Multitrait transcriptomewide affiliation examine TWAS checks

The hypothalamus is a major integrating centre that controls energy homeostasis and plays a major role in hepatic glycogen (HGlyc) turnover. Not only do hypothalamic and hepatic Akt levels influence glucose homeostasis and glycogen synthesis, but exposure to high-sugar/high-fat diets (HSHF) can also lead to hypothalamic inflammation and HGlyc accumulation. HSHF withdrawal overall restores energy and glucose homeostasis, but the actual relationship between hypothalamic inflammation and HGlyc after short-term HSHF withdrawal has not yet been fully elucidated. Here we investigated the short-term effects of HSHF withdrawal preceded by a 30-day HSHF intake on the liver-hypothalamus crosstalk and glucose homeostasis. Sixty-day old male Wistar rats were fed for 30 days a control chow (n = 10) (Ct), or an HSHF diet (n = 20). On the 30th day of dietary intervention, a random HSHF subset (n = 10) had their diets switched to control chow for 48 h (Hw) whilst the remaining HSHF rats remained in the HSHF diet (n = 10) (Hd). All rats were anaesthetized and euthanized at the end of the protocol. We quantified HGlyc, Akt phosphorylation, inflammation and glucose homeostasis biomarkers. We also assessed the effect of propensity to obesity on those biomarkers, as detailed previously. Hd rats showed impaired glucose homeostasis, higher HGlyc and hypothalamic inflammation, and lower pAkt/Akt. Increased HGlyc was significantly associated with HSHF intake on pAkt/Akt lowered levels. We also found that HGlyc breakdown may have prevented a further pAkt/Akt drop after HSHF withdrawal. Propensity to obesity showed no apparent effect on hypothalamic inflammation or glucose homeostasis. Our findings suggest a comprehensive role of HGlyc as a structural and functional modulator of energy metabolism, and such roles may come into play relatively rapidly.Cadmium (Cd), is a heavy metal reported to be associated with oxidative stress and inflammation. In this paper, we investigated the possible protective effects of carvacrol against Cd-induced neurotoxicity in rats. Adult male Sprague Dawley rats were treated orally with Cd (25 mg/kg body weight) and with carvacrol (25 and 50 mg/kg body weight) for 7 days. Carvacrol decreased the levels of malondialdehyde (MDA), glial fibrillary acidic protein (GFAP) and monoamine oxidase (MAO), and significantly increased the levels of glutathione (GSH) and activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in brain tissue. Additionally, carvacrol alleviated the in levels of inflammation and apoptosis related proteins involving p38 mitogen-activated protein kinase (p38 MAPK), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB), B-cell lymphoma-3 (Bcl-3), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), myeloperoxidase (MPO), prostaglandin E2 (PGE2), neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), cysteine aspartate specific protease-3 (caspase-3) and Bcl-2 associated X protein (Bax) in the Cd-induced neurotoxicity. Carvacrol also decreased the mRNA expression of matrix metalloproteinases (MMP9 and MMP13), as well as 8-hydroxy-2'-deoxyguanosine (8 - OHdG) level, a marker of oxidative DNA damage. Collectively, our findings indicated that carvacrol has a beneficial effect in ameliorating the Cd-induced neurotoxicity in the brain of rats.
Occult breast cancer (OBC) is classified as carcinoma of an unknown primary site, and the adequate therapy for OBC remains controversial. This retrospective study aimed to reveal the transition in breast cancer therapy and the frequency of primary breast tumors after resection in clinical OBC (cT0N+) patients using the Japanese Breast Cancer Registry database.
We enrolled OBC patients with cT0N+ from the registry between 2010 and 2018. On the basis of the period of diagnosis, OBC patients were divided into the following two groups 2010-2014 and 2015-2018. We described the transition in treatments and tumor characteristics. After breast resection, the frequency of pathological identification of primary tumors and tumor sizes was assessed.
Of the 687,468 patients registered, we identified 148 cT0N+ patients with a median age of 61years. Of these patients, 64.2% (n = 95) received breast surgery (2010-2014 79.1%, 2015-2018 50.0%). Axillary lymph node dissection was performed in 92.6% (n = 137, 2010-2014 91.6%, 2015-2018 93.4%). The breast tumor size in the resected breast was 0-7.0cm (median 0cm, 2010-2014 0-7.0cm [median 0cm], 2015-2018 0-6.2cm [median 0cm]). The pathological identification rate of the primary tumor was 41.1% (n = 39, 2010-2014 40.4%, 2015-2018 42.1%).
Breast surgery for cT0N+ decreased between 2010 and 2018. Despite the high identification rate of primary tumors, most tumors were small, and there was no significant change in the identification rate or invasive diameter of the identified tumors after 2010.
Breast surgery for cT0N+ decreased between 2010 and 2018. Despite the high identification rate of primary tumors, most tumors were small, and there was no significant change in the identification rate or invasive diameter of the identified tumors after 2010.Idioms entail a competition between bottom-up and top-down activations of literal and figurative meanings. The present study explored the involvement of cognitive control in processing Hebrew ambiguous idioms. Fifty subjects have completed a self-paced reading task and a response inhibition, stop-signal task (SST). Subjects read 26 matched pairs of almost-identical sentences, which included ambiguous idioms (e.g., "break the ice"). The ambiguity was resolved only in the third part of the sentence, which was either literal ("on the parking lot") or figurative ("with funny stories"). Figurative disambiguation parts were read significantly faster than literal ones. The means of the absolute RT difference between the literal and figurative sentences significantly correlated with the SST cognitive control measure. A comparison between three groups of cognitive control levels validated that "Good inhibitors" in the SST were also faster in processing ambiguities. The paper discusses the generality of cognitive control in linguistic processing.We examined if North (n = 123) and South Korean (n = 123) children in Grades 3 to 8 studying in South Korea differ in their reading, vocabulary, and literacy-related cognitive skills, and whether language and literacy-related skills contribute to reading outcomes differently among North and South Korean children. The results showed that South Korean students performed better in syllable deletion, RAN-Letters, vocabulary, decoding fluency, and reading comprehension after controlling for age and SES. No differences were observed in phonological awareness, RAN-Digits, and visual processing tasks. https://www.selleckchem.com/products/colivelin.html A multigroup path analysis showed that phonological awareness and vocabulary were more strongly associated with decoding fluency for the South than the North Korean students, whereas the opposite was true for visual processing. The results suggest that South Korean vocabulary knowledge may be a significant factor in addressing the academic difficulties facing North Korean children in South Korean schools and that it is important to consider linguistic characteristics when examining the variations in reading skills and vocabulary knowledge of North Korean students in South Korean schools. These findings have implications for North Korean children's literacy instruction in South Korean schools.Nanoparticles have unique properties and high design flexibility, which are thought to be safe, site-specific, and efficient drug delivery systems. However, nanoparticles as exogenous materials can provide recognition and be eliminated by the body's immune system, which considerably restricts their applications. To overcome these drawbacks, natural cell membrane coating method has attracted great attention in the field of drug delivery systems, which can prolong nanoparticles blood circulation time and avoiding the capture as well as elimination by the body immune system. Biomimetic nanoparticles via a top-down approach can avoid the laborious group modified engineering and keep the integrity of cell membrane structure and membrane antigens, which can be endowed with unique properties, such as immune escape, longer blood circulation time, targeting delivery and controlling drugs sustain-release. At the present research, erythrocyte membrane, cancer cell membrane, platelet membrane, lymphocyte membrane and hybrid membrane have been successfully coated into the surface of nanoparticles to achieve biological camouflage. Thus, integrating various kinds of cell membranes and nanoparticles into one system, the biomimetic nanoparticles can inherit unique biofunction and drug delivery properties to exhibit tumor targeting-delivery and antitumor outcomes. In this article, we will discuss the prospects and challenges of some basic cell membrane cloaking nanoparticles as a drug delivery system for cancer therapy.Guidelines recommend routinely screening adults with diabetes for psychological concerns, but few diabetes clinics have adopted screening procedures. This study assessed patient and provider perspectives regarding the role of mental health in diabetes care, psychosocial screening procedures, and patients' support needs. Patients with diabetes (n = 15; 73.3% type 2) and their medical providers (n = 11) participated in qualitative interviews. Thematic content analysis was used to categorize results. Participants believed that mental health was important to address within comprehensive diabetes care. Patients expressed positive or neutral opinions about psychosocial screening. Providers had mixed reactions; many thought that screening would be too time-consuming. Both groups emphasized that screening must include referral procedures to direct patients to mental health services. Patients and providers interviewed in this study viewed psychosocial screening as compatible with diabetes care. Including a mental health professional on the treatment team could reduce potential burden on other team members.As the human breast undergoes complex, large-scale, fully three dimensional deformations in vivo, three-dimensional (3D) characterization of its mechanical behavior is fundamental to its diagnosis, treatment, and surgical modifications. Its anisotropic, heterogeneous fibrous structure results in complex behavior at both the tissue and organ levels. Mathematically modeling of this complex anisotropic behavior is thus critical to the proper simulation of the human breast. Yet, current breast tissue constitutive models do not account for these complexities, so that there is a pressing need for more detailed fully 3D analysis. To this end, we performed a full 3D kinematic mechanical evaluation of human fibroglandular and adipose breast tissues. We utilized our recently developed 3D kinematic numerical-experimental approach to acquire force-displacement data from both breast tissue subtypes. This was done by subjecting cuboidal test specimens, aligned to the anatomical axes,to both pure shear and simple compression loading paths. We then developed novel constitutive model that was able to simulate the unique anisotropic tension/compression behaviors observed. Constitutive model parameters were determined using a detailed finite element model of the experimental setup coupled to nonlinear optimization. We found that human breast tissues displayed complex anisotropic behavior, with strong, directionally dependent non-linearities. This was especially true for the fibroglandular tissue. The novel constitutive model was also able fully capture these behaviors, including states of combined tension and compression (i.e. in pure shear). The results of this study suggest that human breast tissue is complex in its mechanical response, exhibiting varying levels of anisotropy. Future studies will be required to link the observed anisotropy to the physical structure of the tissue, as well as mapping this heterogeneity and anisotropy across individuals.