Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity.

Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of difficult-to-treat, often fatal infections in humans1,2. Most humans have antibodies against S. aureus, but these are highly variable and often not protective in immunocompromised patients3. Previous vaccine development programs have not been successful4. A large percentage of human antibodies against S. aureus target wall teichoic acid (WTA), a ribitol-phosphate (RboP) surface polymer modified with N-acetylglucosamine (GlcNAc)5,6. It is currently unknown whether the immune evasion capacities of MRSA are due to variation of dominant surface epitopes such as those associated with WTA. Here we show that a considerable proportion of the prominent healthcare-associated and livestock-associated MRSA clones CC5 and CC398, respectively, contain prophages that encode an alternative WTA glycosyltransferase. This enzyme, TarP, transfers GlcNAc to a different hydroxyl group of the WTA RboP than the standard enzyme TarS7, with important consequences for immune recognition. TarP-glycosylated WTA elicits 7.5-40-fold lower levels of immunoglobulin G in mice than TarS-modified WTA. Consistent with this, human sera contained only low levels of antibodies against TarP-modified WTA. Notably, mice immunized with TarS-modified WTA were not protected against infection with tarP-expressing MRSA, indicating that TarP is crucial for the capacity of S. aureus to evade host defences. High-resolution structural analyses of TarP bound to WTA components and uridine diphosphate GlcNAc (UDP-GlcNAc) explain the mechanism of altered RboP glycosylation and form a template for targeted inhibition of TarP. Our study reveals an immune evasion strategy of S. aureus based on averting the immunogenicity of its dominant glycoantigen WTA. These results will help with the identification of invariant S. aureus vaccine antigens and may enable the development of TarP inhibitors as a new strategy for rendering MRSA susceptible to human host defences.

Prognostic Implication of Platelet Reactivity According to Left Ventricular Systolic Dysfunction Status in Patients Treated With Drug-Eluting Stent Implantation: Analysis of the PTRG-DES Consortium.

BACKGROUND: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated. METHODS: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3-5. RESULTS: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85-2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39-2.78). The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group, P < 0.01, 95% CI 2.51-3.91). The frequency of major bleeding was not associated with the HPR in either group. CONCLUSION: LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734028.

Congruency and its related factors between patients' fall risk perception and nurses' fall risk assessment in acute care hospitals.

INTRODUCTION: Inpatients need to recognize their fall risk accurately and objectively. Nurses need to assess how patients perceive their fall risk and identify the factors that influence patients' fall risk perception. PURPOSE: This study aims to explore the congruency between nurses' fall risk assessment and patients' perception of fall risk and identify factors related to the non-congruency of fall risk. DESIGNS: A descriptive and cross-sectional design was used. The study enrolled 386 patients who were admitted to an acute care hospital. Six nurses assessed the participants' fall risk. Congruency was classified using the Morse Fall Scale for nurses and the Fall Risk Perception Questionnaire for patients. FINDINGS: The nurses' fall risk assessments and patients' fall risk perceptions were congruent in 57% of the participants. Underestimation of the patient's risk of falling was associated with gender (women), long hospitalization period, department (orthopedics), low fall efficacy, and history of falls before hospitalization. Overestimation of fall risk was associated with age group, gender (men), department, and a high health literacy score. In the multiple logistic regression, the factors related to the underestimation of fall risk were hospitalization period and department, and the factors related to the overestimation of fall risk were health literacy and department. CONCLUSIONS: Nurses should consider the patient's perception of fall risk and incorporate it into fall prevention interventions. CLINICAL RELEVANCE: Nurses need to evaluate whether patients perceive the risk of falling consistently. For patients who underestimate or overestimate their fall risk, it may be helpful to consider clinical and fall-related characteristics together when evaluating their perception of fall risk.

Association between toothbrushing and cardiovascular risk factors: a cross-sectional study using Korean National Health and Nutrition Examination Survey 2015-2017.

BACKGROUND: Previous studies have suggested that frequent toothbrushing is associated with a lower risk of future cardiovascular events. We sought to investigate further the relationship between toothbrushing, cardiovascular risk factors, and lifestyle behaviours. METHODS: We analysed a cross-sectional survey including 13,761 adults aged 30 years or older without a history of cardiovascular diseases from the Korean National Health and Nutritional Examination Survey. Conventional cardiovascular risk factors (blood pressure, lipid profiles, and fasting glucose), and inflammatory markers (high-sensitivity C-reactive protein [hsCRP], and white blood cell counts [WBC]) were investigated in relation to the frequency of toothbrushing. RESULTS: The estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the pooled cohort equations was 13.7%, 9.1%, and 7.3% for participants who reported toothbrushing 0-1, 2, and ≥ 3 times a day, respectively. Both conventional risk factors and inflammatory markers were significantly associated with frequent toothbrushing. However, after adjusting potential confounding factors such as age, sex, comorbidities, and lifestyle behaviours, only inflammatory markers were remained as significant factors. CONCLUSIONS: Oral hygiene behaviours are closely linked to cardiovascular risk factors. This study suggests that reduced systemic inflammatory burden may explain the benefit of improved oral hygiene in terms of cardiovascular risk.

Diagnostic Value of a Wearable Continuous Electrocardiogram Monitoring Device (AT-Patch) for New-Onset Atrial Fibrillation in High-Risk Patients: Prospective Cohort Study.

BACKGROUND: While conventional electrocardiogram monitoring devices are useful for detecting atrial fibrillation, they have considerable drawbacks, including a short monitoring duration and invasive device implantation. The use of patch-type devices circumvents these drawbacks and has shown comparable diagnostic capability for the early detection of atrial fibrillation. OBJECTIVE: We aimed to determine whether a patch-type device (AT-Patch) applied to patients with a high risk of new-onset atrial fibrillation defined by the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, sex scale (CHA2DS2-VASc) score had increased detection rates. METHODS: In this nonrandomized multicenter prospective cohort study, we enrolled 320 adults aged ≥19 years who had never experienced atrial fibrillation and whose CHA2DS2-VASc score was ≥2. The AT-Patch was attached to each individual for 11 days, and the data were analyzed for arrhythmic events by 2 independent cardiologists. RESULTS: Atrial fibrillation was detected by the AT-Patch in 3.4% (11/320) of patients, as diagnosed by both cardiologists. Interestingly, when participants with or without atrial fibrillation were compared, a previous history of heart failure was significantly more common in the atrial fibrillation group (n=4/11, 36.4% vs n=16/309, 5.2%, respectively; P=.003). When a CHA2DS2-VASc score ≥4 was combined with previous heart failure, the detection rate was significantly increased to 24.4%. Comparison of the recorded electrocardiogram data revealed that supraventricular and ventricular ectopic rhythms were significantly more frequent in the new-onset atrial fibrillation group compared with nonatrial fibrillation group (3.4% vs 0.4%; P=.001 and 5.2% vs 1.2%; P<.001), respectively. CONCLUSIONS: This study detected a moderate number of new-onset atrial fibrillations in high-risk patients using the AT-Patch device. Further studies will aim to investigate the value of early detection of atrial fibrillation, particularly in patients with heart failure as a means of reducing adverse clinical outcomes of atrial fibrillation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04857268; https://classic.clinicaltrials.gov/ct2/show/NCT04857268.

Predictive Value of Electromechanical Window for Risk of Fatal Ventricular Arrhythmia.

BACKGROUND: As an indicator of electro-mechanical coupling, electromechanical window (EMW) can be used to predict fatal ventricular arrhythmias. We investigated the additive effect of EMW on the prediction of fatal ventricular arrhythmias in high-risk patients. METHODS: We included patients who had implantable cardioverter-defibrillator (ICD) implanted for primary or secondary prevention. The event group was defined as those who received an appropriate ICD therapy. We acquired echocardiograms at ICD implantation and follow-up. The EMW was calculated as the difference between the interval from QRS onset to aortic valve closure and QT interval from the electrocardiogram embedded in the continuous wave doppler image. We evaluated the predictive value of EMW for predicting fatal ventricular arrhythmia. RESULTS: Of 245 patients (67.2 ± 12.8 years, 63.7% men), the event group was 20.0%. EMW at baseline (EMW-Baseline) and follow-up (EMW-FU) was significantly different between event and control groups. After adjustment, both EMW-Baseline (odds ratio [OR]adjust 1.02 [1.01-1.03], P = 0.004) and EMW-FU (ORadjust 1.06 [1.04-1.07], P < 0.001) remained as significant predictors for fatal arrhythmic events. Adding EMW-Baseline significantly improved the discriminating ability of the multivariable model including clinical variables (area under the curve [AUC] 0.77 [0.70-0.84] vs. AUC 0.72 [0.64-0.80], P = 0.004), while a univariable model using EMW-FU alone showed the best performance among models (AUC 0.87 [0.81-0.94], P = 0.060 against model with clinical variables; P = 0.030 against model with clinical variables and EMW-Baseline). CONCLUSION: The EMW could effectively predict severe ventricular arrhythmia in ICD implanted patients. This finding supports the importance of incorporating the electro-mechanical coupling index into the clinical practice for predicting future fatal arrhythmia events.

Performance of a Novel CT-Derived Fractional Flow Reserve Measurement to Detect Hemodynamically Significant Coronary Stenosis.

BACKGROUND: Fractional flow reserve (FFR) based on computed tomography (CT) has been shown to better identify ischemia-causing coronary stenosis. However, this current technology requires high computational power, which inhibits its widespread implementation in clinical practice. This prospective, multicenter study aimed at validating the diagnostic performance of a novel simple CT based fractional flow reserve (CT-FFR) calculation method in patients with coronary artery disease. METHODS: Patients who underwent coronary CT angiography (CCTA) within 90 days and invasive coronary angiography (ICA) were prospectively enrolled. A hemodynamically significant lesion was defined as an FFR ≤ 0.80, and the area under the receiver operating characteristic curve (AUC) was the primary measure. After the planned analysis for the initial algorithm A, we performed another set of exploratory analyses for an improved algorithm B. RESULTS: Of 184 patients who agreed to participate in the study, 151 were finally analyzed. Hemodynamically significant lesions were observed in 79 patients (52.3%). The AUC was 0.71 (95% confidence interval [CI], 0.63-0.80) for CCTA, 0.65 (95% CI, 0.56-0.74) for CT-FFR algorithm A (P = 0.866), and 0.78 (95% CI, 0.70-0.86) for algorithm B (P = 0.112). Diagnostic accuracy was 0.63 (0.55-0.71) for CCTA alone, 0.66 (0.58-0.74) for algorithm A, and 0.76 (0.68-0.82) for algorithm B. CONCLUSION: This study suggests the feasibility of automated CT-FFR, which can be performed on-site within several hours. However, the diagnostic performance of the current algorithm does not meet the a priori criteria for superiority. Future research is required to improve the accuracy.

Bleeding risk in patients with atrial fibrillation treated with combined anti-platelet and non-vitamin K antagonist oral anticoagulant therapy.

BACKGROUND: The use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with non-valvular atrial fibrillation (AF) has been increasing. Accordingly, the combined use of antiplatelet agents (APT) and NOAC therapy is commonly encountered in clinical practice. The purpose of this study was to compare the clinical outcomes between combination therapy (NOAC and APT) vs. monotherapy (NOAC only) in patients with AF. METHODS: We retrospectively analyzed patients who were prescribed NOACs between January 2012 and December 2016. The primary outcome was major bleeding and any bleeding events, and the secondary outcomes were stroke/systemic embolic (SE) events and major adverse cardiac events (MACE). RESULTS: Of the 1068 participants, there were 264 (24.7%) patients in the combination therapy group. The prevalence of diabetes (p = 0.017) and history of stroke and transient ischemic attacks (p < 0.001) was higher in the combination group than in the monotherapy group. During the mean 14.6 ± 9.8 months of follow-up, the incidence of any bleeding was significantly higher in the combination therapy group than in the monotherapy group (p < 0.001). The rate of major bleeding, stroke/SE, and MACE between the two groups was similar. The rate of under-dosage NOAC prescriptions was higher in the combination therapy group than in the monotherapy group (p = 0.024). CONCLUSIONS: The combination therapy group had higher incidences of any bleeding events compared to the monotherapy in patients with appropriate dosing. However, there was no difference in stroke/SE, and MACE. The bleeding risk in AF patients taking the combination of NOACs and APT should be carefully evaluated.

The contribution of transcription factor IRF1 to the interferon-gamma-interleukin 12 signaling axis and TH1 versus TH-17 differentiation of CD4+ T cells.

Interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) drive T helper type 1 (T(H)1) differentiation, but the mechanisms underlying the regulation of the complicated gene networks involved in this differentiation are not fully understood. Here we show that the IFN-gamma-induced transcription factor IRF1 was essential in T(H)1 differentiation by acting on Il12rb1, the gene encoding the IL-12 receptor beta1 subunit (IL-12Rbeta1). IRF1 directly interacted with and activated the Il12rb1 promoter in CD4+ T cells. Notably, the IRF1-dependent induction of IL-12Rbeta1 was essential for IFN-gamma-IL-12 signaling but was dispensable for IL-23-IL-17 signaling. Because both IL-12 and IL-23 bind to and transmit signals through IL-12Rbeta1, our data suggest that distinct thresholds of IL-12Rbeta1 expression are required for T(H)1 versus T(H)-17 differentiation.

Cross-cultural regularities in the cognitive architecture of pride.

Pride occurs in every known culture, appears early in development, is reliably triggered by achievements and formidability, and causes a characteristic display that is recognized everywhere. Here, we evaluate the theory that pride evolved to guide decisions relevant to pursuing actions that enhance valuation and respect for a person in the minds of others. By hypothesis, pride is a neurocomputational program tailored by selection to orchestrate cognition and behavior in the service of: (i) motivating the cost-effective pursuit of courses of action that would increase others' valuations and respect of the individual, (ii) motivating the advertisement of acts or characteristics whose recognition by others would lead them to enhance their evaluations of the individual, and (iii) mobilizing the individual to take advantage of the resulting enhanced social landscape. To modulate how much to invest in actions that might lead to enhanced evaluations by others, the pride system must forecast the magnitude of the evaluations the action would evoke in the audience and calibrate its activation proportionally. We tested this prediction in 16 countries across 4 continents (n = 2,085), for 25 acts and traits. As predicted, the pride intensity for a given act or trait closely tracks the valuations of audiences, local (mean r = +0.82) and foreign (mean r = +0.75). This relationship is specific to pride and does not generalize to other positive emotions that coactivate with pride but lack its audience-recalibrating function.

Mortality reduction with physical activity in patients with and without cardiovascular disease.

AIMS: Physical activity has been shown to reduce mortality in a dose-response fashion. Current guidelines recommend 500-1000 metabolic equivalent task (MET)-min per week of regular physical activity. This study aimed to compare the impact of leisure-time physical activity on mortality in primary versus secondary cardiovascular prevention. METHODS AND RESULTS: This study included a total of 131 558 and 310 240 subjects with and without cardiovascular disease (CVD), respectively, from a population-based cohort. Leisure-time physical activity was measured by self-report questionnaires. The study subjects were followed-up for a median of 5.9 years, and the main study outcome was all-cause mortality. There was an inverse relationship between the physical activity level and the mortality risk in both groups. The benefit in the secondary prevention group was shown to be greater than that in the primary prevention group: every 500 MET-min/week increase in physical activity resulted in a 14% and 7% risk reduction in mortality in the secondary and primary prevention groups, respectively (interaction P < 0.001). In addition, while individuals without CVD benefited the most between 1 and 500 MET-min/week of physical activity, the benefit in those with CVD continued above 500 - 1000 MET-min/week. The adjusted mortality risk of individuals with CVD who performed a high level of physical activity (≥1000 MET-min/week) was shown to be comparable to or lower than that of their counterparts without CVD. CONCLUSION: Individuals with CVD may benefit from physical activity to a greater extent than do healthy subjects without CVD.

Reconsidering the cut-off diastolic blood pressure for predicting cardiovascular events: a nationwide population-based study from Korea.

AIMS: It is unclear whether a J-curve association exists in cardiovascular risk prediction and how independently systolic and diastolic blood pressure (BP) predict cardiovascular outcomes. This study evaluated the association of systolic and diastolic BP with major cardiovascular events to clarify these issues. METHODS AND RESULTS: Antihypertensive medication-naïve subjects with available BP measurements and no history of cardiovascular events were extracted from the National Health Insurance Services Health Screening Cohort. The study endpoint was a composite of cardiac death, myocardial infarction, stroke, and heart failure. The study population comprised 290 600 subjects (median follow-up duration 6.7 years). The risk for major cardiovascular events was lowest at systolic and diastolic BPs of 90-99 mmHg and 40-49 mmHg, respectively, above which BPs demonstrated a log-linear risk prediction. Systolic and diastolic BPs were highly correlated. The risk prediction of diastolic BP was inconsistent when stratified by systolic BP. A wider pulse pressure rather than a higher diastolic BP was significantly associated with cardiovascular outcomes among men aged ≥55 years. In addition, the difference between diastolic BPs of <80 mmHg and 80-89 mmHg mostly disappeared after statistical adjustment or stratification. CONCLUSION: Elevated BP is a strong predictor of future cardiovascular events including cardiac death, myocardial infarction, stroke, and heart failure. This study showed that the log-linear relationship between BP and cardiovascular events extended down to a BP of ≥90/40 mmHg. Although hypertension is defined using a lower systolic BP cut-off of ≥130 mmHg, the diastolic BP component of ≥80 mmHg seems disproportionately low.

Improved oral hygiene care attenuates the cardiovascular risk of oral health disease: a population-based study from Korea.

AIMS: Oral health problems such as periodontal disease, dental caries, and tooth loss have been suggested to have associations with cardiovascular disease. This study aimed to evaluate whether oral hygiene behaviour can alleviate cardiovascular risk associated with oral health status using a nationwide population-based cohort. METHODS AND RESULTS: The data of 247 696 healthy adults aged 40 years or older who underwent an oral health screening programme and had no history of major cardiovascular events were extracted from the National Health Insurance System-National Health Screening Cohort. After a median follow-up of 9.5 years, 14 893 major cardiovascular events occurred including cardiac death, myocardial infarction, stroke, and heart failure. The risk of cardiovascular events was higher when a subject had periodontal disease, a higher number of dental caries, or more tooth loss. Performing one more tooth brushing a day was associated with a 9% significantly lower risk of cardiovascular events after multivariable adjustment. Regular dental visits (once a year or more) for professional cleaning were also shown to reduce cardiovascular risk by 14%. Improved oral hygiene behaviours were shown to attenuate the cardiovascular risk originating from periodontal disease, dental caries, and tooth loss. CONCLUSION: Oral hygiene care such as frequent tooth brushing and regular dental visits for professional cleaning reduced the risk of future cardiovascular events in healthy adults. This study also suggests that improved oral hygiene behaviour may modify the association between oral health and cardiovascular diseases.

Sex Differences in Heart Failure Symptoms and Factors Associated With Heart Failure Symptoms.

BACKGROUND: A majority of patients with heart failure (HF) experience HF symptoms. Some literature suggests sex differences in the status of and also factors associated with HF symptoms. However, information on common HF symptom status and factors associated with HF symptoms in male and female patients is scarce. OBJECTIVES: The aim of this study was to examine HF symptom status and factors associated with HF symptoms in male and female patients with HF. METHODS: Descriptive data on HF symptoms, psychological factors (depressive symptoms and perceived control), sociodemographic factors (age and sex), clinical factors (body mass index, comorbidities, medication, and left ventricular ejection fraction), and a behavioral factor (self-care) were collected in 70 male and 49 female patients with HF. Mann-Whitney U tests, χ tests, and stepwise regression models were used to address the objectives. RESULTS: Fatigue was the most common HF symptom in both sexes, but male patients had less severe HF symptoms, including frequency, severity, and/or distress. In male patients, 2 psychological and 2 clinical factors (comorbidities and use of diuretics) were significantly associated with HF symptoms (adjusted R = 0.669, P < .001), whereas in female patients, only depressive symptoms were significantly associated with HF symptoms (adjusted R = 0.679, P < .001). DISCUSSION: There were sex differences in HF symptoms and the factors associated with HF symptoms. Clinicians and researchers need to recognize and manage psychological factors in both sexes and clinical factors in male patients by using effective interventions to improve HF symptoms.

Validation of the resilience scale for nurses (RSN).

AIM: The purpose of this study was to verify the validity and reliability of the resilience scale for nurses (RSN). METHODS: 27 preliminary items were extracted from previous research. The subjects were 339 nurses who worked at 2 hospitals in South Korea in 2016. Collected data were analyzed using explanatory factor analysis (EFA). EFA was performed with principal axis factoring with oblimin rotation and confirmatory factor analysis (CFA) with SPSS 25.0 and AMOS 25.0 version program. Also, data were examined by construct, discriminant, and convergent validity, and internal consistency reliability. RESULTS: Resilience scale for nurses showed CFA supported the four-factor structure (Philosophical pattern, Relational pattern, Dispositional pattern, and Situational pattern) of the measure. The 19 items for 4 factors identified that explained 67.329% of the total variance in RSN. A total the internal consistency reliability (Cronbach's α = 0.938) was stable. CONCLUSION: Psychometric properties of RSN show that it is a useful and reliable scale to assess Resilience in Korean nurses. Based on these results, effective resilience intervention programs for nurses can be developed.

A randomized clinical trial of therapeutic hypothermia mode during transport for neonatal encephalopathy.

OBJECTIVE: To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice. STUDY DESIGN: We performed a multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation. RESULTS: One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% [IQR 17-88] vs 0% [IQR 0-52], P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001). CONCLUSIONS: Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.

Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis.

Metastatic progression depends on genetic alterations intrinsic to cancer cells as well as the inflammatory microenvironment of advanced tumours. To understand how cancer cells affect the inflammatory microenvironment, we conducted a biochemical screen for macrophage-activating factors secreted by metastatic carcinomas. Here we show that, among the cell lines screened, Lewis lung carcinoma (LLC) were the most potent macrophage activators leading to production of interleukin-6 (IL-6) and tumour-necrosis factor-alpha (TNF-alpha) through activation of the Toll-like receptor (TLR) family members TLR2 and TLR6. Both TNF-alpha and TLR2 were found to be required for LLC metastasis. Biochemical purification of LLC-conditioned medium (LCM) led to identification of the extracellular matrix proteoglycan versican, which is upregulated in many human tumours including lung cancer, as a macrophage activator that acts through TLR2 and its co-receptors TLR6 and CD14. By activating TLR2:TLR6 complexes and inducing TNF-alpha secretion by myeloid cells, versican strongly enhances LLC metastatic growth. These results explain how advanced cancer cells usurp components of the host innate immune system, including bone-marrow-derived myeloid progenitors, to generate an inflammatory microenvironment hospitable for metastatic growth.

Clinical impact of capsulectomy during cardiac implantable electronic device generator replacement: a prospective randomized trial.

BACKGROUND: The avascular capsule around the generator of the cardiac implantable electronic device (CIED) could be susceptible to bacterial colonization and source of infection. Capsulectomy during CIED generator replacement may be beneficial in preventing device infection, but there is a lack of evidence. METHODS: This prospective randomized trial, conducted from December 2013 to December 2019, included 195 patients divided equally into two groups. In the intervention group (n = 97), capsule removal was performed on the floor of the pocket, while it was not performed in the control group (n = 98). In both groups, swab culture was performed in the pocket. The primary outcome was the occurrence of device infection requiring pocket revision. RESULTS: A total of 195 patients were included (mean age 70.2 ± 13.6 years, 55.4% women), with an average follow-up period of 54.3 ± 28.9 months. Among 182 patients undergoing microbiological cultures of pockets, 19 (10.4%) were confirmed positive, and Staphylococcus species were identified most frequently. The primary outcome occurred in 4 (2.1%), and there was no significant difference between the two groups (3.1% vs. 1.0%, p = 0.606). Hematoma has occurred in 10 patients (3.1% vs. 7.1%, p = 0.338), one of them required wound revision. In multivariable analysis, the occurrence of hematoma was the only independent risk factor associated with device infection (HR 13.6, 95% CI 1.02-181.15, p = 0.048). CONCLUSIONS: In this long-term prospective study, capsulectomy during the replacement of the generator did not reduce the incidence of device infection. There was no association between bacterial colonization in the capsule around the generator and CIED infection.

Psychometric Properties of the Fall Risk Perception Questionnaire-Short Version for Inpatients in Acute Care Hospitals.

PURPOSE: Patients' perception of fall risk is a promising new indicator for fall prevention. Therefore, a fall risk perception questionnaire that can be used rapidly and repeatedly in acute care settings is required. This study aimed to develop a short version of the fall risk perception questionnaire (Short-FRPQ) for inpatients. METHODS: For the psychometric measurements, 246 inpatients were recruited from an acute care hospital. The construct (using confirmatory factor analysis and discriminant validity of each item), convergent, and known-group validities were tested to determine the validity of the Short-FRPQ. McDonald's omega coefficient was used to examine the internal consistency of reliability. RESULTS: In the confirmatory factor analysis, the fit indices of the Short-FRPQ, comprising 14 items and three factors, appeared to be satisfactory. The Short-FRPQ had a significantly positive correlation with the original scale, the Korean Falls Efficacy Scale-International, and the Morse Fall Scale. The risk of falls group, assessed using the Morse Fall Scale, had a higher score on the Short-FRPQ. McDonald's omega coefficient was .90. CONCLUSION: The Short-FRPQ presents good reliability and validity. As patient participation is essential in fall interventions, evaluating the fall risk perception of inpatients quickly and repeatedly using scales of acceptable validity and reliability is necessary.

Diabetes Primes Neutrophils for Neutrophil Extracellular Trap Formation through Trained Immunity.

Neutrophils are primed for neutrophil extracellular trap (NET) formation during diabetes, and excessive NET formation from primed neutrophils compromises wound healing in patients with diabetes. Here, we demonstrate that trained immunity mediates diabetes-induced NET priming in neutrophils. Under diabetic conditions, neutrophils exhibit robust metabolic reprogramming comprising enhanced glycolysis via the pentose phosphate pathway and fatty acid oxidation, which result in the accumulation of acetyl-coenzyme A. Adenosine 5'-triphosphate-citrate lyase-mediated accumulation of acetyl-coenzyme A and histone acetyltransferases further induce the acetylation of lysine residues on histone 3 (AcH3K9, AcH3K14, and AcH3K27) and histone 4 (AcH4K8). The pharmacological inhibition of adenosine 5'-triphosphate-citrate lyase and histone acetyltransferases completely inhibited high-glucose-induced NET priming. The trained immunity of neutrophils was further confirmed in neutrophils isolated from patients with diabetes. Our findings suggest that trained immunity mediates functional changes in neutrophils in diabetic environments, and targeting neutrophil-trained immunity may be a potential therapeutic target for controlling inflammatory complications of diabetes.