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A body of literature has demonstrated the beneficial effects of mitochondrial cofactors, such as α-lipoic acid, coenzyme Q10, and carnitine on patients affected by mitochondrial diseases. Altogether, this re-definition of FA as a mitochondrial disease and the prospect use of mitochondrial nutrients may open new gateways toward mitoprotective strategies for FA patients. These strategies are expected to mitigate the mitochondrial dysfunction and prooxidant state in FA patients, and potentially protect transplanted FA patients from post-transplantation malignancies.Hepatic ischemia-reperfusion injury (IRI) is a major complication of liver surgery and transplantation. IRI leads to hepatic parenchymal cell death, resulting in liver failure, and lacks effective therapeutic approaches. Fibroblast growth factor 10 (FGF10) is a paracrine factor which is well-characterized with respect to its pro-proliferative effects during embryonic liver development and liver regeneration, but its role in hepatic IRI remains unknown. In this study, we investigated the role of FGF10 in liver IRI and identified signaling pathways regulated by FGF10. In a mouse model of warm liver IRI, FGF10 was highly expressed during the reperfusion phase. In vitro experiments demonstrated that FGF10 was primarily secreted by hepatic stellate cells and acted on hepatocytes. The role of FGF10 in liver IRI was further examined using adeno-associated virus-mediated gene silencing and overexpression. Overexpression of FGF10 alleviated liver dysfunction, reduced necrosis and inflammation, and protected hepatocytes from apoptosis in the early acute injury phase of IRI. Furthermore, in the late phase of IRI, FGF10 overexpression also promoted hepatocyte proliferation. Meanwhile, gene silencing of FGF10 had the opposite effect. Further studies revealed that overexpression of FGF10 activated nuclear factor-erythroid 2-related factor 2 (NRF2) and decreased oxidative stress, mainly through activation of the phosphatidylinositol-3-kinase/AKT pathway, and the protective effects of FGF10 overexpression were largely abrogated in NRF2 knockout mice. These results demonstrate the protective effects of FGF10 in liver IRI, and reveal the important role of NRF2 in FGF10-mediated hepatic protection during IRI.Campylobacteriosis is a zoonosis and the most frequent cause of food-borne bacterial enteritis in humans. C. AZD4547 in vivo jejuni and C. coli are the most common species implicated in campylobacteriosis. Broilers and their products are considered the most important food sources of human infections. The aim of the present study was to evaluate the presence of thermotolerant Campylobacter in different reservoirs at the farm, and the permanence of this pathogen during four consecutive rearing periods. The samples were taken from the same house farm in the downtime period and during the last week of broiler rearing, prior to their slaughter during four consecutive cycles. Different reservoirs as potential sources of Campylobacter were analysed. The prevalence of Campylobacter in vectors was 23% in A. diaperinus larvae, 20% in wild birds, 13% in A. diaperinus adults, and 9% in flies; as regards fomites, the prevalence was 50% in workers' boots, 27% in litter, and 21% in feed, while in broilers it was 80%. Campylobacter jejuni wd be conducted with the aim of detecting the Campylobacter sources between rearing periods.In Japan, induced pluripotent stem cell (iPSC) Stock Project has started from 2013. The goal of the Project is to manufacture and release clinical-grade HLA homozygous iPSC lines that can cover almost the entire of Japanese population. We show the summary of the cell lines distributed, test results for quality control and future plans.
We examined the association of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) gene expressions, as the key regulators of lipolysis, with dietary fat quantity and composition in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT).

In this observational study, samples were collected from patients undergoing elective abdominal surgery. Participants were categorized into two groups based on their body mass index (BMI) status. Dietary, anthropometric, and biochemical data were collected before surgery. Linear regression was performed to determine the association of dietary fat content with ATGL and HSL gene expressions in SAT and VAT.

152 individuals with a mean ± SD age of 40.7±13.2 years and a median (inter-quartile range) BMI of 39.4 (26.5-45.3kg/m
) participated in this study, of whom 54 were non-obese (BMI<30kg/m
), and 98 were obese (BMI≥30kg/m
). Among non-obese participants, positive associations were observed between ATGL mRNA expression and reported intakes of total fatty acids (TFA) (β=0.306, P=0.025), myristic (β=0.285, P=0.038), palmitic (β=0.417, P=0.002), oleic (β=0.333, P=0.017), dairy trans (β=0.374, P=0.006), and other trans FAs (β=0.369, P=0.006) in SAT. In contrast, inverse associations between HSL mRNA expression and reported intakes of TFAs (β=-0.377, P=0.005), myristic (β=-0.282, P=0.039), palmitic (β=-0.372, P=0.006), stearic (β=-0.314, P=0.020), and oleic acid (β=-0.372, P=0.007) were observed in SAT. No associations were observed among obese participants, nor in VAT among non-obese individuals.

ATGL and HSL mRNA expressions in SAT were associated with dietary fat quantity and composition among non-obese adults.
ATGL and HSL mRNA expressions in SAT were associated with dietary fat quantity and composition among non-obese adults.We previously discovered that palmitic acid methyl ester (PAME) is a potent vasodilator released from the sympathetic ganglion with vasoactive properties. Post-treatment with PAME can enhance cortical cerebral blood flow and functional learning and memory, while inhibiting neuronal cell death in the CA1 region of the hippocampus under pathological conditions (i.e. cerebral ischemia). Since mechanisms underlying PAME-mediated neuroprotection remain unclear, we investigated the possible neuroprotective mechanisms of PAME after 6 min of asphyxial cardiac arrest (ACA, an animal model of global cerebral ischemia). Our results from capillary-based immunoassay (for the detection of proteins) and cytokine array suggest that PAME (0.02 mg/kg) can decrease neuroinflammatory markers, such as ionized calcium binding adaptor molecule 1 (Iba1, a specific marker for microglia/macrophage activation) and inflammatory cytokines after cardiopulmonary resuscitation. Additionally, the mitochondrial oxygen consumption rate (OCR) and respiratory function in the hippocampal slices were restored following ACA (via Seahorse XF24 Extracellular Flux Analyzer) suggesting that PAME can ameliorate mitochondrial dysfunction. Finally, hippocampal protein arginine methyltransferase 1 (PRMT1) and PRMT8 are enhanced in the presence of PAME to suggest a possible pathway of methylated fatty acids to modulate arginine-based enzymatic methylation. Altogether, our findings suggest that PAME can provide neuroprotection in the presence of ACA to alleviate neuroinflammation and ameliorate mitochondrial dysfunction.As an analytic tool in medicine, deep learning has gained great attention and opened new ways for disease diagnosis. Recent studies validate the effectiveness of deep learning algorithms for binary classification of skin lesions (i.e., melanomas and nevi classes) with dermoscopic images. Nonetheless, those binary classification methods cannot be applied to the general clinical situation of skin cancer screening in which multi-class classification must be taken into account. The main objective of this research is to develop, implement, and calibrate an advanced deep learning model in the context of automated multi-class classification of skin lesions. The proposed Deep Convolutional Neural Network (DCNN) model is carefully designed with several layers, and multiple filter sizes, but fewer filters and parameters to improve efficacy and performance. Dermoscopic images are acquired from the International Skin Imaging Collaboration databases (ISIC-17, ISIC-18, and ISIC-19) for experiments. The experimental results of the proposed DCNN approach are presented in terms of precision, sensitivity, specificity, and other metrics. Specifically, it attains 94 % precision, 93 % sensitivity, and 91 % specificity in ISIC-17. It is demonstrated by the experimental results that this proposed DCNN approach outperforms state-of-the-art algorithms, exhibiting 0.964 area under the receiver operating characteristics (AUROC) in ISIC-17 for the classification of skin lesions and can be used to assist dermatologists in classifying skin lesions. As a result, this proposed approach provides a novel and feasible way for automating and expediting the skin lesion classification task as well as saving effort, time, and human life.
The study aimed to investigate the potential pathways mediating early exposure to stressful events and the clinical manifestations of bipolar disorder (BD), such as severity of mood symptoms, hopelessness and suicidal ideation, focusing on the potential role of insomnia symptoms.

A sample of 162 adult participants with BD I or II were assessed during depressed phase using the Structural Clinical Interview for DSM-5 (SCID-5), the Beck Depression Inventory-II (BDI-II), the Young Mania Rating Scale (YMRS), the Early Trauma Inventory Self Report-Short Form (ETISR-SF), the Beck Hopelessness Scale (BHS), the Insomnia Severity Index (ISI) and the Scale for Suicide Ideation (SSI). Participants with or without clinically significant insomnia were compared and we carried out correlations, regression and mediation analyses.

Participants with insomnia showed a greater severity of depressive symptoms,of suicidal risk, of the cognitive component of hopelessness and of early life stressors. Insomnia symptoms mediated the association among early life stress and depressive symptoms (Z=2.72, p=0.0006), the cognitive component of hopelessness (Z=3.02, p=0.0001) and suicidal ideation and plans (Z=2.07 p=0.0006).

Insomnia may mediate the relationship between early life stress and clinical manifestations of BD. Assessing the evolution of insomnia symptoms could offer an approach to characterize BD and to formulate treatment strategies. In particular targeting insomnia symptoms might potentially modify the clinical features of BD in response to early life stressful events.
Insomnia may mediate the relationship between early life stress and clinical manifestations of BD. Assessing the evolution of insomnia symptoms could offer an approach to characterize BD and to formulate treatment strategies. In particular targeting insomnia symptoms might potentially modify the clinical features of BD in response to early life stressful events.Veterans have high rates of suicide, and nonsuicidal self-injury (NSSI) is one of the strongest predictors of suicide risk; however, there is presently little known about antecedents of NSSI that might inform intervention efforts. Accumulating research suggests that anger and hostility play an important role in NSSI, but whether these emotions precede and predict NSSI is currently unknown. The aim of the current study was to examine the temporal relationships between anger/hostility and NSSI urges and behavior among veterans diagnosed with NSSI disorder. Our hypothesis was that angry/hostile affect would predict subsequent NSSI urge and engagement, but not vice versa. Forty veterans with NSSI disorder completed a 28-day ecological momentary assessment study with three daily prompts to report on their affect and NSSI urges and engagement. Multilevel cross-lagged path modeling was used to determine the direction of effects between angry/hostile affect and NSSI urges and engagement over time. Consistent with our hypothesis, results indicated that the lagged effects of angry/hostile affect on subsequent NSSI urge and engagement were significant, whereas the lagged effects of NSSI urge and engagement on angry/hostile affect were not significant.
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