Mood disorders are the most prevalent psychiatric disorders associated with significant disability, morbidity, and mortality. The risk of suicide is associated with severe or mixed depressive ...episodes in patients with mood disorders. However, the risk of suicide increases with the severity of depressive episodes and is often presented with higher incidences in bipolar disorder (BD) patients than in patients with major depression (MDD). Biomarker study in neuropsychiatric disorders is critical for developing better treatment plans by facilitating more accurate diagnosis. At the same time, biomarker discovery also provides more objectivity to develop state-of-the-art personalized medicine with increased accuracy through clinical interventions. Recently, colinear changes in miRNA expression between brain and systemic circulation have added great interest in examining their potential as molecular markers in mental disorders, including MDD, BD, and suicidality. A present understanding of circulating miRNAs in body fluids implicates their role in managing neuropsychiatric conditions. Most notably, their use as prognostic and diagnostic markers and their potential role in treatment response have significantly advanced our knowledge base. The present review discusses circulatory miRNAs and their underlying possibilities to be used as a screening tool for assessing major psychiatric conditions, including MDD, BD, and suicidal behavior.
MicroRNAs, a class of noncoding RNAs, play roles in human diseases. MicroRNA-223 (miR-223) is reported to play critical roles in osteoclastogenesis. The purpose of this study was to analyze the ...expression pattern of miR-223 in rheumatoid arthritis (RA) synovium and examine the suppression of osteoclastogenesis from human peripheral blood mononuclear cells (PBMC) by overexpression of miR-223.
Expression of miR-223 in synovium from RA patients was analyzed by quantitative reverse transcription polymerase chain reaction (RT-PCR) and section in situ hybridization. MiR-223 was overexpressed in an osteoclastogenesis coculture system with PBMC and RA synovial fibroblast. At 3 weeks after transfection of double-stranded miR-223, the formation of tartrate-resistant acid phosphatase (TRAP)-stained multinucleated cells was analyzed to evaluate the inhibitory effect of miR-223 on osteoclastogenesis.
MiR-223 was more highly expressed in RA synovium than in osteoarthritis (OA) synovium due to the increased number of miR-223-positive cells in RA synovium. MiR-223 was expressed in the superficial and sublining layers, and macrophages, monocytes, and CD4 T cells also expressed miR-223. The number of TRAP-positive multinucleated cells was significantly decreased by overexpression of miR-223 in a dose-dependent manner. The expression of osteoclastogenesis marker genes was significantly down-regulated by miR-223 overexpression.
MiR-223 is intensely expressed in RA synovium, and overexpression of miR-223 suppresses osteoclastogenesis in vitro. This study demonstrates the possibility of gene therapy with miR-223 to treat bone destruction in RA patients.
As with cognitive function, the ability to recognize emotions changes with age. In the literature regarding the relationship between recognition of emotion and cognitive function during aging, the ...effects of predictors such as aging, emotional state, and cognitive domains on emotion recognition are unclear. This study was performed to clarify the cognitive functions underlying recognition of emotional facial expressions, and to evaluate the effects of depressive mood on recognition of emotion in elderly subjects, as well as to reproduce the effects of aging on the recognition of emotional facial expressions.
A total of 26 young (mean age = 20.9 years) and 30 elderly subjects (71.6 years) participated in the study. All subjects participated in face perception, face matching, emotion matching, and emotion selection tasks. In addition, elderly subjects were administered a multicomponent cognitive test: the Neurobehavioral Cognitive Status Examination (Cognistat) and the Geriatric Depression Scale-Short Version. We analyzed these factors using multiple linear regression.
There were no significant differences between the two groups in the face perception task, but in the face matching, emotion matching, and emotion selection tasks, elderly subjects showed significantly poorer performance. Among elderly subjects, multiple regression analyses showed that performance on the emotion matching task was predicted by age, emotional status, and cognitive function, but paradoxical relationships were observed between recognition of emotional faces and some verbal functions. In addition, 47% of elderly participants showed cognitive decline in one or more domains, although all of them had total Cognistat scores above the cutoff.
It might be crucial to consider preclinical pathological changes such as mild cognitive impairment when testing for age effects in elderly populations.
An intense white light (WL) continuum from 1600 to 2400 nm is generated in a 20-mm-long YAG irradiated by 1-ps, 1030-nm pulses. Long filamentation formed in the YAG is proven to be responsible for ...the enhancement of the longer-wavelength spectral part of the WL. The WL is compressed down to 24.6 fs ( 3.9 cycles at 1900 nm) after optical parametric chirped-pulse amplification in a lithium niobate crystal near degeneracy, confirming that its spectral phase is well behaved. The pulse compression experiment reveals that the group delay introduced in the WL generation process is dominated by the dispersion of YAG.
The dinuclear copper enzyme, tyrosinase, activates O2 to form a (μ‐η2:η2‐peroxido)dicopper(II) species, which hydroxylates phenols to catechols. However, the exact mechanism of phenolase reaction in ...the catalytic site of tyrosinase is still under debate. We herein report the near atomic resolution X‐ray crystal structures of the active tyrosinases with substrate l‐tyrosine. At their catalytic sites, CuA moved toward l‐tyrosine (CuA1 → CuA2), whose phenol oxygen directly coordinates to CuA2, involving the movement of CuB (CuB1 → CuB2). The crystal structures and spectroscopic analyses of the dioxygen‐bound tyrosinases demonstrated that the peroxide ligand rotated, spontaneously weakening its O−O bond. Thus, the copper migration induced by the substrate‐binding is accompanied by rearrangement of the bound peroxide species so as to provide one of the peroxide oxygen atoms with access to the phenol substrate's ϵ carbon atom.
Let's Cu move: The dinuclear copper enzyme, tyrosinase, activates O2 and hydroxylates phenols to catechols. Substrate binding is shown to induce a rearrangement of the copper–oxygen species for hydroxylation of aromatic C−H bond. A copper center migrates (CuA1→CuA2) activating the bound substrate as well as the dioxygen molecule that is between the copper centers.
Cancer-specific metabolic alterations hyperactivate the kinase activity of the mammalian/mechanistic target of rapamycin (mTOR) for overcoming stressful environments. Rapalogs, which allosterically ...inhibit mTOR complex 1 (mTORC1), have been approved as anticancer agents. However, the immunosuppressive side effect of these compounds results in the promotion of tumor metastasis, thereby limiting their therapeutic efficacy. We first report a nonrapalog inhibitor,
, identified by a hybrid strategy of in silico and in cell selections. Our studies showed that
formed a ternary complex with FK506-binding protein-12 (FKBP12) and FKBP-rapamycin-binding (FRB) domain of mTOR, resulting in the allosteric inhibition of mTORC1.
inhibited the phosphorylation of not only the ribosomal protein S6 kinase 1 (S6K1) but also eIF4E-binding protein-1 (4E-BP1). Hence,
efficiently suppressed tumor growth in mice without promotion of metastasis. These results suggest that
is a potent lead compound for developing anticancer drugs discovered by in silico and in cell methods.
The objective of this study was to present the outcomes of rotational acetabular osteotomy (RAO) over a 30-year period for osteoarthritis (OA) secondary to dysplasia of the hip in pre- or early-stage ...OA.
Between September 1987 and December 1994, we provided treatment to 47 patients (55 hips) with RAO for the management of pre- or early-stage OA due to developmental hip dysplasia. Of those, eight patients (11 hips) with pre-OA (follow-up rate 79%) and 27 patients (32 hips) with early-stage OA (follow-up rate 78%), totalling 35 patients (43 hips) (follow-up rate 78%), were available at a minimum of 28 years after surgery.
In the pre-OA group, the mean Merle d'Aubigné score improved significantly from 14.5 points (SD 0.7) preoperatively to 17.4 points at final follow-up (SD 1.2; p = 0.004) and in the early-stage group, the mean score did not improve significantly from 14.0 (SD 0.3) to 14.6 (SD 2.4; p = 0.280). Radiologically, the centre-edge angle, acetabular roof angle, and head lateralization index were significantly improved postoperatively in both groups. Radiological progression of OA was observed in two patients (two hips) in the pre-OA group and 17 patients (18 hips) in the early-stage group. Kaplan-Meier survival analysis, with radiological progression of OA as the primary outcome, projected a 30-year survival rate of 81.8% (95% confidence interval (CI) 0.59 to 1.00) for the pre-OA group and 42.2% (95% CI 0.244 to 0.600) for the early-stage group. In all cases, the overall survival rate stood at 51.5% (95% CI 0.365 to 0.674) over a 30-year period, and when the endpoint was conversion to total hip arthroplasty, the survival rate was 74.0% (95% CI 0.608 to 0.873).
For younger patients with pre-OA, joint preservation of over 30 years can be expected after RAO.
This paper aims to investigate the drivers of inequality of opportunity in health outcome among children below 5 years of age, using the Tunisian 2018 Multiple Indicator Cluster Survey. This study ...adopts the general entropy measures to examine the pattern of child health inequality. The results of the anthropometric measures show that 1.5% of children in Tunisia are underweight, 8.3% are stunting and 2.1% are wasting. The results of generalized entropy measures indicate that the general disparity in child health is low across demographic characteristics. Inequality of opportunity in Tunisia is particularly high in access to health services between regions. The results also show that geographical location, parental education and wealth are the main factors contributing to inequality of opportunity in child health outcome. On the basis of the results, this research suggests several policy recommendations.
Titanium nitride (TiN) coating by ion plating has properties such as high hardness, wear resistance, corrosion resistance, and surface lubricity, therefore TiN coating is often used in various dental ...appliances and materials. In this study, we evaluated the corrosion behaviors and mechanical properties of TiN coated stainless steel (SS) and nickel titanium (Ni-Ti) orthodontic wires prepared by ion plating. TiN coating by ion plating improves the corrosion resistance of orthodontic wires. The corrosion pitting of the TiN coated wire surface become small. The tensile strength and stiffness of SS wire were increased after TiN coating. In contrast, its elastic force, which is a property for Ni-Ti wire, was decreased. In addition, TiN coating provided small friction forces. The low level of friction may increase tooth movement efficiently. Therefore, TiN coated SS wire could be useful for orthodontics treatment.
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