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Background. Peripheral neuropathy is prevalent among patients with chronic kidney disease (CKD). Sudoscan non-invasively detects polyneuropathy by measuring electrochemical skin conductance (ESC). We conducted a study on sudomotor function in CKD patients across various stages based on their estimated glomerular filtration rate (eGFR). Methods. In this cross-sectional study of 700 CKD patients, all underwent Sudoscan. Pathological ESC was defined as hands < 40 μS or feet < 50 μS. Clinical neuropathy scores including Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique en 4 questionnaire (DN4) were obtained. Results. Among participants, 344 had diabetes and 356 did not. Hands and feet ESC decreased with CKD progression (median (IQR) in stage 1–2, 3, 4–5: 54.0 (39.0–68.0), 45.5 (30.0–63.0), 41.8 (26.5–60.5), p trend < 0.001; 64.5 (53.5–74.0), 60.5 (43.0–72.5), 55.0 (39.0–69.8), p trend < 0.001). Pathological hands and feet ESC increased in later CKD stages (stage 1–2, 3, 4–5: 26.6%, 40.9%, 45.7%, p trend < 0.001; 21.7%, 34.0%, 40.6%, p trend < 0.001). Positive hands and feet ESC-eGFR correlation existed irrespective of diabetes. Diabetic patients had lower hands and feet ESC than non-diabetics as CKD progressed. However, multivariate regression found no significant ESC-eGFR association. Sudoscan correlated with clinical neuropathy scores. Conclusion. Pathological sudomotor function was common in non-dialysis CKD stages 4–5. Diabetic patients had worse function. Sudomotor dysfunction progressed with renal disease but eGFR was not an independent risk factor. [ABSTRACT FROM AUTHOR]

Background: Human enteroviruses A71 (EV-A71) and D68 (EV-D68) are the suspected causative agents of hand-foot-and-mouth disease, aseptic meningitis, encephalitis, acute flaccid myelitis, and acute flaccid paralysis in children. Until now, no cure nor mucosal vaccine existed for EV-A71 and EV-D68. Novel mucosal bivalent vaccines are highly important for preventing EV-A71 and EV-D68 infections. Methods: In this study, formalin-inactivated EV-A71 and EV-D68 were used as antigens, while PS-G, a polysaccharide from Ganoderma lucidum, was used as an adjuvant. Natural polysaccharides have the characteristics of intrinsic immunomodulation, biocompatibility, low toxicity, and safety. Mice were immunized intranasally with PBS, EV-A71, EV-D68, or EV-A71 + EV-D68, with or without PS-G as an adjuvant. Results: The EV-A71 + EV-D68 bivalent vaccine generated considerable EV-A71- and EV-D68-specific IgG and IgA titres in the sera, nasal washes, saliva, bronchoalveolar lavage fluid, and feces. These antibodies neutralized EV-D68 and EV-A71 infectivity. They also cross-neutralized infections by different EV-D68 and EV-A71 sub-genotypes. Furthermore, compared with the PBS group, EV-A71 + EV-D68 + PS-G-vaccinated mice exhibited an increased number of EV-D68- and EV-A71-specific IgA- and IgG-producing cells. In addition, T-cell proliferative responses, and IFN-γ and IL-17 secretion in the spleen were substantially induced when PS-G was used as an adjuvant with EV-A71 + EV-D68. Finally, in vivo challenge experiments demonstrated that the immune sera induced by EV-A71 + EV-D68 + PS-G conferred protection in neonate mice against lethal EV-A71 and EV-D68 challenges as indicated by the increased survival rate and decreased clinical score and viral RNA tissue expression. Taken together, all EV-A71/EV-D68 + PS-G-immunized mice developed potent specific humoral, mucosal, and cellular immune responses to EV-D68 and EV-A71 and were protected against them. Conclusions: These findings demonstrated that PS-G can be used as a potential adjuvant for EV-A71 and EV-D68 bivalent mucosal vaccines. Our results provide useful information for the further preclinical and clinical development of a mucosal bivalent enterovirus vaccine against both EV-A71 and EV-D68 infections. [ABSTRACT FROM AUTHOR]

p-Cresyl sulfate (PCS) is a uremic toxin that causes cardiovascular injury and progression in patients with chronic kidney disease (CKD). Peripheral arterial stiffness (PAS) as measured using the brachial-ankle pulse wave velocity (baPWV) is considered a valuable predictor of cardiovascular event risk in the general population. The study investigated the correlation between serum PCS levels and PAS (baPWV > 18.0 m/s) in 160 patients with stage 3–5 CKD. Liquid chromatography–mass spectrometry was used to assay serum PCS levels. PAS was detected in 54 patients (33.8%), and it was linked to older age, a higher prevalence of hypertension, higher systolic and diastolic blood pressure, higher serum calcium–phosphorus product and PCS levels, and lower height and body weight. Multivariable logistic regression analysis for independent factors associated with PAS illustrated that, in addition to age and diastolic blood pressure, serum PCS levels exhibited an odds ratio (OR) of 1.098 (95% confidence interval = 1.029–1.171, p = 0.005). These findings demonstrated that serum PCS levels were associated with PAS among patients with stage 3–5 CKD. [ABSTRACT FROM AUTHOR]

Serum indices based on creatinine and cystatin C, including creatinine/cystatin C ratio (Cr/CysC), ratio and difference of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcys/eGFRcre and eGFRDiff), and serum creatinine × eGFRcys, are recently identified serum markers for sarcopenia. We aimed to evaluate the association between these serum indices and mortality in patients with chronic kidney disease (CKD). A single-center retrospective cohort study included 1141 adult patients with stage 1–5 CKD between 2016 and 2018. Basic characteristics, comorbidities, laboratory parameters, and serum creatinine and cystatin C values were obtained. Patients were followed up until death, dialysis, transfer to another hospital, or end of the study. The median age (interquartile range) of our participants was 71 (62–81) years. During a median follow-up of 39 months, 116 (10.2%) patients died. Compared to the survivor group, Cr/CysC, eGFRcys/eGFRcre, eGFRDiff, and Cr × eGFRcys were all lower in the non-survivors (p < 0.001 for all). The receiver operating characteristic curves of serum indices for predicting mortality showed that all four indices had significant discriminative power. Based on the Cox proportional hazard models, lower values of four serum indices, both as continuous and categorical variables, independently predicted mortality. Our findings suggest that low serum indices of Cr/CysC, eGFRcys/eGFRcre, eGFRDiff, and Cr × eGFRcys are independent indicators of mortality in patients with non-dialysis CKD. [ABSTRACT FROM AUTHOR]

Background: The relationship between treatment-related, cost-associated distress "financial toxicity" (FT) and quality-of life (QOL) in breast cancer patients remains poorly characterized. This study leverages validated patient-reported outcomes measures (PROMs) to analyze the association between FT and QOL and satisfaction among women undergoing ablative breast cancer surgery.Study Design: This is a single-institution cross-sectional survey of all female breast cancer patients (>18 years old) who underwent lumpectomy or mastectomy between January 2018 and June 2019. FT was measured via the 11-item COmprehensive Score for financial Toxicity (COST) instrument. The BREAST-Q and SF-12 were used to asses condition-specific and global QOL, respectively. Responses were linked with demographic and clinical data. Pearson correlation coefficient and multivariable regression were used to examine associations.Results: Our analytical sample consisted of 532 patients; mean age 58, mostly white (76.7%), employed (63.7%), married/committed (73.7%), with 64.3% undergoing reconstruction. Median household income was $80,000 to $120,000/year, and mean COST score was 28.0. After multivariable adjustment, a positive relationship for all outcomes was noted; lower COST (greater cost-associated distress) was associated with lower BREAST-Q and SF-12 scores. This relationship was strongest for BREAST-Q psychosocial well-being, for which we observed a 0.89 (95% CI 0.76-1.03) change per unit change in COST score.Conclusions: Financial toxicity captured in this study correlates with statistically significant and clinically important differences in BREAST-Q psychosocial well-being, patient satisfaction with reconstructed breasts, and SF-12 global mental and physical quality of life. Treatment costs should be included in the shared decision-making for breast cancer surgery. Future prospective outcomes research should integrate COST. [ABSTRACT FROM AUTHOR]

Background: Team care improves processes and outcomes of care, especially for patients with complex medical conditions that require coordination of care. This study aimed to compare the processes and outcomes of care provided to older patients with diabetes by primary care teams comprised of only primary care physicians (PCPs) versus team care that included nurse practitioners (NPs) or physician assistants (PAs). Methods: We studied 3,524 primary care practices identified via social network analysis and 306,741 patients ≥66 years old diagnosed with diabetes in or before 2015 in Medicare data. Guideline-recommended diabetes care included eye examination, hemoglobin A1c test, and nephropathy monitoring. High-risk medications were based on recommendations from the American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Preventable hospitalizations were defined as hospitalizations for a potentially preventable condition. Results: Compared with patients in the PCP only teams, patients in the team care practices with NPs or PAs received more guideline-recommended diabetes care (annual eye exam: adjusted odds ratio (aOR): 1.04 (95% CI: 1.00–1.08), 1.08 (95% CI: 1.03–1.13), and 1.10 (95% CI: 1.05–1.15), and HbA1C test: aOR: 1.11 (95% CI: 1.04–1.18), 1.11 (95% CI: 1.02–1.20), and 1.15 (95% CI: 1.06–1.25) for PCP/NP, PCP/NP/PA, and PCP/PA teams). Patients in the PCP/NP and the PCP/PA teams had a slightly higher likelihood of being prescribed high-risk medications (aOR: 1.03 (95% CI: 1.00–1.07), and 1.06 (95% CI: 1.02–1.11), respectively). The likelihood of preventable hospitalizations was similar among patients cared for by various types of practices. Conclusion: The team care practices with NPs or PAs were associated with better adherence to clinical practice guideline recommendations for diabetes compared to PCP only practices. Both practices had similar outcomes. Further efforts are needed to explore new and cost-effective team-based care delivery models that improve process, outcomes, and continuity of care, as well as patient care experiences. [ABSTRACT FROM AUTHOR]

Sarcopenia is highly prevalent in patients undergoing chronic hemodialysis (HD). This study investigated the relationship among serum indoxyl sulfate (IS) levels, muscle mass, and strength in HD patients. A total of 108 HD patients were enrolled. Skeletal muscle mass and handgrip strength (HGS) were assessed, using bioimpedance analysis and a hand-held dynamometer, respectively. Skeletal muscle index (SMI) was defined as skeletal muscle mass/height2 (kg/m2). Serum IS, p-cresol sulfate (PCS), and trimethylamine N-oxide (TMAO) levels were determined using liquid chromatography–mass spectrometry. Patients were classified into two groups based on median serum IS values. HGS measurement was repeated after 2 years. Patients in the high IS group had longer HD duration and higher serum TMAO levels than those in the low IS group. Log-normalized IS level was negatively correlated with SMI (r = − 0.227; p = 0.018), but PCS and TMAO levels were not. Among 78 patients who completed 2-year follow-up, those in the high IS group (n = 41) showed greater absolute (− 2.48 kg versus − 0.25 kg, p = 0.035) and relative HGS loss (− 9.1% versus 1.4%, p = 0.036) than those in the low IS group, after adjustment for potential confounders. Indoxyl sulfate (IS) may play a significant role in uremic sarcopenia. Further large-scale studies are needed to confirm our preliminary findings. [ABSTRACT FROM AUTHOR]

This paper extends one of the most extensively used multiple criteria decision analysis (MCDA) methods, the technique for order preference by similarity to ideal solutions (TOPSIS), to adapt to highly complicated uncertain environments based on interval-valued Pythagorean fuzzy (IVPF) sets. In contrast to classical TOPSIS methods, this paper develops a novel concept of Pearson-like IVPF correlation coefficients instead of distance measures to not only construct a useful and effective association measure between two IVPF characteristics but also depict the outranking relationship of IVPF information. Moreover, this paper proposes the (weighted) IVPF correlation-based closeness coefficients to establish a Pearson-like correlation-based TOPSIS model to manage MCDA problems within the IVPF environment. In particular, there is a definite improvement in determining the closeness coefficient required in the TOPSIS procedure. This paper considers anchored judgments with respect to the positive- and negative-ideal IVPF solutions and provides new approach- and avoidance-oriented definitions for the IVPF correlation-based closeness coefficient, which is entirely different from the traditional definition of relative closeness in TOPSIS. Furthermore, this paper proposes a comprehensive IVPF correlation-based closeness index to balance the consequences between ultra-approach orientation and ultra-avoidance orientation and acquire the ultimate compromise solution for decision support and aid. The feasibility and practicability of the developed methodology are illustrated by a practical MCDA problem of rehabilitation treatment for hospitalized patients with acute stroke. The application results, along with experimentations and comparative analyses, demonstrate that the developed methods are rational and effective. [ABSTRACT FROM AUTHOR]

Introduction: Leptin is an adipokine secreted from adipocytes that mediate lipid metabolism and inflammation. This cross‐sectional study investigated the relationship between serum leptin level and nutrition status evaluated by malnutrition‐inflammation score (MIS) among patients undergoing hemodialysis (HD). Methods: This study included 100 patients on HD. Nutritional status was based on MIS (malnutrition ≥7 points). Body composition, biochemistry data, and serum leptin level were evaluated. Findings: Of 100 subjects, 33 (33.0%) were categorized as having malnutrition. Compared with subjects in the well‐nourished group, those in the malnutrition group had on average an older age, longer HD duration, and lower height, weight, body mass index, waist circumference, body fat mass, serum triglyceride level, and creatinine level. Serum leptin levels were also significantly lower in the malnutrition group (P < 0.001), whereas C‐reactive protein (CRP) levels were higher (P = 0.002). Multivariable linear regression analysis revealed that HD duration (β = 2.06, P = 0.009), serum leptin level (β = −5.16, P < 0.001), CRP level (β = 3.33, P < 0.001), and albumin level (β = −1.95, P = 0.008) were factors independently associated with MIS. The discriminative power of serum leptin level to predict malnutrition was 0.834 (95% confidence interval: 0.747‐0.901, P < 0.001). Discussion: Low serum leptin level was associated with malnutrition, and serum leptin level may be a valuable marker for nutrition assessment in patients undergoing HD. [ABSTRACT FROM AUTHOR]

Enterovirus D68 (EV-D68), belonging to the genus Enterovirus of the Picornavirus family, is an emerging pathogen that can cause neurological and respiratory diseases in children. However, there is little understanding of the pathogenesis of EV-D68, and no effective vaccine or drug for the prevention or treatment of the diseases caused by this virus is available. Autophagy is a cellular process that targets cytoplasmic proteins or organelles to the lysosomes for degradation. Enteroviruses strategically harness the host autophagy pathway to facilitate the completion of their life cycle. Therefore, we selected an autophagy compound library to screen for autophagy-related compounds that may affect viral growth. By using the neutralization screening assay, we identified a compound, 'licochalcone A' that significantly inhibited EV-D68 replication. To investigate the mechanism by which licochalcone A inhibits EV-D68 replication and to identify the viral life cycle stage it inhibits, the time-of-addition, viral attachment, viral entry, and dual-luciferase reporter assays were performed. The results of the time-of-addition assay showed that licochalcone A, a characteristic chalcone found in liquorice roots and widely used in traditional Chinese medicine, inhibits EV-D68 replication during the early stages of the viral life cycle, while those of the dual-luciferase reporter assay showed that licochalcone A does not regulate viral attachment and entry, but inhibits EV-D68 IRES-dependent translation. Licochalcone A also inhibited enterovirus A71 and coxsackievirus B3 but did not significantly inhibit dengue virus 2 or human coronavirus 229E replication. Licochalcone A regulates IRES translation to inhibit EV-D68 viral replication. • Licochalcone A inhibits EV-D68 replication. • Licochalcone A regulates the translation of IRES to hinder EV-D68 replication. • Licochalocne A inhibits different genotypes of enterovirus replication. • Licochalcone A didn't significantly inhibit DNEV2 and hCoV-229 E replication. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: Peripheral neuropathy is a common diabetes complication that can increase fall risk. Regarding fall risk, the impact of pain management using tricyclic antidepressants (TCAs) or γ‐aminobutyric acid (GABA) analogs is unclear because these medications can also cause falls. This study investigates the impact of these drugs on fall and fracture risk in older diabetic peripheral neuropathy (DPN) patients. DESIGN: Historical cohort study with 1‐to‐1 propensity matching of TCA/GABA‐analog users and nonusers. SETTING: Nationally representative 5% Medicare sample between the years 2008 and 2010. PARTICIPANTS: After applying all selection criteria, 5,550 patients with prescription and 22,200 patients without prescription of TCAs/GABA‐analogs were identified. Both patient groups were then stratified for fall history and matched based on propensity of receiving TCAs/GABA‐analogs within each group. MEASUREMENTS: Patients were followed until the first incidence of fall or the first incidence of fracture during the follow‐up period (for up to 5 years). RESULTS: After matching, users and nonusers were largely similar. After covariate adjustment, TCA/GABA‐analog use was associated with a statistically significant increase in fall risk (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 1.03‐1.20), but was not associated with fracture risk (adjusted HR = 1.09; 95% CI = 0.99‐1.19) in the conventional analysis. Treating TCA/GABA‐analog use as a time‐dependent covariate resulted in statistically significant associations of TCA/GABA‐analog use with both fall and fracture risk (HR = 1.26 [95% CI = 1.17‐1.36]; and HR = 1.12 [95% CI = 1.02‐1.24], respectively). CONCLUSION: Among older patients with DPN, GABA‐analogs or TCAs increase fall risk and possibly fracture risk. Use of these medications is therefore a potentially modifiable risk factor for falls and fractures in this population. [ABSTRACT FROM AUTHOR]

Background Fatty acid binding protein 4 (FABP4) is found to play a role in skeletal muscle homeostasis. Since the dysregulation of FABP4 and sarcopenia are both highly prevalent in patients on chronic hemodialysis (HD), the correlation between them remains unknown. We aimed to examine this relationship in a cross-sectional study. Methods A total of 120 chronic HD patients were recruited, and whose skeletal muscle mass, handgrip strength, and gait speed were assessed and blood samples were obtained. We grouped these participants into sarcopenia (n = 20) and non-sarcopenia groups according to European Working Group on Sarcopenia in Older People criteria. Results The sarcopenia group exhibited lower weight (P < 0.001), height (P = 0.019), waist circumference (P < 0.001), body mass index (P < 0.001), body fat mass (P = 0.004), and lower serum triglycerides (P = 0.009), creatinine (P < 0.001), phosphorus (P = 0.013), intact parathyroid hormone (P = 0.012), and FABP4 concentrations (P = 0.005), and higher malnutrition–inflammation scores (MIS) (P = 0.031), urea reduction rates (P < 0.001), and fractional clearance index for urea (Kt/V) values (P < 0.001). Serum FABP4 concentrations (odds ratio (OR): 0.98, 95% confidence interval (CI): 0.96–0.99, P = 0.043), body fat mass (OR: 0.86, 95% CI: 0.77–0.97, P = 0.013), MIS (OR: 6.90, 95% CI: 1.31–36.36, P = 0.023), and Kt/V (each increase of 0.1, OR: 2.15, 95% CI: 1.29–3.57, P = 0.003) were independent predictors of sarcopenia in chronic HD patients. Conclusions We delineated the association between serum FABP4 concentrations and sarcopenia in chronic HD patients. [ABSTRACT FROM AUTHOR]

Background: Physical restraint (PR) has to be performed in a well-organized, structured, and careful manner. The safety and effectiveness of the PR procedure in clinical practice are crucial to patient care. Purposes: The aim of this study was to examine the effect in neurological intensive care units of a multidisciplinary PR reduction program on the overall incidence rate of PR, the monthly rate of PR, and the monthly rate of PR of more than and less than 24 hours, respectively, after controlling for associated factors. Methods: A before-and-after study design was conducted in three neurological intensive care units (total of 45 beds) of a medical center in northern Taiwan. A multidisciplinary PR reduction program was implemented, with four phases of data collection. Data on the number and duration of PR were extracted from a database. In the first preintervention phase, data on the rate (number or frequency) and duration of PR were collected for 12 months before program implementation. The next three data collection phases were 1 month (introduction), 3 months (intermediate), and 6 months (maintenance) after program implementation. The chi-square test, one-way analysis of variance with Scheffe's post hoc tests, and logistic regression method were used for data analysis. Results: The results showed that PR was used 72.8 mean times per month before program implementation. After implementation, the mean times per month fell to 40 after the first postimplementation month (introduction), 53.3 after 3 months (intermediate), and 36.2 after 6 months (maintenance). Implementation of the PR reduction program resulted in a decreased incidence rate of PR from 6.1% to 3.2% (event/total patient day) and a decrease in the percentage of patients who were restrained for more than 24 hours from 69.6% to 34.1%. The results of the logistic regression model showed that PR of more than 24 hours was significantly less in the postintervention phases: introduction phase (odds ratio [ OR ] = 0.31), intermediate phase (OR = 0.16), and maintenance phase (OR = 0.18). Moreover, PR of more than 24 hours was significantly higher in patients with endotracheal intubation (OR = 1.51) and nasogastric intubation (OR = 2.16) and with Glasgow Coma Scale scores of 6–8 (OR = 2.36), 9–12 (OR = 2.40), and 13–15 (OR = 2.15). Conclusions/Implications for Practice: The results support that a multidisciplinary collaborative program has the potential to decrease the incidence of PR in neurological intensive care units. A standardized protocol and policies are essential for healthcare professionals to effectively use PR as well as to effectively improve the quality of care that is provided to intensive care patients. [ABSTRACT FROM AUTHOR]

To prevent viral infection at the site of entry, mucosal vaccines are potent tools for inducing IgA secretion for defense. Because Toll-like receptor (TLR) ligands serve as strong adjuvants, two ligands that mimic the structure of mycoplasmal and bacterial lipopeptides represent interesting vaccine candidates. Pam3CSK4, a synthetic triacylated lipopeptide, interacts with TLR2/1. Because fibroblast-stimulating lipopeptide-1 (FSL-1), a synthetic diacylated lipopeptide, is recognized by TLR2/6, we targeted the potential immuno-inducibility of Pam3CSK4 and FSL-1 as adjuvants of an enterovirus 71 (EV71) mucosal vaccine. Naïve BALB/c mice were used for intranasal immunization three times over a 3-week interval, with results showing that EV71-specific IgG and IgA in serum, nasal washes, bronchoalveolar lavage fluid, and feces from the EV71 + FSL-1 group were significantly higher than levels observed in mice treated with EV71 + Pam3CSK4, EV71 alone, or the control group treated with phosphate-buffered saline. Furthermore, we observed more EV71-specific IgG and IgA-producing cells in treatments using EV71 formulated with FSL-1. Additionally, T cell-proliferative responses and interferon-γ and interleukin-17 secretion were significantly increased when inactivated EV71 was formulated using FSL-1. Moreover, serum from immunized mice was capable of neutralizing the infectivity of EV71 (C2 genotype) and was able to cross-neutralize the B4 and B5 genotypes of EV71. Our data suggested that FSL-1 could be used as an efficient adjuvant for intranasal EV71-vaccine immunization. [ABSTRACT FROM AUTHOR]

Objective: Leptin plays a role in stimulating vascular inflammation, vascular smooth muscle hypertrophy, and augmenting blood pressure, which contributes to the pathogenesis of atherosclerosis and leads to arterial stiffness. This vascular damage, measured by carotid-femoral pulse wave velocity (cfPWV), is recognized as an independent predictor of cardiovascular mortality in hemodialysis (HD) patients. The aim of this study was to evaluate the relationship between serum leptin and arterial stiffness in HD patients. Patients and methods: In 112 of the 126 HD patients were eligible and their biochemical data were collected for analysis. Serum leptin level was measured using a commercial enzyme-linked immunosorbent assay kit. Carotid-femoral pulse wave velocity was measured by a validated tonometry system (SphygmoCor). Those have cfPWV values above 10 m/s are defined as the high arterial stiffness group. Results: Among the participants, thirty-eight of them who were in the high arterial stiffness group, had a higher prevalence of diabetes mellitus (p = 0.002), age (p = 0.029), body mass index (BMI, p = 0.018), body fat mass (p = 0.001), hemoglobin (p = 0.040), and serum leptin levels (P<0.001). Multivariable logistic regression analysis showed that leptin (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.04–1.14; p <0.001), diabetes (OR 7.17; CI 1.39–37.00; p = 0.019), body fat mass (OR 1.16; CI 1.02–1.33; p = 0.027); and hemoglobin (OR 2.11; CI 1.15–3.87; p = 0.015) were independently associated with arterial stiffness in HD patients. Conclusion: In our study, hyperleptinemia was positively correlated to the high cfPWV and thus was related to high arterial stiffness in HD patients. [ABSTRACT FROM AUTHOR]

Background Pulmonary hypertension represents a heterogeneous collection of conditions classified into 5 groups according to pathology, pathophysiology and response to treatment. Right heart catheterization is required to classify patients and before initiation of specific therapy for treatment of pulmonary arterial hypertension. The aim of this study was to determine performance of right heart catheterization in patients prescribed pulmonary arterial hypertension (PAH)-specific medications. Methods A retrospective review of administrative claims was performed using the Clinformatics Data Mart database. Individuals with an encounter diagnosis of pulmonary hypertension were identified by ICD-9 codes. An initial encounter diagnosis was defined as continuous enrollment for 12 months without a previous ICD-9 diagnosis of pulmonary hypertension. These individuals were followed for 15 months after initial encounter diagnosis. Individuals prescribed PAH-specific medications were assessed for characteristics, comorbidities and performance of echocardiography and right heart catheterization. Results From 2002 to 2011, 15,772 patients had an outpatient visit with a diagnosis of pulmonary hypertension. From the initial group, 969 (6.1%) patients were prescribed PAH-specific medications within 1 year of encounter diagnosis. Oral PAH-specific medications were prescribed to 94.2% of patients. In patients prescribed PAH-specific medications, 91% had an echocardiogram within 1 year of encounter diagnosis. Cardiac catheterization was performed in 407 patients (42%) within 3 months of initial prescription and in 583 patients (60.2%) during the entire study period. Conclusion Performance of right heart catheterization was low in this population-based study of patients with an ICD-9 diagnosis code of pulmonary hypertension and taking PAH-specific medications. [ABSTRACT FROM AUTHOR]

Purpose: Little is known about how the number of HPV vaccine doses affect adherence to screening guidelines. This study compared adherence to cervical cancer screening by the number of HPV vaccine doses received by young women and assessed whether the specialty of vaccinating providers affected behavior.Methods: This retrospective cohort study using administrative insurance claims records included 24,964 19-26year old women who received at least 1 injection of the HPV vaccine between January 2006 and November 2009. Vaccinated young women continuously enrolled in a nationally-representative private insurance plan for 6months prior to and 37months after HPV vaccine administration were included. Logistic regression was used to compare the odds of Papanicolaou (Pap) testing 3years after vaccine initiation by number of vaccine doses and provider type.Results: In this sample, 79.3% had a Pap test 3years following vaccine initiation. Receiving 1 (aOR: 0.60, 95% CI 0.55-0.65) or 2 (aOR: 0.80, 95% CI 0.74-0.87) doses was associated with decreased odds of Pap testing compared to 3 doses. Many young women in our sample (16.5%) were diagnosed with cervical dysplasia prior to HPV vaccination. Patients vaccinated by non-obstetrician/gynecologists were less likely to get a Pap test following vaccination.Conclusions: Women who received 1 or 2 doses of the HPV vaccine were less likely than those who received 3 doses to be screened for cervical cancer 3years following vaccine initiation. Pediatricians and primary care physicians should convey the importance of initiating and continuing screening to HPV vaccinated patients. [ABSTRACT FROM AUTHOR]

A novel cardiovascular stress biomarker known as galectin-3 might be useful for anticipating adverse cardiovascular outcomes. The objective of the current investigation was to assess the association between serum galectin-3 levels and aortic stiffness (AS) in 196 patients on peritoneal dialysis. An enzyme-linked immunosorbent examination and a cuff-based volumetric displacement were employed to determine the levels of serum galectin-3 and the carotid-femoral pulse wave velocity (cfPWV), respectively. The AS group had 48 patients in total (24.5%) with cfPWV greater than 10 m/s. The AS group, when compared with the group without AS, had a significantly higher prevalence of diabetes mellitus and hypertension in addition to greater fasting glucose levels, waist circumference, systolic blood pressure, and serum galectin-3 levels. Multivariate logistic and linear regression analysis demonstrated that serum glactin-3 levels, in addition to gender and age, were significantly and independently associated with cfPWV and AS. Serum galectin-3 levels were linked with AS, according to a receiver operating characteristic curve analysis, with an area under the curve of 0.648 (95% confidence interval, 0.576–0.714; p = 0.0018). In summary, there was a significant correlation between serum galectin-3 levels and cfPWV in patients undergoing peritoneal dialysis therapy for end-stage kidney disease. [ABSTRACT FROM AUTHOR]

We investigated the combined effects of ataxia telangiectasia and Rad3-related (ATR) inhibition, ablative radiotherapy, and immune checkpoint inhibitor (ICI) therapy against lung cancer. ATR inhibitor was administered combined with ablative radiotherapy to assess its radiosensitizing effect on lung cancer cells. Treatment response and survival were evaluated in vivo using A549 xenograft flank tumor and synchronous LLC lung and flank tumor mouse models. Mice received ablative radiotherapy (12 Gy/d for 2 d), ATR inhibitor, and ICI. The tumor microenvironment was assessed in irradiated flank and non-irradiated lung tumors. Programmed death-ligand 1 expression was upregulated after irradiation. ATR inhibition attenuated this upregulation. ATR inhibitor pretreatment decreased cell survival after irradiation by inhibiting DNA double-strand break repair, inducing mitotic cell death, and altering cell cycle progression. ATR inhibition enhanced radiation-induced damage-associated molecular patterns determined by high mobility group box 1 quantification and activated the cyclic GMP-AMP synthase-stimulator of interferon genes pathway. Combined ATR inhibition and ablative radiotherapy inhibited tumor growth and improved survival in mice. Adding ICI therapy further enhanced local antitumor effects, reducing the metastatic lung tumor burden and remodeling the tumor microenvironment through immunogenic cell death induction and enhanced immune cell infiltration. Triple therapy increased immune cell infiltration in distant non-irradiated lung tumors and stimulated the generation of protective T-cell immunity in splenocytes. Safety analysis showed minimal toxicity. ATR inhibition enhanced the efficacy of ablative radiotherapy and immunotherapy in lung cancer. These findings underscore the importance of combination therapies for enhancing systemic antitumor immune responses and outcomes. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) causes seasonal epidemics of hand-foot-and-mouth disease and has a high mortality rate among young children. We recently demonstrated potent induction of the humoral and cell-mediated immune response in monkeys immunized with EV71 virus-like particles (VLPs), with a morphology resembling that of infectious EV71 virions but not containing a viral genome, which could potentially be safe as a vaccine for EV71. To elucidate the mechanisms through which EV71 VLPs induce cell-mediated immunity, we studied the immunomodulatory effects of EV71 VLPs on human monocyte-derived dendritic cells (DCs), which bind to and incorporate EV71 VLPs. DC treatment with EV71 VLPs enhanced the expression of CD80, CD86, CD83, CD40, CD54, and HLA-DR on the cell surface; increased the production of interleukin (IL)-12 p40, IL-12 p70, and IL-10 by DCs; and suppressed the capacity of DCs for endocytosis. Treatment with EV71 VLPs also enhanced the ability of DCs to stimulate naïve T cells and induced secretion of interferon (IFN)-γ by T cells and Th1 cell responses. Neutralization with antibodies against Toll-like receptor (TLR) 4 suppressed the capacity of EV71 VLPs to induce the production of IL-12 p40, IL-12 p70, and IL-10 by DCs and inhibited EV71 VLPs binding to DCs. Our study findings clarified the important role for TLR4 signaling in DCs in response to EV71 VLPs and showed that EV71 VLPs induced inhibitor of kappaB alpha (IκBα) degradation and nuclear factor of kappaB (NF-κB) activation. [ABSTRACT FROM AUTHOR]

BACKGROUND: The risk of readmission varies among hospitals. This variation has led the Centers of Medicare and Medicaid services to reduce payments to hospitals with excess readmissions. The contribution of patient characteristics, hospital characteristics and provider type to the variation in risk of readmission among hospitals has not been determined. OBJECTIVE: To describe the variation in risk of readmission among hospitals and partition it by patient characteristics, hospital characteristics and provider type. DESIGN: Retrospective research design of 100 % Texas Medicare data using multilevel, multivariable models. SUBJECTS: A total of 514,064 admissions of Medicare beneficiaries to 272 hospitals in Texas for medical diagnoses during the years 2008 and 2009. MAIN MEASURES: Using hierarchical generalized linear models, we describe the hospital-specific variation in risk of readmission that is attributable to patients characteristics, hospital characteristics and provider type by measuring the variance and intraclass correlation coefficients. KEY RESULTS: Of the total variation in risk of readmission, only a small amount (0.84 %) is attributed to hospitals. In further analyses modeling the components of this variation among hospitals, differences in patient characteristics in the hospitals explained 56.2 % of the variation. Hospital characteristics and the type of provider explained 9.3 % of the variation among hospitals and 0.08 % of the total variation in risk of readmission. CONCLUSIONS: Patient characteristics are the largest contributor to variation in risk of readmission among hospitals. Measurable hospital characteristics and the type of inpatient provider contribute little to variation in risk of readmission among hospitals. [ABSTRACT FROM AUTHOR]

Abstract: A mobile ad hoc network (MANET) is a special type of wireless network in which a collection of mobile nodes with wireless network interfaces may form a temporary network, without the aids of any fixed infrastructure. Security has become a hot research topic in mobile ad hoc networks. In 1998, Volker and Mehrdad proposed a tree-based key management and access control scheme for the mobile agents to manage rights to access its own resources for the visited mobile nodes. Latter, Huang et al. showed that Volker and Mehrdad's scheme needs a large amount of storage and costs for managing and storing secret keys. Huang et al. further proposed a new and efficient scheme based on the elliptic curve cryptosystems to reduce costs and gain better efficiency. However, there is a security leak inherent in Huang et al.'s scheme that the malicious node can overstep his authority to access unauthorized information. This paper will propose a secure, robust, and efficient hierarchical key management scheme for MANETs. Some practical issues and solutions about dynamic key management are also considered and proposed. As compared with Huang et al.'s scheme, our proposed scheme can provide better security assurance, while requiring smaller key-size, lower computational complexities, and constant key management costs which is independent on the number of the confidential files and the visited nodes. [Copyright &y& Elsevier]

BACKGROUND: There have been no prior population-based studies of variation in performance of hospitalists. OBJECTIVE: To measure the variation in performance of hospitalists. DESIGN: Retrospective research design of 100 % Texas Medicare data using multilevel, multivariable models. SUBJECTS: 131,710 hospitalized patients cared for by 1,099 hospitalists in 268 hospitals from 2006-2009. MAIN MEASURES: We calculated, for each hospitalist, adjusted for patient and disease factors (case mix), their patients' average length of stay, rate of discharge home or to skilled nursing facility (SNF) and rate of 30-day mortality, readmissions and emergency room (ER) visits. KEY RESULTS: In two-level models (admission and hospitalist), there was significant variation in average length of stay and discharge location among hospitalists, but very little variation in 30-day mortality, readmission or emergency room visit rates. There was stability over time (2008-2009 vs. 2006-2007) in hospitalist performance. In three-level models including admissions, hospitalists and hospitals, the variation among hospitalists was substantially reduced. For example, hospitals, hospitalists and case mix contributed 1.02 %, 0.75 % and 42.15 % of the total variance in 30-day mortality rates, respectively. CONCLUSIONS: There is significant variation among hospitalists in length of stay and discharge destination of their patients, but much of the variation is attributable to the hospitals where they practice. The very low variation among hospitalists in 30-day readmission rates suggests that hospitalists are not important contributors to variations in those rates among hospitals. [ABSTRACT FROM AUTHOR]

Objective To examine whether having a primary care physician ( PCP) is associated with reduced ethnic disparities for colorectal cancer ( CRC) screening and whether clustering of minorities within PCPs contributes to the disparities. Data Sources/Study Setting Retrospective cohort study of Medicare beneficiaries age 66-75 in 2009 in Texas. Study Design The percentage of beneficiaries up to date in CRC screening in 2009 was stratified by race/ethnicity. Multilevel models were used to study the effect of having a PCP and PCP characteristics on the racial and ethnic disparities on CRC screening. Data Collection/Extraction Methods Medicare data from 2000 to 2009 were used to assess prior CRC screening. Principal Findings Odds of undergoing CRC screening were more than twice as high in patients with a PCP ( OR = 2.05, 95 percent CI 2.03-2.07). After accounting for clustering and PCP characteristics, the black-white disparity in CRC screening rates almost disappears and the Hispanic-white disparity decreases substantially. Conclusions Ethnic disparities in CRC screening in the elderly are mostly explained by decreased access to PCPs and by clustering of minorities within PCPs less likely to screen any of their patients. [ABSTRACT FROM AUTHOR]

Abstract: Enterovirus type 71 (EV71) is a virulent form of enteroviruses causing hospitalizations for children less than three years of age. Currently there are no anti-viral therapies or vaccines available for EV71. Due to the high risk of poliomyelitis-like paralysis and fatal encephalitis, an effective vaccine to EV71 could potentially prevent virus-induced morbidity and mortality. In this study, we first tested a potential EV71 vaccine candidate based on virus-like particles (VLP). We vaccinated macaque monkeys to validate the immunogenicity of the VLP vaccine to EV71. We detected the VLP or EV71-specific antibodies, neutralization titers, ELISPOT, and T cell response to find their immune responses to EV71. When the VLP vaccine adjuvanted with alum was given to macaque monkeys, these monkeys developed both specific humoral and cellular immune responses to EV71. Despite lower neutralizing antibodies to EV71 were found in sera of VLP-immunized monkeys than monkeys vaccinated with inactivated EV71, VLP-based vaccine generated a memory immune response to EV71. Hence, VLP-based EV71 vaccine is a potential vaccine against EV71 infection. [Copyright &y& Elsevier]

Summary: Objective: Pediatric surgeons (PS) are specialists in surgical fields, however, not all regional hospitals have the service of a PS. The aim of this study was to analyze the outcome of pediatric surgeries in a regional hospital with and without a PS and to evaluate the need for PS in regional hospitals. Methods: Statistics from all pediatric surgeries between December 2002 and November 2004 were collected at Cheng Ching Hospital and divided into group I (without a PS) and group II (with a PS). Results: There were 365 pediatric surgeries in group I and 630 surgeries in group II. In group I, most surgeries were performed by general surgeons (GS, 37.5%) and urologists (GU, 35.9%), while a smaller portion were performed by otolaryngologists (ENT, 10.7%) and plastic surgeons (PLS, 7.4%). Gynecologists or colorectal, cardiovascular and orthopedic surgeons performed <5% of surgeries. In group II, a majority of operations were performed by a PS (54.4%), and significantly fewer surgeries were performed by GS (p <0.05); a significantly greater number were performed by PLS (p <0.05). A pediatric surgeon performed a greater number of all types of surgeries in group II compared to group I, with the exception of orchiopexies and anal fistulectomy. In group I, although many different types of surgeries could have been performed, none were commonly performed by a PS. Conclusion: The total number of surgeries apparently increased after the participation of a PS. Surgical operations performed by GS decreased significantly and were not affected by GU, ENT or PLS. Results from this study illustrate the importance of having PS in regional hospitals and emphasize the need for surgeons with subspecialty training. The need is especially high and complementary to other surgical subspecialists in regional hospitals. [ABSTRACT FROM AUTHOR]

Abstract: An autoimmune response can be induced with the application of dendritic cells (DCs), offering a viable tumor vaccine for cancer immunotherapy. Previous studies have shown that DC-based tumor vaccines in animal tumor models can inhibit tumor growth and induce autoantibodies transiently without clinical or histological features of autoimmunity. The present study aimed to investigate the role of immune response induced by dendritic cells-based therapy, especially anti-ds DNA antibodies in tumor inhibition. In this study, high titers of anti-ds DNA antibodies were induced after injecting syngeneic dendritic cells into BALB/c mice. In addition, mice immunized with DCs showed the inhibition of RL ♂ 1, BALB/c leukemia cell line, tumor growth, and prolonged survival times of tumor mice but no significant difference was found in specific CTL response and NK cell activity when compared to those of the control group. Anti-ds DNA monoclonal antibodies can recognize RL ♂ 1 cells but not normal cells by FACS analysis. Monoclonal anti-ds DNA antibody was demonstrated to be able to lyse tumor cells via complement mediated reaction in vitro and also exhibits the anti-tumor effects when the antibody was injected into tumor-implanted mice. The data suggested that immunization with dendritic cells can induce autoimmune response, which might exert anti-tumor activity in vivo. [Copyright &y& Elsevier]

Abstract: In order to model geometric property variation and investigate different compression behaviors between compressible (variable volume) and incompressible (invariable volume) soft spherical particles, two compression models based on different shapes of the lateral surface (non-contacted surface of the particle) of the compressed particles are proposed. The shape profiles in various compression degrees calculated by the models showed good agreement with the experimental data. The models can be also used to estimate the surface area and volume of the soft particles. Additionally, according to particle shape profiles, the particle structures, porous or dense, show great influences on the compression behavior for both compressible and incompressible soft particles, where the dense incompressible particle performs a higher degree of lateral extension during compression. This is because its volume can be transferred more completely from the compressed portion to the lateral surface, which is without loading contact on it. [Copyright &y& Elsevier]

Trimethylamine N-oxide (TMAO) is a gut-derived uremic toxin involved in cardiovascular diseases (CVD). Peripheral arterial stiffness (PAS), measured by the brachial-ankle pulse wave velocity (baPWV) is a valuable indicator of the existence of CVD alongside other diseases. The study recruited 157 patients with chronic kidney disease (CKD) stages 3 to 5, and aimed to determine the correlation between serum TMAO and PAS, defined as a baPWV of >18.0 m/s. Patients with CKD who were diagnosed with PAS (68 patients, 43.3%) were older, had a higher percentage of hypertension or diabetes mellitus, higher systolic blood pressure, and higher fasting glucose, C-reactive protein, and TMAO levels. Furthermore, besides old age and SBP, patients with CKD who had higher serum TMAO were more likely to have PAS, with an odds ratio of 1.016 (95% confidence interval = 1.002–1.029, p = 0.021) by multivariate logistic regression analysis. Correlation analysis demonstrated that serum TMAO was positively correlated with C-reactive protein level and either left or right baPWV. Thus, we supposed that serum TMAO levels were associated with PAS in patients with advanced non-dialysis CKD. [ABSTRACT FROM AUTHOR]

Background: Overtreatment is a common concern for patients with ductal carcinoma in situ (DCIS), but this entity is difficult to distinguish from invasive breast cancers in administrative claims data sets because DCIS often is coded as invasive breast cancer. Therefore, the authors developed and validated algorithms to select DCIS cases from administrative claims data to enable outcomes research in this type of data.Methods: This retrospective cohort using invasive breast cancer and DCIS cases included women aged 66 to 70 years in the 2004 through 2011 Texas Cancer Registry (TCR) data linked to Medicare administrative claims data. TCR records were used as "gold" standards to evaluate the sensitivity, specificity, and positive predictive value (PPV) of 2 algorithms. Women with a biopsy enrolled in Medicare parts A and B at 12 months before and 6 months after their first biopsy without a second incident diagnosis of DCIS or invasive breast cancer within 12 months in the TCR were included. Women in 2010 Medicare data were selected to test the algorithms in a general sample.Results: In the TCR data set, a total of 6907 cases met inclusion criteria, with 1244 DCIS cases. The first algorithm had a sensitivity of 79%, a specificity of 89%, and a PPV of 62%. The second algorithm had a sensitivity of 50%, a specificity of 97%. and a PPV of 77%. Among women in the general sample, the specificity was high and the sensitivity was similar for both algorithms. However, the PPV was approximately 6% to 7% lower.Conclusions: DCIS frequently is miscoded as invasive breast cancer, and thus the proposed algorithms are useful to examine DCIS outcomes using data sets not linked to cancer registries. Cancer 2018;124:2815-2823. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Sarcopenia is common in patients undergoing chronic hemodialysis, which leads to poor outcomes. SARC-F (sluggishness, assistance in walking, rising from a chair, climb stairs, falls), a self-report questionnaire, is recommended as an easily applied tool for screening sarcopenia in older people. However, there are limited data regarding its use in patients undergoing chronic hemodialysis. Therefore, we aimed to evaluate the association between SARC-F and mortality in these patients. SARC-F questionnaire was applied in 271 hemodialysis patients (mean age 64.4 ± 14.3 years) at baseline. The association between SARC-F and mortality during a 24-month follow-up was analyzed. During this follow-up period, 40 patients (14.8%) died. The discriminative power of SARC-F score for predicting mortality was 0.716 (95% confidence interval (CI) = 0.659–0.769; p < 0.001). The best cut-off was a score ≥1, which provided 85.0% sensitivity, 47.2% specificity, 21.8% positive predictive value, and 94.8% negative predictive value. Kaplan–Meier curves showed that patients with SARC-F ≥ 1 exhibited a higher risk of mortality than those with SARC-F < 1 (p < 0.001). Moreover, a stepwise decline in survival with higher SARC-F scores was also observed. After full adjustments, SARC-F ≥ 1 was independently associated with increased mortality (hazard ratio = 2.87, 95% CI = 1.11–7.38; p = 0.029). In conclusion, SARC-F applied for sarcopenia screening predicted mortality in patients undergoing chronic hemodialysis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationship of four chronic kidney disease–mineral and bone disorder (CKD–MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14 years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4 m/s, p < 0.001). Among the four CKD–MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127–1790] vs. 1237 [251–3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (β: 0.61, 95% confidence interval: 0.06–1.16, p = 0.029 in DM group; β: 0.10, 95% confidence interval: − 0.24–0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients. [ABSTRACT FROM AUTHOR]

Disruptions in glucose metabolism are frequently observed among patients undergoing peritoneal dialysis (PD) who utilize glucose-containing dialysis solutions. We aimed to investigate the relationship between glucometabolic indices, including fasting glucose, insulin resistance, advanced glycation end products (AGEs), PD-related glucose load, and icodextrin usage, and aortic stiffness in PD patients with and without diabetic mellitus (DM). This study involved 172 PD patients (mean age 58.3 ± 13.5 years), consisting of 110 patients without DM and 62 patients with DM. Aortic stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV). Impaired fasting glucose was defined as a fasting glucose level ≥ 100 mg/dL. Homeostatic model assessment for insulin resistance (HOMA-IR) scores, serum AGEs, dialysate glucose load, and icodextrin usage were assessed. Patients with DM exhibited the highest cfPWV (9.9 ± 1.9 m/s), followed by those with impaired fasting glucose (9.1 ± 1.4 m/s), whereas patients with normal fasting glucose had the lowest cfPWV (8.3 ± 1.3 m/s), which demonstrated a significant trend. In non-DM patients, impaired fasting glucose (β = 0.52, 95% confidence interval [CI] = 0.01–1.03, p = 0.046), high HOMA-IR (β = 0.60, 95% CI = 0.12–1.08, p = 0.015), and a high PD glucose load (β = 0.58, 95% CI = 0.08–1.08, p = 0.023) were independently associated with increased cfPWV. In contrast, none of the glucometabolic factors contributed to differences in cfPWV in DM patients. In conclusion, among PD patients without DM, impaired fasting glucose, insulin resistance, and PD glucose load were closely associated with aortic stiffness. [ABSTRACT FROM AUTHOR]

Background. Irisin is a circulating hormone-like myokine that plays an important role in bone metabolism. We performed a cross-sectional study to investigate whether serum irisin levels correlated with bone mineral density (BMD) in patients on maintenance hemodialysis (MHD). Methods. Blood samples were obtained from 80 patients on MHD, and serum irisin concentrations were determined using a commercially available enzyme-linked immunosorbent assay. BMD was measured by dual-energy X-ray absorptiometry of the L2–L4 vertebrae. Results. In the study cohort, 10 (12.5%) and 19 (23.8%) patients had osteoporosis and osteopenia, respectively, and 51 (63.75%) patients had normal BMD. Lumbar T-score was negatively associated with body height (P = 0.010), body weight (P = 0.002), body mass index (BMI, P = 0.010), and serum irisin (P < 0.001) and was positively associated with advanced age (P = 0.031), female sex (P = 0.001), alkaline phosphatase (ALP, P = 0.010), urea reduction rate (P = 0.018), and fractional clearance index for urea (P = 0.020). Multivariable forward stepwise linear regression analysis revealed that high serum logarithmically transformed irisin (log-irisin, β = 0.450, adjusted R2 change = 0.258; P < 0.001), female sex (β = −0.353, adjusted R2 change = 0.134; P < 0.001), and serum ALP level (β = −0.176, adjusted R2 change = 0.022; P = 0.049) were significantly and independently associated with lumbar BMD in patients on MHD. Conclusions. In addition to female sex and serum ALP level, serum irisin level was positively associated with lumbar BMD in patients on MHD. [ABSTRACT FROM AUTHOR]

Background: Understanding reasons for birth control method choice may inform interventions that help young women choose the best method for them. The purpose of this study was to examine why young women in the general population select their method of contraception. Methods: An online survey was advertised through social media in 2017. After consenting, participants were gated through questions that ensured they were female, within the age range (16–25 years old), lived in the 50 U.S. states, and using intrauterine devices (IUDs), hormonal birth control, or barrier methods specified in the survey. Surveys with incompatible responses were excluded. Satisfaction, plans to discontinue, and primary reason for using current contraceptive method were examined and compared by contraception types using chi-square analyses. Multivariable binary logistic regression was used to examine satisfaction between contraceptive methods and races/ethnicities. Results: A total of 2632 responses were included. A high frequency of women using less effective methods (48.6% of nonhormonal birth control) chose them primarily to prevent pregnancy (20.6% of Copper T IUD, 23.0% of hormonal IUD, and 30.9% of Mirena IUD users), while other more effective birth control methods were often chosen primarily for other reasons. Recommendations from family or friends (14.6%) were used by some to make their contraception decision. Black respondents were less likely and Hispanic respondents were more likely to be satisfied with their birth control compared to white women. Conclusion: Providers should consider that their young patients may want to better understand benefits and side effects of their birth control outside of pregnancy prevention. Furthermore, young women may utilize their friends and family to make their contraceptive choice, which should be taken into consideration when counseling patients. [ABSTRACT FROM AUTHOR]

Background. Leptin acts through the adipose-bone axis to regulate bone mineral density (BMD). This study evaluated the relationship between BMD and serum leptin levels in patients on hemodialysis. Methods. In this cross-sectional study including 98 hemodialysis patients, BMD was measured using dual energy X-ray absorptiometry of the lumbar vertebrae (L2–L4), and serum leptin levels were determined using an enzyme immunoassay. Results. There were 25 (25.5%), 13 (13.3%), and 60 (61.2%) patients with osteopenia, osteoporosis, and normal BMD, respectively. Advanced age P = 0.017 ; decreased body mass index (BMI, P < 0.001); body height P < 0.001 ; prehemodialysis body weight (BW, P < 0.001); post-hemodialysis BW P < 0.001 ; waist circumference P < 0.001 ; and triglyceride P = 0.015 , albumin P = 0.004 , and leptin levels P = 0.017 were associated with lower lumbar T scores, whereas increased urea reduction rate (URR, P = 0.004) and fractional clearance index for urea (Kt/V, P = 0.004) were associated with lower lumbar T scores. The multivariable forward stepwise linear regression analysis with adjustment for sex; age; body height; prehemodialysis BW; BMI; waist circumference; logarithmically transformed triglycerides (log-triglycerides), albumin, creatinine, and leptin (log-leptin) levels; URR; and Kt/V indicated that high serum level of log-leptin (R2 change = 0.184; P < 0.001), increased prehemodialysis BW (R2 change = 0.325; P = 0.008), male sex (R2 change = 0.048; P = 0.001), young age (R2 change = 0.044; P = 0.012), and increased serum albumin level (R2 change = 0.017; P = 0.044) were significantly and independently associated with lumbar BMD. Conclusions. Advanced age and female sex were associated with poor BMD, whereas increased BW, serum albumin, and leptin levels were positively associated with BMD in patients on hemodialysis. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)-related disease remains a significant source of morbidity and mortality, and this underscores the need to increase HPV vaccination to reduce the burden of the disease. The objective of this study was to examine the association between the number of HPV vaccine doses and the risk of histologically confirmed preinvasive cervical disease and high-grade cytology.Methods: This retrospective matched cohort study used administrative data from Optum's Clinformatics DataMart Database to identify females aged 9 to 26 years who received 1 or more quadrivalent HPV vaccine doses between January 2006 and June 2015. Cases and controls were matched on region, age, sexually transmitted disease history, and pregnancy. All had a Papanicolaou test ≥1 year after the date of the matched case's final dose. Cox proportional hazards models were used to examine the association between the number of HPV vaccine doses and the incidence of preinvasive cervical disease and high-grade cytology. The Kaplan-Meier method was used to estimate the cumulative incidence rate at the 5-year follow-up.Results: The study included 133,082 females (66,541 vaccinated and 66,541 unvaccinated) stratified by the number of HPV vaccine doses and the vaccine initiation age. Among those aged 15 to 19 years, the hazard ratio (HR) for high-grade cytology for the 3-dose group was 0.84 (95% confidence interval [CI], 0.73-0.97), whereas the HRs for histologically confirmed preinvasive cervical disease for 1, 2, and 3 doses were 0.64 (95% CI, 0.47-0.88), 0.72 (95% CI, 0.54-0.95), and 0.66 (95% CI, 0.55-0.80), respectively.Conclusions: The receipt of 1, 2, or 3 doses of an HPV vaccine by females aged 15 to 19 years was associated with a lower incidence of preinvasive cervical disease in comparison with unvaccinated females, and this supports the use of any HPV vaccination in reducing the burden of the disease. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • H 2 and CO 2 separation in multiple membrane tube systems is studied. • Membrane system configurations are designed using a two-stage optimization. • Parametric sweep technology followed by the Nelder-Mead method adopted used for design. • The optimized configuration at Re = 10 can improve the hydrogen recovery up to 12.2%. • The CO 2 enrichment can be intensified by up to 7%. Abstract Membrane separation is a promising method to separate CO 2 and H 2 from hydrogen-rich gases. This simultaneously achieves H 2 recovery and CO 2 enrichment. The latter is conducive to subsequent carbon capture and storage, and thereby the development of negative emission technologies. In this study, single-, double-, triple-, and quadruple-tube systems with palladium (Pd) membranes and cross-flow configuration are considered, while the Reynolds number (Re) is in the range of 1–50. To maximize H 2 recovery and CO 2 enrichment in the systems, the systems are designed using a two-stage optimization in which the parametric sweep technology followed by the evolutionary computation of the Nelder-Mead simplex method is applied to find the best configuration and the exit H 2 concentration is chosen as the objective function. On account of the scavenging waves stemming from the upstream tubes, the goals of the optimization is to diminish the concentration polarization effect of the upstream tubes upon the downstream ones. The predictions indicate that an increase in the number of tubes raises the optimization efficiency. Compared to the tubes in tandem, the optimized configuration at Re = 10 can improve the hydrogen recovery up to 12.2%, while the CO 2 enrichment can be intensified by up to 7%. [ABSTRACT FROM AUTHOR]

Ablative radiation therapy (RT) is an important strategy to eliminate primary tumor and can potentially induce the abscopal effect. Human serum albumin nanoparticle (NP) was used for controlled release of cisplatin to decrease cisplatin's systemic toxicity, and gold (Au) was added to increase RT-induced immunogenic cell death and potentiate the abscopal antitumor immunity. The designed albumin-based cisplatin-conjugated AuNPs were administered concurrently with ablative RT. C57BL/6 mice implanted with syngeneic murine Lewis lung carcinoma or murine MB49 tumor models were treated with ablative RT (12 Gy per fraction for 2 fractions, total 24 Gy), cisplatin, or Au–cisplatin NPs. Combining ablative RT with cisplatin or Au–cisplatin NPs both destroyed the primary tumor effectively and elicited immunogenic cell death accompanied by release of danger-associated molecular patterns. This enhanced recruitment of effector tumor-infiltrating immune cells, including natural killer T cells and CD8+ T cells, and elicited an increased percentage of professional antigen-presenting CD11c+ dendritic cells. Transient weight loss, accompanying hepatotoxicity, nephrotoxicity, and hematopoietic suppression, was observed as a systemic adverse event in the cisplatin but not the Au–cisplatin NPs group. Cisplatin and Au–cisplatin NPs both showed equivalent ability to reduce metastatic potential when combined with ablative RT, confirmed by suppressed unirradiated flank tumor growth and decreased metastatic lung tumor burden, which translated to improved survival. Mobilization and abundance of effector tumor-infiltrating immune cells including CD8+ T cells and dendritic cells were observed in the distant lung tumor microenvironment after ablative RT with cisplatin or Au–cisplatin NPs, demonstrating increased antitumor immunotherapeutic activity as an abscopal effect. Compared with cisplatin, the albumin-based Au–cisplatin NPs exhibited equivalent but no superior antitumor immunotherapeutic activity while reducing systemic adverse events and can be safely administered concurrently with ablative RT. Alternative NP formulations may be designed to further improve anticancer outcomes. [ABSTRACT FROM AUTHOR]

To evaluate the therapeutic efficacy of cyclin-dependent kinase (CDK) inhibition in combination with ionizing radiation for lung cancer. Human lung adenocarcinoma (A549) and squamous cell carcinoma (H520) cells were used to evaluate the therapeutic efficacy of CDK inhibition in combination with ionizing radiation in vitro using colony formation assay, γH2AX immunofluorescence staining, western blotting, and cell cycle phase analysis. We also performed in vivo evaluations of ectopic tumor growth. In vitro pretreatment with the CDK inhibitor, seliciclib, before irradiation significantly decreased the survival of A549 and H520 cells in a dose-dependent manner. Although CDK inhibition alone did not increase the intensity of γH2AX foci, its combination with ionizing radiation increased DNA double-strand breaks, as shown by γH2AX immunofluorescence staining and western blotting. The combination of CDK inhibition and ionizing radiation-induced G2/M arrest and increased apoptosis, as evidenced by the increased proportion of cells in G2/M arrest, subG1 apoptotic population, and expression of apoptotic markers (cleaved PARP-1 and cleaved caspase-3). Mechanistic studies showed reduced expression of cyclin A with combined treatment, indicating cell cycle shifting effects. An in vivo xenograft model showed that the combination of CDK inhibition and ionizing radiation delayed xenograft tumor growth, and increased the proportion of cleaved PARP-1- and cleaved caspase-3-positive cells, compared to either treatment alone. We provide preclinical tumoricidal evidence that the combination of CDK inhibition and ionizing radiation is an efficacious treatment for lung cancer. [ABSTRACT FROM AUTHOR]

Aims and objectives: To assess the concurrent validity between logbooks and a single‐item rehabilitation adherence measurement for patients with stroke. Agreement between caregivers and patients and between caregivers and physical therapists regarding a single‐item measurement was investigated, and its predictive validity was explored. Background: Adherence to therapy is a primary determinant of treatment success. There are no standard instruments for measuring rehabilitation adherence available for stroke patients. Design: Prospective longitudinal study. Methods: Seventy‐five patients with stroke were recruited, measured four times and followed for 6 months. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was used to ensure comprehensive reporting. Adherence was documented in logbooks, and single‐item measurements were compared. Predictive validity was explored by assessing associations between adherence levels, self‐care ability and health‐related quality of life. The Spearman's correlation coefficients, weighted kappa, and generalised estimating equations statistics were used to explore the concurrent validity, measurement agreement, and predictive validity, respectively. Results: Logbook records had a fair correlation (rs =.23, p =.04) with the single‐item rehabilitation adherence measurements. There was moderate agreement (kappa = 0.42, p <.001) between caregiver and patient assessments and fair agreement (kappa = 0.29, p =.017) between caregiver and physical therapist assessments of patients' rehabilitation adherence levels. Perfect rehabilitation adherence, based on the logbook and single‐item measurements, predicted better scores for self‐care ability and quality of life than imperfect rehabilitation adherence during 6 months after inclusion. Conclusions: There was fair concurrent validity between logbooks and single‐item rehabilitation adherence measurements and moderate and fair adherence measure agreement between caregivers and patients and caregivers and physical therapists, respectively. Logbooks and single‐item rehabilitation adherence measurements had adequate predictive validity. Relevance to clinical practice: Single‐item rehabilitation adherence measurement is a workable and straightforward method to assess stroke patients' rehabilitation adherence in busy clinical care settings. Caregivers can represent stroke patients regarding their reported rehabilitation adherence. Patient or public contribution: Patients were diagnosed with stroke in the study hospital. Rehabilitation physicians transferred patients to a research nurse who then screened them for the inclusion criteria and invited them and their family caregivers to participate in this study if they met the requirements. We also recruited seven physical therapists responsible for the physical therapy of the study participants. After participants signed informed consent, the research nurse encouraged participants to respond to research questions face to face, including rehabilitation adherence data, daily physical function, and quality of life. Each participant was measured four times at baseline and at 1, 3, and 6 months after inclusion in this study. Physical therapists had to score their patients' rehabilitation adherence levels before discharge. Trial registration details: Not applicable. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the output power and efficiency of a TEG system using waste heat from heat pipes, and then optimize its performance. The TEG material is Bi 0.4 Sb 1.6 Te 3 and its figure-of-merit (ZT) is 1.18 at room temperature. The predictions indicate that a longer length of the elements has greater power output and efficiency based on a fixed heat flux on the hot side surface, whereas a shorter length has greater output power based on a fixed temperature difference. The geometry of the TEG is designed through a multi-objective genetic algorithm (MOGA) to maximize its efficiency. When the temperature difference is fixed at 40 °C, the output power and efficiency of the TEG with optimization is increased by about 51.9% and 5.4%, compared to the TEG without optimization. Once the impedance matching, namely, the internal resistance is equal to the external load resistance, is used, the output power can be further enhanced by about 3.85–4.40%. When the heat flux is fixed at 20,000 Wm −2 along with the temperature difference of 40 °C, the output power and efficiency of a pair of elements can be increased to 7.99 mW and 9.52%, respectively. These results are much higher than those reported in other studies. Accordingly, it is concluded that the MOGA is a powerful tool to design the geometry of a TEG for maximizing its performance and real applications in industry. [ABSTRACT FROM AUTHOR]

Indoxacarb is a recently introduced insecticide whose mode of action is blockage of voltage-gated sodium channels. There are limited data on human ingestion. A case of 68-year-old healthy male who presented with general cyanosis because of methemoglobinemia following the ingestion of indoxacarb is presented. After receiving a methylene blue injection, the patient recovered without sequelae. [ABSTRACT FROM AUTHOR]

An abstract of the article "Metformin and Health Care Utilization in Patients With Coexisting COPD and Diabetes" by Raju Bishwakarma and colleagues is presented.

Hydrogen production from a two-stage reaction, namely, the ethanol steam reforming (ESR) followed by the water gas shift reaction (WGSR), is experimentally investigated in this study. A Ni/Al 2 O 3 catalyst and a Fe/Cr 2 O 3 catalyst are employed to trigger the ESR and WGSR, respectively, and four operating parameters, including the feed liquid flow rate, water-to-carbon (H 2 O/C) molar ratio, ESR temperature, and WGSR temperature, are taken into account. To analyze the impact of the operating parameters upon the chemical reactions and maximize the H 2 yield from ethanol, the Taguchi method considering the four factors along with three levels is adopted. The results suggest that the influences of the factors on the H 2 yield are ranked by H 2 O/C ratio > ESR temperature > WGSR temperature > liquid flow rate. In light of the optimal operation suggested by the Taguchi approach, ethanol is completely consumed and the maximum H 2 yield is 4.26 mol/(mol C 2 H 5 OH). This value accounts for around 73% of theoretical H 2 yield based on thermodynamic analysis. Meanwhile, the CO 2 concentration in the product gas is enriched to 21.77%, whereas the CO one is as low as 0.81%. These evidences reveal that the two-stage reaction can reach the requirement of high H 2 yield along with low CO formation, and is conducive to CO 2 capture. [ABSTRACT FROM AUTHOR]

The membrane reactor is a promising device to produce pure hydrogen and enrich CO 2 from syngas. To figure out the detailed reaction phenomena of high-temperature water gas shift reaction (WGSR) in a Pd-based membrane reactor, a computational fluid dynamics (CFD) model is developed to simulate the chemical reaction where the feed gas temperature and steam-to-CO molar ratio (S/C ratio) are in the ranges of 400–700 °C and 1–3, respectively. The predictions suggest that the WGSR proceeds from kinetically controlled reaction to thermodynamically governed one when the feed gas temperature increases. The CO conversion at high temperatures can be improved up to 83% when the membrane is in the reactor compared to that without the membrane. This is mainly attributed to the intensification of the membrane’s permeance with increasing temperature, even though high temperatures disadvantage CO conversion. The analysis also reveals that the breakthrough in the thermodynamic limit of CO conversion can be achieved in the membrane reactor when the feed gas temperature is higher than 500 °C. The CO conversion in the membrane reactor can be higher than the thermodynamic equilibrium up to 61%. [ABSTRACT FROM AUTHOR]

Introduction: BRCA mutation testing has been used for screening women at high risk of breast and ovarian cancer and for selecting the best treatment for those with breast cancer. To optimize the infrastructure and medical resources allocation for genetic testing, it is important to understand the use of BRCA mutation testing in the U.S. health system.Methods: This retrospective cohort study included 53,254 adult women with insurance claims for BRCA mutation testing between 2004 and 2014 from ClinformaticsTM Data Mart Database. Data analysis was performed in 2016. This study assessed trends in the use of BRCA mutation testing in women with previously diagnosed breast or ovarian cancer and those without (unaffected women).Results: Between 2004 and 2014, of those receiving BRCA testing, the proportion of BRCA tests performed in unaffected women increased significantly (p<0.001), from 24.3% in 2004 to 61.5% in 2014. An increase in the proportion of BRCA tests used in unaffected women was found in each characteristic subgroup. In 2014, most subgroups had a proportion surpassing 50%, except for those aged 51-65 years and those without a family history of breast cancer. There was a much lower proportion of those aged 20-40 years among tested women with previously diagnosed breast or ovarian cancer than in unaffected women (17.6% vs 41.7%, p<0.001).Conclusions: During the past decade, the role of BRCA testing has gradually shifted from being used primarily in cancer patients to being used in unaffected women in the U.S. [ABSTRACT FROM AUTHOR]

A multichannel palladium (Pd) membrane system in association with flow bypass is designed for hydrogen separation with high recovery, and the mass transfer phenomena in the system are simulated by developing a computational fluid dynamics (CFD) model. Two Pd membranes are installed in the system. The predictions suggest that the H 2 recovery (HR) can be substantially improved by the bypass. The higher the feed gas Reynolds number, the more pronounced the improvement of H 2 recovery by the bypass. The HR by the first membrane is independent of the bypass ratio (BR), revealing that the enhancement of HR is completely contributed by the second membrane. An increase in H 2 /CO 2 molar ratio in the feed gas reduces HR, but raises the H 2 permeation rate. The maximum HR by the second membrane always develops at the feed gas Reynolds number (Re r,M1 ) of 500, regardless of bypass ratio. This reveals that the aforementioned Reynolds number is an appropriate condition for H 2 separation in the designed membrane system. Based on the HR in the absence of flow bypass (i.e., BR = 0), the higher the Re r,M1 , the larger the intensification of H 2 permeation. A contour map and a correlation from regression analysis in terms of Re r,M1 and BR are established. Under a desired H 2 recovery, the combination of Re r,M1 and BR can be suggested to provide flexible operation for H 2 separation in the membrane system. [ABSTRACT FROM AUTHOR]

Background: The Improving Medicare Post-Acute Care Transformation (IMPACT) Act of 2014 stipulates that standardized functional status (self-care and mobility) and cognitive function data will be used for quality reporting in post-acute care settings. Thirty-day post-discharge unplanned rehospitalization is an established quality metric that has recently been extended to post-acute settings. The relationships between the functional domains in the IMPACT Act and 30-day unplanned rehospitalization are poorly understood.Objective: To determine the degree to which discharge mobility, self-care, and cognitive function are associated with 30-day unplanned rehospitalization following discharge from post-acute care.Design: This was a retrospective cohort study.Setting: Inpatient rehabilitation facilities submitting claims and assessment data to the Centers for Medicare and Medicaid Services in 2012-2013.Participants: Medicare fee-for-service enrollees discharged from post-acute rehabilitation in 2012-2013. The sample included community-dwelling adults admitted for rehabilitation following an acute care stay who survived for 32 days following discharge (N = 252,406).Interventions: Not applicable.Main Measures: Thirty-day unplanned rehospitalization following post-acute rehabilitation.Key Results: The unadjusted 30-day unplanned rehospitalization rate was 12.0 % (n = 30,179). Overall, patients dependent at discharge for mobility had a 50 % increased odds of rehospitalization (OR = 1.50, 95 % CI: 1.42-1.59), patients dependent for self-care a 36 % increased odds (OR = 1.36, 95 % CI: 1.27-1.47), and patients dependent for cognition a 19 % increased odds (OR = 1.19, 95 % CI: 1.09-1.29). Patients dependent for both self-care and mobility at discharge (n = 8312, 3.3 %) had a 16.1 % (95 % CI: 15.3-17.0 %) adjusted rehospitalization rate versus 8.5 % (95 % CI: 8.3-8.8 %) for those independent for both (n = 74,641; 29.6 %).Conclusions: The functional domains identified in the IMPACT Act were associated with 30-day unplanned rehospitalization following post-acute care in this large national sample. Further research is needed to better understand and improve the functional measures, and to determine if their association with rehospitalizations varies across post-acute settings, patient populations, or episodes of care. [ABSTRACT FROM AUTHOR]