[Predictive value of CONUT score and dialysis age for peritoneal dialysis-associated peritonitis].

Objective: To explore the predictive value of controlling nutritional status (CONUT) score and dialysis age for peritoneal dialysis-associated peritonitis (PDAP). Methods: This study was a follow-up study. Patients with end-stage renal disease who received peritoneal dialysis (PD) for the first time in the Department of Nephrology, the Third Affiliated Hospital of Suzhou University from January 2010 to December 2020 were enrolled in the study. Patients were divided into non-peritonitis group, mono group (only once PDAP occurred in one year) and frequent group (twice or more PDAP occurred in one year) according to the occurrence and frequency of PDAP during follow-up. The demographic, clinical and laboratory data of patients were collected, and the body mass index and CONUT score were recorded after half a year. Cox regression analysis was used to screen the relevant factors, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of CONUT score and dialysis age for PDAP. Results: A total of 324 PD patients were included, with 188 males (58.0%) and 136 females (42.0%), and aged［M（Q1，Q3）］48 (37, 60) years old. The follow-up time was 33 (19, 56) months. PDAP occurred in 112 patients (34.6%), including 63 patients (19.4%) in mono group and 49 patients (15.1%) in frequent group. Multivariate Cox regression analysis showed that half-year CONUT score (HR=1.159, 95%CI: 1.047-1.283, P=0.004) was a risk factor for PDAP, and the baseline CONUT score (HR=1.194, 95%CI: 1.012-1.408, P=0.036) was a risk factor for frequent peritonitis. The area under ROC curve of baseline CONUT score combined with dialysis age in predicting PDAP and frequent peritonitis was 0.682 (95%CI: 0.628-0.733) and 0.676 (95%CI: 0.622-0.727), respectively. Conclusion: CONUT score and dialysis age have certain predictive value for PDAP, and the predictive value of combined diagnosis is higher, which may be used as a potential predictor for PDAP in PD patients.

Acute Bronchitis and Bronchiolitis Infection in Children with Asthma and Allergic Rhinitis: A Retrospective Cohort Study Based on 5,027,486 Children in Taiwan.

This study evaluated the risks of childhood acute bronchitis and bronchiolitis (CABs) for children with asthma or allergic rhinitis (AR). Using insurance claims data of Taiwan, we identified, from children of ≤12 years old in 2000-2016, cohorts with and without asthma (N = 192,126, each) and cohorts with and without AR (N = 1,062,903, each) matched by sex and age. By the end of 2016, the asthma cohort had the highest bronchitis incidence, AR and non-asthma cohorts followed, and the lowest in the non-AR cohort (525.1, 322.4, 236.0 and 169.9 per 1000 person-years, respectively). The Cox method estimated adjusted hazard ratios (aHRs) of bronchitis were 1.82 (95% confidence interval (CI), 1.80-1.83) for the asthma cohort and 1.68 (95% CI, 1.68-1.69) for the AR cohort, relative to the respective comparisons. The bronchiolitis incidence rates for these cohorts were 42.7, 29.5, 28.5 and 20.1 per 1000 person-years, respectively. The aHRs of bronchiolitis were 1.50 (95% CI, 1.48-1.52) for the asthma cohort and 1.46 (95% CI, 1.45-1.47) for the AR cohort relative to their comparisons. The CABs incidence rates decreased substantially with increasing age, but were relatively similar for boys and girls. In conclusion, children with asthma are more likely to develop CABs than are children with AR.

Roles of Ambient Temperature and PM2.5 on Childhood Acute Bronchitis and Bronchiolitis from Viral Infection.

Studies have associated the human respiratory syncytial virus which causes seasonal childhood acute bronchitis and bronchiolitis (CABs) with climate change and air pollution. We investigated this association using the insurance claims data of 3,965,560 children aged ≤ 12 years from Taiwan from 2006−2016. The monthly average incident CABs increased with increasing PM2.5 levels and exhibited an inverse association with temperature. The incidence was 1.6-fold greater in January than in July (13.7/100 versus 8.81/100), declined during winter breaks (February) and summer breaks (June−August). The highest incidence was 698 cases/day at <20 °C with PM2.5 > 37.0 µg/m3, with an adjusted relative risk (aRR) of 1.01 (95% confidence interval [CI] = 0.97−1.04) compared to 568 cases/day at <20 °C with PM2.5 < 15.0 µg/m3 (reference). The incidence at ≥30 °C decreased to 536 cases/day (aRR = 0.95, 95% CI = 0.85−1.06) with PM2.5 > 37.0 µg/m3 and decreased further to 392 cases/day (aRR = 0.61, 95% CI = 0.58−0.65) when PM2.5 was <15.0 µg/m3. In conclusion, CABs infections in children were associated with lowered ambient temperatures and elevated PM2.5 concentrations, and the high PM2.5 levels coincided with low temperature levels. The role of temperature should be considered in the studies of association between PM2.5 and CABs.

A cohort study evaluating the risk of stroke associated with long-term exposure to ambient fine particulate matter in Taiwan.

BACKGROUND: Evidences have shown that the stroke risk associated with long-term exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) varies among people in North America, Europe and Asia, but studies in Asia rarely evaluated the association by stroke type. We examined whether long-term exposure to PM2.5 is associated with developing all strokes, ischemic stroke and hemorrhagic stroke. METHODS: The retrospective cohort study consisted of 1,362,284 adults identified from beneficiaries of a universal health insurance program in 2011. We obtained data on air pollutants and meteorological measurements from air quality monitoring stations across Taiwan in 2010-2015. Annual mean levels of all environmental measurements in residing areas were calculated and assigned to cohort members. We used Cox proportional hazards models to estimate hazard ratio (HR) and 95% confidence interval (CI) of developing stroke associated with 1-year mean levels of PM2.5 at baseline in 2010, and yearly mean levels from 2010 to 2015 as the time-varying exposure, adjusting for age, sex, income and urbanization level. RESULTS: During a median follow-up time of 6.0 years, 12,942 persons developed strokes, 9919 (76.6%) were ischemic. The adjusted HRs (95% CIs) per interquartile range increase in baseline 1-year mean PM2.5 were 1.03 (1.00-1.06) for all stroke, 1.06 (1.02-1.09) for ischemic stroke, and 0.95 (0.89-1.10) for hemorrhagic stroke. The concentration-response curves estimated in the models with and without additional adjustments for other environmental measurements showed a positively linear association between baseline 1-year mean PM2.5 and ischemic stroke at concentrations greater than 30 µg/m3, under which no evidence of association was observed. There was an indication of an inverse association between PM2.5 and hemorrhagic stroke, but the association no longer existed after controlling for nitrogen dioxide or ozone. We found similar shape of the concentration-response association in the Cox regression models with time-varying PM2.5 exposures. CONCLUSION: Long-term exposure to PM2.5 might be associated with increased risk of developing ischemic stroke. The association with high PM2.5 concentrations remained significant after adjustment for other environmental factors.

Epidemiology and Factors Affecting Functional Outcome of Distal Radial Fracture in an Urban Tertiary Medical Centre in Malaysia.

INTRODUCTION: Distal radial fracture is a commonly encountered fracture. This study aims to study the epidemiology of distal radial fracture and factors affecting the patients' functional outcome one to two years after the injury. MATERIALS AND METHODS: This is a retrospective cohort study. The records of patients, fulfilling the radiographical diagnosis of distal radial fracture, and aged 18 and above, who presented to our Emergency Department from 1st January 2018 to 31st December 2018 were retrieved. According to AO classification, we grouped our patients into A (extra-articular), B (partial articular) and C (complete articular). Patients with congenital abnormalities were excluded. Epidemiological data and relevant medical history were obtained and tabulated. A Malaysian language translation of Disability of the Arm, Shoulder and Hand (DASH) questionnaire was used to assess the functional outcome. RESULTS: Out of 168 patients' data retrieved, only 110 patients' data were found complete for purposes of this study. The mean DASH score was 13.7 ± 7.87 approximately one to two years post-injury regardless of treatment method. Increasing age was associated with higher DASH score with r=0.407(p<0.001). Several variables had significantly better functional outcome: male gender (p=0.01), Type A fracture configuration (p=0.007) and non-operational treatment (p=0.03). There was no significant difference between treatment modalities in Type A fracture (p=0.094), but Type B (p=0.043) and Type C (p=0.007) had better outcome without surgery. There was no significant difference between different ethnic groups, open or closed fracture and mechanism of injury. CONCLUSION: Better functional outcome after sustaining distal radial fracture was associated with young age, male gender, type A fracture and treated non-operatively. Interestingly, more complex fracture pattern had better functionality were observed without surgery.

Childhood Rotavirus Infection Associated with Temperature and Particulate Matter 2.5 µm: A Retrospective Cohort Study.

No study has ever investigated how ambient temperature and PM2.5 mediate rotavirus infection (RvI) in children. We used insurance claims data from Taiwan in 2006-2012 to evaluate the RvI characteristics in children aged ≤ 9. The RvI incidence rates were higher in colder months, reaching the highest in March (117.0/100 days), and then declining to the lowest in July (29.2/100 days). The age-sex-specific average incident cases were all higher in boys than in girls. Stratified analysis by temperature (<20, 20-24, and ≥25 °C) and PM2.5 (<17.5, 17.5-31.4, 31.5-41.9, and ≥42.0 µg/m3) showed that the highest incidence was 16.4/100 days at average temperatures of <20 °C and PM2.5 of 31.5-41.9 µg/m3, with Poisson regression analysis estimating an adjusted relative risk (aRR) of 1.26 (95% confidence interval (CI) = 1.11-1.43), compared to the incidence at the reference condition (<20 °C and PM2.5 < 17.5 µg/m3). As the temperature increased, the incident RvI cases reduced to 4.84 cases/100 days (aRR = 0.40, 95% CI = 0.35-0.45) when it was >25 °C with PM2.5 < 17.5 µg/m3, or to 9.84/100 days (aRR = 0.81, 95% CI = 0.77-0.93) when it was >25 °C with PM2.5 > 42 µg/m3. The seasonal RvI is associated with frequent indoor personal contact among children in the cold months. The association with PM2.5 could be an alternative assessment due to temperature inversion.

Differential diagnosis between acinic cell carcinoma and pleomorphic adenoma using the quantitative parameters of contrast-enhanced ultrasound.

OBJECTIVE: To investigate the value of differential diagnosis between acinic cell carcinoma (ACC) and pleomorphic adenoma (PA) using the quantitative parameters of contrast-enhanced ultrasound (CEUS). PATIENTS AND METHODS: Twenty-two ACC and 98 PA were retrospectively analyzed. These patients had been examined via routine pre-surgical two-dimensional ultrasound and CEUS. The examination results were confirmed by biopsy pathology. Qontrast 4.0 imaging analysis software was applied to obtain the maximum intensity (PEAK), time to peak (TTP), regional blood volume (RBV), regional blood flow (RBF), maximum signal intensity (SImax) and mean signal intensity (SImean) through quantitative analysis. The differences between ACC and PA were compared regarding the conventional ultrasound images and the quantitative parameters of CEUS. ROC curves were drawn to evaluate the diagnostic value of these parameters. RESULTS: There were no statistically significant differences between salivary gland ACC and PA in the manifestations of conventional two-dimensional ultrasound examination regarding morphology, internal echo and the boundary (p > 0.05). However, there were significant differences in PEAK, RBV, RBF, SImax and SImean between ACC and PA (p < 0.05). Additionally, the five quantitative parameters of CEUS were all highly accurate diagnostic indicators. The maximum area under the curve of each parameter was 0.888, sensitivity 72.6%, specificity 90.9% and accuracy 81.8%. CONCLUSIONS: The quantitative parameters of CEUS are helpful for differentially diagnosing salivary ACC and PA.

An effective CTL peptide vaccine for Ebola Zaire Based on Survivors' CD8+ targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design.

The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple Class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.

Creation and annihilation of topological meron pairs in in-plane magnetized films.

Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in chiral magnet Co8Zn9Mn3 raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction.

Interleukin (IL)-8 and IL-36γ but not IL-36Ra are related to acrosyringia in pustule formation associated with palmoplantar pustulosis.

BACKGROUND: Palmoplantar pustulosis (PPP) is a refractory, nonbacterial impetigo confined to the palms and soles. Its pathogenesis is still obscure, but it may be associated with the large eccrine sweat glands and pores of palmoplantar skin. PPP is considered to be a localized pustular psoriasis. Interleukin (IL)-8, IL-36γ and IL-36Ra play important roles in the pathogenesis of pustular psoriasis, but their role in PPP is unclear. AIM: To evaluate IL-8, IL-36γ and IL-36Ra expression in PPP, and their relationship with acrosyringia and pustule formation. METHODS: mRNA expression was quantified in skin samples from patients with PPP (n = 7), patients with psoriasis vulgaris (PSV; n = 8) and healthy controls (HCs) (n = 6) by reverse-transcription-real-time PCR. Protein expression was characterized by immunohistochemistry (PPP, n = 17; PSV, n = 14; HCs, n = 12). Sweat ducts, including acrosyringia, were stained for epithelial membrane antigen (EMA). RESULTS: IL-8 mRNA and protein were markedly increased in PPP lesions compared with PSV lesions or HC skin. IL-36γ mRNA and protein were significantly more abundant in PPP lesions than in HC skin. IL-36Ra mRNA was significantly overexpressed in PPP lesions compared with HC skin, but there was no difference in IL-36Ra protein between PPP, PSV and HCs. IL-8 was abundantly expressed by neutrophils in PPP pustules, while IL36Ra was localized in the keratinocytes of PPP, PSV and HC skin. IL-36γ and EMA were colocalized in cells surrounding PPP pustules, and IL-36γ was also expressed in sweat duct cells in the dermis. CONCLUSION: IL-8, IL-36γ and IL-36Ra are overexpressed in PPP lesions. IL-8, IL-36γ and acrosyringia, rather than IL-36Ra, are associated with pustule formation in PPP.

Extraction of the Landau-Migdal Parameter from the Gamow-Teller Giant Resonance in

The key parameter to discuss the possibility of the pion condensation in nuclear matter, i.e., the so-called Landau-Migdal parameter g^{'}, was extracted by measuring the double-differential cross sections for the (p,n) reaction at 216 MeV/u on a neutron-rich doubly magic unstable nucleus, ^{132}Sn with the quality comparable to data taken with stable nuclei. The extracted strengths for Gamow-Teller (GT) transitions from ^{132}Sn leading to ^{132}Sb exhibit the GT giant resonance (GTR) at the excitation energy of 16.3±0.4(stat)±0.4(syst) MeV with the width of Γ=4.7±0.8 MeV. The integrated GT strength up to E_{x}=25 MeV is S_{GT}^{-}=53±5(stat)_{-10}^{+11}(syst), corresponding to 56% of Ikeda's sum rule of 3(N-Z)=96. The present result accurately constrains the Landau-Migdal parameter as g^{'}=0.68±0.07, thanks to the high sensitivity of the GTR energy to g^{'}. In combination with previous studies on the GTR for ^{90}Zr and ^{208}Pb, the result of this work shows the constancy of this parameter in the nuclear chart region with (N-Z)/A=0.11 to 0.24 and A=90 to 208.

Feasibility of using urinary TDGA as a biomarker for VCM exposures.

Thiodiglycolic acid (TDGA) is a major metabolite of vinyl chloride monomer (VCM), and it has been suggested as an exposure biomarker for VCM. The validity of this biomarker when the level of VCM is less than 5 ppm, however, is questionable. The objective of this article is to evaluate the feasibility of using urinary TDGA as a biomarker of VCM exposure in a community health risk assessment setting where the concentration of VCM in air is typically very low (likely below 1 ppm). To achieve this objective, we examine the fraction of urinary TDGA associated with different levels of VCM exposures of three studies from different countries, using estimations of the TDGA metabolite predicted by a PBPK model. It is demonstrated that differences in background TDGA have considerable effect on the adequacy of TDGA as a biomarker of VCM. We conclude that, in a community health assessment setting, TDGA should not be used as an exposure biomarker for VCM without having a proper control group, and a PBPK model can be used first to determine whether or not the amount of TDGA in urine is of concern.

Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.

Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity phosphatase family. Deregulation of VHR is observed in various malignant diseases. We identified focal adhesion kinase (FAK) as a VHR-interacting molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did not have obvious abnormality; however, VHR-knockout cells showed decreased expression of integrins and FAK but stronger FAK and paxillin phosphorylation upon attachment to fibronectin. Additionally, VHR-knockout fibroblast and lung epithelial cells had elevated ligand-induced epidermal growth factor receptor (EGFR) phosphorylation. Inducible expression of VHR suppressed directional cell migration, and VHR deficiency resulted in a higher cell migratory ability. VHR-knockout cells have stronger FAK phosphorylation in cell adhesions, long-lasting trailing ends and slower turnover of focal adhesions. These collective data indicate that VHR is a FAK phosphatase and participates in regulating the formation and disassembly of focal adhesions.

An innovative SNP genotyping method adapting to multiple platforms and throughputs.

KEY MESSAGE: An innovative genotyping method designated as semi-thermal asymmetric reverse PCR (STARP) was developed for genotyping individual SNPs with improved accuracy, flexible throughputs, low operational costs, and high platform compatibility. Multiplex chip-based technology for genome-scale genotyping of single nucleotide polymorphisms (SNPs) has made great progress in the past two decades. However, PCR-based genotyping of individual SNPs still remains problematic in accuracy, throughput, simplicity, and/or operational costs as well as the compatibility with multiple platforms. Here, we report a novel SNP genotyping method designated semi-thermal asymmetric reverse PCR (STARP). In this method, genotyping assay was performed under unique PCR conditions using two universal priming element-adjustable primers (PEA-primers) and one group of three locus-specific primers: two asymmetrically modified allele-specific primers (AMAS-primers) and their common reverse primer. The two AMAS-primers each were substituted one base in different positions at their 3' regions to significantly increase the amplification specificity of the two alleles and tailed at 5' ends to provide priming sites for PEA-primers. The two PEA-primers were developed for common use in all genotyping assays to stringently target the PCR fragments generated by the two AMAS-primers with similar PCR efficiencies and for flexible detection using either gel-free fluorescence signals or gel-based size separation. The state-of-the-art primer design and unique PCR conditions endowed STARP with all the major advantages of high accuracy, flexible throughputs, simple assay design, low operational costs, and platform compatibility. In addition to SNPs, STARP can also be employed in genotyping of indels (insertion-deletion polymorphisms). As vast variations in DNA sequences are being unearthed by many genome sequencing projects and genotyping by sequencing, STARP will have wide applications across all biological organisms in agriculture, medicine, and forensics.

Phosphorylation of glycogen synthase kinase-3ß in metabolically abnormal obesity affects immune stimulation-induced cytokine production.

BACKGROUND: Obesity is a severe health problem worldwide, which leads to multiple comorbidities including type 2 diabetes mellitus and cardiovascular diseases. Inflammation has been found to be an important characteristic of adipose tissue in obese subjects. However, obesity is also associated with compromised immune responses to infections and the impact of obesity on immune function has not been fully understood. SUBJECTS/METHODS: To clarify the role of obesity in the immune responses, we investigated the Toll-like receptor (TLR)-induced cytokine secretion by leukocytes from obese and lean subjects. We also investigated the relationship between insulin-induced intracellular signaling and cytokine production using peripheral blood mononuclear cells (PBMCs) and a monocytic cell line THP-1. RESULTS: We found decreased TLR-induced interferon-γ, interleukin-6 (IL-6) and tumor necrosis factor-α secretions and elevated IL-10 secretion by leukocytes from obese subjects when compared with lean controls. PBMCs from obese subjects showed enhanced basal Akt and glycogen synthase kinase-3ß (GSK-3ß) phosphorylation, which did not further increase with insulin and lipopolysaccharide (LPS) stimulation. We also found that LPS-induced IκBα degradation was inhibited in PBMCs from obese subjects. By using THP-1 cells with GSK-3ß knockdown or cells treated with hyperinsulinemic and high-fatty acid conditions, we found that LPS-induced nuclear factor κB (NF-κB) activation was inhibited and cyclic adenosine monophosphate response element-binding protein (CREB) activation was enhanced. CONCLUSIONS: These findings indicate that GSK-3ß is important in the regulation of NF-κB and CREB activation in leukocytes under the metabolic condition of obesity. Our study revealed a key mechanism through which metabolic abnormalities compromise leukocyte functions in people with obesity.

Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis.

BACKGROUND AND PURPOSE: Cardiolipin plays an important role in mitochondrial respiration and cardiolipin peroxidation is associated with age-related diseases. Hydrophobic interactions between cytochrome c and cardiolipin converts cytochrome c from an electron carrier to a peroxidase. In addition to cardiolipin peroxidation, this impedes electron flux and inhibits mitochondrial ATP synthesis. SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH2 ) selectively binds to cardiolipin and inhibits cytochrome c peroxidase activity. Here, we examined whether SS-31 also protected the electron carrier function of cytochrome c. EXPERIMENTAL APPROACH: Interactions of SS-31 with cardiolipin were studied using liposomes and bicelles containing phosphatidylcholine alone or with cardiolipin. Structural interactions were assessed by fluorescence spectroscopy, turbidity and nuclear magnetic resonance. Effects of cardiolipin on electron transfer kinetics of cytochrome c were determined by cytochrome c reduction in vitro and oxygen consumption using mitoplasts, frozen and fresh mitochondria. KEY RESULTS: SS-31 interacted only with liposomes and bicelles containing cardiolipin in about 1:1 ratio. NMR studies demonstrated that the aromatic residues of SS-31 penetrated deep into cardiolipin-containing bilayers. SS-31 restored cytochrome c reduction and mitochondrial oxygen consumption in the presence of added cardiolipin. In fresh mitochondria, SS-31 increased state 3 respiration and efficiency of ATP synthesis. CONCLUSIONS AND IMPLICATIONS: SS-31 selectively targeted cardiolipin and modulated its interaction with cytochrome c. SS-31 inhibited the cytochrome c/cardiolipin complex peroxidase activity while protecting its ability to serve as an electron carrier, thus optimizing mitochondrial electron transport and ATP synthesis. This novel class of cardiolipin therapeutics has the potential to restore mitochondrial bioenergetics for treatment of numerous age-related diseases.