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Abstract Integrinβ-1 (ITGB1) is a crucial member of the transmembrane glycoprotein signaling receptor family and is also central to the integrin family. It forms heterodimers with other ligands, participates in intracellular signaling and controls a variety of cellular processes, such as angiogenesis and the growth of neurons; because of its role in bidirectional signaling regulation both inside and outside the membrane, ITGB1 must interact with a multitude of substances, so a variety of interfering factors can affect ITGB1 and lead to changes in its function. Over the past 20 years, many studies have confirmed a clear causal relationship between ITGB1 dysregulation and cancer development and progression in a wide range of benign diseases and solid tumor types, which may imply that ITGB1 is a prognostic biomarker and a therapeutic target for cancer treatment that warrants further investigation. This review summarizes the biological roles of ITGB1 in benign diseases and cancers, and compiles the current status of ITGB1 function and therapy in various aspects of tumorigenesis and progression. Finally, future research directions and application prospects of ITGB1 are suggested. Video Abstract

Abstract To analyze the status of binocular visual functions, the relationship between binocular visual function and computer vision-related symptoms in the high-tech industry group. The study sample was comprised of 33 participants aged between 20 and 40 years of age. After completing basic information and the Computer Vision Symptom Scale (CVSS-17) questionnaire, the participants underwent a comprehensive examination of binocular visual function. All data were statistically analyzed with SPSS V26.0 software. The value of the binocular vision function of the Taiwan high-tech industry group was significantly different compared with the Scheiman and Morgan standard value. Study subjects were generally found to exhibit larger exophoric at distance, which in turn might lead to a lower ability to maintain binocular fusion to a single image, or recover from fusional disruption at distance. Subjects also experienced accommodation and convergence problems at near at the same time. Age, gender, and refractive errors had no significant impact on CVSS-17 scores, only the duration of computer usage showed a significant effect, particularly for internal symptom factor (ISF) dimensions. In addition, the interaction between the ISF and external symptom factor resulted in more severe visual symptoms. Long-term use of electronic devices may lead to an imbalance in binocular vision function, thereby increasing or exacerbating visual symptoms. If the use of electronic devices is an unchangeable trend, interventions in prescription, visual training or the visual design of electronic products become worthwhile topics for development.

Background It has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine the effect of lung function impairments on lung cancer risks.Methods This was a retrospective cohort study (1 January 1994 to 31 December 2017) of individuals from a health surveillance programme in Taiwan who underwent baseline spirometry tests at the entry point. PRISm was defined as an FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >0.7 and FEV1

Abstract Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation‐specific homologous factor (EHF), a member of the E26 transformation‐specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma‐associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor‐associated macrophages (TAMs) through the C‐C motif chemokine 2/C‐C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co‐expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF‐mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2‐TAMs to inhibit EHF‐driven CCA development.

Abstract Hypertension is characterized by endothelial dysfunction and arterial stiffness, which contribute to the pathogenesis of atherosclerotic cardiovascular diseases. Nicotinamide adenine dinucleotide (NAD+) is an indispensable cofactor in all living cells that is involved in fundamental biological processes. However, in hypertensive patients, alterations in NAD+ levels and their relation with blood pressure (BP) elevation and vascular damage have not yet been studied. Here we reported that hypertensive patients exhibited lower NAD+ levels, as detected by high-performance liquid chromatography-mass spectrometry (HPLC-MS), in both peripheral blood mononuclear cells (PBMCs) and aortas, which was parallel to vascular dysfunction. NAD+ boosting therapy with nicotinamide mononucleotide (NMN) supplement reduced BP and ameliorated vascular dysfunction in hypertensive patients (NCT04903210) and AngII-induced hypertensive mice. Upregulation of CD38 in endothelial cells led to endothelial NAD+ exhaustion by reducing NMN bioavailability. Pro-inflammatory macrophages infiltration and increase in IL-1β generation derived from pro-inflammatory macrophages resulted in higher CD38 expression by activating JAK1-STAT1 signaling pathway. CD38 KO, CD38 inhibitors treatment, or adeno-associated virus (AAV)-mediated endothelial CD38 knockdown lowered BP and improved vascular dysfunction in AngII-induced hypertensive mice. The present study demonstrated for the first time that endothelial CD38 activation and subsequently accelerated NAD+ degradation due to enhanced macrophage-derived IL-1β production was responsible for BP elevation and vascular damage in hypertension. NAD+ boosting therapy can be used as a novel therapeutic strategy for the management of hypertensive patients.

Background: To evaluate the efficacy of stent-assisted coiling (SAC) for the treatment of carotid ophthalmic segment aneurysm segment aneurysms (OSAs) of the internal carotid artery (ICA) through detailed long-term follow-up of a large patient cohort. Methods: We retrospectively analyzed 88 consecutive patients with OSAs between January 2009 and January 2020 ​at our center. Angiographic results were evaluated using the modified Raymond grading system and clinical outcomes were evaluated using the mRS scale. The primary endpoints were major aneurysm recurrence and poor clinical outcomes for at least 18 months of follow-up. The patients were asked to attend clinical follow-up assessments and possibly undergo DSA or MR via telephone. Results: We enrolled 88 patients with 99 OSAs treated with coiling, of whom 76 were treated with SAC. The coiling procedures were successful in all 88 patients. Overall, complications occurred in 8 patients (9.1%). No procedure-related mortality was observed. 67 (76.1%) experienced immediate aneurysm occlusion at the end of the procedure. Long-term angiographic follow-up (18 months) was available in 45/88 aneurysms (51%) (average 18.7 ​± ​5.2 months). Four patients continued their follow-up for 5 years after initial aneurysm treatment. After a clinical follow-up time of 28.7 months (range, 12–51 months), 85 patients (95.5%) achieved favorable clinical outcomes (mRS scores of 0–2). Conclusions: This study indicates that SAC treatment is a safe and effective therapeutic alternative for ruptured and unruptured OSAs. The procedural risks are low with relatively long-term effectiveness.

Abstract Low-cost particulate matter (PM) sensors have been widely used following recent sensor-technology advancements; however, inherent limitations of low-cost monitors (LCMs), which operate based on light scattering without an air-conditioning function, still restrict their applicability. We propose a regional calibration of LCMs using a multivariate Tobit model with historical weather and air quality data to improve the accuracy of ambient air monitoring, which is highly dependent on meteorological conditions, local climate, and regional PM properties. Weather observations and PM2.5 (fine inhalable particles with diameters ≤ 2.5 μm) concentrations from two regions in Korea, Incheon and Jeju, and one in Singapore were used as training data to build a visibility-based calibration model. To validate the model, field measurements were conducted by an LCM in Jeju and Singapore, where R2 and the error after applying the model in Jeju improved (from 0.85 to 0.88) and reduced by 44% (from 8.4 to 4.7 μg m−3), respectively. The results demonstrated that regional calibration involving air temperature, relative humidity, and other local climate parameters can efficiently correct the bias of the sensor. Our findings suggest that the proposed post-processing using the Tobit model with regional weather and air quality data enhances the applicability of LCMs.

Abstract Background Adiponectin is a key protein produced in adipose tissue, with crucial involvement in multiple metabolic processes. Di-(2-ethylhexyl) phthalate (DEHP), one of the phthalate compounds used as a plasticizer, has been shown to decrease adiponectin levels in vitro and in vivo studies. However, the role of angiotensin I-converting enzyme (ACE) gene polymorphism and epigenetic changes in the relationship between DEHP exposure and adiponectin levels is not well understood. Methods This study examined the correlation between urine levels of DEHP metabolite, epigenetic marker 5mdC/dG, ACE gene phenotypes, and adiponectin levels in a sample of 699 individuals aged 12–30 from Taiwan. Results Results showed a positive relationship between mono-2-ethylhexyl phthalate (MEHP) and 5mdC/dG, and a negative association between both MEHP and 5mdC/dG with adiponectin. The study found that the inverse relationship between MEHP and adiponectin was stronger when levels of 5mdC/dG were above the median. This was supported by differential unstandardized regression coefficients (− 0.095 vs. − 0.049, P value for interaction = 0.038)). Subgroup analysis also showed a negative correlation between MEHP and adiponectin in individuals with the I/I ACE genotype, but not in those with other genotypes, although the P value for interaction was borderline significant (0.06). The structural equation model analysis indicated that MEHP has a direct inverse effect on adiponectin and an indirect effect via 5mdC/dG. Conclusions In this young Taiwanese population, our findings suggest that urine MEHP levels are negatively correlated with serum adiponectin levels, and epigenetic modifications may play a role in this association. Further study is needed to validate these results and determine causality.

Background Handwriting synthesis techniques have been extensively studied in the detection of cognitive impairment in dementia and Parkinson's disease. But handwriting characteristics in older adults with mild cognitive impairment (MCI) still need to be studied further. Objective To explore the differences between the handwriting characteristics of elderly patients with MCI and normal elderly people, and to assess the value of handwriting features in MCI screening. Methods By use of convenience sampling, 33 older adults with MCI were recruited from Huzhou communities from January to April 2022 (observation group), and were compared to age-, sex- and education level-matched 43 community-living older adults with normal cognitive function (control group). The General Information Questionnaire, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment-Basic (MoCA-B), the Activity of Daily Living Scale (ADL), and the 15-item Geriatric Depression Scale (GDS-15) were used to survey subjects. Subjects were invited to complete six handwriting tasks (four are Chinese characters tasks and the other two are graphical drawing tasks) using a dot matrix digital pen to collect their kinematic parameters of handwriting. The classification accuracy, sensitivity and specificity of handwriting characteristics for the diagnosis of MCI were analyzed by discriminant analysis and receiver operating characteristic (ROC) curve, and predictive values of different schemes for MCI were analyzed. Results Compared with the control group, the observation group had higher average pressure in writing (Z=-2.122, P=0.034), longer time in air (Z=-4.302, P

Background: The main objective of this study was to investigate the risk of falls among middle-aged and older adults with dynapenic abdominal obesity. Methods: A systematic literature search was conducted to review and analyze relevant studies. Dynapenia was measured by handgrip strength, and abdominal obesity was measured by waist circumference. The search keywords included “older people” OR “elderly” OR “middle age” AND “dynapenia” AND “abdominal obesity” AND “fall.” The search was not limited by time and included articles published up until April 2023. The literature search process followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, involving extraction and examination of the retrieved relevant articles. Systematic literature searches were performed in databases such as Embase, PubMed, MEDLINE, CINAHL, and Cochrane Library. Results: This study collected a total of eight articles with a combined sample size of 15,506 participants. The findings revealed that the average follow-up period for falls was 6.6 years (SD = 3.67). The overall results of the study showed that individuals with dynapenic abdominal obesity had a higher risk of falls compared to those without dynapenic abdominal obesity (RR = 6.91, 95% CI: 5.42–8.80). Subgroup analysis demonstrated that both prospective studies (HR = 6.61; 95% CI = 4.29–10.20) and retrospective studies (OR = 7.37; 95% CI = 5.13–10.59) consistently found a higher risk of falls among individuals with dynapenic abdominal obesity. However, there was no significant difference in fall risk between community-dwelling individuals with dynapenic abdominal obesity and hospitalized individuals with dynapenic abdominal obesity (Qbetweenx2 = 0.29, p = 0.58). Additionally, there was no difference in fall risk between individuals with dynapenic abdominal obesity residing in Europe and Latin America compared to those residing in Asia (Qbetweenx2 = 0.05, p = 0.81). It was worth noting that male individuals with dynapenic abdominal obesity had a higher risk of falls compared to females (Qbetweenx2 = 4.73, p = 0.03). Conclusions: Empirical studies have demonstrated that individuals with dynapenic abdominal obesity have a higher risk of falls. Therefore, healthcare professionals should conduct early fall risk assessments and develop effective preventive strategies specifically targeted at individuals with dynapenic abdominal obesity.

Objective To establish a rapid diagnosis method for the biological toxicity of soil, accurately and rapidly evaluate the toxicity of contaminated sites and identify the dominant pollutants. Methods Take the soil pollution of a galvanized factory as an example, while the metal concentration level was analyzed and detected, a rapid biological toxicity detection method based on the acute toxicity test of luminescent bacteria （Vibrio qinghaiensis sp.-Q67） was established, and the dominant pollutants were identified by stepwise multiple regression. Results The pollutants came from wastewater and metal plating fragments directly discharged from the manufacturing line of the factory. The concentration of those pollutants was correlated with the acute toxicity of Vibrio qinghaiensis sp.-Q67. The dominant pollutants in the study were zinc （Zn）, aluminum （Al） and copper （Cu）. Conclusion The luminescent bacteria toxicity test method based on Vibrio qinghaiensis sp.-Q67 can conveniently and rapidly assess the degree of toxic damage of polluted soil and identify the dominant pollutants and can be applied to the acute toxicity evaluation of polluted soil.

Abstract Background Hypertension often presents with microvascular rarefaction (MVR), which is closely associated with impaired angiogenesis. Early detection of MVR is essential for systemic assessment in patient with hypertension. We aimed to determine the systemic MVR through both optical coherence tomography angiography (OCTA) and intravital capillaroscopy, and to investigate their respective efficacies and related mechanisms associated with late endothelial progenitor cells (LEPCs) dysfunction. Methods Seventy-one hypertensive and sixty-nine age-match normotensive subjects were included in this study. All subjects received intravital capillaroscopy for skin capillary density (SCD) and OCTA for retinal capillary density (RCD) and non-perfused areas (R-NPA). Subsequently, correlation of LEPCs activities and microvascular rarefaction were examined. Results Compared with normotensive subjects, hypertensive patients had significantly lower RCD [(52.9 ± 2.9)% vs. (57.8 ± 1.6)%, P

The main purpose of this study was to investigate the relationship between sarcopenia and injury events (falls, fractures, hospitalization, disability, and death). This study systemically searched the literature from Embase, PubMed, MEDLINE, CINAHL, and Cochrane Library and analyzed the collected literature using the random effects model to demonstrate the relationship between sarcopenia and injury events. This study followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and collected a total of 38 prospective studies, and the results showed that, when compared to robust individuals, the risk of injury events for older individuals with sarcopenia was significantly higher for fractures (HR = 9.66, CI: 5.07–18.38), hospital admissions (HR = 11.80, CI: 4.86–28.65), and death (HR = 9.57, CI: 3.17–28.94). In consideration of the negative impact of sarcopenia on the subsequent health of older adults, professional nursing personnel should assess older adults for sarcopenia as early as possible and propose relevant care policies to further reduce negative health impacts.

The introductory pharmacy practice experiences (IPPE) in Taiwan, which are traditionally conducted in physical hospital settings, incorporated up to 30% distance learning from May 2021 due to Coronavirus Disease 2019 (COVID-19). A web-based cross-sectional survey was adopted to investigate pharmacy students’ experiences and perceptions of transitioning from in-hospital internships to distance learning due to COVID-19 in the pharmacy department of a university in Southern Taiwan. We analyzed the results to discover factors that significantly affected students’ perceptions of transitioning from in-hospital internships to distance learning. In total, 81 interns from the university’s pharmacy department responded to the questionnaire. Approximately half of the participants felt happy when they learned, before the internship began, that the internship would be partially replaced with distance learning. The overall satisfaction rate was 67.9%, and no significant differences was observed in students’ satisfaction between hospital size or distance-learning time. However, more students in the medical center felt they had insufficient time to finish assignments compared to those in the regional hospitals, and the students who had 11–15 days of distance learning felt that they interacted more smoothly with their peers compared to those who had other durations. Program designers should make distance internship courses more student-centered, with a focus on increasing interactions between students, teachers, and peers to compensate for the lack of physical presence.

Background: Our previous study revealed that PLAGL2 or POFUT1 can promote tumorigenesis and maintain significant positive correlations in colorectal cancer (CRC). However, the mechanism leading to the co-expression and the underlying functional and biological implications remain unclear. Methods: Clinical tumor tissues and TCGA dataset were utilized to analyze the co-expression of PLAGL2 and POFUT1. Luciferase reporter assays, specially made bidirectional promoter vectors and ectopic expression of 3’UTR were employed to study the mechanisms of co-expression. In vitro and in vivo assays were performed to further confirm the oncogenic function of both. The sphere formation assay, immunofluorescence, Western blot and qRT-PCR were performed to investigate the effect of both genes in colorectal cancer stem cells (CSCs). Findings: PLAGL2 and POFUT1 maintained co-expression in CRC (r = 0.91, p

Background: Hypertensive patients exhibit decline in capillary density and endothelial progenitor cells (EPCs). However, whether capillary rarefaction in hypertension is associated with defect angiogenesis of EPCs remains unknown. We hypothesized that impaired mitochondrial function of late EPCs in hypertension is associated with the structural lack of capillary microcirculation via deficient CXCR4/JAK2/SIRT5 signaling. Methods: We performed capillary microcirculation detection in hypertensive patients and healthy subjects. Angiogenic capacity and mitochondrial function of circulating EPCs were evaluated. The underlying mechanisms were further investigated by genetic inhibition and overexpression. Findings: Capillary density of nail fold and eye fundus were significantly reduced in hypertensive patients, which was paralleled to decreased in vitro late EPC function and in vivo angiogenic capacity. Meanwhile the decline of EPC function in hypertension was accompanied by impaired mitochondrial ultrastructure, diminished mitochondrial membrane potential, reduced oxygen consumption, increased ROS generation and NADH level. Rotenone induced inhibition of oxygen consumption rate, excessive ROS generation and loss of MMP, which markedly decreased the in vitro functions of EPCs. Furthermore, SIRT5 expression of EPCs in hypertension was markedly reduced, which was correlated to mitochondrial dysfunction. CXCR4 gene transfer enhanced SIRT5 expression, improved mitochondrial functions and augmented angiogenic capacity of EPCs. The beneficial impacts of SIRT5 up-regulation on late EPC-mediated angiogenesis can be abrogated by blockade of CXCR4/JAK2/SIRT5 signaling pathway. Interpretation: Mitochondrial dysfunction-mediated fall in angiogenic capacity due to deficient CXCR4/JAK2/SIRT5 signaling of late EPCs is probably responsible for the capillary rarefaction in hypertension. Our findings provide insight into the potential of EPC mitochondria as a novel target for the treatment of hypertension-related loss of microvascular density. Funds: National Nature Science Foundation of China, 973Program, the Nature Science Foundation of Guangdong. Keywords: Hypertension, EPCs, CXCR4, Mitochondria, SIRT5, Angiogenesis, Microcirculation

Renal dysfunction is common after stroke. We aimed to investigate the clinical predictability of the ankle–brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) on poststroke renal deterioration. A total of 956 consecutive participants with acute ischemic stroke between 1 July 2016, and 31 December 2017 were enrolled and a final of 637 patients were recruited for final analysis. By using the group-based trajectory model (GBTM), the patients’ renal function trajectories were grouped into the low, intermediate, and high categories (LC, IC, and HC). Significant deterioration in the slope was noted in the IC (p < 0.001) and LC (p = 0.002) groups but was nonsignificant in the HC (p = 0.998) group. Abnormal ABI (ABI ≤ 0.9) was independently related to LC (adjusted odds ratio: 2.40; 95% CI, 1.16–4.95; p = 0.019) and was also independently associated with increased risks of a ≥30% decline in eGFR (adjusted hazard ratio [aHR], 2.28; 95% CI, 1.29–4.05; p = 0.005), a doubling of serum creatinine (aHR, 3.60; 95% CI, 1.93–8.34; p < 0.001) and ESRD (HR, 3.28; 95% CI, 1.23–8.74; p = 0.018). However, baPWV did not have a significant relationship with any of the renal outcomes. Patients with a lower ABI during acute stroke should receive regular renal function tests and should be closely monitored to improve poststroke renal care.

Purpose: The transition of Taiwan from an aging to a super-aging society has come with a cost as more elderly now suffer from cognitive impairment. The main purpose of our study was to investigate if early detection can be developed so that timely intervention can be instituted. We analyzed the correlation of cognitive function with ocular physiology and visual functions between senior citizens aged 60 years or older in Taiwan. Methods: Thirty-six healthy subjects were recruited for the study. Addenbrooke’s cognitive examination III (ACE-III), binocular functions (including objective and subjective refraction, distance and near dissociated phoria, stereopsis, contrast sensitivity, adult developmental eye movement (ADEM), and ocular physiology (by using optical coherence tomography, OCT, and macular pigment measurement, MPS) were performed, and the data were analyzed via independent t-test, chi-square test, Pearson correlation, linear regression, and ROC (receiver operating characteristic) curve. Results: Data analysis showed that (1) patients with poor eye movement had a strong correlation with the total score and all dimensions of cognitive functions, (2) the thickness of the macula had a strong correlation with attention and memory, and (3) patients with poor eye movement and poor stereopsis in combination with thinner inferior macula appeared to have lower cognitive abilities. Discussion and Conclusions: Cognitive dysfunction is not readily identified during the early stage of cognitive decline. The use of simple and inexpensive ADEM or stereopsis test and comparing the OCT results that are popular in optometry clinics for reference can be diagnostic in identifying patients with mild cognitive impairments. With the combined use of macular pigment density or retinal thickness measurements, it was possible to effectively predict the early degradation of cognition.

Heart rate trajectory patterns integrate information regarding multiple heart rate measurements and their changes with time. Different heart rate patterns may exist in one population, and these are associated with different outcomes. Our study investigated the association of adverse outcomes with heart rate trajectory patterns. This was a prospective cohort study based on the Chin-Shan Community Cardiovascular Cohort in Taiwan. A total of 3,015 Chinese community residents aged > 35 years were enrolled in a prospective investigation of cardiovascular risk factors and outcomes from 1990 to 2013.The primary outcome was all-cause mortality, and the secondary outcome was a composite of coronary artery disease and cerebrovascular accidents. The following trajectory patterns were identified: stable, 61%; decreased, 5%; mildly increased, 32%; and markedly increased, 2%. During follow-up (median, 13.9 years), 557 participants died and 217 experienced secondary outcomes. The adjusted hazard ratios of primary and secondary outcomes for participants with a markedly increased trajectory pattern were 1.80 (95% CI [1.18–2.76]) and 1.45 (95% CI [0.67–3.12]), respectively, compared to those for participants with a stable trajectory pattern. A markedly increased heart rate trajectory pattern may be associated with all-cause mortality risks. Heart rate trajectory patterns demonstrated the utility of repeated heart rate measurements for risk assessment.

Protein-energy wasting is prevalent in peritoneal dialysis patients, which causes a heavy burden for individuals and healthcare systems. We aimed to investigate the effect of nutritional education, and/or protein supplementation on nutritional biomarkers in hypoalbuminemic peritoneal dialysis patients. A quasi-experimental study was conducted in two dialysis centers at Taipei Tzu Chi Hospital and Shin Kong Wu Ho-Su Memorial Hospital. Patients were allocated in three groups including control (n = 12), milk protein (n = 21) and soy protein (n = 20). All patients received dietary guidelines from dietitians and completed 3-day dietary records during monthly visits for consecutive three months. Nutrients were analyzed using Nutritionist Professional software. Blood urea nitrogen (BUN), creatinine, albumin, total protein, hemoglobin, serum calcium, phosphorus, sodium, and potassium were assessed monthly. Total cholesterol and triglycerides were measured every three months. After three-month intervention, protein intake (percent of total calories), and serum albumin were significantly increased in three groups. Protein, phosphorus intake, and BUN were increased in two intervention groups. Total serum protein increased in control and milk protein groups, and creatinine increased the control group. Serum phosphorus was not significantly changed. Nutritional education alone, or combined with protein supplementation, significantly improve protein intake, and nutritional status by increasing serum albumin, but not serum phosphorus in hypoalbuminemic peritoneal dialysis patients.

The impact of leukoaraiosis on the risk of symptomatic intracerebral hemorrhage (SICH) after stroke thrombolysis is conflicting, and the data on Asian populations are lacking. Therefore, in this study, we assessed the association between leukoaraiosis and SICH, and the association between leukoaraiosis and the 90-day functional outcome in the Asian population.Data were collected from a two-center prospective registry of acute ischemic stroke patients given intravenous tissue plasminogen activator between 2006 and 2014. A total of 614 pretreatment brain CT and 455 posttreatment MRI were retrospectively assessed using two different rating scales for the presence of leukoaraiosis. Outcome measures were the occurrence of SICH with three definitions and any hemorrhage after thrombolysis and functional outcome at 3 months.Of the 614 patients assessed, 30.3% showed severe leukoaraiosis on the baseline brain CT. The SICH rate was 4.6% - 7.2% based on different definitions, and overall, 24.9% of patients showed any post-tPA hemorrhage. No association was observed between the severity of leukoaraiosis and SICH, regardless of having used different leukoaraiosis rating scales or as assessment using different imaging modalities. However, severe leukoaraiosis was independently associated with poor functional outcome at 3 months (OR 1.96, 95% C1 1.24-3.11, P = 0.004) after adjustment for confounders.Our results showed no association between leukoaraiosis and the risk of SICH. Although the presence of severe leukoaraiosis predicted a poor functional outcome after stroke, IV thrombolysis might not be withheld in acute ischemic stroke patients solely based on the presence of severe leukoaraiosis on pre-thrombolytic CT scans.

[This corrects the article DOI: 10.1371/journal.pone.0193899.].

This study aimed to assess predictive ability of heart rate variability (HRV) for pregnancy outcomes with in vitro fertilization (IVF) treatment.A total of 180 women with 261 cycles of IVF and 211 embryo transfers (ETs) were analyzed. HRV was measured at four times during IVF treatment: the first date of menstruation, r-HCG (Ovidrel) administration, and before and after ET. Pregnancy indicators included chemical pregnancy, ongoing pregnancy (> 10 weeks), and live birth (pregnancy > 24 weeks). Mixed effect models were applied to identify predictors for IVF pregnancy. The area under the receiver operating characteristic curve (AUC) was used to assess prediction models for pregnancy.The HRV values increased during IVF treatment and then decreased after ET. The trend of changes in HRV values during IVF treatment was significant among patients with chemical pregnancy (p < 0.01) and those with live birth (p = 0.02). Women without pregnancy had lower HRV compared to those with IVF pregnancy (p < 0.05). With a one unit increase in HRV difference before and after ET, the odds of chemical pregnancy decreased by 18% (odds ratio; OR: 0.82, 95% CI: 0.70-0.97, p < 0.02). With a one year increase in maternal age, the odds decreased by 16% (OR: 0.84, 95% CI: 0.76-0.93, p < 0.01), 25% (OR: 0.75, 95% CI: 0.58-0.93, p = 0.02), and 28% (OR: 0.72, 95% CI: 0.54-0.91, p = 0.01) for chemical pregnancy, ongoing pregnancy, and live birth, respectively. The AUCs were 0.77 (95% CI: 0.70, 0.84), 0.89 (0.79, 0.98), and 0.91(0.83, 0.99) for the prediction models for chemical pregnancy, ongoing pregnancy, and live birth, respectively.Reduced HRV may be an indicator for low chance of IVF pregnancy. The changes in HRV before and after ET and maternal age might be prognostic predictors of IVF pregnancy.

AIMS:Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS:From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS:We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.