Gastric-type adenocarcinoma of the uterine cervix: clinical features and future directions.

The concept of gastric-type mucinous carcinoma of the uterine cervix (GAS) has been accepted worldwide because of its aggressive clinical behaviour and the absence of high-risk human papilloma virus infection. The World Health Organization (WHO) 2020 classification divides cervical tumours into two categories: human papilloma virus-associated and human papilloma virus-independent. Hence, GAS is now classified as an human papilloma virus-independent gastric type. Because clinical studies have reported that GAS is refractory to conventional treatments such as chemotherapy and radiotherapy, especially at an advanced stage, and has aggressive features with widespread dissemination to unusual sites, such as the omentum, peritoneum and distant organs, it is urgent to establish new treatment strategies by comparing the molecular profiles of human papilloma virus-associated adenocarcinomas. A series of genetic mutations characteristic to GAS encourage the development of future treatment strategies such as targeted therapy and immunotherapy.

Graft Failure after Uterus Transplantation in 16 Recipients: A Review.

Uterus transplantation (UTx) is now an alternative to surrogacy and adoption for women with uterine factor infertility to have children; however, there are still unresolved clinical and technical issues. One of these is that the graft failure rate after transplantation is somewhat higher than that of other life-saving organ transplants, which is a critical concern. Herein, we summarize the details of 16 graft failures after UTx with living or deceased donors using the published literature in order to learn from these negative outcomes. To date, the main causes of graft failure are vascular factors (arterial and/or venous thrombosis, atherosclerosis, and poor perfusion). Many recipients with thrombosis develop graft failure within one month of surgery. Therefore, it is necessary to devise a safe and stable surgical technique with higher success rates for further development in the UTx field.

High quantum yield photochemical water oxidation using a water-soluble cobalt phthalocyanine as a homogenous catalyst.

We demonstrated high catalytic activity (TON = 670, TOFmax = 2.7 s-1) of a water-soluble cobalt phthalocyanine complex (CoPcTS, PcTS = phthalocyaninetetrasulfonate) for visible light-driven photochemical water oxidation and investigated its reaction mechanism by electrochemical and spectroscopic measurements.

Psychological disturbances and their association with sleep disturbances in patients admitted for cardiovascular diseases.

BACKGROUND: Depression and anxiety are common mental health problems that are strongly associated with sleep disturbances, according to community-based researches. However, this association has not been investigated among patients admitted for cardiovascular diseases (CVDs). We examined the prevalence of depression and anxiety in inpatients with various CVDs and their association with sleep disturbances. MATERIALS AND METHODS: This cross-sectional study included 1294 patients hospitalized for CVDs in a Japanese university hospital were evaluated for their mental status using the Hospital Anxiety and Depression Scale (HADS), for sleep-disordered breathing (SDB) using pulse oximetry, and for sleep quality using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Patient characteristics were as below: mean age, 63.9±14.7 years; 25.7% female. Overall, 18.9% had depression (HADS-depression≥8) and 17.1% had anxiety (HADS-anxiety≥8). The presence of depression was associated with female sex, older age, higher plasma brain natriuretic peptide level, lower estimated glomerular filtration rate, and the prevalence of heart failure. Overall, 46.5% patients were categorized as having a poor sleep quality (PSQI>5), and 28.5% patients had SDB (3% oxygen desaturation index>15). Although depression and anxiety were not associated with SDB, they were independently associated with poor sleep quality (OR = 3.09, 95% CI 2.19-4.36; OR = 3.93, 95% CI 2.71-5.69, respectively). CONCLUSIONS: Depression and anxiety were not uncommon in patients with CVDs. Poor sleep quality could be an important risk factor linked to psychological disturbances.

Identification of human glycerophosphodiesterase 3 as an ecto phospholipase C that converts the G protein-coupled receptor 55 agonist lysophosphatidylinositol to bioactive monoacylglycerols in cultured mammalian cells.

A family of glycerol-based lysolipid mediators comprises lysophosphatidic acid as a representative phospholipidic member but also a monoacylglycerol as a non-phosphorus-containing member. These critical lysolipid mediators are known to be produced from different lysophospholipids by actions of lysophospholipases C and D in mammals. Some members of the glycerophosphodiesterase (GDE) family have attracted recent attention due to their phospholipid-metabolizing activity. In this study, we found selective depletion of lysophosphatidylinositol among lysophospholipids in the culture medium of COS-7 cells transfected with a vector containing glycerophosphodiester phosphodiesterase 2 (GDPD2, GDE3). Thin-layer chromatography and liquid chromatography-tandem mass spectrometry of lipids extracted from GDE3-transfected COS-7 cells exposed to fluorescent analogs of phosphatidylinositol (PI) revealed that GDE3 acted as an ecto-type lysophospholipase C preferring endogenous lysophosphatidylinositol and PI having a long-chain acyl and a short-chain acyl group rather than endogenous PI and its fluorescent analog having two long chain acyl groups. In MC3T3-E1 cells cultured with an osteogenic or mitogenic medium, mRNA expression of GDE3 was increased by culturing in 10% fetal bovine serum for several days, concomitant with increased activity of ecto-lysophospholipase C, converting arachidonoyl-lysophosphatidylinositol, a physiological agonist of G protein-coupled receptor 55, to arachidonoylglycerol, a physiological agonist of cannabinoid receptors 1 and 2. We suggest that GDE3 acts as an ecto-lysophospholipase C, by switching signaling from lysophosphatidylinositol to that from arachidonoylglycerol in an opposite direction in mouse bone remodeling.

A low level of lysophosphatidic acid in human gingival crevicular fluid from patients with periodontitis due to high soluble lysophospholipase activity: Its potential protective role on alveolar bone loss by periodontitis.

We previously detected a submicromolar concentration of lysophosphatidic acid (LPA) in human saliva. Here, we compare LPA concentrations in human gingival crevicular fluid (GCF) from patients with periodontitis and healthy controls, and examine how the local LPA levels are regulated enzymatically. The concentrations of LPA and its precursor lysophospholipids in GCF was measured by liquid chromatography-tandem mass spectrometry. The LPA-producing and LPA-degrading enzymatic activities were measured by quantifying the liberated choline and free fatty acid, respectively. The concentration of LPA in GCF of periodontitis patients was lower than that of healthy controls, due to higher soluble lysophospholipase activity toward LPA. LPA was found to prevent survival of Sa3, a human gingival epithelium-derived tumor cell line, activate Sa3 through Ca2+ mobilization, and release interleukin 6 from Sa3 in vitro. Furthermore, local injection of LPA into the gingiva attenuated ligature-induced experimental alveolar bone loss induced by oral bacteria inoculation in a rat model of periodontitis in vivo. A high concentration of LPA in human GCF is necessary to maintain normal gingival epithelial integrity and function, protecting the progression of periodontitis.

Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase.

BACKGROUND: Aspartate, which is converted from oxaloacetate (OAA) by aspartate aminotransferase, is considered an important precursor for purine salvage and pyrimidine de novo biosynthesis, and is thus indispensable for the growth of Plasmodium parasites at the asexual blood stages. OAA can be produced in malaria parasites via two routes: (i) from phosphoenolpyruvate (PEP) by phosphoenolpyruvate carboxylase (PEPC) in the cytosol, or (ii) from fumarate by consecutive reactions catalyzed by fumarate hydratase (FH) and malate:quinone oxidoreductase (MQO) in the mitochondria of malaria parasites. Although PEPC-deficient Plasmodium falciparum and Plasmodium berghei (rodent malaria) parasites show a growth defect, the mutant P. berghei can still cause experimental cerebral malaria (ECM) with similar dynamics to wild-type parasites. In contrast, the importance of FH and MQO for parasite viability, growth and virulence is not fully understood because no FH- and MQO-deficient P. falciparum has been established. In this study, the role of FH and MQO in the pathogenicity of asexual-blood-stage Plasmodium parasites causing cerebral malaria was examined. RESULTS: First, FH- and MQO-deficient parasites were generated by inserting a luciferase-expressing cassette into the fh and mqo loci in the genome of P. berghei ANKA strain. Second, the viability of FH-deficient and MQO-deficient parasites that express luciferase was determined by measuring luciferase activity, and the effect of FH or MQO deficiency on the development of ECM was examined. While the viability of FH-deficient P. berghei was comparable to that of control parasites, MQO-deficient parasites exhibited considerably reduced viability. FH activity derived from erythrocytes was also detected. This result and the absence of phenotype in FH-deficient P. berghei parasites suggest that fumarate can be metabolized to malate by host or parasite FH in P. berghei-infected erythrocytes. Furthermore, although the growth of FH- and MQO-deficient parasites was impaired, the development of ECM was suppressed only in mice infected with MQO-deficient parasites. CONCLUSIONS: These findings suggest that MQO-mediated mitochondrial functions are required for development of ECM of asexual-blood-stage Plasmodium parasites.

The prevalence of poor sleep quality and its association with depression and anxiety scores in patients admitted for cardiovascular disease: A cross-sectional designed study.

BACKGROUND: Poor sleep quality contributes to the development of various cardiovascular conditions. However, its real-world prevalence among cardiovascular inpatients and association with psychological disturbance is unknown. This study aimed to assess the prevalence of poor sleep quality and its association with depression and anxiety in cardiovascular patients, and explored whether sex and cardiovascular comorbidities modified these associations. METHODS: A total of 1071 patients hospitalized for a broad spectrum of cardiovascular diseases at a single university hospital were assessed (790 men, mean age 64±14years). We assessed sleep quality during their index hospitalization period using the Pittsburgh Sleep Quality Index (PSQI); poor sleep quality was defined as PSQI>5. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS). RESULTS: The median PSQI score was 5.0 [3.0-7.0], and 461 inpatients (43%) had poor sleep quality. Multivariate regression analysis adjusting for patient background, medical risk factors, and laboratory data revealed that poor sleep quality was associated with higher HADS subscores for depression (HADS-depression; odds ratio [OR]: 1.09, 95% confidence interval [CI]: 1.03-1.15) and anxiety (HADS-anxiety; OR: 1.17, 95% CI: 1.11-1.24). Poor sleep quality was associated with markedly higher HADS-depression among women than men (p value for interaction: 0.008). The association between poor sleep quality and HADS-anxiety was more significant among patients without coronary artery diseases (p value for interaction: 0.017). CONCLUSIONS: Poor sleep quality was highly prevalent and associated with depression and anxiety in cardiovascular patients. These associations may be modified by sex and the presence of coronary artery diseases.

Influence of Occlusal Force on Electroencephalograms in Edentulous Patients.

PURPOSE: This study explored the effect of improved occlusal force resulting from complete denture treatment on electroencephalogram (EEG) findings to determine if such an outcome is a factor contributing to activation of synaptic/neuronal dysfunction in the brain. MATERIALS AND METHODS: Twenty-three individuals with complete upper and lower dentures who visited the Department of Removable Prosthodontics at Tsurumi University Dental Hospital were included in this study. The Dental Prescale Occluzer FPD-705 system was used to perform an objective measurement of occlusal force before and after denture treatment. EEGs were recorded for 3 minutes in patients receiving complete dentures before and after denture treatment. Then, Dα values were calculated using a diagnosis method of neuronal dysfunction analysis to evaluate changes in synaptic/neuronal dysfunction of the brain. To investigate whether occlusal force affects Dα, Spearman's rank correlation coefficient (α = 0.05) was used to test the association between occlusal force (N) and Dα based on the rates of change in occlusal force and Dα calculated by dividing the measurement values after denture treatment by the measurement values before denture treatment. RESULTS: Medial occlusal force increased from 184.9 N before treatment to 277.2 N after treatment. A statistically significant increase in occlusal force (p < 0.05) was observed, with a total of 22 participants exhibiting increased occlusal force after denture treatment. The medial Dα value increased from 0.943 before treatment to 0.957 after treatment. A statistically significant increase in Dα (p < 0.05) was observed, and a total of 19 participants exhibited increased Dα values after denture treatment. The regression line was calculated as Y = 14.049X - 12.450. As occlusal force increased, Dα values increased as well. A significant positive correlation was observed between occlusal force and Dα (r = 0.498, p < 0.05). CONCLUSIONS: A positive correlation was observed between improved occlusal force attained via complete denture treatment and the activation of Dα. This finding reveals occlusal force as a denture treatment outcome that contributes to the activation of synaptic/neuronal dysfunction in the brain.

Influence of vertical dimension of occlusion changes on the electroencephalograms of complete denture wearers.

PURPOSE: The present study was conducted to identify how changes in the vertical dimension of occlusion (VDO) affect the sensory perception and activity of the brain in complete denture wearers using an electroencephalogram (EEG). METHODS: Subjects were 21 individuals wearing complete dentures who regularly visited the Division of Prosthodontics at Tsurumi University Dental Hospital for checkups (12 males and 9 females, average age: 76.6). Based on their original dentures, two duplicate dentures with different VDO (-3mm and +5mm) were fabricated. EEG activity and occlusal force were measured before and after gum chewing with each denture in all subjects. Negative indicator scores for psychological conditions and stable neuronal activity (Dα) were calculated using EEG data. Statistical analysis was performed using the Wilcoxon test to compare changes in the sensory perception, activity of the brain, and occlusal force (α=0.05). RESULTS: After gum chewing with the +5-mm denture, a significant increase was observed in the negative indicator score (p<0.05). No significant difference was found in the Dα values before and after gum chewing with any of the dentures (p>0.05). A significant decrease was observed in the occlusal force between the original denture and the -3-mm denture (p<0.05). CONCLUSION: Psychological condition and occlusal force were influenced by immediate changes in the VDO of the complete denture.

Functional analysis of Drosophila DNA polymerase ε p58 subunit.

DNA polymerase ε (polε) plays a central role in DNA replication in eukaryotic cells, and has been suggested to the main synthetic polymerase on the leading strand. It is a hetero-tetrameric enzyme, comprising a large catalytic subunit (the A subunit ~250 kDa), a B subunit of ~60 kDa in most species (~80 kDa in budding yeast) and two smaller subunits (each ~20 kDa). In Drosophila, two subunits of polε (dpolε) have been identified. One is the 255 kDa catalytic subunit (dpolεp255), and the other is the 58 kDa subunit (dpolεp58). The functions of the B subunit have been mainly studied in budding yeast and mammalian cell culture, few studies have been performed in the context of an intact multicellular organism and therefore its functions in this context remain poorly understood. To address this we examined the in vivo role of dpolεp58 in Drosophila. A homozygous dpolεp58 mutant is pupal lethal, and the imaginal discs are less developed in the third instar larvae. In the eye discs of this mutant S phases, as measured by BrdU incorporation assays, were significantly reduced. In addition staining with an anti-phospho histone H3 (PH3) antibody, (a marker of M phase), was increased in the posterior region of eye discs, where usually cells stop replicating and start differentiation. These results indicate that dpolεp58 is essential for Drosophila development and plays an important role in progression of S phase in mitotic cell cycles. We also observed that the size of nuclei in salivary gland cells were decreased in dpolεp58 mutant, indicating that dpolεp58 also plays a role in endoreplication. Furthermore we detect a putative functional interaction between dpolε and ORC2 in discs suggesting that polε plays a role in the initiation of DNA replication in Drosophila.

Drosophila DREF acting via the JNK pathway is required for thorax development.

The Drosophila Jun N-terminal kinase (JNK) gene basket (bsk) promoter contains a DNA replication-related element (DRE)-like sequence, raising the possibility of regulation by the DNA replication-related element-binding factor (DREF). Chromatin immunoprecipitation assays with anti-DREF IgG showed the bsk gene promoter region to be effectively amplified. Luciferase transient expression assays revealed the DRE-like sequence to be important for bsk gene promoter activity, and knockdown of DREF decreased the bsk mRNA level and the bsk gene promoter activity. Furthermore, knockdown of DREF in the notum compartment of wing discs by pannier-GAL4 and UAS-DREFIR resulted in a split thorax phenotype. Monitoring of JNK activity in the wing disc by LacZ expression in a puckered (puc)-LacZ enhancer trap line revealed the reduction in DREF knockdown clones. These findings indicate that DREF is involved in regulation of Drosophila thorax development via actions on the JNK pathway.