Whole exome sequencing identifies genetic markers of enterovirus susceptibility in East Asians.

INTRODUCTION: Following acute enterovirus (EV) infection, outcomes vary based on factors like the immune response, viral cell entry receptor expression levels, tissue tropism, and genetic factors of both the host and virus. While most individuals exhibit mild, self-limited symptoms, others may suffer severe complications or prolonged infections that can lead to autoimmune disorders. METHODS: To elucidate host responses to EV infection, we performed whole exome sequencing on blood samples from both infected and uninfected individuals. Our initial focus was on genes encoding EV entry receptors-PSGL-1, SCARB2, and ANAXA2 for EV-A71, and CD155 for poliovirus-and on host genes ACBD3 and PI4KΒ, crucial for EV replication. RESULTS: Although no specific genetic variants directly associated with EV infection were identified, we discovered 118 variants across 116 genes enriched in East Asian populations through multi-layered variant filtering. These variants were further analyzed for their potential impacts on organs, biological processes, and molecular pathways. Phenome-wide association studies were conducted to refine our understanding of their contributions to EV infection susceptibility. DISCUSSION: Our findings aim to develop a predictive panel based on these 118 variants, which could help susceptible individuals during EV outbreaks, guiding targeted clinical interventions and preventative strategies

Development of the Malocclusion Impact Questionnaire (MIQ) to measure the oral health-related quality of life of young people with malocclusion: part 2 - cross-sectional validation.

OBJECTIVE: To test the items, identified through qualitative inquiry that might form the basis of a new Malocclusion Impact Questionnaire (MIQ) to measure the oral health-related quality of life (OHQoL) of young people with malocclusion. METHODS: Piloting with 13 young people reduced the number of items from 37 to 28. Cross-sectional testing involved a convenience sample aged 10-16 years, attending the Orthodontic Department of the Charles Clifford Dental Hospital, Sheffield. The fit and function of the initial MIQ questions were examined using item response theory. RESULTS: 184 participants (113 females; 71 males) completed a questionnaire (response 85%), seven participants were excluded due to missing responses. The mean age of participants was 12·9 years (SD 1·4) and they had a wide range of malocclusions. The majority were White British (67·4%). Data from 47 participants were used to analyse test-retest reliability. Rasch analysis was undertaken, which further reduced the number of items in the questionnaire from 28 to 17. Unidimensionality of the scale was confirmed. The analysis also identified that the original 5-point response scale could be reduced to three points. The new measure demonstrated good criterion validity (r = 0·751; P < 0·001) and construct validity with the two global questions ('Overall bother' ρ = 0·733 and 'Life overall' ρ = 0·701). Internal consistency (Cronbach's alpha = 0·906) and test-retest reliability Intraclass correlation coefficient (ICC = 0·78; 95% CI 0·61-0·88) were also good. CONCLUSION: Cross-sectional testing has shown the new MIQ to be both valid and reliable. Further evaluation is required to confirm the generalisability as well as the ability of the new measure to detect change over time (responsiveness)

Heritability and major gene effects on left ventricular mass in the Chinese population: a family study

BACKGROUND: Genetic components controlling for echocardiographically determined left ventricular (LV) mass are still unclear in the Chinese population. METHODS: We conducted a family study from the Chin-San community, Taiwan, and a total of 368 families, 1145 subjects, were recruited to undergo echocardiography to measure LV mass. Commingling analysis, familial correlation, and complex segregation analysis were applied to detect component distributions and the mode of inheritance. RESULTS: The two-component distribution model was the best-fitting model to describe the distribution of LV mass. The highest familial correlation coefficients were mother-son (0.379, P < .0001) and father-son (0.356, P < .0001). Genetic heritability (h(2)) of LV mass was estimated as 0.268 ± 0.061 (P < .0001); it decreased to 0.153 ± 0.052 (P = .0009) after systolic blood pressure adjustment. Major gene effects with polygenic components were the best-fitting model to explain the inheritance mode of LV mass. The estimated allele frequency of the gene was 0.089. CONCLUSION: There were significant familial correlations, heritability and a major gene effect on LV mass in the population-based families

More on the Nambu-Poisson M5-brane Theory: Scaling limit, background independence and an all order solution to the Seiberg-Witten map

We continue our investigation on the Nambu-Poisson description of M5-brane in a large constant C-field background (NP M5-brane theory) constructed in Refs.[1, 2]. In this paper, the low energy limit where the NP M5-brane theory is applicable is clarified. The background independence of the NP M5-brane theory is made manifest using the variables in the BLG model of multiple M2-branes. An all order solution to the Seiberg-Witten map is also constructed.Comment: expanded explanations, minor corrections and typos correcte

Changes in Plasma Membrane Surface Potential of PC12 Cells as Measured by Kelvin Probe Force Microscopy

The plasma membrane of a cell not only works as a physical barrier but also mediates the signal relay between the extracellular milieu and the cell interior. Various stimulants may cause the redistribution of molecules, like lipids, proteins, and polysaccharides, on the plasma membrane and change the surface potential (Φs). In this study, the Φss of PC12 cell plasma membranes were measured by atomic force microscopy in Kelvin probe mode (KPFM). The skewness values of the Φss distribution histogram were found to be mostly negative, and the incorporation of negatively charged phosphatidylserine shifted the average skewness values to positive. After being treated with H2O2, dopamine, or Zn2+, phosphatidylserine was found to be translocated to the membrane outer leaflet and the averaged skewness values were changed to positive values. These results demonstrated that KPFM can be used to monitor cell physiology status in response to various stimulants with high spatial resolution

The Views of Mental Health Manager Towards the Use of a Family Work Model for Psychosis in Guangzhou, China

Family Interventions in Psychosis (FIP) have been promoted internationally but have been criticised for being based on western cultural models. This paper reports on a focus group study with 10 Integrated Mental Health Service Managers in Guangzhou, China using thematic analysis. Managers believed FIP might benefit families but identified potential difficulties due to (a) families avoiding services due to the ‘shame’ of mental illness (b) unrealistic expectations of services amongst families (c) deferral to ‘key decision-makers’ within families when discussing family issues with workers. The findings indicate that FIP work should focus on interaction between carers in the first instance with service users being introduced into sessions at a later date and that more attention needs to be given by the research community to how FIP may be adapted to cultural norms within China

Cultural adaptation and validation of an instrument on barriers for the use of research results

ABSTRACT Objective: to culturally adapt The Barriers to Research Utilization Scale and to analyze the metric validity and reliability properties of its Brazilian Portuguese version. Method: methodological research conducted by means of the cultural adaptation process (translation and back-translation), face and content validity, construct validity (dimensionality and known groups) and reliability analysis (internal consistency and test-retest). The sample consisted of 335 nurses, of whom 43 participated in the retest phase. Results: the validity of the adapted version of the instrument was confirmed. The scale investigates the barriers for the use of the research results in clinical practice. Confirmatory factorial analysis demonstrated that the Brazilian Portuguese version of the instrument is adequately adjusted to the dimensional structure the scale authors originally proposed. Statistically significant differences were observed among the nurses holding a Master's or Doctoral degree, with characteristics favorable to Evidence-Based Practice, and working at an institution with an organizational cultural that targets this approach. The reliability showed a strong correlation (r ranging between 0.77 and 0.84, p<0.001) and the internal consistency was adequate (Cronbach's alpha ranging between 0.77 and 0.82). Conclusion: the Brazilian Portuguese version of The Barriers Scale was valid and reliable in the group studied

Functional Remineralization of Dentin Lesions Using Polymer-Induced Liquid-Precursor Process

It was hypothesized that applying the polymer-induced liquid-precursor (PILP) system to artificial lesions would result in time-dependent functional remineralization of carious dentin lesions that restores the mechanical properties of demineralized dentin matrix. 140 µm deep artificial caries lesions were remineralized via the PILP process for 7–28 days at 37°C to determine temporal remineralization characteristics. Poly-L-aspartic acid (27 KDa) was used as the polymeric process-directing agent and was added to the remineralization solution at a calcium-to-phosphate ratio of 2.14 (mol/mol). Nanomechanical properties of hydrated artificial lesions had a low reduced elastic modulus (ER = 0.2 GPa) region extending about 70 μm into the lesion, with a sloped region to about 140 μm where values reached normal dentin (18–20 GPa). After 7 days specimens recovered mechanical properties in the sloped region by 51% compared to the artificial lesion. Between 7–14 days, recovery of the outer portion of the lesion continued to a level of about 10 GPa with 74% improvement. 28 days of PILP mineralization resulted in 91% improvement of ER compared to the artificial lesion. These differences were statistically significant as determined from change-point diagrams. Mineral profiles determined by micro x-ray computed tomography were shallower than those determined by nanoindentation, and showed similar changes over time, but full mineral recovery occurred after 14 days in both the outer and sloped portions of the lesion. Scanning electron microscopy and energy dispersive x-ray analysis showed similar morphologies that were distinct from normal dentin with a clear line of demarcation between the outer and sloped portions of the lesion. Transmission electron microscopy and selected area electron diffraction showed that the starting lesions contained some residual mineral in the outer portions, which exhibited poor crystallinity. During remineralization, intrafibrillar mineral increased and crystallinity improved with intrafibrillar mineral exhibiting the orientation found in normal dentin or bone

Microscale characterization of prostate biopsies tissues using optical coherence elastography and second harmonic generation imaging

© 2018 USCAP, Inc All rights reserved. Photonics, especially optical coherence elastography (OCE) and second harmonic generation (SHG) imaging are novel high-resolution imaging modalities for characterization of biological tissues. Following our preliminary experience, we hypothesized that OCE and SHG imaging would delineate the microstructure of prostate tissue and aid in distinguishing cancer from the normal benign prostatic tissue. Furthermore, these approaches may assist in characterization of the grade of cancer, as well. In this study, we confirmed a high diagnostic accuracy of OCE and SHG imaging in the detection and characterization of prostate cancer for a large set of biopsy tissues obtained from men suspected to have prostate cancer using transrectal ultrasound (TRUS). The two techniques and methods described here are complementary, one depicts the stiffness of tissues and the other illustrates the orientation of collagen structure around the cancerous lesions. The results showed that stiffness of cancer tissue was ∼57.63% higher than that of benign tissue (Young's modulus of 698.43±125.29 kPa for cancerous tissue vs 443.07±88.95 kPa for benign tissue with OCE. Using histology as a reference standard and 600 kPa as a cut-off threshold, the data analysis showed sensitivity and specificity of 89.6 and 99.8%, respectively. Corresponding positive and negative predictive values were 99.5 and 94.6%, respectively. There was a significant difference noticed in terms of Young's modulus for different Gleason scores estimated by OCE (P-value<0.05). For SHG, distinct patterns of collagen distribution were seen for different Gleason grade disease with computed quantification employing a ratio of anisotropic to isotropic (A:I ratio) and this correlated with disease aggressiveness