Electronic Structure of Water from Koopmans-Compliant Functionals.

Obtaining a precise theoretical description of the spectral properties of liquid water poses challenges for both molecular dynamics (MD) and electronic structure methods. The lower computational cost of the Koopmans-compliant functionals with respect to Green's function methods allows the simulations of many MD trajectories, with a description close to the state-of-art quasi-particle self-consistent GW plus vertex corrections method (QSGW + fxc). Thus, we explore water spectral properties when different MD approaches are used, ranging from classical MD to first-principles MD, and including nuclear quantum effects. We have observed that different MD approaches lead to up to 1 eV change in the average band gap; thus, we focused on the band gap dependence with the geometrical properties of a system to explain such spread. We have evaluated the changes in the band gap due to variations in the intramolecular O-H bond distance and HOH angle, as well as the intermolecular hydrogen bond O···O distance and the OHO angles. We have observed that the dominant contribution comes from the O-H bond length; the O···O distance plays a secondary role, and the other geometrical properties do not significantly influence the gap. Furthermore, we analyze the electronic density of states (DOS), where the KIPZ functional shows good agreement with the DOS obtained with state-of-art approaches employing quasi-particle self-consistent GW plus vertex corrections. The O-H bond length also significantly influences the DOS. When nuclear quantum effects are considered, broadening of the peaks driven by the broader distribution of the O-H bond lengths is observed, leading to a closer agreement with the experimental photoemission spectra.

Normal Values and Associated Factors in Highresolution Anorectal Manometry in Healthy Vietnamese Adults / Valores normais e fatores associados na manometria anorretal de alta resolução em adultos vietnamitas saudáveis

Abstract Introduction The present study aims to identify normal high-resolution anorectal manometry (HRAM) values and related factors in healthy Vietnamese adults. Methods The present cross-sectional study was conducted at the Viet Duc hospital, Hanoi, Vietnam, during April and May 2019. Healthy volunteers were recruited to participate in the study. Anorectal measurement values from the digestive tract, including pressure, were recorded. Results A total of 76 healthy volunteers were recruited. The mean functional anal canal length was 4.2 ± 0.5 cm, while the mean anal high-pressure zone length was 3.4 ± 0.5 cm. Themean defecation index was 1.4 ± 0.8, with values ranging from 0.3 to 5.0. The mean threshold volume to elicit the rectoanal inhibitory reflex (RAIR) was 18.1 mL. The mean rectal sensation values were 32.4mL, 81.6mL, and 159 mL for first sensation, desire to defecate, and urge to defecate, respectively. Dyssynergic patterns occurred in ~ 50% of the study participants and included mainly types I (27.6%) and III (14.6%). There were significant differences between male and female patients in terms of maximum anal squeeze pressure, maximum anal cough pressure, maximum anal strain pressure, maximum rectal cough pressure, and maximum rectal strain pressure (all p<0.01). Conclusions The present study establishes normal HRAM values in healthy Vietnamese adults, particularly regarding normal values of anorectal pressure and rectal sensation. Further studies that include larger sample sizes should be conducted to further confirm the constants and their relationships.

Resumo Introdução O presente estudo tem como objetivo identificar valores normais de manometria anorretal de alta resolução e fatores relacionados em adultos vietnamitas saudáveis. Métodos O presente estudo transversal foi conduzido no hospital Viet Duc, Hanói, Vietnã, durante abril e maio de 2019. Voluntários saudáveis foram recrutados para participar do estudo. Valores de medição anorretal, incluindo pressão do trato digestivo, foram registrados. Resultados Um total de 76 voluntários saudáveis foram recrutados. O comprimento funcional médio do canal anal foi de 4,2 ± 0,5 cm, enquanto o comprimento médio da zona anal de alta pressão foi de 3,4 ± 0,5 cm. O índice médio de defecação foi de 1,4 ± 0,8, com valores variando de 0,3 a 5,0. O volume limite médio para eliciar o reflexo inibitório retoanal (RAIR, sigla em inglês) foi de 18,1 mL. Os valores médios da sensação retal foram 32,4mL, 81,6mL e 159 mL para a primeira sensação, o desejo de defecar e a urgência de defecar, respectivamente. Os padrões dissinérgicos ocorreram em aproximadamente 50% dos participantes do estudo e incluíram principalmente os tipos I (27,6%) e III (14,6%). Houve diferenças significativas entre homens e mulheres na pressão de compressão anal máxima, pressão de tosse anal máxima, pressão de distensão anal máxima, pressão de tosse retal máxima e pressão de distensão retal máxima (todos p<0,01). Conclusões O presente estudo estabelece valores normais de HRAM em adultos vietnamitas saudáveis, particularmente no que diz respeito aos valores normais de pressão anorretal e sensação retal. Mais estudos que incluam tamanhos de amostra maiores devemser realizados a fim de confirmar melhor as constantes e suas relações.

Personalized 3D kidney model produced by rapid prototyping method and its usefulness in clinical applications

ABSTRACT Background: Three-dimensional (3D) printing has been introduced as a novel technique to produce 3D objects. We tried to evaluate the clinical usefulness of 3D-printed renal model in performing partial nephrectomy (PN) and also in the education of medical students. Materials and Methods: We prospectively produced personalized renal models using 3D-printing methods from preoperative computed tomography (CT) images in a total of 10 patients. Two different groups (urologist and student group) appraised the clinical usefulness of 3D-renal models by answering questionnaires. Results: After application of 3D renal models, the urologist group gave highly positive responses in asking clinical usefulness of 3D-model among PN (understanding personal anatomy: 8.9 / 10, preoperative surgical planning: 8.2 / 10, intraoperative tumor localization: 8.4 / 10, plan for further utilization in future: 8.3 / 10, clinical usefulness in complete endophytic mass: 9.5 / 10). The student group located each renal tumor correctly in 47.3% when they solely interpreted the CT images. After the introduction of 3D-models, the rate of correct answers was significantly elevated to 70.0% (p < 0.001). The subjective difficulty level in localizing renal tumor was also significantly low (52% versus 27%, p < 0.001) when they utilized 3D-models. Conclusion: The personalized 3D renal model was revealed to significantly enhance the understanding of correct renal anatomy in patients with renal tumors in both urologist and student groups. These models can be useful for establishing the perioperative planning and also education program for medical students.

Personalized 3D kidney model produced by rapid prototyping method and its usefulness in clinical applications.

BACKGROUND: Three-dimensional (3D) printing has been introduced as a novel technique to produce 3D objects. We tried to evaluate the clinical usefulness of 3D-printed renal model in performing partial nephrectomy (PN) and also in the education of medical students. MATERIALS AND METHODS: We prospectively produced personalized renal models using 3D-printing methods from preoperative computed tomography (CT) images in a total of 10 patients. Two different groups (urologist and student group) appraised the clinical usefulness of 3D-renal models by answering questionnaires. RESULTS: After application of 3D renal models, the urologist group gave highly positive responses in asking clinical usefulness of 3D-model among PN (understanding personal anatomy: 8.9 / 10, preoperative surgical planning: 8.2 / 10, intraoperative tumor localization: 8.4 / 10, plan for further utilization in future: 8.3 / 10, clinical usefulness in complete endophytic mass: 9.5 / 10). The student group located each renal tumor correctly in 47.3% when they solely interpreted the CT images. After the introduction of 3D-models, the rate of correct answers was significantly elevated to 70.0% (p < 0.001). The subjective difficulty level in localizing renal tumor was also significantly low (52% versus 27%, p < 0.001) when they utilized 3D-models. CONCLUSION: The personalized 3D renal model was revealed to significantly enhance the understanding of correct renal anatomy in patients with renal tumors in both urologist and student groups. These models can be useful for establishing the perioperative planning and also education program for medical students.

Association of TNFSF8 regulatory variants with excessive inflammatory responses but not leprosy per se

BACKGROUND: Type 1 reactions (T1R) affect a considerable proportion of patients with leprosy. In those with T1R, the host immune response pathologically overcompensates for the actual infectious threat, resulting in nerve damage and permanent disability. Based on the results of a genome-wide association study of leprosy per se, we investigated the TNFSF15 chromosomal region for a possible contribution to susceptibility to T1R. METHODS: We performed a high-resolution association scan of the TNFSF15 locus to evaluate the association with T1R in 2 geographically and ethnically distinct populations: a family-based sample from Vietnam and a case-control sample from Brazil, comprising a total of 1768 subjects. RESULTS: In the Vietnamese sample, 47 single-nucleotide polymorphisms (SNPs) overlapping TNFSF15 and the adjacent TNFSF8 gene were associated with T1R but not with leprosy. Of the 47 SNPs, 39 were cis-expression quantitative trait loci (cis-eQTL) for TNFSF8 including SNPs located within the TNFSF15 gene. In the Brazilian sample, 18 of these cis-eQTL SNPs overlapping the TNFSF8 gene were validated for association with T1R. CONCLUSIONS: Taken together, these results indicate TNFSF8 and not TNFSF15 as an important T1R susceptibility gene. Our data support the need for infection genetics to go beyond genes for pathogen control to explore genes involved in a commensurate host response.

Comparison of self-care behaviors of heart failure patients in 15 countries worldwide.

OBJECTIVE: Clinicians worldwide seek to educate and support heart failure patients to engage in self-care. We aimed to describe self-care behaviors of patients from 15 countries across three continents. METHODS: Data on self-care were pooled from 5964 heart failure patients from the United States, Europe, Australasia and South America. Data on self-care were collected with the Self-care of Heart Failure Index or the European Heart Failure Self-care Behavior Scale. RESULTS: In all the samples, most patients reported taking their medications as prescribed but exercise and weight monitoring were low. In 14 of the 22 samples, more than 50% of the patients reported low exercise levels. In 16 samples, less than half of the patients weighed themselves regularly, with large differences among the countries. Self-care with regard to receiving an annual flu shot and following a low sodium diet varied most across the countries. CONCLUSION: Self-care behaviors are sub-optimal in heart failure patients and need to be improved worldwide. PRACTICE IMPLICATIONS: Interventions that focus on specific self-care behaviors may be more effective than general educational programs. Changes in some health care systems and national policies are needed to support patients with heart failure to increase their self-care behavior.

Differential effects of TR ligands on hormone dissociation rates: evidence for multiple ligand entry/exit pathways.

Some nuclear receptor (NR) ligands promote dissociation of radiolabeled bound hormone from the buried ligand binding cavity (LBC) more rapidly than excess unlabeled hormone itself. This result was interpreted to mean that challenger ligands bind allosteric sites on the LBD to induce hormone dissociation, and recent findings indicate that ligands bind weakly to multiple sites on the LBD surface. Here, we show that a large fraction of thyroid hormone receptor (TR) ligands promote rapid dissociation (T(1/2)<2h) of radiolabeled T(3) vs. T(3) (T(1/2) approximately 5-7h). We cannot discern relationships between this effect and ligand size, activity or affinity for TRbeta. One ligand, GC-24, binds the TR LBC and (weakly) to the TRbeta-LBD surface that mediates dimer/heterodimer interaction, but we cannot link this interaction to rapid T(3) dissociation. Instead, several lines of evidence suggest that the challenger ligand must interact with the buried LBC to promote rapid T(3) release. Since previous molecular dynamics simulations suggest that TR ligands leave the LBC by several routes, we propose that a subset of challenger ligands binds and stabilizes a partially unfolded intermediate state of TR that arises during T(3) release and that this effect enhances hormone dissociation.

Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy.

Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases.

Susceptibility to leprosy is associated with PARK2 and PACRG.

Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25-q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy.

Chromosome 6q25 is linked to susceptibility to leprosy in a Vietnamese population

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, affects an estimated 700,000 persons each year. Clinically, leprosy can be categorized as paucibacillary or multibacillary disease. These clinical forms develop in persons that are intrinsically susceptible to leprosy per se, that is, leprosy independent of its specific clinical manifestation. We report here on a genome-wide search for loci controlling susceptibility to leprosy per se in a panel of 86 families including 205 siblings affected with leprosy from Southern Vietnam. Using model-free linkage analysis, we found significant evidence for a susceptibility gene on chromosome region 6q25 (maximum likelihood binomial (MLB) lod score 4.31; P = 5 x 10(-6)). We confirmed this by family-based association analysis in an independent panel of 208 Vietnamese leprosy simplex families. Of seven microsatellite markers underlying the linkage peak, alleles of two markers (D6S1035 and D6S305) showed strong evidence for association with leprosy (P = 6.7 x 10(-4) and P = 5.9 x 10(-5), respectively).