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Venous thromboembolism (VTE) is commonly treated with oral anticoagulants, including warfarin or direct oral anticoagulants (DOACs). Although DOACs are associated with favorable treatment satisfaction, few studies have assessed whether quality of life differs between DOAC and warfarin users.We invited adults enrolled in two California-based integrated health care delivery systems and with a history of VTE between January 1, 2015 and June 30, 2018 to complete a survey on their experience with anticoagulants. Health-related quality of life (QOL) was assessed using the RAND 36-item Short Form Health Survey (SF-36), which measures QOL in 2 general component scores (physical and mental). We used multivariable linear regression to compare mean QOL component scores between DOAC-users and warfarin-users, adjusting for patient and clinical characteristics.Overall, 2230 patients (43.1 % women and 31.8 %75 years of age) taking anticoagulants answered at least 1 question on the SF-36, 975 taking DOACs and 1255 taking warfarin. After adjustment for patient-level factors, there were no significant differences in either physical component scores (39.2 v 38.3, p = 0.24) or mental component scores (48.5 v 49.0, p = 0.42) between DOAC and warfarin users.Health-related QOL did not significantly differ between DOAC and warfarin users with a history of VTE.

Aims This study aimed to develop and apply natural language processing (NLP) algorithms to identify recurrent atrial fibrillation (AF) episodes following rhythm control therapy initiation using electronic health records (EHRs). Methods and results We included adults with new-onset AF who initiated rhythm control therapies (ablation, cardioversion, or antiarrhythmic medication) within two US integrated healthcare delivery systems. A code-based algorithm identified potential AF recurrence using diagnosis and procedure codes. An automated NLP algorithm was developed and validated to capture AF recurrence from electrocardiograms, cardiac monitor reports, and clinical notes. Compared with the reference standard cases confirmed by physicians’ adjudication, the F-scores, sensitivity, and specificity were all above 0.90 for the NLP algorithms at both sites. We applied the NLP and code-based algorithms to patients with incident AF (n = 22 970) during the 12 months after initiating rhythm control therapy. Applying the NLP algorithms, the percentages of patients with AF recurrence for sites 1 and 2 were 60.7% and 69.9% (ablation), 64.5% and 73.7% (cardioversion), and 49.6% and 55.5% (antiarrhythmic medication), respectively. In comparison, the percentages of patients with code-identified AF recurrence for sites 1 and 2 were 20.2% and 23.7% for ablation, 25.6% and 28.4% for cardioversion, and 20.0% and 27.5% for antiarrhythmic medication, respectively. Conclusion When compared with a code-based approach alone, this study's high-performing automated NLP method identified significantly more patients with recurrent AF. The NLP algorithms could enable efficient evaluation of treatment effectiveness of AF therapies in large populations and help develop tailored interventions.

Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 1:1 match of incident AF: no AF by age at index date, sex, estimated glomerular filtration rate category, and study site. Subsequent dementia was identified through previously validated diagnosis codes. Fine‐Gray subdistribution hazard models were used to examine the association of incident AF (versus no AF) with risk of incident dementia, adjusting for sociodemographics and comorbidity and accounting for competing risk of death. Subgroup analyses by age, sex, race, ethnicity, and chronic kidney disease status were also performed. Among 196 968 matched adults, mean (SD) age was 73.6 (11.3) years, with 44.8% women, and 72.3% White. Incidence rates (per 100 person‐years) for dementia over a median follow‐up of 3.3 (interquartile range, 1.7–5.4) years were 2.79 (95% CI, 2.72–2.85) and 2.04 (95% CI, 1.99–2.08) per 100 person‐years in persons with versus without incident AF, respectively. In adjusted models, incident AF was associated with a significantly greater risk of diagnosed dementia (subdistribution hazard ratio [sHR], 1.13 [95% CI, 1.09–1.16]). With additional adjustment for interim stroke events, the association of incident AF with dementia remained statistically significant (sHR, 1.10 [95% CI, 1.07–1.15]). Associations were stronger for age P P Conclusions In a large, diverse community‐based cohort, incident AF was associated with a modestly increased risk of dementia that was more prominent in younger patients and those without chronic kidney disease but did not substantially vary across sex, race, or ethnicity. Further studies should delineate mechanisms underpinning these findings, which may inform use of AF therapies.

Background Limited existing data suggest that the novel COVID-19 may increase risk of VTE, but information from large, ethnically diverse populations with appropriate control participants is lacking. Research Question Does the rate of VTE among adults hospitalized with COVID-19 differ from matched hospitalized control participants without COVID-19? Study Design and Methods We conducted a retrospective study among hospitalized adults with laboratory-confirmed COVID-19 and hospitalized adults without evidence of COVID-19 matched for age, sex, race or ethnicity, acute illness severity, and month of hospitalization between January 2020 and August 2020 from two integrated health care delivery systems with 36 hospitals. Outcomes included VTE (DVT or pulmonary embolism ascertained using diagnosis codes combined with validated natural language processing algorithms applied to electronic health records) and death resulting from any cause at 30 days. Fine and Gray hazards regression was performed to evaluate the association of COVID-19 with VTE after accounting for competing risk of death and residual differences between groups, as well as to identify predictors of VTE in patients with COVID-19. Results We identified 6,319 adults with COVID-19 and 6,319 matched adults without COVID-19, with mean ± SD age of 60.0 ± 17.2 years, 46% women, 53.1% Hispanic, 14.6% Asian/Pacific Islander, and 10.3% Black. During 30-day follow-up, 313 validated cases of VTE (160 COVID-19, 153 control participants) and 1,172 deaths (817 in patients with COVID-19, 355 in control participants) occurred. Adults with COVID-19 showed a more than threefold adjusted risk of VTE (adjusted hazard ratio, 3.48; 95% CI, 2.03-5.98) compared with matched control participants. Predictors of VTE in patients with COVID-19 included age ≥ 55 years, Black race, prior VTE, diagnosed sepsis, prior moderate or severe liver disease, BMI ≥ 40 kg/m2, and platelet count > 217 k/μL. Interpretation Among ethnically diverse hospitalized adults, COVID-19 infection increased the risk of VTE, and selected patient characteristics were associated with higher thromboembolic risk in the setting of COVID-19.

Background Little population-based data exist about adults with primary nephrotic syndrome. Methods To evaluate kidney, cardiovascular, and mortality outcomes in adults with primary nephrotic syndrome, we identified adults within an integrated health care delivery system (Kaiser Permanente Northern California) with nephrotic-range proteinuria or diagnosed nephrotic syndrome between 1996 and 2012. Nephrologists reviewed medical records for clinical presentation, laboratory findings, and biopsy results to confirm primary nephrotic syndrome and assigned etiology. We identified a 1:100 time-matched cohort of adults without diabetes, diagnosed nephrotic syndrome, or proteinuria as controls to compare rates of ESKD, cardiovascular outcomes, and death through 2014, using multivariable Cox regression. Results We confirmed 907 patients with primary nephrotic syndrome (655 definite and 252 presumed patients with FSGS [40%], membranous nephropathy [40%], and minimal change disease [20%]). Mean age was 49 years; 43% were women. Adults with primary nephrotic syndrome had higher adjusted rates of ESKD (adjusted hazard ratio [aHR], 19.63; 95% confidence interval [95% CI], 12.76 to 30.20), acute coronary syndrome (aHR, 2.58; 95% CI, 1.89 to 3.52), heart failure (aHR, 3.01; 95% CI, 2.16 to 4.19), ischemic stroke (aHR, 1.80; 95% CI, 1.06 to 3.05), venous thromboembolism (aHR, 2.56; 95% CI, 1.35 to 4.85), and death (aHR, 1.34; 95% CI, 1.09 to 1.64) versus controls. Excess ESKD risk was significantly higher for FSGS and membranous nephropathy than for presumed minimal change disease. The three etiologies of primary nephrotic syndrome did not differ significantly in terms of cardiovascular outcomes and death. Conclusions Adults with primary nephrotic syndrome experience higher adjusted rates of ESKD, cardiovascular outcomes, and death, with significant variation by underlying etiology in the risk for developing ESKD.

Treatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied with DOACs. We surveyed adults from two large integrated health systems taking DOACs or warfarin for incident VTE occurring between January 1, 2015 and June 30, 2018. Treatment satisfaction was assessed using the validated Anti-Clot Treatment Scale (ACTS), divided into the ACTS Burdens and ACTS Benefits scores; higher scores indicate greater satisfaction. Mean treatment satisfaction was compared using multivariable linear regression, adjusting for patient demographic and clinical characteristics. The effect size of the difference in means was calculated using a Cohen’s d (0.20 is considered a small effect and ≥ 0.80 is considered large). We surveyed 2217 patients, 969 taking DOACs and 1248 taking warfarin at the time of survey. Thirty-one point five percent of the cohort was aged ≥ 75 years and 43.1% were women. DOAC users were on average more satisfied with anticoagulant treatment, with higher adjusted mean ACTS Burdens (50.18 v. 48.01, p

Venous thromboembolism (VTE) treatment requires complex management, and patients with limited health literacy (HL) may perceive higher burden and lower benefits associated with their treatment.To examine the association of HL with treatment satisfaction among patients with VTE.Retrospective cohort study PARTICIPANTS: Kaiser Permanente Southern and Northern California members who were taking oral anticoagulants (OAC) for incident VTE between 2015 and 2018 were surveyed. Main Measures HL was assessed using a 3-item HL assessment and dichotomized as having adequate or limited HL. High treatment burden and low treatment benefit were defined as Anti-Clot Treatment Scale (ACTS) scores below the 25th percentile of the distributions for ACTS Burdens and Benefits survey components, respectively. Using Poisson regression, multivariable adjusted risk ratios (RR) and 95% confidence intervals (CI) were calculated for the association of HL with high treatment burden and low treatment benefits.Among 2154 respondents, 397 (18.4%) had limited HL. Patients with limited vs adequate HL were older (47.9% vs 27.5% aged ≥ 75 years, p0.001), more likely to use a non-English language when discussing their health (10.8% vs 1.7%, p0.001), to have less than high school education (10.1% vs 1.7%, p0.001), and to self-rate their health as fair or poor (47.6% vs 25.5%, p0.001). After multivariable adjustment, patients with limited HL were more likely to have higher perceived treatment burden (RR 1.24, 95% CI 1.07, 1.45) and lower perceived treatment benefits (RR 1.21, 95% CI 1.08, 1.37).Limited HL was associated with lower OAC treatment satisfaction, though absolute differences in satisfaction scores were small. Further examination of the intersection of HL with VTE treatment satisfaction and compliance among older and non-English speaking patients is warranted.

ImportancePatients hospitalized with COVID-19 have higher rates of venous thromboembolism (VTE), but the risk and predictors of VTE among individuals with less severe COVID-19 managed in outpatient settings are less well understood.ObjectivesTo assess the risk of VTE among outpatients with COVID-19 and identify independent predictors of VTE.Design, Setting, and ParticipantsA retrospective cohort study was conducted at 2 integrated health care delivery systems in Northern and Southern California. Data for this study were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Participants included nonhospitalized adults aged 18 years or older with COVID-19 diagnosed between January 1, 2020, and January 31, 2021, with follow-up through February 28, 2021.ExposuresPatient demographic and clinical characteristics identified from integrated electronic health records.Main Outcomes and MeasuresThe primary outcome was the rate per 100 person-years of diagnosed VTE, which was identified using an algorithm based on encounter diagnosis codes and natural language processing. Multivariable regression using a Fine-Gray subdistribution hazard model was used to identify variables independently associated with VTE risk. Multiple imputation was used to address missing data.ResultsA total of 398 530 outpatients with COVID-19 were identified. The mean (SD) age was 43.8 (15.8) years, 53.7% were women, and 54.3% were of self-reported Hispanic ethnicity. There were 292 (0.1%) VTE events identified over the follow-up period, for an overall rate of 0.26 (95% CI, 0.24-0.30) per 100 person-years. The sharpest increase in VTE risk was observed during the first 30 days after COVID-19 diagnosis (unadjusted rate, 0.58; 95% CI, 0.51-0.67 per 100 person-years vs 0.09; 95% CI, 0.08-0.11 per 100 person-years after 30 days). In multivariable models, the following variables were associated with a higher risk for VTE in the setting of nonhospitalized COVID-19: age 55 to 64 years (HR 1.85 [95% CI, 1.26-2.72]), 65 to 74 years (3.43 [95% CI, 2.18-5.39]), 75 to 84 years (5.46 [95% CI, 3.20-9.34]), greater than or equal to 85 years (6.51 [95% CI, 3.05-13.86]), male gender (1.49 [95% CI, 1.15-1.96]), prior VTE (7.49 [95% CI, 4.29-13.07]), thrombophilia (2.52 [95% CI, 1.04-6.14]), inflammatory bowel disease (2.43 [95% CI, 1.02-5.80]), body mass index 30.0-39.9 (1.57 [95% CI, 1.06-2.34]), and body mass index greater than or equal to 40.0 (3.07 [1.95-4.83]).Conclusions and RelevanceIn this cohort study of outpatients with COVID-19, the absolute risk of VTE was low. Several patient-level factors were associated with higher VTE risk; these findings may help identify subsets of patients with COVID-19 who may benefit from more intensive surveillance or VTE preventive strategies.

Background Helicobacter pylori (H. pylori) encodes numerous outer membrane proteins (OMPs), with considerable geographic heterogeneity and related to different clinical outcomes. This study aimed to investigate the distribution characteristics of five important OMP genes (sabA, hofC, homA, homB and frpB-4) in different regions of China. Materials and method A total of 266 strains were isolated from 348 stomach biopsy specimens in Shandong, Guangxi, Heilongjiang, Hunan, and Qinghai provinces. The presence of sabA, hofC, homA, homB and frpB-4 gene was detected by polymerase chain reaction (PCR) from H. pylori genomic DNA. Results Among the strains in five regions, the prevalence of frpB-4 was 100% and that of hofC was 97.7%. The prevalence of homB in the isolates from Qinghai (45.5%) was significantly lower than that in Shandong (75.3%), Guangxi (76.9%) and Hunan (69.6%) (PhomA in Shandong (30.1%) was significantly lower than in Guangxi (57.7%) and Qinghai (63.6%) (PsabA gene in Shandong, Guangxi, Heilongjiang, Hunan and Qinghai provinces was 21.9%, 59.7%, 45.9%, 52.2%, and 18.2%, respectively (PsabA “on” status was significantly more frequent in isolates from Guangxi (46.8%), Heilongjiang (37.8%), and Hunan (47.8%) than Qinghai (3.0%) (PhomA and sabA genes may be negatively correlated with the development of gastritis. There was no significant association between the frpB-4, hofC, homB gene and clinical outcomes. Conclusion The prevalence of homA, homB, and sabA genes and the sabA “on” or “off” status have significant geographical differences among five provinces in China. The presence of homA and sabA genes may be protective factors of gastritis.

Background To examine the individual and combined associations of noncardiac-related conditions and mobility limitation with morbidity and mortality in adults with heart failure (HF). Methods We conducted a retrospective cohort study in a large, diverse group of adults with HF from five U.S. integrated healthcare delivery systems. We characterized patients with respect to the presence of noncardiac conditions ( Results Among 114,553 adults diagnosed with HF (mean age: 73 years old, 46% women), compared with Conclusions There is an additive association of mobility limitation, beyond the burden of noncardiac multimorbidity, on mortality for patients with HF, and especially prominent in younger patients.

As a potential anti-Helicobacter pylori agent, zinc causes impairment of Helicobacter pylori growth, and this property of zinc is of broad interest to biological investigators. However, little is known about the molecular mechanisms by which zinc inhibits the growth of Helicobacter pylori. Here, an in vitro experiment revealed that zinc at specific concentrations inhibits Helicobacter pylori growth. Furthermore, an RNA sequencing-based investigation of the global regulatory response to zinc revealed that exposure to zinc altered the Helicobacter pylori transcriptional profile in numerous ways. A high concentration of zinc induced the upregulation of genes related to ribosomal subunit, ribosome biosynthesis, chaperone and adhesins. However, flagellar assembly genes and some type IV secretion system genes were repressed. In addition, the expression levels of some genes that encode transporters of metal ions and that play key roles in Helicobacter pylori pathogenicity were altered under conditions of zinc-induced stress. In summary, high concentrations of zinc initiated antimicrobial activity to Helicobacter pylori under the combined effect of multiple repressed or altered pathogenetic genes and metabolic pathways associated with bacteria growth. This result has significant implications for understanding not only the antimicrobial activity mechanism of zinc but also the role of zinc-mediated homeostasis in Helicobacter pylori.

Background: There were geographical differences in the distribution of Helicobacter pylori (H. pylori) genotypes (cagA, vacA, iceA, oipA and dupA, et al). The population in different regions in China have grant different patterns of gastroduodenal diseases which are associated with these genotypes, but the geographical characteristics of H. pylori genotypes were still unknown. Materials and Methods: Gastric biopsy specimens were obtained from 348 patients from five regions in China. The regional distribution was 89 patients from Shandong, 91 from Guangxi, 57 from Hunan, 58 from Qinghai and 53 from Heilongjiang. DNA extracted from cultured isolates were analyzed by polymerase chain reaction (PCR) to determine the presence of cagA, vacA, iceA, oipA and dupA genotypes.Results: A total of 269 H. pylori isolates were obtained, of which 74 isolates were from Shandong, 78 from Guangxi, 46 from Hunan, 33 from Qinghai and 38 from Heilongjiang. The cagA gene was predominant in all the five regions (e.g. 100% in Hunan, Qinghai and Heilongjiang). The predominant vacA genotypes in the 269 isolates were s1a (88.1%) and m1(72.1%). vacA s1b was not detected in our study. In strains from Guangxi and Hunan, s1c was dominant; in contrast, s1a was dominant in Shandong, Qinghai and Heilongjiang. The prevalence of m1 strains in Heilongjiang (92.1%) was significantly higher (PoipA-positive strains were more prevalent in Guangxi (100%) and Hunan (100%) than in Qinghai (78.8%) (PdupA-positive strains were less than half in Guangxi (15.4%) and Shandong (32.4%), whereas it was 73.9% in Hunan and 81.8% in Qinghai (PConclusions: There are significant geographic differences in the distribution of H. pylori genotypes. These datas may be used to explain the gastroduodenal diseases patterns in different geographic regions of China.

OBJECTIVES To assess multimorbidity burden and its association with clinical outcomes in adults with heart failure (HF) according to sex, age, and HF type. DESIGN Retrospective cohort study. SETTING Five healthcare delivery systems across the United States. PARTICIPANTS Adults with HF (N=114,553). MEASUREMENTS We characterized participants with respect to the presence of 26 chronic conditions categorized into quartiles based on overall burden of comorbidity (

Trigger factor (TF) is a key component of the prokaryotic chaperone network, which is involved in many basic cellular processes, such as protein folding, protein trafficking, and ribosome assembly. The major chaperone site of TF has a cradle-like structure in which protein substrate may fold without interference from other proteins. Here, we investigated in vivo and in vitro the roles of hydrophobic and charged patches on the edge and interior of cradle during TF-assisted protein folding. Our results showed that most of the surface of the cradle was involved in TF-assisted protein folding, which was larger than found in early studies. Although the inner surface of cradle was mostly hydrophobic, both hydrophobic and electrostatic patches were indispensable for TF to facilitate correct protein folding. However, hydrophobic patches were more important for the antiaggregation activity of TF. Furthermore, it was found that the patches on the surface of cradle were involved in TF-assisted protein folding in a spatial and temporal order. These results suggest that the folding-favorable interface between the cradle and substrate was dynamic during TF-assisted protein folding, which enabled TF to be involved in the folding of substrate in an aggressive manner rather than acting as a classic holdase.-Fan, D., Cao, S., Zhou, Q., Zhang, Y., Yue, L., Han, C., Yang, B., Wang, Y., Ma, Z., Zhu, L., Liu, C. Exploring the roles of substrate-binding surface of chaperone site in the chaperone activity of trigger factor.

Autothermal reforming of methane couples exothermal partial oxidation of methane and endothermal steam or dry reforming of methane to achieve high energy efficiency, which can be operated through solid oxide fuel cells (SOFCs) so that expensive oxygen is not required and safety issue caused by CH4/O2 mixture is avoided. In addition, electric power is simultaneously generated. This study has demonstrated the efficient electrochemical autothermal reforming of methane over a SOFC reactor integrated with catalyst beds within anode channel structure. The catalyst bed reformer increases syngas yield by a factor of about 6 owing to the increased methane conversion and syngas selectivity. By numerical assessment, enhanced mass transportation is well validated by high fuel accessibility at the electrode-electrolyte interface benefiting from the integrated catalyst beds. Compared with conventional catalyst layer on anode surface, the catalyst beds are more efficient for conducting methane reforming. After the initial stabilization of cell microstructure, the SOFC reactor has demonstrated stable cell performance and syngas yield during the test for 120 h. The integrated SOFC reactor has demonstrated a promising application in performing catalytic reforming reactions.

Co-generation of electricity and syngas from methane via solid oxide fuel cells (SOFCs) to achieve zero emission is highly attractive for enhancing the energy efficiency of methane utilization. However, it remains a great challenge to simultaneously achieve high power output and syngas formation rate, and sufficient operational stability in existing SOFCs. In this work, we successfully demonstrate the efficient co-generation by the innovative integration of a catalytic microchannel reactor within anodes. The integrated anode has unique dendritic channels loaded with highly efficient nanofibrous Ni-based composite that functions as an internal catalyst bed reformer. The resulting SOFC demonstrates both thermal coupling and materials coupling effects between exothermal fuel oxidation reactions and endothermal reforming reactions and thus improves peak power density by 25 %, syngas yield by more than 2 times and improved operational stability compared to the SOFC without the microchannel reactor. The new SOFC design holds great potential for practical applications.

Administrative data are frequently used to identify venous thromboembolism (VTE) for research and quality reporting. However, the validity of these codes, particularly in outpatients, has not been well-established. To determine how well International Classification of Diseases, Ninth Revision (ICD-9) codes for VTE predict chart-confirmed acute VTE in inpatient and outpatients. We selected 4642 adults with an incident ICD-9 diagnosis of VTE between years 2004 and 2010 from the Cardiovascular Research Network Venous Thromboembolism cohort study. Medical charts were reviewed to determine validity of events. Positive predictive values (PPVs) of ICD-9 codes were calculated as the number of chart-validated VTE events divided by the number with specific VTE codes. Analyses were stratified by VTE type [pulmonary embolism (PE), deep venous thrombosis (DVT)], code position (primary, secondary), and setting [hospital/emergency department (ED), outpatient]. The PPV for any diagnosis of VTE was 64.6% for hospital/ED patients and 30.9% for outpatients. Primary diagnosis codes from hospital/ED patients were more likely to represent acute VTE than secondary diagnosis codes (78.9% vs. 44.4%, P

Background Studies using administrative data commonly rely on diagnosis codes to identify venous thromboembolism (VTE) events. Our objective was to assess the validity of using International Classification of Disease, 9th Revision (ICD-9) codes in identifying recurrent VTE. Materials and methods Among 5497 adults with confirmed incident VTE from four healthcare delivery systems in the Cardiovascular Research Network (CVRN), we identified all subsequent inpatient, emergency department (ED), and ambulatory clinical encounters associated with an ICD-9 code for VTE (combined with relevant radiology procedure codes for inpatient/ED VTE codes in the secondary discharge position or outpatient codes) during the follow-up period. Medical records were reviewed using standardized diagnostic criteria to assess for the presence of new, recurrent VTE. The positive predictive value (PPV) of codes was calculated as the number of valid events divided by total encounters. Results We identified 2397 encounters that were considered potential recurrent VTE by ICD-9 codes. However, only 31.1% (95%CI: 29.3–33.0%) of encounters were verified by reviewers as true recurrent VTE. Hospital or ED encounters with VTE codes in the primary position were more likely to represent valid recurrent VTE (PPV 61.3%, 95%CI: 56.7–66.3%) than codes in secondary positions (PPV 35.4%, 95%CI: 31.9–39.3%), or outpatient codes (PPV 20.3%, 95%CI: 18.3–22.5%). PPV was low for all VTE types (29.9% for pulmonary embolism, 38.3% for lower and 37.7% for upper extremity deep venous thrombosis, and 14.1% for other VTE). Conclusions ICD-9 codes do not accurately identify new VTE events in patients with a prior history of VTE.

The association between statins and diabetes mellitus (DM) remains controversial. The Kaiser Permanente CHAMP Study identified adults without DM who had cardiovascular (CV) risk factors and no previous lipid lowering therapy (LLT) between 2008 and 2010. The CV risk factors included known atherosclerotic CV disease (ASCVD), elevated low-density lipoprotein cholesterol ≥190 mg/dl, or a low-density lipoprotein cholesterol between 70 and 189 mg/dl and an estimated 10-year ASCVD risk ≥7.5%. Incident DM was defined as ≥2 abnormal tests (i.e., A1C ≥6.5% or a fasting blood glucose ≥126 mg/dl) or ≥1 abnormal test result plus a new diagnostic code or medication for DM. Among 213,289 eligible adults, 28,149 patients initiating statins were carefully matched to an equal number of patients who remained off LLT during follow-up. Compared with matched patients not receiving statins, those initiating statin therapy had the same mean age (67.9 ± 9.4 years) and gender (42.8% women). The crude rate (per 100 person-years) of incident DM was low (0.55, 95% confidence interval [CI] 0.52 to 0.59) but was marginally higher in patients who were treated with a statin (0.69, 95% CI 0.64 to 0.74) versus no LLT (0.42, 95% CI 0.38 to 0.46). After additional adjustment, statin therapy was associated with a modestly increased risk of incident DM (adjusted hazard ratio 1.17, 95% CI 1.02 to 1.34). In conclusion, in adults without DM at increased ASCVD risk, initiation of statin therapy was independently associated with a modestly higher risk of incident DM.

Few studies describe both inpatient and outpatient treatment and outcomes of patients with acute venous thromboembolism in the United States.A multi-institutional cohort of patients diagnosed with confirmed pulmonary embolism or deep venous thrombosis during the years 2004 through 2010 was established from 4 large, US-based integrated health care delivery systems. Computerized databases were accessed and medical records reviewed to collect information on patient demographics, clinical risk factors, initial antithrombotic treatment, and vital status. Multivariable Cox regression models were used to estimate the risk of death at 90 days.The cohort comprised 5497 adults with acute venous thromboembolism. Pulmonary embolism was predominantly managed in the hospital setting (95.0%), while 54.5% of patients with lower extremity thrombosis were treated as outpatients. Anticoagulant treatment differed according to thromboembolism type: 2688 patients (92.8%) with pulmonary embolism and 1625 patients (86.9%) with lower extremity thrombosis were discharged on anticoagulants, compared with 286 patients (80.1%) with upper extremity thrombosis and 69 (54.8%) patients with other thrombosis. While 4.5% of patients died during the index episode, 15.4% died within 90 days. Pulmonary embolism was associated with a higher 90-day death risk than lower extremity thrombosis (adjusted hazard ratio 1.23; 95% confidence interval, 1.04-1.47), as was not being discharged on anticoagulants (adjusted hazard ratio 5.56; 95% confidence interval, 4.76-6.67).In this multicenter, community-based study of patients with acute venous thromboembolism, anticoagulant treatment and outcomes varied by thromboembolism type. Although case fatality during the acute episode was relatively low, 15.4% of people with thromboembolism died within 90 days of the index diagnosis.

Some amoxicillin-resistant strains of H. pylori show a sharp decrease in amoxicillin resistance after freezing. In China, most clinical gastric mucosal specimens are frozen and transported for isolation and drug susceptibility testing for H. pylori, which may lead to an underestimation of the amoxicillin resistance. The objective of this study is to investigated reasons for the decreased amoxicillin resistance after cryopreservation. A high-level amoxicillin-resistant clone (NX24r) was obtained through amoxicillin pressure screening. After cryopreservation at −80 °C for 3 months, the minimum inhibitory concentration (MIC) of NX24r was reduced sharply. Mutations and changes of transcriptome were analyzed after amoxicillin screening and cryopreservation. Mutations in PBP1 (I370T, E428K, T556S) and HefC (M337K, L378F, D976V) were detected in NX24r, which may be the main reason for the induced amoxicillin resistance. No mutations were found in PBP1 or HefC after cryopreservation. However, transcriptome analysis showed that down-regulated genes in the cryopreserved clone were significantly enriched in plasma membrane (GO:0005886), including lepB, secD, gluP, hp0871 and hp1071. These plasma membrane genes are involved in the biosynthesis and transport function of the membrane. The decreased amoxicillin resistance after cryopreservation may be related to the down-regulation of genes involved in membrane structure and transport function.

Helicobacter pylori (H. pylori) adhesion to human gastric epithelial cells is closely linked with fucosylated glycans. Therefore, investigation of fucosylation in the interaction of gastric epithelial cells with H. pylori is critical. In this study we used lectin microarrays to detect the expression of fucosylated glycans in gastric epithelial cells (GES-1) infected with H. pylori strains isolated from patients with different diseases including chronic gastritis, duodenal ulcers, and gastric cancer (each containing two strains) at 4 h. In addition, we investigated the time-course expression of fucosyltransferase (FUT) 1–6 genes in GES-1 cells stimulated with H. pylori strains at 0.5–8 h. At 4 h post-infection, Lotus, AAA, BC2LCN, PA-IIL, CNL and ACG lectins had increased signals in H. pylori-infected GES-1 cells compared to uninfected cells. Higher expression of FUT1 and FUT2 was detected in all H. pylori-infected GES-1 cells within 2 h, regardless of the H. pylori strain. In particular, the expression of FUT2 was higher in H. pylori-infected GES-1 cells with a higher fold change in levels of BC2LCN lectin specific to α1-2 linked fucose (Fuc) at 4 h. The results suggest that the high levels of α1, 2-linked Fuc synthesized by FUT1/2, might play a role in the preliminary stage of H. pylori infection. This provides us with pivotal information to understand the adhesion of H. pylori to human gastric epithelial cells.

Trigger factor (TF) is a key component of prokaryotic chaperone network, which is involved various basic cellular processes such as nascent peptide folding, protein trafficking, ribosome assembly. To better understanding the physiological roles of TF, global transcriptome profiles of a variety of TF deletion mutant strains of Escherichia coli were determined. We found that deletion of the tig gene, encoding TF, led to a dramatic alteration of transcriptome profile, not only affecting the gene expression of members of the chaperone network, but also changing the levels of quite a few RNAs related to metabolism and other cellular processes. Further studies showed that this alteration was only partially recovered by knockin of TF domain-deletion mutants into the endogenous tig locus, indicating that structural integrity is crucial for the biological function of TF. Finally, by combining the transcriptome and phenotype results, a physiological mechanism underlying the impact of TF deletion on the transcriptome profile was proposed. J. Cell. Biochem. 118: 141-153, 2017. © 2016 Wiley Periodicals, Inc.

Terpenoids are the largest and most diverse class of plant-specialized metabolites, which function in diverse physiological processes during plant development. In the biosynthesis of plant terpenoids, short-chain prenyltransferases (SC-PTs), together with terpene synthases (TPSs), play critical roles in determining terpenoid diversity. SC-PTs biosynthesize prenyl pyrophosphates with different chain lengths, and these compounds are the direct precursors of terpenoids. Arabidopsis thaliana possesses a subgroup of SC-PTs whose functions are not clearly known. In this study, we focus on 10 geranylgeranyl pyrophosphate synthase-like [GGPPSL] proteins, which are commonly thought to produce GGPP [C20]. We found that a subset of members of the Arabidopsis GGPPSL gene family have undergone neo-functionalization: GGPPSL6, 7, 9, and 10 mainly have geranylfarnesyl pyrophosphate synthase activity (C25; renamed AtGFPPS1, 2, 3, and 4), and GGPPSL8 produces even longer chain prenyl pyrophosphate (≥ C30; renamed polyprenyl pyrophosphate synthase 2, AtPPPS2). By solving the crystal structures of AtGFPPS2, AtPPPS2, and AtGGPPS11, we reveal the product chain-length determination mechanism of SC-PTs and interpret it as a "three floors" model. Using this model, we identified a novel GFPPS clade distributed in Brassicaceae plants and found that the GFPPS gene typically occurs in tandem with a gene encoding a TPS, forming a GFPPS-TPS gene cluster.

Methane-fueled solid oxide fuel cells (SOFCs) are promising to achieve high energy conversion efficiency while no study focuses on the conversion efficiency of methane into power, which is greatly restrained by gas diffusion within anode supports. This study employs microchanneled anode supports to provide fast gas diffusion pathway. To confirm the advantage, the anodes with half-channels and without channels are also used for comparison. The microchannel structure increases the maximum power density up to 2.5 times because of diminishing or eliminating concentration polarization within anode supports and improving catalyst coating over anode internal surface. As a compromise of fuel utilization and power output, methane conversion efficiency is defined as power output per mol methane input in feeding gas to compare with the reported results, and the microchanneled SOFCs achieve the record high methane conversion efficiency.

Background Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation ( AF ). In a large diverse population of adults with AF , we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes. Methods and Results The Cardiovascular Research Network WAVE (Community‐Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision ( ICD‐9 ), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person‐years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01–2.28). Results were not materially changed after additional adjustment for patient‐level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03–2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes. Conclusions Diagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors or achieved anticoagulation quality.

Monoterpenes, together with sesquiterpenes, play varying roles in plant interactions with the environment depending on the organs in which they are produced; these compounds likely function to attract pollinators when they are present in flowers and can protect plants against herbivores or microbes when produced in leaves or in roots. It is well known that geranyl diphosphate (GPP), the common precursor of monoterpenes, is biosynthesized by geranyl diphosphate synthase (GPPS). To date, two types of GPPS (EC 2.5.1.1) have been reported from plants: homomeric GPPS and heteromeric GPPS.

Although superficial thrombophlebitis (SVTE) is generally considered a benign, self-limited disease, accumulating evidence suggests that it often leads to more serious forms of venous thromboembolism. We reviewed the medical charts of 329 subjects with SVTE from the Cardiovascular Research Network Venous Thromboembolism cohort study to collect information on the acute treatment of SVTE and subsequent diagnosis of deep venous thrombosis within 1 year. All participants received care within Kaiser Permanente Northern California, a large, integrated healthcare delivery system. Fourteen (4.3%) subjects with SVTE received anticoagulants, 148 (45.0%) were recommended antiplatelet agents or nonsteroidal anti-inflammatory drugs, and in 167 (50.8%) there was no documented antithrombotic therapy. In the year after SVTE diagnosis, 19 (5.8%) patients had a subsequent diagnosis of a deep venous thrombosis or pulmonary embolism. In conclusion, clinically significant venous thrombosis within a year after SVTE was uncommon in our study despite infrequent use of antithrombotic therapy. Journal of Hospital Medicine 2016;11:432-434. © 2016 Society of Hospital Medicine.

In order to solve the phase-coded signal Doppler sensitive problem, the Doppler search algorithm based on frequency domain is often used. However, in tracking and measuring radar, the traditional algorithm is difficult to meet the requirements due to the requirement of target measurement accuracy and real-time signal processing. This paper focuses on the 13 bit Barker code signal, based on the analysis of the characteristics of the Barker code signal, completes the high precision Doppler compensation of the single pulse signal under the CPU+GPU software platform using a Doppler compensation algorithm based on time-domain. At the same time, combined with classical tracking radar algorithm, effectively improve the real-time signal processing. Completed the phase code on the target of precision measurement and tracking.

Background Statin therapy is highly efficacious in the prevention of fatal and nonfatal atherosclerotic events in persons at increased cardiovascular risk. However, its long-term effectiveness in practice depends on a high level of medication adherence by patients. Methods We identified nondiabetic adults with cardiovascular risk factors between 2008 and 2010 within a large integrated health care delivery system in Northern California. Through 2013, we examined the use and adherence of newly initiated statin therapy based on data from dispensed prescriptions from outpatient pharmacy databases. Results Among 209,704 eligible adults, 68,085 (32.5%) initiated statin therapy during the follow-up period, with 90.4% receiving low-potency statins. At 12 and 24 months after initiating statins, 84.3% and 80.2%, respectively, were actively receiving statin therapy, but only 42% and 30%, respectively, had no gaps in treatment during those time periods. There was also minimal switching between statins or use of other lipid-lowering therapies for augmentation during follow-up. Age ≥ 50 years, Asian/Pacific Islander race, Hispanic ethnicity, prior myocardial infarction, prior ischemic stroke, hypertension, and baseline low-density lipoprotein cholesterol > 100 mg/dL were associated with higher adjusted odds, whereas female gender, black race, current smoking, dementia were associated with lower adjusted odds, of active statin treatment at 12 months after initiation. Conclusions There remain opportunities for improving prevention in patients at risk for cardiovascular events. Our study identified certain patient subgroups that may benefit from interventions to enhance medication adherence, particularly by minimizing treatment gaps and discontinuation of statin therapy within the first year of treatment.

Despite the high burden of multimorbidity among patients with heart failure (HF), few studies have examined the impact of multiple chronic conditions on important clinical outcomes by gender, age, and type of HF. We identified 114,553 adults with HF and known left ventricular systolic function from five healthcare delivery systems and characterized the presence of 26 chronic conditions into quartiles of multimorbidity burden (0–4 morbidities, 5–6 morbidities, 7–8 morbidities, and ≥9 morbidities) based on data from electronic medical records. Outcomes included all-cause death, all-cause hospitalization, and HF hospitalization. Compared with 0–4 morbidities, adjusted hazard ratios (HR) for death among those with 5–6, 7–8, or 9 or more morbidities were: HR 1.27 (95% CI:1.24–1.31), HR 1.52 (1.48–1.57) and HR 1.92 (1.86–1.99), respectively. Compared with 0–4 morbidities, there was a graded adjusted risk of any-cause hospitalization for 5–6, 7–8, or 9 or more morbidities: HR 1.28 (1.25–1.30), HR 1.47 (1.44–1.50), and HR 1.77 (1.73–1.82). Similar findings were observed for HF-specific hospitalization in those with 5–6, 7–8, or 9 or more morbidities (vs. 0–4): HR 1.22 (1.19–1.26), HR 1.39 (1.34–1.44), and HR 1.68 (1.61–1.74). Comparable findings were observed by gender, age, and HF type (preserved, reduced, borderline HF) for the relationship between multimorbidity burden and outcomes, which was especially prominent among those

Trigger factor (TF) is a key component of prokaryotic chaperone network, which is involved various basic cellular processes such as nascent peptide folding, protein trafficking, ribosome assembly. To better understanding the physiological roles of TF, global transcriptome profiles of a variety of TF deletion mutant strains of Escherichia coli were determined. We found that deletion of the tig gene, encoding TF, led to a dramatic alteration of transcriptome profile, not only affecting the gene expression of members of the chaperone network, but also changing the levels of quite a few RNAs related to metabolism and other cellular processes. Further studies showed that this alteration was only partially recovered by knockin of TF domain-deletion mutants into the endogenous tig locus, indicating that structural integrity is crucial for the biological function of TF. Finally, by combining the transcriptome and phenotype results, a physiological mechanism underlying the impact of TF deletion on the transcriptome profile was proposed. J. Cell. Biochem. 118: 141-153, 2017. © 2016 Wiley Periodicals, Inc.

Background and objectives: Relatively little is known about clinical outcomes, especially long-term outcomes, among patients who have chronic kidney disease (CKD) and experience superimposed acute renal failure (ARF; acute on chronic renal failure). Design, setting, participants, & measurements: We tracked 39,805 members of an integrated health care delivery system in northern California who were hospitalized during 1996 through 2003 and had prehospitalization estimated GFR (eGFR)

There is limited information about the true incidence of acute renal failure (ARF). Most studies could not quantify disease frequency in the general population as they are hospital-based and confounded by variations in threshold and the rate of hospitalization. Earlier studies relied on diagnostic codes to identify non-dialysis requiring ARF. These underestimated disease incidence since the codes have low sensitivity. Here we quantified the incidence of non-dialysis and dialysis-requiring ARF among members of a large integrated health care delivery system - Kaiser Permanente of Northern California. Non-dialysis requiring ARF was identified using changes in inpatient serum creatinine values. Between 1996 and 2003, the incidence of non-dialysis requiring ARF increased from 322.7 to 522.4 whereas that of dialysis-requiring ARF increased from 19.5 to 29.5 per 100,000 person-years. ARF was more common in men and among the elderly, although those aged 80 years or more were less likely to receive acute dialysis treatment. We conclude that the use of serum creatinine measurements to identify cases of non-dialysis requiring ARF resulted in much higher estimates of disease incidence compared with previous studies. Both dialysis-requiring and non-dialysis requiring ARFs are becoming more common. Our data underscore the public health importance of ARF.

Rates of ESRD are rising faster in Hispanic than non-Hispanic white individuals, but reasons for this are unclear. Whether rates of cardiovascular events and mortality differ among Hispanic and non-Hispanic white patients with chronic kidney disease (CKD) also is not well understood. Therefore, this study examined the associations between Hispanic ethnicity and risks for ESRD, cardiovascular events, and death in patients with CKD. A total of 39,550 patients with stages 3 to 4 CKD from Kaiser Permanente of Northern California were included. Hispanic ethnicity was obtained from self-report supplemented by surname matching. GFR was estimated from the abbreviated Modification of Diet in Renal Disease equation, and clinical outcomes, patient characteristics, and longitudinal medication use were ascertained from health plan databases and state mortality files. After adjustment for sociodemographic characteristics, Hispanic ethnicity was associated with an increased risk for ESRD (hazard ratio [HR] 1.93; 95% confidence interval [CI] 1.72 to 2.17) when compared with non-Hispanic white patients, which was attenuated after controlling for diabetes and insulin use (HR 1.50; 95% CI 1.33 to 1.69). After further adjustment for potential confounders, Hispanic ethnicity remained independently associated with an increased risk for ESRD (HR 1.33; 95% CI 1.17 to 1.52) as well as a lower risk for cardiovascular events (HR 0.82; 95% CI 0.76 to 0.88) and death (HR 0.72; 95% CI 0.66 to 0.79). Among a large cohort of patients with CKD, Hispanic ethnicity was associated with lower rates of death and cardiovascular events and a higher rate of progression to ESRD. The higher prevalence of diabetes among Hispanic patients only partially explained the increased risk for ESRD. Further studies are required to elucidate the cause(s) of ethnic disparities in CKD-associated outcomes.

Background— Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD. Methods and Results— We studied adults with CKD (defined as estimated glomerular filtration rate eGFR 2 by the Chronic Kidney Disease Epidemiology Collaboration equation) enrolled in Kaiser Permanente Northern California who were identified between 2002 and 2010 and who did not have previous ESRD or previously documented AF. Incident AF was identified by using primary hospital discharge diagnoses or 2 or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206 229 adults with CKD, 16 463 developed incident AF. During a mean follow-up of 5.1±2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) in comparison with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P Conclusions— Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD.

Low high-density lipoprotein (HDL) cholesterol level is common in patients with chronic kidney disease, but associations between severity of chronic kidney disease, obesity, and HDL level have not been well defined.Cross-sectional study.Within a large integrated health care delivery system, we identified all adult individuals without diabetes who had measured kidney function (estimated glomerular filtration rate [eGFR]), body mass index (BMI), and HDL level, but no substantial proteinuria, confounding medications, or prior renal replacement therapy.The primary predictors for our analyses were eGFR and BMI.Low HDL cholesterol level was the outcome. We performed multivariable logistic regression to investigate whether the relationship between BMI and low HDL level (men,40 mg/dL; women,50 mg/dL) varied as a function of eGFR.Of 380,207 individuals who met cohort entry criteria, there were 26,089 (7%) with chronic kidney disease by eGFR level. Compared with eGFR of 60 mL/min/1.73 m(2) or greater, lower eGFR category (in mL/min/1.73 m(2)) was associated with an increased adjusted odds of low HDL level independent of BMI and other confounders. However, there was a significant interaction between eGFR and BMI (P0.001). In separate models stratified by eGFR category (or=60, 45 to 59, and 30 to 44 mL/min/1.73 m(2)), greater BMI was associated with a graded increased adjusted odds of low HDL level in each eGFR category, but this relationship was attenuated in patients with lower eGFR.Information for undiagnosed diabetes and proteinuria was unavailable.Decreased eGFR is independently associated with greater odds of having a low HDL level. Across a spectrum of eGFR, greater BMI was associated with lower HDL level, but the magnitude of this association was diminished at lower eGFR, suggesting that other factors may also contribute to low HDL levels in patients with advanced chronic kidney disease.

When assessing a correlation between two exposure or biological marker variables, one sometimes encounters the problem of indeterminate values for one of the variables due to an assay detection limit. In this event, investigators often report correlation coefficients computed after removing the pairs involving non-detectable values, or after substituting some small constant for those values. These ad hoc practices can lead to bias in both point and confidence interval estimates of the true correlation coefficient. To address this issue, we consider two parametric techniques for estimating the correlation in the presence of left censoring for one of the variables. The first is a maximum likelihood approach, and the second is an adaptation of multiple imputation motivated primarily by potential benefits in confidence interval coverage. Both of the estimators studied reduce to the standard Pearson's correlation coefficient in the event of no censoring, and hence are valid in cases where this measure would be appropriate for the complete data. We assess these approaches empirically and contrast them with ad hoc methods for estimating the correlation between cervicovaginal human immunodeficiency virus (HIV) viral load measurements and CD4+ lymphocyte counts from HIV positive women enrolled in a clinical trial conducted in Bangkok, Thailand.

Background End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined. Methods We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization. Results The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1....