Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not ...fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.
La0.3(Ba0.5Sr0.5)0.7Co0.8Fe0.2O3−δ is a promising bifunctional perovskite catalyst for the oxygen reduction reaction and the oxygen evolution reaction. This catalyst has circa 10 nm‐scale ...rhombohedral LaCoO3 cobaltite particles distributed on the surface. The dynamic microstructure phenomena are attributed to the charge imbalance from the replacement of A‐site cations with La3+ and local stress on Co‐site sub‐lattice with the cubic perovskite structure.
The perovskite La0.3(Ba0.5Sr0.5)0.7Co0.8Fe0.2O3−δ (La0.3‐5582) is introduced as a bifunctional catalyst to compete with precious‐metal‐based catalysts. The newly introduced perovskite bears rhombohedral phase LaCoO3−δ particles on the surface of the grains.
Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyper-inflammation, acute respiratory distress syndrome, and multiple organ failure. Cytokine storm refers to a set of clinical ...conditions caused by excessive immune reactions and has been recognized as a leading cause of severe COVID-19. While comparisons have been made between COVID-19 cytokine storm and other kinds of cytokine storm such as hemophagocytic lymphohistiocytosis and cytokine release syndrome, the pathogenesis of cytokine storm has not been clearly elucidated yet. Recent studies have shown that impaired response of type-1 IFNs in early stage of COVID-19 infection played a major role in the development of cytokine storm, and various cytokines such as IL-6 and IL-1 were involved in severe COVID-19. Furthermore, many clinical evidences have indicated the importance of anti-inflammatory therapy in severe COVID-19. Several approaches are currently being used to treat the observed cytokine storm associated with COVID-19, and expectations are especially high for new cytokine-targeted therapies, such as tocilizumab, anakinra, and baricitinib. Although a number of studies have been conducted on anti-inflammatory treatments for severe COVID-19, no specific recommendations have been made on which drugs should be used for which patients and when. In this review, we provide an overview of cytokine storm in COVID-19 and treatments currently being used to address it. In addition, we discuss the potential therapeutic role of extracorporeal cytokine removal to treat the cytokine storm associated with COVID-19.
Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At ...first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia.
Background and Aims
How Wnt signaling is orchestrated in liver regeneration and tumorigenesis remains elusive. Recently, we identified transmembrane protein 9 (TMEM9) as a Wnt signaling amplifier.
...Approach and Results
TMEM9 facilitates v‐ATPase assembly for vesicular acidification and lysosomal protein degradation. TMEM9 is highly expressed in regenerating liver and hepatocellular carcinoma (HCC) cells. TMEM9 expression is enriched in the hepatocytes around the central vein and acutely induced by injury. In mice, Tmem9 knockout impairs hepatic regeneration with aberrantly increased adenomatosis polyposis coli (Apc) and reduced Wnt signaling. Mechanistically, TMEM9 down‐regulates APC through lysosomal protein degradation through v‐ATPase. In HCC, TMEM9 is overexpressed and necessary to maintain β‐catenin hyperactivation. TMEM9–up‐regulated APC binds to and inhibits nuclear translocation of β‐catenin, independent of HCC‐associated β‐catenin mutations. Pharmacological blockade of TMEM9‐v‐ATPase or lysosomal degradation suppresses Wnt/β‐catenin through APC stabilization and β‐catenin cytosolic retention.
Conclusions
Our results reveal that TMEM9 hyperactivates Wnt signaling for liver regeneration and tumorigenesis through lysosomal degradation of APC.
In this study, silicon (Si) was doped on a tetrahedral amorphous carbon (ta-C) coating and the tribological characteristics of the resulting Si-doped diamond-like carbon (DLC; a-C:Si:H) were ...investigated against a SUJ2 ball. The Si fraction in the coating was varied from 0 to ~ 20 at.% by increasing the trimethylsilane gas flow rate during filtered cathodic vacuum arc deposition. The coefficient of friction (CoF) showed no obvious change when the Si fraction was less than ~ 7 at.%. However, after Si doping, it significantly decreased when the Si fraction was greater than ~ 8 at.%. The running-in period also decreased to less than 1000 cycles after Si doping. The rapid formation of Si-rich debris and transfer layer led to the fabrication of a low-friction tribofilm, which was induced by the tribochemical reaction with moisture under ambient conditions. When the Si fraction was ~ 17 at.%, the lowest CoF of less than 0.05 was obtained. Further Si doping beyond the critical point led to the destruction of the film because of reduced hardness.
A heat‐treatment approach for Ba0.5Sr0.5Co0.8Fe0.2O3–δ (BSCF5582) is introduced as a way of enhancing the electrocatalytic performance of perovskite catalysts. The perovskite made by heat‐treatment ...in oxygen atmosphere loses around 30 nm of spinel layer on the surface relative to the untreated version, and demonstrates enhanced oxygen reduction reaction and oxygen evolution reaction catalytic activities.
The loss of retinal ganglion cells observed in Alzheimer's disease (AD) may be attributable to a neurodegeneration of the neuro-retinal structure. Amnestic mild cognitive impairment (aMCI) has been ...considered a prodromal stage of AD. We evaluated retinal thicknesses in patients with aMCI and AD compared to healthy controls using spectral-domain optical coherence tomography (OCT) to investigate whether changes in retinal thickness are correlated with the clinical severity of dementia.
Patients with aMCI (n = 14), mild to moderate AD (n = 7), severe AD (n = 9), and age-matched controls (n = 17) underwent neuro-ophthalmologic examinations. Global deterioration scale (GDS), clinical dementia rating (CDR), and mini-mental status examination (MMSE) were used to evaluate the clinical overall severity of dementia. The thicknesses of the peripapillary retinal nerve fiber layer (RNFL), total macula, and macular ganglion cell-inner plexiform layer (GC-IPL) were measured using Cirrus HD-OCT.
The severe AD group had overall significantly thinner GC-IPL, total macula, and peripapillary RNFL compared to the controls (p<0.05). In the mild to moderate AD group, the total macula, average RNFL, and superior RNFL thickness were each significantly reduced compared to controls (p<0.05). The aMCI group had reduced total macula, average RNFL, and inferior RNFL thickness, but there were no significant differences compared to the controls. The GDS and CDR scores had a negative correlation with the thickness of the GC-IPL and the total macula. The MMSE scores had a positive correlation with both the total macular and average RNFL thickness, when adjusted for age (p<0.05).
This study confirmed that retinal thickness is decreased in AD patients. There is a correlation between reduced retinal thickness and the clinical severity of dementia.
The half-bridge (HB) LLC converter is one of the most attractive dc-dc converters for medium power supplies due to its soft switching capability. However, its conversion efficiency is considerably ...degraded in wide-link-voltage applications because of a small magnetizing inductance and wide switching frequency variation for a high voltage gain. In this paper, a boost power factor correction (PFC) stage, which can also play an important role during the hold-up time, is proposed for a high-efficiency HB LLC converter. In the proposed PFC stage, the boost PFC converter can be effectively utilized as a HB converter by replacing a boost diode and inductor with a synchronous switch and transformer, respectively. After the ac line is lost, the proposed PFC stage can operate as the HB converter and regulate the output voltage instead of the HB LLC converter. Thus, it enables the HB LLC converter to be designed with a large magnetizing inductance and narrow switching frequency variation. As a result, the proposed PFC stage can enhance the overall efficiency of the PSU by improving the efficiency of the HB LLC converter. To confirm the validity of this paper, a prototype with 180-264-Vrms ac line, 250-400-V link voltage, and 48 V/480 W output is tested.
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