’ g = −0.24, 95 % CIs = −0.41 to −0.07, p = 0.005). Subgroup analysis showed that both selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs significant reduced agitation and depressive symptoms (For agitation, SSRIs, k = 6, n = 605, Hedges’ g = −0.25, 95 % CIs = −0.41 to −0.09, p=0.002; non-SSRIs, k = 3, n = 144, Hedges’ g = −0.41, 95 % CIs = −0.74 to −0.08, p = 0.016; For depression, SSRIs, k = 6, n = 736, Hedges’ g = −0.29, 95 % CIs = −0.48 to −0.09, p=0.004; non-SSRIs, k = 343, n = 144, Hedges’ g = −0.43, 95 % CIs = −0.78 to −0.09, p = 0.016), whereas only SSRIs reduced overall NPS (k = 9, n = 1109, Hedges’ g = −0.49, 95 % CIs = −0.78 to −0.20, p = 0.001) and care burden (k = 5, n = 740, Hedges’ g = −0.29, 95 % CIs = −0.50 to −0.08, p=0.007).
The present meta-analysis indicates that serotonergic antidepressants effectively alleviate overall NPS, agitation, depressive symptoms, and care burden, and improve cognitive function.
Transposons are generally kept silent by epigenetic mechanisms including DNA methylation. Here, we identified a pair of Harbinger transposon-derived Rroteins （HDPs）, HDP1 and HDP2, as anti-silencing ...factors in Arabidopsis. hdp1 and hdp2 mutants displayed an enhanced silencing of transgenes and some transposons. Phylogenetic analyses revealed that HDP1 and HDP2 were co-domesticated from the Harbinger transposon-encoded transposase and DNA-binding protein, respectively. HDP1 interacts with HDP2 in the nucleus, analogous to their transposon counterparts. Moreover, HDP1 and HDP2 are associated with IDMI, IDM2, IDM3 and MBD7 that constitute a histone acetyltransferase complex functioning in DNA demethylation. HDP2 and the methyl-DNA-binding protein MBD7 share a large set of common genomic binding sites, indicating that they jointly determine the target specificity of the histone acetyltransferase complex. Thus, our data revealed that HDP1 and HDP2 constitute a functional module that has been recruited to a histone acetyltransferase complex to prevent DNA hypermethylation and epigenetic silencing.
Cranial electrotherapy stimulation (CES) is beneficial in reducing anxiety in psychiatric patients. However, no studies have reported on elderly patients with generalized anxiety disorders (GAD). ...This study aimed to determine the efficacy and safety of a 6-week CES intervention for late-life GAD.
This single-arm pilot study assessed 6-week CES treatment (Alpha-Stim AID) for late-life GAD and 4-week follow-up post intervention. The Hamilton Rating Scale for Anxiety (HAMA) and Beck Anxiety Inventory (BAI) were used as baseline and outcome measures at weeks 4, 6, and 10, respectively. Treatment response was defined as 50 % or more reduction of the HAMA score and remission was defined as a of score ≤7 on the HAMA. Other measures included depression, sleep quality, and quality of life assessment.
We included participants (n = 27) aged 68.0 ± 5.0 years, 81.5 % of whom were female. Fifteen (55.6 %), 18 (66.7 %), and 15 (55.6 %) patients were concurrently treated with antidepressants, BZDs, and antipsychotics, respectively. Intention-to-treat (ITT) analysis revealed a significant decrease in HAMA scores from baseline (20.96 ± 3.30) to week 6 (12.26 ± 7.09) and one-month (12.85 ± 7.08) follow-up at W10 (all p < 0.001). The response and remission rates were 33.3 %, 40.7 %, and 48.1 % and 25.9 %, 29.6 %, and 25.9 % at W4, W6, and W10, respectively. The CES improved depression and sleep conditions as measured by the Beck Depression Inventory-II and Pittsburgh Sleep Quality Index.
CES clinically reduces symptoms of anxiety and depression and may improve sleep quality in late-life GAD. Future randomized controlled study is needed.
To date, there is limited evidence on the antidepressant effects of memantine in patients with major mental diseases. We conducted a systematic review and meta-analysis to assess the efficacy of ...memantine in such populations.
A literature search was performed for randomized controlled trials (RCTs) from the date of their inception until September 28, 2021, using PubMed, Medline, Embase, and the Cochrane Library. Changes in depression scores were the primary outcome. The response rate and remission rate to the treatment were secondary outcomes. We also assessed the dropout rate for tolerance.
Eleven double-blind RCTs were included with 899 participants. Memantine significantly reduced depressive symptom scores compared with the control group (k = 11, n = 899, Hedges' g = −0.17, 95% confidence interval CI = −0.30 to −0.04, p = 0.009) with a small effect size. For secondary outcomes, memantine did not show a significant effect on response rate nor remission rate. In the subgroup analysis, memantine significantly reduced depressive symptom scores in patients with mood disorders (k = 8, n = 673, Hedges' g = −0.17, 95% CI = −0.32 to −0.01, p = 0.035) with a small effect size, but not in patients with schizophrenia.
The present meta-analysis indicates that memantine effectively alleviates depressive symptoms in patients with mood disorders with a small effect size. Furthermore, memantine is well-tolerated and acceptable.
•Memantine improved depressive symptoms in patients with major mental diseases with a small effect size.•Memantine did not show a significant effect on response rate or remission rate in depressive symptoms in patients with major mental diseases.•Memantine improved the depressive symptoms in mood disorder, but only with a trend in schizophrenia.
In several eukaryotic organisms, heterochromatin (HC) in the introns of genes can regulate RNA processing, including polyadenylation, but the mechanism underlying this regulation is poorly ...understood. By promoting distal polyadenylation, the bromo-adjacent homology (BAH) domain-containing and RNA recognition motif-containing protein ASI1 and the H3K9me2-binding protein EDM2 are required for the expression of functional full-length transcripts of intronic HC-containing genes in Arabidopsis. Here we report that ASI1 and EDM2 form a protein complex in vivo via a bridge protein, ASI1-Immunoprecipitated Protein 1 (AIPP1), which is another RNA recognition motif-containing protein. The complex also may contain the Pol II CTD phosphatase CPL2, the plant homeodomain-containing protein AIPP2, and another BAH domain protein, AIPP3. As is the case with dysfunction of ASI1 and EDM2, dysfunction of AIPP1 impedes the use of distal polyadenylation sites at tested intronic HC-containing genes, such as the histone demethylase gene IBM1, resulting in a lack of functional full-length transcripts. A mutation in AIPP1 causes silencing of the 35S-SUC2 transgene and genome-wide CHG hypermethylation at gene body regions, consistent with the lack of full-length functional IBM1 transcripts in the mutant. Interestingly, compared with asi1, edm2, and aipp1 mutations, mutations in CPL2, AIPP2, and AIPP3 cause the opposite effects on the expression of intronic HC-containing genes and other genes, suggesting that CPL2, AIPP2, and AIPP3 may form a distinct subcomplex. These results advance our understanding of the interplay between heterochromatic epigenetic modifications and RNA processing in higher eukaryotes.
We previously identified certain peripheral biomarkers of bipolar II disorder (BD-II) including circulating miRNAs (miR-7-5p, miR-142–3p, miR-221–5p, and miR-370–3p) and proteins (Matrix ...metallopeptidase 9 (MMP9), phenylalanyl-tRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin type 9 (PCSK9)). We try to explore the connection between these biomarkers.
We explored correlations between the peripheral levels of above circulating miRNAs and proteins in our previously collected BD-II (N = 96) patients and control (N = 115) groups. We further searched TargetScan and BioGrid websites to identify direct and indirect interactions between these protein-coding genes and circulating miRNAs.
In the BD-II group, we identified significant correlations between the miR-221–5p and CA-1 (rho = −0.323, P = 0.001), FARSB (rho = 0.251, P = 0.014), MMP-9 (rho = 0.313, P = 0.002) and PCSK9 (rho = 0.252, P = 0.014). The miR-370–3p also significantly correlated with FARSB expression (rho = 0.330, P = 0.001) and PCSK9 expression (rho = 0.221, P = 0.031) in the BD-II group. Our findings were in line with the modulating axis identified from TargetScan and BioGrid, miR-221–5p/CA-1/MMP9 and miR-370–3p/FARSB/PCSK9, suggesting their association with BD-II.
Our result supported that peripheral candidate miRNA and protein biomarkers may interact in BD-II. We concluded that miR-221–5p/CA-1/MMP9 and miR-370–3p/FARSB/PCSK9 axes might act a critical role in the pathomechanism of BD-II.
Some studies have suggested that depressive disorders may play a vital role in the incidence of hip fractures. However, nationwide data are lacking regarding the association between depressive ...disorders and hip fractures.
We aimed to explore the association between depressive disorders and new-onset hip fractures.
We conducted a retrospective study of 11,207 patients with depressive disorders and 11,207 control patients using Taiwan's National Health Insurance Research Database. A Cox regression model was used to evaluate the risk of hip fractures in patients with depressive disorders.
The incidence rate ratio of hip fractures between patients with depressive disorders and controls was 1.6 (95% confidence interval CI = 1.29-1.99, P < .001). After adjustment for potential confounders in multivariate analysis using the Cox regression model, patients with depressive disorders were found to have 1.34 times higher risk of hip fractures than controls (95% CI = 1.08-1.66, P = .008). Furthermore, age (hazard ratio HR = 7.43, 95% CI = 4.94-11.19, P < .001), hypertension (HR = 1.63, 95% CI = 1.17-2.28, P = .004), diabetes mellitus (HR = 1.47, 95% CI = 1.08-1.99, P = .014), cerebrovascular disease (HR = 1.76, 95% CI = 1.31-2.35, P < .001), living in rural areas (HR = 1.88, 95% CI = 1.30-2.70, P = .001), and low monthly income (NT$0-NT$19,000: HR = 4.08, 95% CI = 1.79-9.29, P = .001 and NT$19,100-NT$42,000: HR = 4.09, 95% CI = 1.76-9.49, P = .001) were independent risk factors for new-onset hip fractures in patients with depressive disorders.
Depressive disorders might increase the risk of new-onset hip fractures, particularly in older patients and patients with hypertension, diabetes mellitus, cerebrovascular disease, or low socioeconomic status.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
We aimed to investigate the efficacy and tolerability of cranial electrotherapy stimulation (CES) for patients with anxiety symptoms.
Method
We searched the Pubmed, Cochrane Central ...Register of Controlled Trials (CENTRAL), Embase and Medline for randomized control trials (RCTs) from the time of inception until November 15, 2021, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were pooled using a random-effects model. The primary outcomes were the mean change scores for anxiety symptoms. The secondary outcomes were the mean change scores for depressive symptoms.
Results
Eleven RCTs were eligible (
n
= 794, mean age: 41.4, mean population of female: 64.8%). CES significantly reduced the anxiety symptoms compared to the control group
k
= 11,
n
= 692, Hedge's g = −0.625, 95% confidence intervals (CIs) = −0.952 to −0.298,
P
< 0.001 with moderate effect size. The subgroup analysis showed that CES reduced both primary and secondary anxiety (primary anxiety,
k
=3,
n
= 288, Hedges' g = −1.218, 95% CIs = −1.418 to −0.968,
P
= 0.007; secondary anxiety,
k
= 8,
n
= 504, Hedges' g = −0.334, 95% CIs = −0.570 to −0.098,
P
= 0.006). After performing between group analysis, we found CES has significant better efficacy for patients with primary anxiety than those with secondary anxiety (
P
< 0.001). For secondary outcome, CES significantly reduced depressive symptoms in patients with anxiety disorders (
k
= 8,
n
= 552, Hedges' g = −0.648, 95% CIs = −1.062 to −0.234,
P
= 0.002). No severe side effects were reported and the most commonly reported adverse events were ear discomfort and ear pain.
Conclusion
We found CES is effective in reducing anxiety symptoms with moderate effect size in patients with both primary and secondary anxiety. Furthermore, CES was well-tolerated and acceptable.
Systematic Review Registration:
PROSPERO,
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021267916
.
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