Suppressive effects of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer on the adherence of Candida species and MRSA to acrylic denture resin

Objectives: The effects of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer on the adherence of microorganisms such as non-Candida albicans Candida (NCAC) and methicillin-resistant Staphylococcus aureus (MRSA), frequently detected in oral infections in immunocompromised and/or elderly people, to denture resin material, are still unclear. Here, we report the effects of MPC-polymer on the adherence of C. albicans, NCAC, and MRSA to acrylic denture resin. Methods: Sixteen strains of C. albicans, seven strains of C. glabrata, two strains of C. tropicalis, one strain of C. parapsilosis, and six strains of MRSA were used. We cultured the fungal/bacterial strains and examined the cell growth and adherence of fungi/bacteria to mucin-coated acrylic denture resin plates (ADRP) with or without MPC-polymer coating, by scanning electron microscopy. The cell surface hydrophobicity of the fungal/bacterial strains was measured by the adsorption to hydrocarbons. Results: MPC-polymer did not affect the growth of all strains of Candida species and MRSA, but significantly suppressed adherence to ADRP in most strains of C. albicans and all strains of NCAC and MRSA. A significant positive correlation was found between cell hydrophobicity and the reduction rates of microbial adherence to ADRP treated with 5% of MPC-polymer. Conclusions: MPC-polymer treatment for acrylic resin material suppresses the adherence of C. albicans, NCAC and MRSA via their hydrophilicity interaction. Clinical significance: The application of MPC-polymer for denture hygiene is potent to prevent oral candidiasis, denture stomatitis and opportunistic infection, caused by Candida species and MRSA, via suppressing the adherence of those fungus/bacteria

Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes

<p>Abstract</p> <p>Background</p> <p>The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto's thyroiditis (HT), although fourteen EAATD patients with Graves' disease (GD) have been also reported.</p> <p>Methods</p> <p>We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term.</p> <p>Results</p> <p>Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management.</p> <p>Conclusions</p> <p>GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.</p

CNS targets of adipokines

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this record.Our understanding of adipose tissue as an endocrine organ has been transformed over the last twenty years. During this time a number of adipocyte-derived factors or adipokines have been identified. This paper will review evidence for how adipokines acting via the central nervous system (CNS) regulate normal physiology and disease pathology. The reported CNS-mediated effects of adipokines are varied and include the regulation of energy homeostasis, autonomic nervous system activity, the reproductive axis, neurodevelopment, cardiovascular function, and cognition. Due to the wealth of information available and the diversity of their known functions, the archetypal adipokines leptin and adiponectin will be the focused on extensively. Other adipokines with established CNS actions will also be discussed. Due to the difficulties associated with studying CNS function on a molecular level in humans, the majority of our knowledge, and as such the studies described in this paper, comes from work in experimental animal models; however, where possible the relevant data from human studies are also highlighted

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

ネコ ノ スイブン セッシュリョウ ト ニョウリョウ ニョウ ヒジュウチ ニ カンスル ケンキュウ

Domestic cats (Felissilvestriscatus ) are known to have lesser and hypertonic urine excretion(urine volume: 22&#8211;30 mL/kg per day; specific gravity: 1.015&#8211;1.050) than those of domestic dogs( Canislupus familiaris); urine volume: 24&#8211;40 mL/kg perday; specific gravity: 1.015&#8211;1.040). These have been implicated as factors for feline incidence of struviteurolithiasis and felinelower urinary tract disease, which are diseases that affect the bladder or urethra. We conducted comparative studies on therelationship between fluid intake and urine volume/urine specific gravity under 2 conditions&#8212;diet (condition A) comprising"dry food"( 5.6% moisture) and ad libitum drinking water and diet( condition B) comprising" wet food"( 74.8% moisture) andad libitum drinking water&#8212;in acclimated cats( n=7) kept separately in cat cages in an animal rearing room at 25°C. The perdiem water intake (apparent water intake) in condition A was on an average 66.9 ± 22.1(mL), while the totalfluid intake (absolute water intake), which is the sum of the amounts of water in the food and the water intake, was on anaverage68.2 ± 23.3(mL).Further, the average water intake under condition B was only 22.7 ± 20.13( mL), but the absolutewater intake was on average 95.6 ± 37.6( mL), meaning that wet food resulted in a higher absolute water intake amountthan dry food. Regarding the urine volume and the urine specific gravity, urine volume and urine specific gravity with the dry food diet(condition A) were 28.8 ± 11.8 (mL) and 1.049 ± 0.01, respectively, but the mean urine volume and urine specific gravityunder condition B were 49.5 ± 31.4(mL) and 1.030 ± 0.01, respectively, showing that compared to the dry food group, thewet food group had a significantly higher urine volume and lower urine specific gravity. The present study proves that in an average rearing environment, the urine volume does not increase and urine specificgravity is hypertonic when the cats are provided dry food diet, despite increase in the apparent water intake. Further, theurine volume increases and urine specific gravity decreases when the cats are provided wet food diet( canned or pouched),although the apparent water intake is low. The present study shows that differences in the diet are factors for the increasedincidence of struviteurolithiasis and FLUTD in cats

Effects of Counterion and Solvent on Proton Location and Proton Transfer Dynamics of N–H···N Hydrogen Bond of Monoprotonated 1,8-Bis(dimethylamino)naphthalene

The proton location and proton transfer (PT) dynamics of a hydrogen bond are under the influence of the static and dynamical properties of the solvent and counterions. In the present study, the N–H distances were determined for salts of 1,8-bis­(dimethylamino)­naphthalene, DMANH⁺X^– (X^– = BPh₄^–, ClO₄^–, and Cl^–), in acetonitrile (AN) solution, and DMANH⁺Br^– in water by observing the ¹⁵N spin–lattice relaxation caused by the ¹⁵N–¹H magnetic dipolar coupling under assumption that the PT time was shorter than the NH reorientation time (∼10^–11 s). The obtained N–H distances decreased in the following order: DMANH⁺BPh₄^– > DMANH⁺ClO₄^– > DMANH⁺Br^–/H₂O > DMANH⁺Cl^–, indicating that interactions with the environment affect the PT potentials. To understand the results at the molecular level, Car–Parrinello molecular dynamics simulations were performed for DMANH⁺, DMANH⁺ in water, and DMANH⁺–Cl^– ion-pair in AN. The results of simulation suggest that (1) the N–H distance decreases in the presence of a solvent and counterion; (2) the PT time is probably ∼10^–12 s, which confirms the above assumption used for the NMR relaxation data analyses; and (3) fluctuation of the interactions with the solvent or counterion has a significant role in PT. Quantum nuclear effects on the hydrogen bond were also examined