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Nguyen Huu Dung,1 Nguyen Trung Kien,2 Nguyen Thi Thu Hai,1 Phan The Cuong,1 Nguyen Thi Thu Huong,3 Dao Bui Quy Quyen,4 Nguyen Minh Tuan,4 Do Manh Ha,2 Truong Quy Kien,2 Nguyen Thi Thuy Dung,2 Pham Quoc Toan,2 Hoang Trung Vinh,2 Tomoko Usui,5 Le Viet Thang21Bach Mai Hospital, Ha Noi, Vietnam; 2Military Hospital 103, Ha Noi, Vietnam; 3Ha Noi Kidney Hospital, Ha Noi, Vietnam; 4Cho Ray Hospital, Ho Chi Minh, Vietnam; 5University of Tokyo Hospital, Tokyo, JapanPurpose: Beta2-microglobulin (β2-M) is recognized as a surrogate marker relating to the mechanisms of dialysis-associated amyloidosis. Few studies have evaluated the association of serum β2-M with clinical outcome in hemodialysis patients using high-flux type. However, study on patients using low-flux dialyzer reuse has not been done yet.Patients and methods: Using serum β2-M level on predicting long-term mortality of hemodialysis patients was examined in 326 prevalent hemodialysis patients (45.59±14.46 years, hemodialysis duration of 47.5 (26–79) months, 186 males and 140 females). The patients were divided into 3 groups with equal number of patients, according to their serum β2-M levels: group A (n=109, serum β2-M concentration ≤55.7 mg/L), group B (n=109, serum β2-M level from 55.8 mg/L to 75.4 mg/L) and group C (n=108, serum β2-M concentration >75.4 mg/L).Results: During the follow-up period of 5 years, there were 75 all-cause deaths (23.0%). Kaplan–Meier analysis revealed that all-cause mortality in the higher β2-M group was significantly higher compared to that in the lower β2-M groups (p

Purpose: Our goal was to evaluate the neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios measured before transplantation and their correlation with new-onset diabetes after transplantation (NODAT) in renal transplant recipients., Patients and Methods: We conducted our study in 324 adult patients consecutively admitted to Military Hospital 103, Ha Noi, Viet Nam, who received kidney allografts from living donors. These patients were followed-up during the first 2 years post-transplantation for NODAT. We examined the association between NLR and PLR measured prior to transplantation in patients with NODAT: NLR and PLR were calculated based on the results of the complete blood count. The criteria for diagnosis of a fully symptomatic NODAT case were based on the guidelines established by the American Diabetes Association and included fasting venous blood glucose and glycosylated hemoglobin A1c (HbA1c) levels, with or without an oral glucose tolerance test., Results: The overall rate of NODAT during the two years after kidney transplantation was 13.6%. We found mean values of age and body mass index (BMI), and median values of NLR, PLR, high sensitivity C-reactive protein (hs-CRP) levels, and the arteriosclerosis ratio in the NODAT group to be significantly higher than those of the non-NODAT group (all p < 0.05). Furthermore, an adjusted multivariate regression analysis showed that age (area under the curve [AUC] = 0.727, p < 0.001), BMI (AUC = 0.846, p < 0.001), serum hs-CRP levels (AUC = 0.884, p < 0.001), NLR (AUC = 0.888; p < 0.001), and PLR (AUC = 0.818; p < 0.001) had predictive value for NODAT., Conclusion: NLR and PLR measured before transplantation were good predictors for NODAT in the first 2 years post-renal transplantation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Following curative-intent therapy of lung cancer, many survivors experience dyspnea and physical inactivity. We investigated the feasibility, acceptability, safety, and potential efficacy of inspiratory muscle training (IMT) and walking promotion to disrupt a postulated "dyspnea-inactivity" spiral., Methods: Between January and December 2022, we recruited lung cancer survivors from Kaiser Permanente Colorado who completed curative-intent therapy within 1-6 months into a phase-IIb, parallel-group, pilot randomized trial (1:1 allocation). The 12-week intervention, delivered via telemedicine, consisted of exercise training (IMT + walking), education, and behavior change support. Control participants received educational materials on general exercise. We determined feasibility a priori: enrollment of ≥ 20% eligible patients, ≥ 75% retention, study measure completion, and adherence. We assessed acceptability using the Telemedicine-Satisfaction-and-Usefulness-Questionnaire and safety events that included emergency department visits or hospitalizations. Patient-centered outcome measures (PCOMs) included dyspnea (University-of-California-San-Diego-Shortness-of-Breath-Questionnaire), physical activity (activPAL™ steps/day), functional exercise capacity (mobile-based-six-minute-walk-test), and health-related quality of life (HRQL, St.-George's-Respiratory-Questionnaire). We used linear mixed-effects models to assess potential efficacy., Results: We screened 751 patients, identified 124 eligible, and consented 31 (25%) participants. Among 28 participants randomized (14/group), 22 (11/group) completed the study (79% retention). Intervention participants returned > 90% of self-reported activity logs, completed > 90% of PCOMs, and attended > 90% of tele-visits; 75% of participants performed IMT at the recommended dose. Participants had high satisfaction with tele-visits and found the intervention useful. There was no statistically significant difference in safety events between groups. Compared to control participants from baseline to follow-up, intervention participants had statistically significant and clinically meaningful improved HRQL (SGRQ total, symptom, and impact scores) (standardized effect size: -1.03 to -1.30)., Conclusions: Among lung cancer survivors following curative-intent therapy, telemedicine-based IMT + walking was feasible, acceptable, safe, and had potential to disrupt the "dyspnea-inactivity" spiral. Future efficacy/effectiveness trials are warranted and should incorporate IMT and walking promotion to improve HRQL., Trial Registration: ClinicalTrials.gov NCT05059132., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives: To inform personalised home-based rehabilitation interventions, we sought to gain in-depth understanding of lung cancer survivors' (1) attitudes and perceived self-efficacy towards telemedicine; (2) knowledge of the benefits of rehabilitation and exercise training; (3) perceived facilitators and preferences for telerehabilitation; and (4) health goals following curative intent therapy., Design: We conducted semi-structured interviews guided by Bandura's Social Cognitive Theory and used directed content analysis to identify salient themes., Setting: One USA Veterans Affairs Medical Center., Participants: We enrolled 20 stage I-IIIA lung cancer survivors who completed curative intent therapy in the prior 1-6 months. Eighty-five percent of participants had prior experience with telemedicine, but none with telerehabilitation or rehabilitation for lung cancer., Results: Participants viewed telemedicine as convenient, however impersonal and technologically challenging, with most reporting low self-efficacy in their ability to use technology. Most reported little to no knowledge of the potential benefits of specific exercise training regimens, including those directed towards reducing dyspnoea, fatigue or falls. If they were to design their own telerehabilitation programme, participants had a predominant preference for live and one-on-one interaction with a therapist, to enhance therapeutic relationship and ensure correct learning of the training techniques. Most participants had trouble stating their explicit health goals, with many having questions or concerns about their lung cancer status. Some wanted better control of symptoms and functional challenges or engage in healthful behaviours., Conclusions: Features of telerehabilitation interventions for lung cancer survivors following curative intent therapy may need to include strategies to improve self-efficacy and skills with telemedicine. Education to improve knowledge of the benefits of rehabilitation and exercise training, with alignment to patient-formulated goals, may increase uptake. Exercise training with live and one-on-one therapist interaction may enhance learning, adherence, and completion. Future work should determine how to incorporate these features into telerehabilitation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fatigue is the most common symptom among cancer survivors. Cancer-related fatigue (CRF) may occur at any point in the cancer care continuum. Multiple factors contribute to CRF development and severity, including cancer type, treatments, presence of other symptoms, comorbidities, and medication side effects. Clinically, increasing physical activity, enhancing sleep quality, and recognizing sleep disorders are integral to managing CRF. Unfortunately, CRF is infrequently recognized, evaluated, or treated in lung cancer survivors despite more frequent and severe symptoms than in other cancers. Therefore, increased awareness and understanding of CRF are needed to improve health-related quality of life in lung cancer survivors. Objectives: 1 ) To identify and prioritize knowledge and research gaps and 2 ) to develop and prioritize research questions to evaluate mechanistic, diagnostic, and therapeutic approaches to CRF among lung cancer survivors. Methods: We convened a multidisciplinary panel to review the available literature on CRF, focusing on the impacts of physical activity, rehabilitation, and sleep disturbances in lung cancer. We used a three-round modified Delphi process to prioritize research questions. Results: This statement identifies knowledge gaps in the 1 ) detection and diagnostic evaluation of CRF in lung cancer survivors; 2 ) timing, goals, and implementation of physical activity and rehabilitation; and 3 ) evaluation and treatment of sleep disturbances and disorders to reduce CRF. Finally, we present the panel's initial 32 research questions and seven final prioritized questions. Conclusions: This statement offers a prioritized research agenda to 1 ) advance clinical and research efforts and 2 ) increase awareness of CRF in lung cancer survivors.

Background: No specific antiviral drug can effectively treat BKV reactivation after kidney transplantation. Thus, we evaluated stepwise-reduced immunosuppression to treat BKV reactivation. Methods: 341 kidney-transplant recipients were monitored for BKV infection (BKV-viremia, BKV-viruria). Positive samples with a significant virus load were nested PCR-genotyped in the VP1 region. In 97/211 patients presenting BKV viremia ≥104 copies/mL and/or BKV viruria ≥107 copies/mL, or BKV-nephropathy immunosuppression (i.e., mycophenolate mofetil [MMF]) was reduced by 50%. If viral load did not decrease within 28 days, MMF dose was further reduced by 25%, although calcineurin-inhibitor (CNI) therapy remained unchanged. If BKV viral load did not decrease within another 28 days, MMF was withdrawn and replaced by everolimus combined with reduced CNIs. Results: Only 41/97 BKV (+) cases completed the 6-month follow-up. Among these, 29 (71%) were in the BKV-I group and 12 (29%) were in BKV-IV. BKV viruria and BKV viremia were significantly decreased from 9.32 to 6.09 log10 copies/mL, and from 3.59 to 2.45 log10 copies/mL (p < 0.001 and p = 0.024, respectively). 11/32 (34.4%) patients were cleared of BKV viremia; 2/32 (6.3%) patients were cleared of BKV in both serum and urine, and 9/9 (100%) only had BKV viruria but did not develop BKV viremia. eGFR remained stable. No patient with BKV-related nephropathy had graft loss. There was a significant inverse relationship between changes in eGFR and serum BKV load (r = −0.314, p = 0.04). Conclusions: This stepwise immunosuppressive strategy proved effective at reducing BKV viral load in kidney transplant recipients that had high BKV loads in serum and/or urine. Renal function remained stable without rejection.

Objective: This study was conducted to determine the seasonal characteristics of odorous material emissions from a swine finishing barn equipped with a continuous pit recirculation system (CPRS) using aerobically treated manure., Methods: The CPRS consists of an aerobic manure treatment process and a pit recirculation system, where the solid fraction is separated and composted. The aerated liquid fraction (290.0%±21.0% per day of total stored pig slurry) is continuously recirculated to the top of the slurry in the pit. Four confinement pig barns in three piggery farms were used: two were equipped with CPRS, and the other two operated a slurry pit under the slatted floor across all seasons., Results: The indoor, exhaust, and outside odor intensities were significantly lower in the CPRS group than in the control group (p<0.001). In the CPRS group, the odor intensity outside was significantly lower in the fall than in the other seasons (p = 0.015). In the indoor atmosphere, the temperature and CO2, NH3, and H2S contents of the CPRS group were significantly lower than those of the control group (p<0.05). In the CPRS group, indoor temperature did not significantly change in the spring, summer, and fall seasons and was significantly lower in the winter (p = 0.002). NH3, H2S, methyl mercaptan, dimethyl disulfide, trimethylamine, phenol, indole, and skatole levels were significantly lower in the CPRS group than in the control group (p<0.05). There were significant seasonal differences on the odorous material in both the control and CPRS groups (p<0.05), but the pattern was not clear across seasons., Conclusion: The CPRS can reduce the indoor temperature in the summer to a level similar to that in the spring and fall seasons. The CPRS with aerated liquid manure is expected to reduce and maintain malodorous emissions within acceptable limits in swine facilities.

This study aimed to estimate the fermentation characteristics of bedded pack barn dairy cattle manure (BDCM) in terms of methane yield, fibrous material, and nitrogen content in batch solid-state anaerobic digestion (SSAD). SSAD was performed in triplicate using a 1,400 ml polypropylene bottle at a constant temperature of 39 °C until less than 1% methane was produced. The cumulative methane content of BDCM was 142.5 N mL/g volatile solids (VSs). The methane content rapidly increased for 18 days, reaching 63.4 ± 4.6% until the end of the experiment. The ultimate biodegradability and total VS removal of BDCM were 23.1 and 19.0%, respectively. The slopes of the non-fibrous and hemicellulose carbon fractions, and acid detergent insoluble carbon by digestion time were -0.174 ( p  < 0.001), -0.141 ( p  = 0.003), and -0.051 ( p  < 0.001), respectively. The non-fibrous and hemicellulose nitrogen fraction contents quadratically decreased during SSAD ( p  = 0.001 and p  = 0.008). No significant decrease was observed in the acid detergent insoluble nitrogen content ( p  = 0.840). The results of the present study provide basic data on the digestion characteristics of BDCM and could help determine fermentation conditions in the anaerobic digestion of BDCM., Competing Interests: The authors declare there are no competing interests. Youngjun Na is an employer (chief executive officer) of Animal Data Lab., Antller Inc., (©2022 Choi et al.)

Background: Dyspnea is a common and debilitating symptom that affects many different patient populations. Dyspnea measures should assess multiple domains., Objective: To evaluate the reliability, validity, and responsiveness of an ultra-brief, multi-dimensional dyspnea measure., Design: We adapted the DEG from the PEG, a valid 3-item pain measure, to assess average dyspnea intensity (D), interference with enjoyment of life (E), and dyspnea burden with general activity (G)., Participants: We used data from a multi-site randomized clinical trial among outpatients with heart failure., Main Measures: We evaluated reliability (Cronbach's alpha), concurrent validity with the Memorial-Symptom-Assessment-Scale (MSAS) shortness-of-breath distress-orbothersome item and 7-item Generalized-Anxiety-Disorder (GAD-7) scale, knowngroups validity with New-York-Heart-Association-Functional-Classification (NYHA) 1-2 or 3-4 and presence or absence of comorbid chronic obstructive pulmonary disease (COPD), responsiveness with the MSAS item as an anchor, and calculated a minimal clinically important difference (MCID) using distribution methods., Key Results: Among 312 participants, the DEG was reliable (Cronbach's alpha 0.92). The mean (standard deviation) DEG score was 5.26 (2.36) (range 0-10) points. DEG scores correlated strongly with the MSAS shortness of breath distress-or-bothersome item (r=0.66) and moderately with GAD-7 categories (ρ=0.36). DEG scores were statistically significantly lower among patients with NYHA 1-2 compared to 3-4 [mean difference (standard error): 1.22 (0.27) points, p<0.01], and those without compared to with comorbid COPD [0.87 (0.27) points, p<0.01]. The DEG was highly sensitive to change, with MCID of 0.59-1.34 points, or 11-25% change., Conclusions: The novel, ultra-brief DEG measure is reliable, valid, and highly responsive. Future studies should evaluate the DEG's sensitivity to interventions, use anchor-based methods to triangulate MCID estimates, and determine its prognostic usefulness among patients with chronic cardiopulmonary and other diseases., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objectives: The purpose of this study was to identify the SNP sites and determine the BKV genotype circulating in kidney-transplant Vietnamese recipients based on the VP1 gene region., Methods: 344 samples were collected from post-kidney-transplant recipients at the 103 Vietnam Military Hospital to investigate the number of BKV infections. Positive samples with a sufficient virus concentration were analyzed by nested PCR in the VP1 region, sequencing detected genotyping and single-nucleotide polymorphism., Results: BKV infection was determined in 214 patients (62.2%), of whom 11 (5.1%) were diagnosed with BKV-associated nephropathy. Among the 90 BKV-I strains sequenced, 89 (98.88%) were strains of I/b-1 and 1 (1.12%) was strain I/b-2. The 60 BKV-IV strains had a greater diversity of subgroups, including 40% IV/a-1, 1.66% IV/a-2, 56.68% IV/c-1, and 1.16% IV/c-2. Additionally, of 11 cases diagnosed with BKVN, seven belonged to subgroup I/b-1 (63.6%) and four to subgroup IV/c-1 (36.4%). Moreover, 22 specific SNPs that were genotype I or IV were determined in this Vietnamese population. Specifically, at position 1745, for the Vietnamese BKV-IV strains, the SNP position (A→G) appeared in 57/60 samples (95%). This causes transformation of the amino acid N→S. This SNP site can enable detection of genotype IV in Vietnam. It represents a unique evolution pattern and mutation that has not been found in other international strains., Conclusion: The BKV-I genotype was more common than BKV-IV; however, mutations that occur on the VP1 typing region of BKV-IV strains were more frequent than in BKV-I strains.

Objective: This study was conducted to determine reduction of various odorous materials from a swine farm equipped with a continuous pit recirculation system (CPRS) with aerobically treated liquid manure., Methods: The CPRS is used in swine farms in South Korea, primarily to improve air quality in pig houses. In this study, CPRS consists of a manure aerobic treatment system and a fit recirculation system; the solid fraction is separated and composted, whereas the aerobically treated liquid fraction (290.0%±21.0% per day of total stored swine slurry) is continuously returned to the pit. Four confinement pig barns in three piggery farms were used; two were equipped with CPRS and the other two operated a slurry pit under the slatted floor., Results: All chemical contents of slurry pit manure in the control were greater than those of slurry pit manure in the CRPS treatment (p<0.05). Electrical conductivity and pH contents did not differ among treatments. The biological oxygen demand of the slurry pit treatment was greater than that of the other treatments (p<0.05). Total nitrogen, total phosphorus, and ammonia nitrogen contents of the slurry pit treatment were greater than those of other treatments (p<0.05). Odor intensity of the CPRS treatment was lower than that of the control at indoor, exhaust, and outside sampling points (p<0.05). The temperature and carbon dioxide of the CPRS treatment in the pig barn was significantly lower than those of control (p<0.05). All measured odorous material contents of the CPRS group were significantly lower than those of the control group (p<0.05)., Conclusion: The CPRS application in pig farms is considered a good option as it continuously reduces the organic load of animal manure and lowers the average odorant concentration below the threshold of detecting odorous materials.

Objective: The number of lung cancer survivors is increasing along with advances in screening, diagnosis, and treatment. Following curative intent therapy, many lung cancer survivors experience significant health-related quality of life (HRQL) impairments. We sought to identify potentially modifiable factors that contribute to the HRQL of these patients., Materials and Methods: In this cross-sectional observational study of disease-free, stage I-IIIA lung cancer survivors following curative intent therapy, we used a conceptual model to examine factors that included behavioral, objective functional and physiologic, self-rated function and symptom burden, specific comorbidities, and non-modifiable demographic and clinical lung cancer-related characteristics. We assessed HRQL using the valid and prognostic European Organization for Research and Treatment of Cancer Quality of Life (QoL) Core 30 global health/QoL subscale. We used univariable and multivariable linear regression modeling with backward elimination of potentially modifiable and non-modifiable factors, and interpreted clinically and statistically significant, consistent, and independent modifiable factors as meaningful., Results: Among 75 participants at a median of 12 months since treatment completion, the mean (standard deviation) C30 global health/QoL score was 62.7 (23.3) points (0-100 scale range). In multivariable analysis, with and without non-modifiable factors, we identified three clinically and statistically significant, consistent, and independent factors (unstandardized β range) associated with global health/QoL: 1) abnormal exercise-induced dyspnea (-9.23 to -10.0 points); 2) impaired self-rated role function (or inability to perform work or daily activities and pursuing leisure-time activities) (-12.6 to -16.4 points); and 3) abnormal insomnia (or trouble sleeping) (-12.6 to -16.4 points)., Conclusion: We identified meaningful modifiable factors associated with the HRQL of disease-free, stage I-IIIA lung cancer survivors following curative intent therapy. Interventions to improve the HRQL of these patients should aim to reduce exercise-induced dyspnea, improve role function - the ability to perform work and other daily including leisure-time activities, and control insomnia., (Published by Elsevier B.V.)

Rationale: Exercise assessments may help predict outcomes for patients with diagnosed lung cancer. Objectives: We examined the relationship between prediagnosis exercise behavior and clinical outcomes among patients with stage I-IIIA lung cancer. Methods: In a retrospective cohort study of patients with stage I-IIIA lung cancer at Kaiser Permanente Colorado who had at least one Exercise Vital Sign assessment-a questionnaire tool to help promote exercise in chronic disease management-within the year before diagnosis, we defined exercise behavior as active (any min/wk of moderate-to-vigorous-intensity physical activity) or inactive (no moderate-to-vigorous physical activity). The outcomes were 1 ) overall survival (OS) and 2 ) acute healthcare use (AHCU). We used the Kaplan-Meier method, Cox proportional hazard model, and negative binomial regression model to analyze the effects of exercise on outcomes, adjusting for demographic, socioeconomic, clinical, and lung-cancer characteristics. Results: Among 552 patients with lung cancer, 230 (42%) were identified as physically active before their diagnosis of cancer. There was no significant difference in the stage distribution between active and inactive patients. The median survival times were 2.4 years for the active group and 1.8 years for inactive patients ( P  < 0.001). The mean rates (standard deviations) of AHCU were 1.09 (1.55) and 2.31 (5.61) per person-year for active and inactive groups, respectively ( P  < 0.01). Active exercise, compared with inactivity, was associated with better OS (hazard ratio, 0.52 [0.39-0.69]) and lower AHCU (rate ratio, 0.63 [0.49-0.80]) in unadjusted analyses; in adjusted analyses, active exercise was associated with better OS (hazard ratio, 0.62 [0.45-0.86]), but AHCU was not lower by a statistically significant amount (rate ratio, 0.82 [0.65-1.04]). Conclusions: Prediagnosis active exercise was associated with better OS after diagnosis of stage I-IIIA lung cancer. Exercise assessments may help predict outcomes, risk-stratify patients for curative-intent therapy, and identify those who would benefit from increased physical activity and exercise.

Background: This study aims to determine the ratio of delayed graft function in renal transplant recipients from living donors and the predictive value of hemodialysis time before transplant for delayed graft function., Methods: We conducted a study on 116 adult patients who were diagnosed with end-stage kidney disease and were treated with hemodialysis and transplanted kidneys from living donors for 2 years (from June 2018 to June 2020). Delayed graft function event was collected for each patient., Results: The recipients had a median age of 36.5 years old, in which 55.2% of them were men, 4.3% of them had the diabetic mellitus, and the median hemodialysis duration was 6 months. The ratio of positive panel-reactive antibody was 33.6% and vascular reconstruction of the donor's kidney was 16.4%. The ratio of delayed graft function was 12.2% (14 of 116 patients). Delayed graft function significantly related to positive panel-reactive antibody, long duration of hemodialysis before transplant, and vascular reconstruction of donor's kidney with P < .001. Duration of hemodialysis before kidney transplant had a predictive value for delayed graft function (area under the curve, 0.83; P < .001)., Conclusion: Delayed graft function was not rare in renal transplant recipients from living donors. Duration of hemodialysis before kidney transplant was a good predictor for delayed graft function., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Peripheral artery disease (PAD), a severe atherosclerotic condition primarily of the elderly, afflicts 200 million individuals, worldwide, and is associated with lower extremity myopathy. Circulating markers of inflammation have been linked to risk and severity of PAD but the contribution of local inflammation to myopathy remains unknown. We evaluated, by ELISA, calf muscle of PAD patients (N = 23) and control subjects (N = 18) for local expression of inflammatory cytokines including Granulocyte/Monocyte Colony-Stimulating Factor (GM-CSF), Interleukin 17A (IL-17A), Interferon ϒ (IFN-ϒ), tumor necrosis factor α (TNF-α), and Interleukin 6 (IL-6). One or more of these cytokines were expressed in nineteen patients and 2 controls and coordinated expression of GM-CSF, IL-17A, IFN-ϒ, and TNF-α, a signature of activated, MHC Class II dependent autoreactive Th-cells, was unique to 11 patients. GM-CSF is the central driver of tissue-damaging myeloid macrophages. Patients with this cytokine signature had a shorter (P= 0.017) Claudication Onset Distance (17 m) compared with patients lacking the signature (102 m). Transforming Growth Factor β1 (TGFβ1) and Chemokine Ligand 5 (CCL5) were expressed coordinately in all PAD and control muscles, independently of GM-CSF, IL-17A, IFN-ϒ, TNF-α, or IL-6. TGFβ1 and CCL5 and their gene transcripts were increased in PAD muscle, consistent with increased age-associated inflammation in these patients. Serum cytokines were not informative of muscle cytokine expression. We have identified a cytokine profile of autoimmune inflammation in calf muscles of a significant proportion of claudicating PAD patients, in association with decreased limb function, and a second independent profile consistent with increased "inflammaging" in all PAD patients., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Physical activity and exercise improve function, symptom control, and health-related quality of life (QoL) for many cancer survivors; however, the evidence is limited and inconsistent in lung cancer. We examined the relationship between leisure-time physical activity (LTPA) and health-related QoL in a national sample of US lung cancer survivors., Methods: We conducted a cross-sectional study using the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System. We defined LTPA as a self-report of engaging in any physical activity or exercise such as running, calisthenics, golf, gardening, or walking for exercise in the past 30 days, health-related QoL as the number of days of having poor physical or mental health in the past 30 days, and general health status. We analyzed using multivariable logistic regressions with 95% confidence intervals (CIs)., Results: Among 614 lung cancer survivors, 316 (51.5%) reported engaging in LTPA. The counts (and proportions) of participants who engaged in LTPA vs no LTPA were, respectively, 135 (42.7%) vs 63 (21.1%) for 0 days of poor physical health, 222 (70.3%) vs 174 (58.4%) for 0 days of poor mental health, and 158 (50.0%) vs 77 (25.8%) for good to excellent general health. In multivariable analyses, participating in LTPA was associated with odds ratios of 2.64 (95% CI = 1.76 to 3.96) and 1.43 (95% CI = 0.97 to 2.10) for 0 days of poor physical and mental health, respectively, and 2.61 (95% CI = 1.74 to 3.91) for good to excellent general health., Conclusions: Participating in LTPA was associated with improved health-related QoL. Interventions to promote LTPA and/or exercise-based rehabilitation may improve QoL among lung cancer survivors., (Published by Oxford University Press 2021.)

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine produced during acute inflammation. Few studies have evaluated the association between serum TNF-α and its receptors and their clinical outcomes in hemodialysis patients. However, a study assessing patients using a low-flux dialyzer reuse has not been conducted yet. The serum TNF-α concentrations of 319 prevalent hemodialysis patients (mean age, 45 ± 15 years; median duration of hemodialysis, 48 [interquartile range, 26-79] months; 185 males and 134 females) was examined to predict their 3-year mortality. The patients were divided into tertiles according to their serum TNF-α concentrations: T1 (n = 106; serum TNF-α concentration, <41.22 pg/mL), T2 (n = 106; serum TNF-α level, from 41.22 to 67.28 pg/mL), and T3 (n = 107; serum TNF-α concentration, ≥ 67.29 pg/mL). During the 36-month follow-up period, a total of 50 (15.7%) patients died from all causes. The Kaplan-Meier analysis revealed that the all-cause mortality in T3 was significantly higher compared to that in T1 and T2 (log-rank test, P < .001). The serum TNF-α level was a significant predictor for all-cause mortality (area under the curve = 0.887, P < .001, cutoff value, 89.812 pg/mL, sensitivity = 76%, specificity = 96.3%). The serum TNF-α level was a better predictor of mortality than the duration of hemodialysis and serum albumin, serum high-sensitivity C-reactive protein, and serum beta-2 microglobulin concentrations. The serum TNF-α concentration was a good predictor of the 3-year mortality in low-flux hemodialysis patients., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Bronchoalveolar lavage (BAL) is a commonly used procedure in the evaluation of lung disease as it allows for sampling of the lower respiratory tract. In many circumstances, BAL differential cell counts have been reported to be typical of specific lung disorders. In addition, more specific diagnostic tests including molecular assays such as polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay, special cytopathologic stains, or particular microscopic findings have been described as part of BAL fluid analysis. This review focuses on common cellular and molecular findings of BAL in a wide range of lung diseases. Since the performance of the first lung irrigation in 1927, BAL has become a common and important diagnostic tool. While some pulmonary disorders have a highly characteristic signature of BAL findings, BAL results alone often lack specificity and require interpretation along with other clinical and radiographic details. Development of new diagnostic assays is certain to reinforce the utility of BAL in the future. Our review of the BAL literature is intended to serve as a resource to assist clinicians in the care of patients with lung disorders., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-651). EDC serves as an unpaid editorial board member of Journal of Thoracic Disease. The other author has no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

The article "Interleukin 6 is a better predictor of 5-year cardiovascular mortality than high-sensitivity C-reactive protein in hemodialysis patients using reused low-fux dialyzers".

Purpose: In this study, we focused on the role of elevated serum interleukin 6 (IL-6) concentration in predicting 5-year cardiovascular mortality in hemodialysis patients using low-flux dialyzer reuse., Materials and Methods: We measured serum IL-6 concentrations in 236 hemodialysis patients (138 males and 98 females) to predict 5-year cardiovascular mortality. We assessed the baseline demographics of all patients who had a mean age of 44 years and a median hemodialysis duration of 38.5 months. We divided all patients into two equal groups based on the serum IL-6 concentration: G1 (n = 118) with serum IL-6 concentration < 6.78 pg/L and G2 (n = 118) with serum IL-6 concentration ≥ 6.78 pg/L., Results: After the 5-year follow-up, 45 patients died due to cardiovascular causes (19.1%). Lipid disorder, hemoglobin, serum albumin, β2-M, and IL-6 concentration were independent risk factors for predicting cardiovascular mortality during the 60-month follow-up in hemodialysis patients. Based on the Kaplan-Meier analysis, we realized that patients with a higher interleukin 6 concentration (G2) had a significantly higher cardiovascular mortality rate than patients in G1 (log-rank test p < 0.001). Serum IL-6 concentration was a better predictor of 5-year cardiovascular mortality than high-sensitivity C-reactive protein in hemodialysis patients using low-flux dialyzer reuse (AUC = 0.818; p < 0.001; cut-off value: 8.055 pg/mL, Se = 77.8%, Sp = 78.5%)., Conclusion: Serum IL-6 concentration was a better predictor of 5-year cardiovascular mortality than high-sensitivity C-reactive protein in maintenance hemodialysis patients using low-flux dialysis reuse.

Diluted magnetic semiconductors including Mn-doped GaAs are attractive for gate-controlled spintronics but Curie transition at room temperature with long-range ferromagnetic order is still debatable to date. Here, the room-temperature ferromagnetic domains with long-range order in semiconducting V-doped WSe 2 monolayer synthesized by chemical vapor deposition are reported. Ferromagnetic order is manifested using magnetic force microscopy up to 360 K, while retaining high on/off current ratio of ≈10 5 at 0.1% V-doping concentration. The V-substitution to W sites keeps a V-V separation distance of 5 nm without V-V aggregation, scrutinized by high-resolution scanning transmission electron microscopy. More importantly, the ferromagnetic order is clearly modulated by applying a back-gate bias. The findings open new opportunities for using 2D transition metal dichalcogenides for future spintronics., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Claudication is the most common manifestation of peripheral artery disease (PAD), producing significant ambulatory compromise. Limited information exists on the routine physical activity of claudicating patients. Our objective was to record the intensity/time profiles of physical activity and the timing and duration of sedentary behavior of a sample of community-dwelling claudicating patients., Methods: Forty-four claudicating patients referred to our vascular clinic were recruited. Physical activity was recorded using the ActiGraph GT1M activity monitor. The Actigraph monitor is a lightweight instrument designed to measure human movement through changes in acceleration, measured as counts over 1-minute time periods. Data from 7 consecutive days were used for the calculations. We processed the data using the ActiLife software program., Results: The average daily activity of the claudicating patients shows a steady increase beginning approximately 05:30 AM until a peak plateau from approximately 10:00 AM to 01:30 PM followed by a steady decrease until approximately 09:30 PM, when a sustained period of inactivity begins. The average claudicating patient takes 3586 steps per day at an average intensity of 1.77 metabolic equivalents of task (METs, a physiological measure expressing the energy cost of physical activities). Average physical activity intensity and peak intensity fluctuate very little during the day, and they rarely exceed the level of light activity (light = <3 METs maximum effort, such as casual walking or light housework). During awake time, approximately 7 hours are spent in sedentary behaviors (<1.5 METs), and sedentary time is spread throughout the day mostly in short intervals between periods of low-energy activity., Conclusions: Our study objectively demonstrates the reduced physical activity of claudicating patients and documents physical activity/duration profiles throughout the day. The intensity of the physical activity of the average claudicating patient fluctuates very little during the day and rarely exceeds a light intensity level. Claudicating patients spend approximately half of their awake time in sedentary behavior and when they walk they do it in short bursts followed by several minutes of rest. We anticipate that changes in routine physical activity/duration profiles of patients with PAD will provide relevant, sensitive, and direct measures of the effectiveness of therapeutic interventions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In the version of this article initially published, the URL listed for TubercuList was incorrect. The correct URL is https://mycobrowser.epfl.ch/. The error has been corrected in the HTML and PDF versions of the article.

Objectives: The purpose of this study was to compare the discontinuation rates of tofacitinib and biologics (tumour necrosis factor inhibitors (TNFi), abatacept, rituximab, and tocilizumab) in rheumatoid arthritis (RA) patients considering inadequate responses (IRs) to previous treatment(s)., Methods: Randomised controlled trials of tofacitinib and biologics - reporting at least one total discontinuation, discontinuation due to lack of efficacy (LOE), and discontinuation due to adverse events (AEs) - were identified through systematic review. The analyses were conducted for patients with IRs to conventional synthetic disease-modifying anti-rheumatic drugs (cDMARDs) and for patients with biologics-IR, separately. Bayesian network meta-analysis was used to estimate rate ratio (RR) of a biologic relative to tofacitinib with 95% credible interval (CrI), and probability of RR being <1 (P[RR<1])., Results: The analyses of 34 studies showed no significant differences in discontinuation rates between tofacitinib and biologics in the cDMARDs-IR group. In the biologics-IR group, however, TNFi (RR 0.17, 95% CrI 0.01-3.61, P[RR<1] 92.0%) and rituximab (RR 0.20, 95% CrI 0.01-2.91, P[RR<1] 92.3%) showed significantly lower total discontinuation rates than tofacitinib did. Despite the difference, discontinuation cases owing to LOE and AEs revealed that tofacitinib was comparable to the biologics., Conclusions: The comparability of discontinuation rate between tofacitinib and biologics was different based on previous treatments and discontinuation reasons: LOE, AEs, and total (due to other reasons). Therefore, those factors need to be considered to decide the optimal treatment strategy.

Background: Lower leg ischemia, myopathy, and limb dysfunction are distinguishing features of peripheral artery disease (PAD). The myopathy of PAD is characterized by myofiber degeneration in association with extracellular matrix expansion, and increased expression of transforming growth factor-beta 1 (TGF-β1; a pro-fibrotic cytokine). In this study, we evaluated cellular expression of TGF-β1 in gastrocnemius of control (CTRL) and PAD patients and its relationship to deposited collagen, fibroblast accumulation and limb hemodynamics., Methods: Gastrocnemius biopsies were collected from PAD patients with claudication (PAD-II; N = 25) and tissue loss (PAD-IV; N = 20) and from CTRL patients (N = 20). TGF-β1 in slide-mounted specimens was labeled with fluorescent antibodies and analyzed by quantitative wide-field, fluorescence microscopy. We evaluated co-localization of TGF-β1 with vascular smooth muscle cells (SMC) (high molecular weight caldesmon), fibroblasts (TE-7 antigen), macrophages (CD163), T cells (CD3) and endothelial cells (CD31). Collagen was stained with Masson Trichrome and collagen density was determined by quantitative bright-field microscopy with multi-spectral imaging., Results: Collagen density increased from CTRL to PAD-II to PAD-IV specimens (all differences p < 0.05) and was prominent around microvessels. TGF-β1 expression increased with advancing disease (all differences p < 0.05), correlated with collagen density across all specimens (r = 0.864; p < 0.001), associated with fibroblast accumulation, and was observed exclusively in SMC. TGF-β1 expression inversely correlated with ankle-brachial index across PAD patients (r = -0.698; p < 0.001)., Conclusions: Our findings support a progressive fibrosis in the gastrocnemius of PAD patients that is caused by elevated TGF-β1 production in the SMC of microvessels in response to tissue hypoxia.

Background: Wound healing has being extensively investigated over the world. Healing impairment is caused by many reasons including increasing of free-radicals-mediated damage, delaying in granulation tissue formation, reducing in angiogenesis and decreasing in collagen reorganization. These facts consequently lead to chronic wound healing. Piper betle Linn (Betle) leaves have been folklore used as an ingredient of drugs for cutaneous wound treatment. However, the effect of betle leaf on wound healing is not yet well elucidated. In this study, we aimed to investigate the healing efficacy of methanol leaf extract of Piper betle Linn on proliferation of fibroblast NIH3T3 cells as well as full-thickness burn and excision wounds in swiss mice., Methods: Scratch wound healing assays were conducted to examine the effects of betle leaf extract on healing activity of fibroblast cells. Burn and excision wounds on swiss mouse skins were created for investigating the wound healing progress caused by the betle leaf extract. Malondialdehyde (MDA) was also evaluated to examine the products of lipid hydroperoxide (LPO) under conditions of with or without betle leaf extract treatment., Results: The results of this study showed that Piper betle Linn leaf extract in methanol increased proliferation of NIH3T3 cells and promoted wound healing in vitro and in vivo with both burn wound and excision wound models. In addition, this extract significant decreased level of malondialdehyde (MDA) in liver of treated-mice compared with that in non-treated mice., Conclusions: Our results suggest that Piper betle Linn can be used as an ingredient in developing natural origin drugs for treatment of cutaneous wounds.

Background: Peripheral artery disease (PAD), which affects an estimated 27 million people in Europe and North America, is caused by atherosclerotic plaques that limit blood flow to the legs. Chronic, repeated ischemia in the lower leg muscles of PAD patients is associated with loss of normal myofiber morphology and myofiber degradation. In this study, we tested the hypothesis that myofiber morphometrics of PAD calf muscle are significantly different from normal calf muscle and correlate with reduced calf muscle strength and walking performance., Methods: Gastrocnemius biopsies were collected from 154 PAD patients (Fontaine stage II) and 85 control subjects. Morphometric parameters of gastrocnemius fibers were determined and evaluated for associations with walking distances and calf muscle strength., Results: Compared with control myofibers, PAD myofiber cross-sectional area, major and minor axes, equivalent diameter, perimeter, solidity, and density were significantly decreased (P < 0.005), whereas roundness was significantly increased (P < 0.005). Myofiber morphometric parameters correlated with walking distances and calf muscle strength. Multiple regression analyses demonstrated myofiber cross-sectional area, roundness, and solidity as the best predictors of calf muscle strength and 6-min walking distance, whereas cross-sectional area was the main predictor of maximum walking distance., Conclusions: Myofiber morphometrics of PAD gastrocnemius differ significantly from those of control muscle and predict calf muscle strength and walking distances of the PAD patients. Morphometric parameters of gastrocnemius myofibers may serve as objective criteria for diagnosis, staging, and treatment of PAD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Patients with peripheral artery disease (PAD) develop a myopathy in their ischemic lower extremities, which is characterized by myofiber degeneration, mitochondrial dysfunction and impaired limb function. Desmin, a protein of the cytoskeleton, is central to maintenance of the structure, shape and function of the myofiber and its organelles, especially the mitochondria, and to translation of sarcomere contraction into muscle contraction. In this study, we investigated the hypothesis that disruption of the desmin network occurs in gastrocnemius myofibers of PAD patients and correlates with altered myofiber morphology, mitochondrial dysfunction, and impaired limb function. Using fluorescence microscopy, we evaluated desmin organization and quantified myofiber content in the gastrocnemius of PAD and control patients. Desmin was highly disorganized in PAD but not control muscles and myofiber content was increased significantly in PAD compared to control muscles. By qPCR, we found that desmin gene transcripts were increased in the gastrocnemius of PAD patients as compared with control patients. Increased desmin and desmin gene transcripts in PAD muscles correlated with altered myofiber morphology, decreased mitochondrial respiration, reduced calf muscle strength and decreased walking performance. In conclusion, our studies identified disruption of the desmin system in gastrocnemius myofibers as an index of the myopathy and limitation of muscle function in patients with PAD., (© The Author(s) 2015.)

This study compared the effects of varying lipid content and dietary concentration of a lipid-encapsulated (LE) ZnO product to those of native ZnO and thereby to find insights into optimal lipid coating and dosage of the Zn supplement. A total of 192 21-d-old weanling pigs were allotted to 48 pens, after which each six pens received a ZnO-free basal diet supplemented with 125 ppm ZnO (100 ppm Zn; BASAL), 2,500 ppm Zn as native ZnO (HIGH), or 100 or 200 ppm Zn as LE ZnO (LE-100 or LE-250) containing 8%, 10%, or 12% lipid [LE-8%, LE-10%, or LE-12%, respectively; 2 × 3 factorial arrangement within the LE-ZnO diets (LE-ALL)] for 14 d. Forty pigs were killed at the end for histological and biochemical examinations. None of ADG, ADFI, gain:feed, and fecal consistency score differed between the LE-ALL and either of the BASAL and HIGH groups. Hepatic and serum Zn concentrations were greater (p <0.05) in the HIGH vs. LE-ALL group, but did not differ between LE-ALL and BASAL, between LE-100 and -250, or among LE-8%, -10%, and -12% groups. Villus height (VH), crypt depth (CD), and the VH:CD ratio in the duodenum, jejunum, and ileum did not differ between the LE-ALL and either of the BASAL and HIGH groups, except for a greater CD in the duodenum in the LE-ALL vs. HIGH group. Additionally, VH and CD in the duodenum and VH:CD in the jejunum were greater in the LE-250 vs. LE-100 group. Specific activities of sucrase, maltase, and leucine aminopeptidase in these intestinal regions and those of amylase and trypsin in the pancreas were not influenced by the lipid content or dietary concentration of LE ZnO and also did not differ between the LE-ALL and either of the BASAL and HIGH groups, except for a greater pancreatic amylase activity in the former vs. HIGH group. In conclusion, the present results indicate that the LE ZnO, regardless of its lipid percentage or supplementation level examined in this study, has no significant effect on growth performance, fecal consistency, or digestive enzyme activities of weanling pigs under the experimental conditions.

The present study was performed to investigate the effects of two groups of sires with 'medium' and 'high' weight gain potentials (M-sires and H-sires, respectively) on growth of their progenies on varying planes of nutrition during the growing-finishing period. The ADG of the M-sires' progeny was greater (P < 0.05) than that of the H-sires' progeny (0.51 vs. 0.47 kg) during a 26- to 29-d early grower phase beginning from 55 d of age, but the opposite was true (0.66 vs. 0.72 kg) during the latter grower phase. Overall grower-phase ADG was greatest on the high plane of nutrition (H plane) followed by the medium (M) and low (L) planes (0.65, 0.61, and 0.51 kg, respectively; P < 0.05) in the M-sires' progeny, whereas in the H-sires' progeny, ADG was greater on the H and M planes vs. L plane (0.63, 0.62, and 0.54 kg, respectively). The ADG of pigs on the M or H plane during the grower phase and switched to the H plane thereafter (M-to-H or H-to-H planes) was greater than that of pigs on the L-to-L planes (0.99 vs. 0.78 kg) during the early finisher phase in the M-sires' progeny (P < 0.01). However, in the H-sires' progeny, ADG of pigs on the L-to-L planes did not differ from that of pigs on the M-to-M or H-to-M planes (0.94 vs. 0.96 kg). Results suggest that the H-to-H or H-to-M planes and M-to-M or M-to-L planes are optimal for maximal growth of the M- and H-sires' progenies, respectively.

This study was aimed at investigating the long-term effects of provision of liquid milk replacer (MR) and solid starter diet (SD) during lactation on post-weaning (PW) growth of pigs. In experiment 1, 33 cross-bred litters were allotted to four treatments: no supplement (CON), MR ad libitum, SD ad libitum and 100 g SD/litter/day from lactation day 4 through weaning at day 21 during late fall. In experiment 2, 40 litters received MR or none in July. PW pigs received commercial diets to marketing. In experiment 1, weaning weight (WW), pre-weaning average daily gain (ADG) and mortality (2.4%) were not influenced by creep-feeding MR or SD. ADG was greater (P < 0.05) in the MR group versus CON during days 21-54, but did not differ across the treatments during days 54-162. In experiment 2, ADG during lactation and WW were greater in the MR group versus CON, with mortality lower in the former (5.6 vs. 10.3%). However, PW ADG to day 175 did not differ between the two groups. Results suggest that creep-feeding MR or SD has no effect on PW growth. However, it remains possible that MR reduces PW mortality during the hot season., (© 2014 Japanese Society of Animal Science.)

Background: Peripheral artery disease (PAD), a manifestation of systemic atherosclerosis that produces blockages in the arteries supplying the legs, affects approximately 5% of Americans. We have previously, demonstrated that a myopathy characterized by myofiber oxidative damage and degeneration is central to PAD pathophysiology., Objectives: In this study, we hypothesized that increased oxidative damage in the myofibers of the gastrocnemius of PAD patients is myofiber-type selective and correlates with reduced myofiber size., Methods: Needle biopsies were taken from the gastrocnemius of 53 PAD patients (28 with early PAD and 25 with advanced PAD) and 25 controls. Carbonyl groups (marker of oxidative damage), were quantified in myofibers of slide-mounted tissue, by quantitative fluorescence microscopy. Myofiber cross-sectional area was determined from sarcolemma labeled with wheat germ agglutinin. The tissues were also labeled for myosin I and II, permitting quantification of oxidative damage to and relative frequency of the different myofiber Types (Type I, Type II and mixed Type I/II myofibers). We compared PAD patients in early (N=28) vs. advanced (N=25) disease stage for selective, myofiber oxidative damage and altered morphometrics., Results: The carbonyl content of gastrocnemius myofibers was higher in PAD patients compared to control subjects, for all three myofiber types (p<0.05). In PAD patients carbonyl content was higher (p<0.05) in Type II and I/II fibers compared to Type I fibers. Furthermore, the relative frequency and cross-sectional area of Type II fibers were lower, while the relative frequencies and cross-sectional area of Type I and Type I/II fibers were higher, in PAD compared to control gastrocnemius (p<0.05). Lastly, the type II-selective oxidative damage increased and myofiber size decreased as the disease progressed from the early to advanced stage., Conclusions: Our data confirm increased myofiber oxidative damage and reduced myofiber size in PAD gastrocnemius and demonstrate that the damage is selective for type II myofibers and is worse in the most advanced stage of PAD.

Background and Aim: The contribution of human genetic polymorphisms to Helicobacter pylori infection and gastric cancer (GC) development remains unclear due to geographic variation in the association between specific host genetic polymorphisms and GC. In the current study we investigated the association between polymorphisms related to immune and cancer-related pathways and H. pylori infection among the major ethnicities, Chinese, Malay and Indian, resident in Singapore and Malaysia as well as the association between these polymorphisms and GC development in ethnic Chinese patients., Methods: Thirty-four polymorphisms in 26 genes were typed by mass spectrometry in 422 patients undergoing endoscopy (162 Chinese, 113 Indian and 87 Malay controls and 60 Chinese GC cases). Patients were assessed for evidence of H. pylori infection. Odds ratios (OR) and confidence intervals (CI) were obtained using logistic regression models., Result: The prevalence of 16 polymorphisms varied significantly among the ethnicities. In the Chinese subgroup, nominally significant associations were shown between (i) EBBR2+1963G (rs1801200) and H. pylori infection (per-allele OR: 0.48, 95% CI 0.23, 0.98, P = 0.04), (ii) PTGS2-1195G (rs689466) and an increased risk of GC on adjusting for H. pylori status (OR: 1.53, 95% CI 0.99, 2.37, P = 0.05), and (iii) IL1B-1473C (rs1143623) and a decreased risk of GC (OR: 0.64, 95% CI 0.41, 0.99, P = 0.05). Borderline significant associations were seen between IL2-330G (rs2069762) (OR 1.45, 95% CI 0.95, 2.15, P = 0.06) and IL13-1111T (rs1800925) (OR 0.65, 95% CI 0.42, 1.01, P = 0.06) and H. pylori infection., Conclusion: These findings contribute to the understanding of the genetic variation between ethnicities, which may influence H. pylori susceptibility and the outcome of infection., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Neurodegenerative diseases, notably Alzheimer's and Parkinson's diseases, are amongst the most devastating disorders afflicting the elderly. Currently, no curative treatments or treatments that interdict disease progression exist. Over the past decade, immunization strategies have been proposed to combat disease progression. Such strategies induce humoral immune responses against misfolded protein aggregates to facilitate their clearance. Robust adaptive immunity against misfolded proteins, however, accelerates disease progression, precipitated by induced effector T cell responses that lead to encephalitis and neuronal death. Since then, mechanisms that attenuate such adaptive neurotoxic immune responses have been sought. We propose that shifting the balance between effector and regulatory T cell activity can attenuate neurotoxic inflammatory events. This review summarizes advances in immune regulation to achieve a homeostatic glial response for therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are also discussed.

Cytotoxicity-guided fractionation and separation of MeOH extract from Androsace umbellata (Lour.) Merr. led to the isolation of four triterpenoid saponins. Compounds isolated from the n-BuOH soluble fraction were identified as saxifragifolin C (1), A (2), B (3), and D (4) by spectroscopic analysis. Antiproliferative effect of isolated compounds were evaluated by the sulforhodamin B assay against multidrug resistance (MDR; MES-SA/DX5 and HCT15/CLO2) and non-MDR (A549, SK-OV-3, SK-MEL-2, MES-SA, and HCT15) human tumor cell lines. All compounds exhibited strong cytotoxicity against non-MDR human tumor cell lines with IC(50) values of 0.19-2.37 muM. MDR cells and non-MDR cells had similar sensitivity to these compounds, however, MDR cells were highly resistant to doxorubicin. Compounds 1-4 induced an increase in the percentage of Annexin V-binding cells, indicating that 1-4 induced apoptosis in RAW 264.7 cells. Also, the condensation of nuclei, a characteristic morphological change of apoptosis, was observed in RAW 264.7 cells by the treatment with n-BuOH fraction, compounds 3 and 4, respectively.

Neuregulin-1 (NRG1) signaling has multiple functions in neurons and glia. The data in this study show that NRG1 may also possess significant signaling and cytoprotective properties in human brain microvascular endothelial cells (BMECs). Neuregulin-1 mRNA and protein expression are present in these cells, and NRG1 receptors erbB2 and erbB3 are phosphorylated in response to NRG1. Neuregulin-1 triggers clear biologic responses in BMECs--elevated phospho-Akt levels, increased ring formation in a Matrigel assay, and decreased cell death after oxidative injury with H(2)O(2). These data suggest that NRG1 signaling is functional and cytoprotective in BMECs.

Effect of envenomation of ectoparasitoid Bracon hebetor was determined on the heart rate and the expression of shsp, hsc70 and hsp90 of the lepidopteran host Plodia interpunctella. Envenomated host larvae were promptly immobilized but heart rate was not changed until 4 days after envenomation. Northern hybridization showed that each hsp gene was differentially influenced by envenomation: continued high induction of shsp, gradual strong induction of hsc70, but no induction of hsp90. Our results suggest that upregulation of both shsp and hsc70 may produce potent factors that have important roles in the mechanism of host-parasitoid relationship.

Despite numerous studies showing neurotrophic and neuroprotective effects of estrogen in animal models, the long-term effects of estrogen use on brain morphology in older women are not known. Thus, we compared ventricular, cerebrospinal fluid, white matter, and grey matter volumes estimated from magnetic resonance images of postmenopausal women with more than 20 years exposure to unopposed estrogen, women who were not on estrogen, and young healthy women. Estrogen users had significantly smaller ventricles and greater white matter volumes than non-users, but hormone exposure did not affect grey matter volumes. Young healthy women had significantly smaller ventricles, less cerebrospinal fluid and more grey matter than both groups of older women. However, they had comparable white matter volumes to older women on estrogen. These findings suggest that long-term estrogen protects against white matter loss in aging. This adds to findings from other studies suggesting estrogen is neuroprotective of the hippocampus and other regions in older women.

The cDNA sequence of the Japanese flounder (Paralychthys olivaceus) IgD has been previously reported (GenBank accession no. AB052658) and this was followed by the detection of IgD mRNA expression in some flounder organ tissues. However, it has not been determined whether the flounder IgD gene is virtually expressed into IgD protein. To characterize the flounder immunoglobulins utilized in elucidating the mechanism, evolution and diversity of the flounder immune system, antibodies specific to IgD and IgM were necessary. In the present study, partial flounder recombinant IgD (rIgD), IgM (rIgM) and the conserved regions of IgD and IgM (rCIg) were produced by cloning the cDNA sequence using isotype specific primers which were designed to produce unique fragments of IgD and IgM specific amino acid sequences. The production of recombinant Igs was ascertained by SDS-gel electrophoresis and immunoblot analysis using anti-T7 d Taq antibody. The produced recombinant Igs were purified using affinity columns, and used as immunogens. Antibodies specific to the isotype of flounder Igs were generated by immunizing rabbits with rfIgs and the antibodies produced were identified by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Specificities of the generated antibodies were evaluated by testing cross-reactivity between recombinant IgM and IgD. By ELISA, rabbit antibodies against the rfIgD fragment (anti-rfIgD) failed to recognize any kind of flounder serum Igs, whereas respective antibodies against rfCIg (anti-rfCIg) and rfIgM fragments (anti-rfIgM) reacted with serum Igs. Likewise, in immunoblot assays, though anti-rfIgD did not, both anti-rfCIg and anti-rfIgM bound with the ~85 kd flounder IgM heavy chain. By flow cytometry analysis, anti-rfCIg, anti-rfIgD and anti-rfIgM reacted with 6%, 3% and 6.5% of cells, respectively, suggesting that flounder IgD is not secreted in serum but expressed on flounder B-like cell surfaces as in mammals. Antibodies produced against recombinant flounder Igs could be used to develop sandwich assay systems for detecting flounder Igs and for further investigating the flounder immune system.

We isolated a heat shock cognate 70 (hsc70) gene from the two-spotted spider mite, Tetranychus urticae, a serious agricultural pest. The hsc70 cDNA is 2275 bp and contains a 1962 bp open reading frame. The translated amino acid sequence consists of 654 residues with a calculated molecular mass of 71,275 Da and an isoelectronic point (pI) of 5.52. It also contains the highly conserved functional motifs of the Hsp70 family. A comparison of the deduced amino acid sequence shows a high identity (81-84%) with Hsp70s/Hsc70s of insects but the highest identity is with mussel Hsc71 (86%). Northern blot hybridization indicates that the hsc70 transcript level of female adults is higher than that of male adults. We evaluated the response of hsc70 gene to stresses from temperature and starvation. The level of hsc70 mRNA was not significantly changed by heat and cold shocks nor by recovery after the shocks. However, the hsc70 mRNA level was decreased by food restriction of female mites. Analysis of nucleotide and deduced amino acid sequences of hsc70 gene from T. urticae suggests that it is a member of heat shock cognate 70 gene in the highly conserved Hsp70 family but that its expression is influenced by food restriction rather than thermal stress. This is the first molecular analysis of a heat shock protein gene in an acarid.