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Objectives One primary concern about receiving care at home is that survival might be shortened because the quality and quantity of treatment provided at home will be inferior to that given in the hospital. Although our previous study demonstrated a longer survival of those with home-based palliative care (PC), it lacked adjustment for some potential confounders including symptoms and treatments during the stay. We aimed to compare the survival times among advanced cancer patients receiving home-based and hospital-based PC with adjusting for symptoms and treatments. Method We compared survival time of participants who enrolled two multicenter, prospective cohort studies of advanced cancer patients at 45-home-based PC services between July 2017 and December 2017, and at 23-hospital-based PC services between January 2017 and December 2017. We analyzed with stratification by the estimated survival of Days, Weeks, and Months, which were defined by modified Prognosis in Palliative care Study predictor models-A. We conducted a Cox regression analysis with adjusting for potential confounders including symptoms and treatments during the stay. Results A total of 2,998 patients were enrolled in both studies and 2,878 patients were analyzed; 988 patients receiving home-based PC and 1,890 receiving hospital-based PC. The survival time of patients receiving home-based PC was significantly longer than that of patients receiving hospital-based PC for the Days Prognosis (estimated median survival time: 10 days [95% CI 8.1–11.8] vs. 9 days [95% CI 8.3–10.4], p = 0.157), the Weeks prognosis (32 days [95% CI 28.9–35.4] vs. 22 days [95% CI 20.3–22.9], p < 0.001), and the Months Prognosis, (65 days [95% CI 58.2–73.2] vs. 32 days [95% CI 28.9–35.4], p < 0.001). Conclusion In this cohort of advanced cancer patients with a Weeks or Months prognosis, those receiving home-based PC survived longer than those receiving hospital-based PC after adjusting for symptoms and treatments.

Estrogen action is mediated by various genes, including estrogen-responsive genes (ERGs). ERGs have been used as reporter-genes and markers for gene expression. Gene expression profiling using a set of ERGs has been used to examine statistically reliable transcriptomic assays such as DNA microarray assays and RNA sequencing (RNA-seq). However, the quality of ERGs has not been extensively examined. Here, we obtained a set of 300 ERGs that were newly identified by six sets of RNA-seq data from estrogen-treated and control human breast cancer MCF-7 cells. The ERGs exhibited statistical stability, which was based on the coefficient of variation (CV) analysis, correlation analysis, and examination of the functional association with estrogen action using database searches. A set of the top 30 genes based on CV ranking were further evaluated quantitatively by RT-PCR and qualitatively by a functional analysis using the GO and KEGG databases and by a mechanistic analysis to classify ERα/β-dependent or ER-independent types of transcriptional regulation. The 30 ERGs were characterized according to (1) the enzymes, such as metabolic enzymes, proteases, and protein kinases, (2) the genes with specific cell functions, such as cell-signaling mediators, tumor-suppressors, and the roles in breast cancer, (3) the association with transcriptional regulation, and (4) estrogen-responsiveness. Therefore, the ERGs identified here represent various cell functions and cell signaling pathways, including estrogen signaling, and thus, may be useful to evaluate estrogenic activity.

This study examined the differences in medical and long-term care costs over 18 months between pet owners and non-owners among community-dwelling older Japanese. Pet ownership data were collected from 460 community-dwelling adults age 65 years and older. These data were matched with data from the National Health Insurance, health insurance for older people, and Long-Term Care Insurance beneficiaries for 17 months back from the survey on pet ownership. Pet-ownership group-specific trajectories in monthly medical and long-term care costs were modeled by a generalized estimating equation. Among pet owners (n = 96, 20.9%) and non-pet owners (n = 364, 79.1%) there were no significant differences in baseline demographic or health characteristics including chronic disease and self-reported long-term care level. At baseline, pet owners had estimated monthly medical costs of ¥48,054 (SE = 0.11; $418), compared to ¥42,260 (SE = 0.06; $367) for non-pet owners. The monthly medical costs did not differ significantly between the two groups during the 18-month follow-up period. At baseline, estimated monthly long-term care costs of pet owners and non-pet owners were ¥676 (SE = 0.75; $6) and ¥1,420 (SE = 0.52; $12), respectively. During the follow-up period, the non-pet owner to owner ratio of monthly long-term care costs was 1.2 at minimum and 2.3 at maximum. This study showed that monthly long-term care costs for pet owners were approximately half those of non-pet owners. Pet owners might use long-term care services less frequently, or use lighter care services.

Clinical isolates of Clostridioides difficile sometimes exhibit multidrug resistance and cause diarrhea after antibiotic administration. Metronidazole and vancomycin are often used as therapeutic agents, but resistance to these antibiotics has been found clinically. Therefore, the development of alternative antimicrobial agents is needed. Nisin A, produced by Lactococcus lactis, has been demonstrated to be effective against C. difficile infection. In this study, we evaluated the susceptibility of 11 C. difficile clinical isolates to nisin A and found that they could be divided into 2 groups: high and low susceptibility. Since CprABC and DltDABC, which are responsible for nisin A efflux and cell surface charge, respectively, have been reported to be related to nisin A susceptibility, we investigated the expression of cprA and dltA among the 11 strains. cprA expression in all strains was induced by nisin A, but dltA expression was not. The expression levels of both genes did not correlate with nisin A susceptibility in these clinical isolates. To evaluate cell surface charge, we performed a cytochrome C binding assay and found no relationship between charge and nisin A susceptibility. Then, we determined the whole genome sequence of each clinical isolate and carried out phylogenetic analysis. The 11 isolates separated into two major clusters, which were consistent with the differences in nisin A susceptibility. Furthermore, we found common differences in several amino acids in the sequences of CprA, CprB, and CprC between the two clusters. Therefore, we speculated that the different amino acid sequences of CprABC might be related to nisin A susceptibility. In addition, C. difficile strains could be divided in the same two groups based on susceptibility to epidermin and mutacin III, which are structurally similar to nisin A. These results suggest that genotypic variations in C. difficile strains confer different susceptibilities to bacteriocins.

In post-stroke patients, muscle synergy (the coordination of motor modules during walking) is impaired. In some patients, the muscle synergy termed module 1 (hip/knee extensors) is merged with module 2 (ankle plantar flexors), and in other cases, module 1 is merged with module 4 (knee flexors). However, post-stroke individuals with a merging pattern of module 3 (hip flexor and ankle dorsiflexor) and module 4, which is the swing-muscle synergy, have not been reported. This study aimed to determine the muscle-synergy merging subtypes of post-stroke during comfortable walking speed (cws). We also examined the effect of experimental lower-limb angle modulation on the muscle synergy patterns of walking in each subtype. Forty-one participants were assessed under three conditions: cws, long stepping on the paretic side (p-long), and long stepping on the non-paretic side (np-long). Lower-limb flexion and extension angles and the electromyogram were measured during walking. Subtype classification was based on the merging pattern of the muscle synergies, and we examined the effect of different lower-limb angles on the muscle synergies. We identified three merging subtypes: module 1 with module 2 (subtype 1), module 1 with module 4 (subtype 2), and module 3 with module 4 (subtype 3). In the cws condition, the lower-limb flexion angle was reduced in subtype 3, and the lower-limb extension angle was decreased in subtype 1. A more complex muscle synergy was observed only in subtype 3 in the p-long condition versus cws (p = 0.036). This subtype classification of walking impairments based on the merging pattern of the muscle synergies could be useful for the selection of a rehabilitation strategy according to the individual’s particular neurological condition. Rehabilitation with increased lower-limb flexion may be effective for the training of patients with merging of modules 3 and 4 in comfortable walking.

Commonly used prediction methods for acute myocardial infarction (AMI) were created before contemporary percutaneous coronary intervention was recognized as the primary therapy. Although several studies have used machine learning techniques for prognostic prediction of patients with AMI, its clinical application has not been achieved. Here, we developed an online application tool using a machine learning model to predict in-hospital mortality in patients with AMI. A total of 2,553 cases of ST-elevation AMI were assigned to 80% training subset for cross validation and 20% test subset for model performance evaluation. We implemented random forest classifier for the binary classification of in-hospital mortality. The selected best feature set consisted of ten clinical and biological markers including max creatine phosphokinase, hemoglobin, heart rate, creatinine, systolic blood pressure, blood sugar, age, Killip class, white blood cells, and c-reactive protein. Our model achieved high performance: the area under the curve of the receiver operating characteristic curve for the test subset, 0.95: sensitivity, 0.89: specificity, 0.91: precision, 0.43: accuracy, 0.91 respectively, which outperformed common scoring methods. The freely available application tool for prognostic prediction can contribute to risk triage and decision-making in patient-centered modern clinical practice for AMI.

This study aimed to evaluate the 3-year long-term outcomes of primary Baerveldt glaucoma implant (BGI) surgery for neovascular glaucoma (NVG). We retrospectively evaluated 27 consecutive patients with NVG between November 2013 and November 2017. All the patients were treated with panretinal photocoagulation and pars plana vitrectomy before BGI surgery without anti-vascular endothelial growth factor treatment. The surgical success of the BGI was defined as an IOP of

Background and purpose The impact of the paraoxonase-1 (PON1) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of PON1 Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention. Methods Post-clopidogrel platelet reactivity was measured using a VerifyNow® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for PON1 Q192R and CYP2C19*2 and *3 (no function alleles), and *17. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 PON1 192R allele and HPR defined as original and corrected PRU ≥208. Results Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 PON1 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 PON1 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03–3.76) and corrected PRU (OR 2.34, 95% CI 1.21–4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 CYP2C19 no function allele. Conclusions Carrying ≥1 PON1 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded.

Background:Lower socioeconomic status (SES) may be related to inactivity lifestyle; however, the association between SES and physical inactivity has not been sufficiently investigated in Japan., Methods:The study population is the participants of NIPPON DATA2010, which is a prospective cohort study of the National Health and Nutrition Survey 2010 in Japan. They were residents in 300 randomly selected areas across Japan. This study included 2,609 adults. Physical activity was assessed by physical activity index (PAI) calculated from activity intensity and time. The lowest tertile of PAI for each 10-year age class and sex was defined as physical inactivity. Multivariable logistic regression analyses were conducted to examine the association of SES (employment status, educational attainment, living status, and equivalent household expenditure (EHE)) with physical inactivity., Results:In the distribution of PAI by age classes and sex, the highest median PAI was aged 30-39 years among men (median 38.6), aged 40-49 years among women (38.0), and median PAI was decreased with increasing age. Multivariable-adjusted model shows that not working was significantly associated with physical inactivity after adjustment for age in all age groups and sexes. Not living with spouse for adult women and elderly men was significantly associated with physical inactivity compared to those who living with spouse. However, neither educational attainment nor EHE had any significant associations with physical inactivity., Conclusions:The result indicated that physical inactivity was associated with SES in a general Japanese population. SES of individuals need to be considered in order to prevent inactivity lifestyle.

Glycemic control is essential to manage metabolic diseases such as diabetes. Frequent measurements of systemic glucose levels with prompt managements can prevent organ damages. The eye is a glucose highly demanding organ in our body, and the anterior chamber (AC) in the eye has been suggested for a noninvasive blood glucose monitoring site. However, calculating blood glucose levels from measuring glucose levels in AC has been difficult and unclear. In this study, we aimed to examine glucose levels from AC and find a correlation with blood glucose levels. A total of 30 patients with cataracts (men and women, study 1; 7 and 3, study 2; 9 and 11) who visited Keio University Hospital from 2015 to 2018 and agreed to participate in this study were recruited. Glucose levels from AC and the blood were examined by a UV-hexokinase or H2O2-electrode method before/during the cataract surgery. These values were analyzed with regression analyses depending on the groups (blood glucose-ascending and descending groups). In the blood glucose-descending group, glucose levels from AC were strongly correlated with blood glucose levels (a high R2 value, 0.8636). However, the relatively moderate correlation was seen in the blood glucose-ascending group (a low R2 value, 0.5228). Taken together, we showed different correlation ratios on glucose levels between AC and the blood, based on blood glucose dynamics. Stacking data regarding this issue would enable establishing noninvasive blood glucose monitoring from measuring glucose levels in AC more correctly, which will be helpful for proper and prompt managements for glucose-mediated complications.

Sense of agency (SoA), the feeling of control over one’s own actions and their effects, is fundamental to goal-directed actions at the individual level and may constitute a cornerstone of everyday life, including cooperative behavior (i.e., goal sharing). Previous studies have demonstrated that goal sharing can activate the motor prediction of both agent’s action and partner’s action in joint-action tasks. Moreover, given that from an SoA perspective, predictive processes are an essential basis, there is a possibility that goal sharing may modulate SoA. However, the possibility for goal sharing to modulate SoA remains unclear. This study aimed to investigate whether goal sharing modulates the intentional binding (IB) effect (a method that can quantitatively measure SoA) of self-generated and observed partner’s actions and improves motor accuracy. Participants were required to stop a circular horizontal moving object by pressing a key when the object reaches the center of a target in a social situation. This task measured IB by having participants estimate the time interval between action and effect in several 100 milliseconds, with shorter time interval estimations indicating enhancement of SoA. Participants were randomly divided into 13 Cooperative groups (goal sharing) and 13 Independent groups (non-goal sharing). Cooperative groups were instructed to perform the task together, while Independent groups did so individually. Participants estimated the time interval between them by pressing the key and hearing the corresponding sound (Self-generated action) and the other person pressing the key and hearing the sound (Observed action). Our results indicated that goal sharing improved motor accuracy and enhanced both the IB of Self-generated and Observed actions compared to non-goal sharing. We suggest that SoA can be modulated by goal sharing in specific social contexts.

Proliferative diabetic retinopathy (PDR) is the most severe case of diabetic retinopathy that can cause visual impairment. This study aimed to reveal the factors correlated with better postoperative visual acuity after a long follow-up in patients who underwent vitrectomy for PDR. We retrospectively analyzed the data set including systemic findings, ocular findings, and surgical factors from registered patients who could be completely followed up for 2 or 4 years after vitrectomy. We ultimately enrolled 128 eyes from 100 patients who underwent vitrectomy for PDR between January 2008 and September 2012 and were followed up for >2 years. Among them, 91 eyes from 70 patients could be followed up for 4 years. Factors related to the postoperative visual acuity of ≥20/40 and ≥20/30 after 2 and 4 years were investigated by logistic regression analysis. Better postoperative visual acuity correlated with the following factors: no rubeosis iridis ([≥20/40 at 2 years; odds ratio {OR}, 0.068; 95% confidence interval {CI}, 0.012–0.39; P = 0.003], [≥20/30 at 2 years; OR, 0.07; 95% CI, 0.01–0.40; P = 0.03], [≥20/30 at 4 years; OR, 0.078; 95% CI, 0.006–0.96; P = 0.04]), no fibrovascular membrane [(≥20/40 at 2 years; OR, 0.22; 95% CI, 0.061–0.81; P = 0.02), (≥20/40 at 4 years; OR, 0.26; 95% CI, 0.07–0.94; P = 0.04), (≥20/30 at 4 years; OR, 0.14; 95% CI, 0.04–0.52; P = 0.004)], existing vitreous hemorrhage (≥20/30 at 2 years; OR, 9.55; 95% CI, 1.03–95.27; P = 0.04), and no reoperation ([≥20/40 at 4 years; OR, 0.15; 95% CI, 0.03–0.78; P = 0.02], [≥20/30 at 4 years; OR, 0.06; 95% CI, 0.07–0.54; P = 0.01]). Treatment provision before disease severity and treatment without complications were associated with good postoperative visual acuity.

It is well investigated that the expression of racial prejudice is often induced by news coverage on the internet, and the exposure to media contributes to the cultivation of long-term prejudice. However, there is a lack of information regarding the immediate effects of news delivered through television or television-like media on the expression of racial prejudice. This study provides a framework for understanding such effects by focusing on content-audience associations using the logs of an “online television” service, which provides television-like content and user experiences. With these logs, we found an association between the news-watching and comment-posting behaviors. Consequently, logs relevant to two distinct forms of racism, modern and old-fashioned racism, were extracted. Using mathematical modeling, which considers the different levels of program inducements to racist expression, personal inclinations of audiences to racism, and certainty of prediction of audience behaviors, we found three associative patterns between the news programs and audiences. The relevance of the topics covered to the basic beliefs of each form of racism was characterized into three clusters: expression as a reaction to news that is directly relevant to the basic beliefs of racism with weak inducements by non-bigots, minority abuse by distorting the meanings of news content indirectly relevant to the beliefs but with strong inducements by audiences with a strong bias, and racial toxic opinions independent of the news content by clear bigots. Our findings provide implications for inhibiting the expression of online prejudice based on the characteristics of these patterns.

Foot-and-mouth disease virus (FMDV) serotype O, topotype CATHAY is a known porcinophilic virus that has caused devastating damage to the pig industry. However, the minimum infectious dose via a natural infection route in pigs, the infection dynamics in cattle, and risk of viral transmission from infected cattle to pigs have not been quantitatively analyzed. The FMDV strain O/HKN/1/2015 was serially diluted and inoculated into pigs via an intraoral route to determine the infectious dose. We found that a 104.0 tissue culture infectious dose (TCID50) of the virus was insufficient, but 105.5 TCID50 was sufficient to infect pigs via the oral route. While cows inoculated with the strain showed increased temperature in their feet, typical clinical signs including vesicular development were not observed. The cows showed short-term and low levels of viremia and virus excretion only before the detection of virus neutralizing antibodies. FMDV genes were not detected in esophageal-pharyngeal fluid from cows after 14 days post inoculation. No genetic insertions that could be associated with host adaptation were observed in viruses isolated from infected cows. These findings indicate that cows infected with FMDV of O/CATHAY have a low risk of viral transmission or persistence. Information on the dynamics of virus infection is essential for ensuring the rapid and accurate diagnosis of this disease, and its surveillance.

Background Occult hepatitis B (OHB) is a major concern in HIV infected patients as it associates with a high risk of HBV reactivation and disease progression. However, data on the prevalence of OHB among HIV positive patients in Ethiopia is lacking. This study aims to determine the prevalence of OHB in HBV/HIV co-infected patients from Gondar, Ethiopia. Methods A total of 308 consented HIV positive patients were recruited from the University of Gondar Teaching Hospital, Ethiopia. Clinical and demographic data of the participants were recorded. Plasma was tested for HBsAg and anti-HBc using commercial assays (Abbott Architect). In HBsAg negative anti-HBc positive patient samples, total DNA was isolated and amplified using nested PCR with primers specific to HBV polymerase, surface and pre-core/core regions, followed by Sanger sequencing and HBV mutational analysis using MEGA 7.0. Results Of the total study subjects, 62.7% were female, median age 38.4 years, interquartile range (IQR): 18–68, and 208 (67.5%) had lifestyle risk factors for HBV acquisition. Two hundred and ninety-one study subjects were HIV+/HBsAg-, out of which 115 (39.5%) were positive for anti-HBc. Occult hepatitis B was detected in 19.1% (22/115) of anti-HBc positive HIV patients. HBV genotype D was the predominant genotype (81%) among OHB positive patients. Mutations associated with HBV drug resistance, HBV reactivation, and HCC risk were detected in 23% (5/22), 14% (3/22) and 45.5% (10/22) of patients, respectively. Conclusion This study found a high rate of occult hepatitis B in HIV patients. Further, high rates of mutations associated with HBV reactivation, drug resistance, and HCC risk were detected in these patients. These data highlighted the need for integrating OHB screening for proper management of liver diseases in HIV patients.

Primary ovarian insufficiency (POI) is a heterogeneous disorder associated with several genes. The majority of cases are still unsolved. Our aim was to identify the molecular diagnosis of a Brazilian cohort with POI. Genetic analysis was performed using a customized panel of targeted massively parallel sequencing (TMPS) and the candidate variants were confirmed by Sanger sequencing. Additional copy number variation (CNV) analysis of TMPS samples was performed by CONTRA. Fifty women with POI (29 primary amenorrhea and 21 secondary amenorrhea) of unknown molecular diagnosis were included in this study, which was conducted in a tertiary referral center of clinical endocrinology. A genetic defect was obtained in 70% women with POI using the customized TMPS panel. Twenty-four pathogenic variants and two CNVs were found in 48% of POI women. Of these variants, 16 genes were identified as BMP8B, CPEB1, INSL3, MCM9, GDF9, UBR2, ATM, STAG3, BMP15, BMPR2, DAZL, PRDM1, FSHR, EIF4ENIF1, NOBOX, and GATA4. Moreover, a microdeletion and microduplication in the CPEB1 and SYCE1 genes, respectively, were also identified in two distinct patients. The genetic analysis of eleven patients was classified as variants of uncertain clinical significance whereas this group of patients harbored at least two variants in different genes. Thirteen patients had benign or no rare variants, and therefore the genetic etiology remained unclear. In conclusion, next-generation sequencing (NGS) is a highly effective approach to identify the genetic diagnoses of heterogenous disorders, such as POI. A molecular etiology allowed us to improve the disease knowledge, guide decisions about prevention or treatment, and allow familial counseling avoiding future comorbidities.

The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM.