Loneliness Factors in Older People and the Influence on Attitudes Toward Informal Care: A Study of Older Chinese People in Urban Areas.

OBJECTIVES: Loneliness is thought to be more likely to occur in older people and influences their lives. This study aimed to verify the influence of loneliness in older Chinese people on their attitudes toward informal care, as well as the demographic, social, and economic factors that may cause loneliness. METHODS: Data was collected from older P (age: >60 years) using an online questionnaire. Hierarchical linear regression was used to analyze the associations between demographic, social, and economic factors, loneliness, and attitudes toward informal care. RESULTS: Results have shown that cohabitation and family savings could significantly negatively influence loneliness. Educational background and cohabitation could significantly positively influence attitudes toward informal care. However, loneliness could significantly negatively influence attitudes toward informal care. CONCLUSION: Older people living alone and with worse economic conditions may need attention from the community and society because they are more likely to suffer from loneliness. Loneliness may also significantly impact older people's attitudes toward long-term care. Older people are more likely to feel lonely may have more negative attitudes toward informal care. Communities need to make more efforts to improve community health services or formal care services for these older people to address situations where informal care is not sufficiently provided.

Continuous drainage for the treatment of gastric cancer with pericardial metastasis and cardiac tamponade: A case report.

Key Clinical Message: Signet-ring cell gastric carcinomas presenting as pericardial effusion early in diagnosis are rare and associated with high mortality and a poor prognosis. There are two interesting aspects of this case: primary gastric carcinoma presenting as cardiac tamponade and the metastatic behavior of gastric signet-ring cell carcinoma. Abstract: This report describes an 83-year-old man diagnosed to have cardiac tamponade due to massive pericardial effusion. A cytological analysis of the pericardial effusion disclosed adenocarcinoma. The patient was treated with continuous pericardial drainage and the amount of pericardial effusion decreased.

Helicobacter pylori Reinfection Diagnosed by Endoscopic and Histologic Recurrence in a Patient with Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

Helicobacter pylori infection is a major cause of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Successful H. pylori eradication can induce a complete remission (CR); however, it takes a long time. In this case, the recurrence of gastric MALT lymphoma was observed by endoscopic and histologic findings during a 11-year follow-up and due to H. pylori reinfection twice. After the first successful eradication and achieving histologic CR, the patient was starting to work at a nursing home for older adults, where she frequently came in contact with their vomitus or feces. In the examinations 2 years later after the first successful eradication, endoscopic and histologic findings have demonstrated deterioration. Similar findings were continuously observed in the examinations 3 months later, and H. pylori reinfection was confirmed by the rapid urease test. After the second successful eradication, endoscopic and histologic CR of gastric MALT lymphoma was achieved. However, endoscopic and histologic findings have shown deterioration again 1 year later after the histologic CR and at 3.5 years later after the second successful eradication. H. pylori reinfection was confirmed by the repeated urea breath test, and the patient had received the third eradication treatment; and the patient had achieved successful eradication. In addition, proper hygiene practices were advised to avoid H. pylori reinfection. H. pylori reinfection is very rare in adults after successful eradication in developed countries. After successful eradication and proper hygiene practice, endoscopic and histologic CR has been maintained for 2 years up to the present.

Comparative pharmacokinetics of new curcumin preparations and evidence for increased bioavailability in healthy adult participants.

OBJECTIVE: Theracurmin, which contains the curcumin composition, CR-033P, has been demonstrated to be highly bioavailable. To compare the pharmacokinetics of the three compositions, CR-033P, CR-043P using modified starch as an alternative to the dispersant gum ghatti used in the CR-033P, and TS-P1 containing the newly developed amorphous curcumin, a randomized double-blind crossover study (3-way, 3-period) was conducted. MATERIALS AND METHODS: A single dose of the curcumin capsules (TS-P1 45 mg, CR-033P 90 mg, and CR-043P 90 mg) was administered to healthy adult participants. Blood sampling was performed 24 hours after capsule administration, and the plasma concentration of total curcumin was determined using high-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: TS-P1 and CR-043P tended to have a slightly lower area under the concentration time curve (AUC) 0-24h than CR-033P, while TS-P1 displayed bioequivalence to CR-043P. Further, TS-P1 displayed bioequivalence to CR-033P in terms of AUC0-12h, while that of CR-043P tended to be lower than that of CR-033P. TS-P1 had a higher AUC0-12h than CR-043P. A statistically significant difference (p < 0.001) was found between the preparations in terms of Cmax. TS-P1 tended to have a higher Cmax than CR-033P, CR-043P tended to have a slightly lower Cmax than CR-033P, and TS-P1 tended to have a higher Cmax than CR-043P. CONCLUSION: The newly developed TS-P1 composition seemed to display similar curcumin systemic exposure except for a higher plasma concentration than the CR-033P composition. Further, only a few significant differences were found between CR-043P and CR-033P.

Expression of Grainyhead-like 2 in the Process of Ductal Development of Mouse Mammary Gland.

Grainyhead-like 2 (Grhl2) is a transcription factor regulating cell adhesion genes. Grhl2 acts as an epithelial-mesenchymal transition suppressor, and it is a proto-oncogene involved in estrogen-stimulated breast cancer proliferation. However, its expression during ovarian hormone-dependent mammary ductal development remains obscure. We here examined Grhl2 expression in the mammary gland of normal and steroid-replaced ovariectomized mice. Grhl2 protein signals were detected in both the mammary luminal epithelial and myoepithelial nuclei. The ratio and density of Grhl2-positive nuclei increased after the onset of puberty and progressed with age, whereas Grhl2-negative epithelial cells were detected in mature ducts. Claudin 3, claudin 4, claudin 7, and E-cadherin gene expression in the mammary gland was upregulated, and their expression was highly correlated with Grhl2 gene expression. Furthermore, Grhl2 mRNA expression and ductal lumen width were significantly increased by the combined treatment of estrogen and progesterone compared with estrogen alone. These results suggest that Grhl2 expressed in the luminal epithelial and myoepithelial cells from the early phase of ductal development, controlling the expression of cell adhesion molecules to establish functional ducts.

Intramammary infection caused by Staphylococcus aureus increases IgA antibodies to iron-regulated surface determinant-A, -B, and -H in bovine milk.

The aim of this study was to identify virulence factors that have high immunogenicity. An in vivo-expressed Staphylococcus aureus antigen was identified by probing bacteriophage expression libraries of S. aureus with antibodies in bovine mastitis milk. Eighteen clones were isolated, and their proteins were identified as 5 characterised proteins (IsdA, Protein A, IsdB, autolysin, and imidazole glycerol phosphate dehydratase) and 13 hypothetical proteins. We focused on IsdA, IsdB, and IsdH as virulence factors that have a high immunogenicity and are capable of inducing a specific humoral immune response in S. aureus-infected quarters. The optical density (OD) values of IsdA and IsdB IgA and IgG antibodies in milk affected by naturally occurring mastitis caused by S. aureus increased significantly compared to those in healthy milk. In the experimental infection study, the OD values of IsdA- and B-specific IgA and IgG antibodies were significantly increased from 2 to 4 weeks after S. aureus infection compared to day 0 (P < 0.05). On the other hand, we demonstrated that milk from natural and experimental intramammary infections caused by S. aureus are associated with significantly higher IgA levels against IsdH (P < 0.05), but no significant change in IgG levels. Our findings facilitated our understanding of the pathogenicity of S. aureus in bovine mastitis, as well as the mechanisms by which specific humoral immune responses to S. aureus infection are induced. In addition, the results obtained could provide insight into how bovine mastitis can be controlled, for example, through vaccination.

Evaluating the usefulness of breast strain elastography for intraductal lesions.

PURPOSE: Strain elastography for imaging lesion stiffness is being used as a diagnostic aid in the malignant/benign discrimination of breast diseases. While acquiring elastography in addition to B-mode images has been reported to help avoid performing unnecessary biopsies, intraductal lesions are difficult to discriminate whether they are malignant or benign using elastography. An objective evaluation of strain in lesions was performed in this study by measuring the elasticity index (E-index) and elasticity ratio (E-ratio) of lesions as semi-quantitative numerical indicators of the color distribution of strain. We examined whether ductal carcinoma in situ (DCIS) and intraductal papilloma could be distinguished using these semi-quantitative numerical indicators. METHODS: In this study, 170 ultrasonographically detected mass lesions in 162 cases (106 malignant lesions and 64 benign lesions)-in which tissue biopsy by core needle biopsy and vacuum-assisted biopsy, or surgically performed histopathological diagnosis, was performed-were selected as subjects from among 1978 consecutive cases (from January 2014 to December 2016) in which strain elastography images were acquired, in addition to standard B-mode breast ultrasonography, by measuring the E-index and E-ratio. RESULTS: The cut-off values for E-index and E-ratio in the malignant/benign discrimination of breast lesions were determined to be optimal values at 3.5 and 4.2, respectively, based on receiver operating characteristic (ROC) curve analysis. E-index sensitivity, specificity, accuracy, and AUC value (area under the curve) were 85%, 86%, 85%, and 0.860, respectively, while those for E-ratio were 78%, 74%, 74%, and 0.780, respectively. E-index yielded superior results in all aspects of sensitivity, specificity, accuracy, and AUC values, compared to those of E-ratio. The mean E-index values for malignant tumors and benign tumors were 4.46 and 2.63, respectively, indicating a significant difference (P < 0.001). E-index values of 24 DCIS lesions and 25 intraductal papillomas were 3.88 and 3.35, respectively, which showed a considerably close value, while the false-negative rate for DCIS was 29.2%, and the false-positive rate for intraductal papilloma was as high as 32.0%. CONCLUSION: E-index in strain elastography yielded better results than E-ratio in the malignant/benign discrimination of breast diseases. On the other hand, E-index has a high false-negative rate and false-positive rate for intraductal lesions, a factor which should be taken into account when making ultrasound diagnoses.

Author Correction: A spatial similarity of stereochemical environments formed by amino acid residues defines a common epitope of two non-homologous proteins.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A spatial similarity of stereochemical environments formed by amino acid residues defines a common epitope of two non-homologous proteins.

It is critical for development of high-quality antibodies in research and diagnostics to predict accurately their cross-reactivities with "off-target" molecules, which potentially induce false results. Herein, we report a good example of such a cross-reactivity for an off-target due to a stereochemical environment of epitopes, which does not simply depend on amino acid sequences. We found that significant subpopulation of a polyclonal peptide antibody against Bcnt (Bucentaur) (anti-BCNT-C antibody) cross-reacted with a completely different protein, glutamine synthetase (GS), and identified four amino acids, GYFE, in its C-terminal region as the core amino acids for the cross-reaction. Consistent with this finding, the anti-BCNT-C antibody strongly recognized endogenously and exogenously expressed GS in tissues and cultured cells by Western blotting and immunohistochemistry. Furthermore, we elucidated that the cross-reaction is caused by a spatial similarity between the stereochemical environments formed by amino acid residues, including the GYFE of GS and the GYIE of Bcnt, rather than by their primary sequences. These results suggest it is critical to comprehensively analyze antibody interactions with target molecules including off-targets with special attention to the physicochemical environments of epitope-paratope interfaces to decrease the risk of false interpretations of results using antibodies in science and clinical applications.

Optimal lesion size index to prevent conduction gap during pulmonary vein isolation.

INTRODUCTION: A novel real-time lesion size index (LSI) that incorporates contact force (CF), time, and power has been developed for safe and effective catheter ablation. The optimal LSI was evaluated to eliminate gap formation during pulmonary vein isolation (PVI). METHODS AND RESULTS: Consecutive patients were enrolled, who underwent their first PVI using a fiber-optic CF-sensing catheter for atrial fibrillation between December 2016 and October 2017. The CF parameters, force-time integral (FTI), and LSI for 3095 ablation points in 34 patients were evaluated. The FTI and LSI in the lesions with gaps or dormant conduction (gaps/DC) were significantly lower than those in the lesion without gaps/DC (FTI: 140.5 ± 54.5 and 232.4 ± 121.4 g s, P < 0.0001; LSI: 4.0 ± 0.6 and 4.7 ± 0.9, P < 0.0001, respectively). On receiver operating characteristic curve analysis, the optimal LSI threshold was 4.05 (sensitivity, 63.4%; specificity, 76.3%). The LSI of <5.25 predicted a gap or DC with a high sensitivity (sensitivity, 97.6%; specificity, 25.7%). In the posterior wall, which was 37% thinner than the nonposterior wall, a lower LSI of <3.95 showed a relatively high sensitivity (92.3%) and specificity (65.6%). CONCLUSIONS: The LSI can be used to predict gaps/DC during the PVI procedure. An LSI of 5.2 may be a suitable target for effective lesion formation. An LSI of 4.0 may be acceptable in the posterior wall, especially in areas adjacent to the esophagus.

General anesthesia improves contact force and reduces gap formation in pulmonary vein isolation: a comparison with conscious sedation.

Compared to conscious sedation (CS), the use of general anesthesia (GA) in pulmonary vein isolation (PVI) is associated with a lower recurrence rate of atrial fibrillation (AF). GA may improve catheter stability and mapping system accuracy compared to CS, but its influence on contact force (CF) parameters during ipsilateral PVI has not previously been investigated. The study population comprised 176 consecutive patients (107 in GA group and 69 in CS group) with AF who underwent their first PVI procedure. We retrospectively assessed CF parameters, force-time integral (FTI), FTI/wall thickness during anatomical ipsilateral PVI and long-term outcome after ablation. Complete PVI with single continuous circular lesions around the ipsilateral PVs was achieved in 54 patients (50.5%) in the GA group but only 24 patients (34.8%) in the CS group (P = 0.04). The distribution of gaps did not differ between the groups. All CF parameters were significantly higher in the GA group than in the CS group (average CF: 19.4 ± 8.7 vs. 16.7 ± 7.7 g, P < 0.0001; FTI: 399.0 ± 262.5 vs. 293.9 ± 193.4 gs, P < 0.0001; FTI/wall thickness: 155.5 ± 106.1 vs. 115.7 ± 85.5 gs, P < 0.0001). GA was associated with lower AF recurrence rate in patients with paroxysmal AF but not with persistent AF. Compared with CS, GA improves CF parameters, FTI and FTI/wall thickness, and reduced gap formation after ipsilateral PVI.

Optimal Force-Time Integral for Pulmonary Vein Isolation According to Anatomical Wall Thickness Under the Ablation Line.

BACKGROUND: Low contact force and force-time integral (FTI) during catheter ablation are associated with ineffective lesion formation, whereas excessively high contact force and FTI may increase the risk of complications. We sought to evaluate the optimal FTI for pulmonary vein (PV) isolation based on atrial wall thickness under the ablation line. METHODS AND RESULTS: Contact force parameters and FTI during anatomical ipsilateral PV isolation for atrial fibrillation and atrial wall thickness were assessed retrospectively in 59 consecutive patients for their first PV isolation procedure. The PV antrum was divided into 8 segments, and the wall thickness of each segment under the ablation line was determined using multidetector computed tomography. The FTI for each ablation point was divided by the wall thickness of the PV antrum segment where each point was located to obtain FTI/wall thickness. In total, 5335 radiofrequency applications were delivered, and 85 gaps in PV isolation ablation lines and 15 dormant conductions induced by adenosine were detected. The gaps or dormant conductions were significantly associated with low contact force, radiofrequency duration, FTI, and FTI/wall thickness. Among them, FTI/wall thickness had the best prediction value for gaps or dormant conductions by receiver operating characteristic curve analysis. FTI/wall thickness of <76.4 gram-seconds per millimeter (gs/mm) predicted gaps or dormant conductions with sensitivity (88.0%) and specificity (83.6%), and FTI/wall thickness of <101.1 gs/mm was highly predictive (sensitivity 97.0%; specificity 69.6%). CONCLUSIONS: FTI/wall thickness is a strong predictor of gap and dormant conduction formation in PV isolation. An FTI/wall thickness ≈100 gs/mm could be a suitable target for effective ablation.

Chronic Ischemia Induced by Woven Coronary Artery Anomaly with Typical Atrial Flutter: Insights from Multiple Imaging Devices.

A 75-year-old man with a 120-bpm tachycardia and typical atrial flutter was admitted. Echocardiography showed a dilated left ventricle with anterior and apical wall akinesia. Tachycardia was terminated with cavotricuspid isthmus ablation. Multiple imaging findings revealed a woven coronary artery anomaly (WCAA) in the left anterior descending artery. Stress myocardial perfusion imaging was performed after ablation in the sinus rhythm and revealed stress-induced ischemia and a fixed low uptake in the WCAA territory. WCAA is generally regarded as a benign condition; however, compromised blood flow within the anomaly, caused by tachycardia-related diastolic shortening, may induce ischemia.

Retinoid X receptor agonists modulate Foxp3⁺ regulatory T cell and Th17 cell differentiation with differential dependence on retinoic acid receptor activation.

Retinoic acid (RA) enhances TGF-ß-dependent differentiation of Foxp3(+) inducible regulatory T cells (iTregs) and inhibits Th17 differentiation by binding to the RA receptor (RAR)/retinoid X receptor (RXR) heterodimer. The major physiologic RA, all-trans-RA, binds to RAR but not to RXR at physiological concentrations. It remained unclear whether RXR-mediated stimulation affected the iTregs and Th17 differentiation. We found in this study that the RXR agonists, PA024 and tributyltin, augmented the ability of all-trans-RA or the RAR agonist Am80 to enhance CD4(+)CD25(-) T cells to acquire Foxp3 expression and suppressive function. However, they failed to enhance Foxp3 expression in the presence of the RAR antagonist LE540, suggesting that the effect depends on RAR-mediated signals. They exerted the effect largely by augmenting the ability of all-trans-RA to suppress the production of IL-4, IL-21, and IFN-γ that inhibited Foxp3 expression. Agonists of peroxisome proliferator-activated receptors and liver X receptors (LXRs), permissive partners of RXR, failed to enhance Foxp3 expression. In contrast, RXR agonists and LXR agonists suppressed IL-17 expression. The RXR-mediated suppression was not canceled by blocking RAR stimulation but was likely to involve permissive activation of LXRs. All-trans-RA and an agonist of RXR or LXR additively suppressed IL-17 expression when the all-trans-RA concentration was low. RXR agonists also suppressed Ccr6 expression that is essential for Th17 cells to enter the CNS. Accordingly, tributyltin treatment of mice ameliorated experimental autoimmune encephalomyelitis through regulating Th17 cell activities. These results suggest that RXR stimulation modulates Foxp3(+) iTreg and Th17 differentiation with differential dependence on RAR-mediated stimulation.

Early infantile growth and cardiovascular risks in adolescent Japanese women.

OBJECTIVE: Early life events connected with the risk of later disease can occur not only in utero, but also in infancy. In study of the developmental origins of health and disease, the relationship between infantile growth patterns and adolescent body mass index and blood pressure is one of the most important issues to verify. MATERIALS AND METHODS: We analyzed the correlation of current body mass index and systolic blood pressure of 168 female college students with their growth patterns in utero and in infancy. RESULTS: Body mass index and systolic blood pressure in adolescence showed positive correlations with changes in weight-for-age z scores between 1 and 18 months but not with those between 18 and 36 months. Stepwise multiple regression analysis showed that both change in weight-for-age z scores from 1 to 18 months and body mass index at 1 month were significantly and independently associated with systolic blood pressure in adolescence. Body mass index at 36 months was positively correlated with body mass index in adolescence, while body mass index at birth was negatively correlated with body mass index in adolescence. CONCLUSION: Our findings shows that restricted growth in utero and accelerated weight gain in early infancy are associated with the cardiovascular risk factors of high systolic blood pressure and high body mass index in adolescence. In Japan, an increasing proportion of low birth weight infants and accelerated catch-up growth after birth have been observed in recent decades. This might be an alarming harbinger of an increase in diseases related to the developmental origins of health and disease in Japan.

Influence of proton pump inhibitor treatment on Helicobacter pylori stool antigen test.

AIM: To investigate the effects of proton pump inhibitor (PPI) treatment on stool antigen test using the TestMate pylori enzyme immunoassay. METHODS: This study assessed 28 patients [16 men and 12 women; mean age (63.1 ± 5.9) years; range, 25-84 years] who underwent stool antigen test and urea breath test (UBT) before and after PPI administration. RESULTS: Using the UBT as the standard, the sensitivity, specificity and agreement of the stool antigen test in all 28 patients were 95.2%, 71.4%, and 89.3%, respectively, before PPI administration, and 88.9%, 90.9%, and 89.3%, respectively, after PPI treatment. Mean UBT values were 23.98% ± 5.33% before and 16.19% ± 4.75% after PPI treatment and, in 15 patients treated for ≥ 4 wk, were significantly lower after than before 4 wk of PPI treatment (12.58% ± 4.49% vs 24.53% ± 8.53%, P = 0.048). The mean optical density (A(450/630)) ratios on the stool antigen test were 1.16 ± 0.20 before and 1.17 ± 0.24 after PPI treatment (P = 0.989), and were 1.02 ± 0.26 and 0.69 ± 0.28, respectively, in the group treated for > 4 wk (P = 0.099). CONCLUSION: The stool antigen test was equally sensitive to the UBT, making it a useful and reliable diagnostic method, even during PPI administration.