Adjunctive Use of Wide-Area Transepithelial Sampling-3D in Patients With Symptomatic Gastroesophageal Reflux Increases Detection of Barrett's Esophagus and Dysplasia.

INTRODUCTION: Patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy for Barrett's esophagus (BE) frequently demonstrate columnar-lined epithelium, with forceps biopsies (FBs) failing to yield intestinal metaplasia (IM). Repeat endoscopy is then often necessary to confirm a BE diagnosis. The aim of this study was to assess the yield of IM leading to a diagnosis of BE by the addition of wide-area transepithelial sampling (WATS-3D) to FB in the screening of patients with GERD. METHODS: We performed a prospective registry study of patients with GERD undergoing screening upper endoscopy. Patients had both WATS-3D and FB. Patients were classified by their Z line appearance: regular, irregular (<1 cm columnar-lined epithelium), possible short-segment BE (1 to <3 cm), and possible long-segment BE (≥3 cm). Demographics, IM yield, and dysplasia yield were calculated. Adjunctive yield was defined as cases identified by WATS-3D not detected by FB, divided by cases detected by FB. Clinicians were asked if WATS-3D results affected patient management. RESULTS: Of 23,933 patients, 6,829 (28.5%) met endoscopic criteria for BE. Of these, 2,878 (42.1%) had IM identified by either FB or WATS-3D. Among patients fulfilling endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and absolute yield was 18.1%. One thousand three hundred seventeen patients (19.3%) who fulfilled endoscopic BE criteria had IM detected solely by WATS-3D. Of 240 patients with dysplasia, 107 (44.6%) were found solely by WATS-3D. Among patients with positive WATS-3D but negative FB, the care plan changed in 90.7%. DISCUSSION: The addition of WATS-3D to FB in patients with GERD being screened for BE resulted in confirmation of BE in an additional one-fifth of patients. Furthermore, dysplasia diagnoses approximately doubled.

Validation of an automated artificial intelligence system for 12­lead ECG interpretation.

BACKGROUND: The electrocardiogram (ECG) is one of the most accessible and comprehensive diagnostic tools used to assess cardiac patients at the first point of contact. Despite advances in computerized interpretation of the electrocardiogram (CIE), its accuracy remains inferior to physicians. This study evaluated the diagnostic performance of an artificial intelligence (AI)-powered ECG system and compared its performance to current state-of-the-art CIE. METHODS: An AI-powered system consisting of 6 deep neural networks (DNN) was trained on standard 12­lead ECGs to detect 20 essential diagnostic patterns (grouped into 6 categories: rhythm, acute coronary syndrome (ACS), conduction abnormalities, ectopy, chamber enlargement and axis). An independent test set of ECGs with diagnostic consensus of two expert cardiologists was used as a reference standard. AI system performance was compared to current state-of-the-art CIE. The key metrics used to compare performances were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score. RESULTS: A total of 932,711 standard 12­lead ECGs from 173,949 patients were used for AI system development. The independent test set pooled 11,932 annotated ECG labels. In all 6 diagnostic categories, the DNNs achieved high F1 scores: Rhythm 0.957, ACS 0.925, Conduction abnormalities 0.893, Ectopy 0.966, Chamber enlargement 0.972, and Axis 0.897. The diagnostic performance of DNNs surpassed state-of-the-art CIE for the 13 out of 20 essential diagnostic patterns and was non-inferior for the remaining individual diagnoses. CONCLUSIONS: Our results demonstrate the AI-powered ECG model's ability to accurately identify electrocardiographic abnormalities from the 12­lead ECG, highlighting its potential as a clinical tool for healthcare professionals.

International evaluation of an artificial intelligence-powered electrocardiogram model detecting acute coronary occlusion myocardial infarction.

Aims: A majority of acute coronary syndromes (ACS) present without typical ST elevation. One-third of non-ST-elevation myocardial infarction (NSTEMI) patients have an acutely occluded culprit coronary artery [occlusion myocardial infarction (OMI)], leading to poor outcomes due to delayed identification and invasive management. In this study, we sought to develop a versatile artificial intelligence (AI) model detecting acute OMI on single-standard 12-lead electrocardiograms (ECGs) and compare its performance with existing state-of-the-art diagnostic criteria. Methods and results: An AI model was developed using 18 616 ECGs from 10 543 patients with suspected ACS from an international database with clinically validated outcomes. The model was evaluated in an international cohort and compared with STEMI criteria and ECG experts in detecting OMI. The primary outcome of OMI was an acutely occluded or flow-limiting culprit artery requiring emergent revascularization. In the overall test set of 3254 ECGs from 2222 patients (age 62 ± 14 years, 67% males, 21.6% OMI), the AI model achieved an area under the curve of 0.938 [95% confidence interval (CI): 0.924-0.951] in identifying the primary OMI outcome, with superior performance [accuracy 90.9% (95% CI: 89.7-92.0), sensitivity 80.6% (95% CI: 76.8-84.0), and specificity 93.7 (95% CI: 92.6-94.8)] compared with STEMI criteria [accuracy 83.6% (95% CI: 82.1-85.1), sensitivity 32.5% (95% CI: 28.4-36.6), and specificity 97.7% (95% CI: 97.0-98.3)] and with similar performance compared with ECG experts [accuracy 90.8% (95% CI: 89.5-91.9), sensitivity 73.0% (95% CI: 68.7-77.0), and specificity 95.7% (95% CI: 94.7-96.6)]. Conclusion: The present novel ECG AI model demonstrates superior accuracy to detect acute OMI when compared with STEMI criteria. This suggests its potential to improve ACS triage, ensuring appropriate and timely referral for immediate revascularization.

Sequential measurement of the neurosensory retina in hypertensive disorders of pregnancy: a model of microvascular injury in hypertensive emergency.

Optical coherence tomography of the eye suggests the retina thins in normal pregnancy. Our objectives were to confirm and extend these observations to women with hypertensive disorders of pregnancy (HDP). Maternal demographics, clinical/laboratory findings and measurements of macular thickness were repeatedly collected at gestational ages <20 weeks, 20-weeks to delivery, at delivery and postpartum. The primary outcome was the change in macular thickness from non-pregnant dimensions in women with incident HDP compared to non-hypertensive pregnant controls. Secondary outcomes were the relationship(s) between mean arterial pressure (MAP) and macular response. Data show macular thicknesses diminished at <20 weeks gestation in each of 27 pregnancies ending in HDP (mean 3.94 µm; 95% CI 4.66, 3.21) and 11 controls (mean 3.92 µm; 5.05, 2.79; P < 0.001 versus non-pregnant dimensions in both; P = 0.983 HDP versus controls). This thinning response continued to delivery in all controls and in 7 women with HDP superimposed on chronic hypertension. Macular thinning was lost after 20 weeks gestation in the other 20 women with HDP. MAP at loss of macular thinning in women without prior hypertension (n = 12) was identical to MAP at enrollment. However, mean MAP subsequently rose 19 mmHg (15, 22) leading to de novo HDP in all 12 women. Loss of thinning leading to a rise in MAP was also observed in 8 of 15 women with HDP superimposed on chronic hypertension. We conclude the macula thins in most women in early pregnancy. Those who lose this early macular thinning response often develop blood pressure elevations leading to HDP.

A Systematic Review of Electrocardiographic Changes in Populations Temporarily Ascending to High Altitudes.

High altitudes can cause hypobaric hypoxia, altering human physiology and the corresponding electrocardiogram (ECG). As part of the Altitude Nondifferentiated ECG Study (ANDES), this paper reviews ECG changes in subjects ascending to high altitudes. This review was conducted following PRISMA guidelines. PubMed, EMBASE, OVID Medline, and Web of Science were searched. 19 studies were ultimately included. Notable ECG changes at high altitudes include T wave inversion in the precordial leads and rightward QRS axis deviation in leads I, II and aVF. Less common findings were increases in P wave amplitude, QRS amplitude, and QTc interval. These ECG deviations typically self-resolved within 2-6 weeks following return to sea level. Consideration must be taken when interpreting ECG changes in individuals during ascent to, at, or upon return from high altitudes. Further large-scale studies are needed to elucidate temporal and altitude-dependent ECG patterns and establish reference standards for clinicians.

Association of Mild-to-Moderate Aortic Regurgitation With Outcomes in Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: To assess aortic regurgitation (AR) prevalence, its hemodynamic effect, and long-term prognostic implications in patients admitted with de novo or worsened heart failure with preserved ejection fraction (HFpEF). METHODS: Consecutive patients hospitalized with de novo or worsened HFpEF between 2014 and 2020 were enrolled. Patients with more than moderate aortic and/or mitral valve disease were excluded. Based on the presence and degree of AR, patients were divided into those without AR, those with mild, and those with moderate AR. Data on cardiovascular death, heart failure (HF) rehospitalization, and their composite (major adverse cardiovascular events) were collected. RESULTS: The final study population consisted of 458 HFpEF patients: 156 (34.1%) with mild-AR, 153 (33.4%) with moderate-AR, and the remaining 149 (32.5%) with no AR. Mild-to-moderate AR patients were older, with larger left atrium-left ventricle (LV) volumes, greater LV mass index, higher filling pressure, and prevalence of diastolic dysfunction compared with the no-AR group (all P<.05). During 5-year follow-up, 113 patients died of cardiovascular causes, 124 patients were rehospitalized for HF, whereas 196 experienced the composite endpoint. Mild-to-moderate AR was identified as an independent predictor of all-cause death (HR, 1.62; 95% CI, 1.14 to 1.58; P=.04) and major adverse cardiovascular event occurrence (HR, 1.48; 95% CI, 1.05 to 2.09; P=.02). A total of 126 (35.5%) of 355 patients showed progression of AR at follow-up echocardiography. CONCLUSION: Mild-to-moderate AR is common among patients hospitalized for HFpEF. It is associated with adverse LV remodeling and worse long-term outcomes. These findings warrant further prospective studies addressing the importance of AR in prognostic stratification and exploring therapeutic strategies to mitigate its hemodynamic effect on HF.

Reliability of the one-repetition-maximum power clean test in adolescent athletes.

Although the power clean test is routinely used to assess strength and power performance in adult athletes, the reliability of this measure in younger populations has not been examined. Therefore, the purpose of this study was to determine the reliability of the 1-repetition maximum (1RM) power clean in adolescent athletes. Thirty-six male athletes (age 15.9 ± 1.1 years, body mass 79.1 ± 20.3 kg, height 175.1 ±7.4 cm) who had >1 year of training experience in weightlifting exercises performed a 1RM power clean on 2 nonconsecutive days in the afternoon following standardized procedures. All test procedures were supervised by a senior level weightlifting coach and consisted of a systematic progression in test load until the maximum resistance that could be lifted for 1 repetition using proper exercise technique was determined. Data were analyzed using an intraclass correlation coefficient (ICC[2,k]), Pearson correlation coefficient (r), repeated measures analysis of variance, Bland-Altman plot, and typical error analyses. Analysis of the data revealed that the test measures were highly reliable demonstrating a test-retest ICC of 0.98 (95% confidence interval = 0.96-0.99). Testing also demonstrated a strong relationship between 1RM measures in trials 1 and 2 (r = 0.98, p < 0.0001) with no significant difference in power clean performance between trials (70.6 ± 19.8 vs. 69.8 ± 19.8 kg). Bland-Altman plots confirmed no systematic shift in 1RM between trials 1 and 2. The typical error to be expected between 1RM power clean trials is 2.9 kg, and a change of at least 8.0 kg is indicated to determine a real change in lifting performance between tests in young lifters. No injuries occurred during the study period, and the testing protocol was well tolerated by all the subjects. These findings indicate that 1RM power clean testing has a high degree of reproducibility in trained male adolescent athletes when standardized testing procedures are followed and qualified instruction is present.

Utilizing longitudinal data in assessing all-cause mortality in patients hospitalized with heart failure.

AIMS: Risk stratification in patients with a new onset or worsened heart failure (HF) is essential for clinical decision making. We have utilized a novel approach to enrich patient level prognostication using longitudinally gathered data to develop ML-based algorithms predicting all-cause 30, 90, 180, 360, and 720 day mortality. METHODS AND RESULTS: In a cohort of 2449 HF patients hospitalized between 1 January 2011 and 31 December 2017, we utilized 422 parameters derived from 151 451 patient exams. They included clinical phenotyping, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions reflecting the standard of care as captured in individual electronic records. The development of predictive models consisted of 101 iterations of repeated random subsampling splits into balanced training and validation sets. ML models yielded area under the receiver operating characteristic curve (AUC-ROC) performance ranging from 0.83 to 0.89 on the outcome-balanced validation set in predicting all-cause mortality at aforementioned time-limits. The 1 year mortality prediction model recorded an AUC of 0.85. We observed stable model performance across all HF phenotypes: HFpEF 0.83 AUC, HFmrEF 0.85 AUC, and HFrEF 0.86 AUC, respectively. Model performance improved when utilizing data from more hospital contacts compared with only data collected at baseline. CONCLUSIONS: Our findings present a novel, patient-level, comprehensive ML-based algorithm for predicting all-cause mortality in new or worsened heart failure. Its robust performance across phenotypes throughout the longitudinal patient follow-up suggests its potential in point-of-care clinical risk stratification.

Amazonian terrestrial water balance inferred from satellite-observed water vapor isotopes.

Atmospheric humidity and soil moisture in the Amazon forest are tightly coupled to the region's water balance, or the difference between two moisture fluxes, evapotranspiration minus precipitation (ET-P). However, large and poorly characterized uncertainties in both fluxes, and in their difference, make it challenging to evaluate spatiotemporal variations of water balance and its dependence on ET or P. Here, we show that satellite observations of the HDO/H2O ratio of water vapor are sensitive to spatiotemporal variations of ET-P over the Amazon. When calibrated by basin-scale and mass-balance estimates of ET-P derived from terrestrial water storage and river discharge measurements, the isotopic data demonstrate that rainfall controls wet Amazon water balance variability, but ET becomes important in regulating water balance and its variability in the dry Amazon. Changes in the drivers of ET, such as above ground biomass, could therefore have a larger impact on soil moisture and humidity in the dry (southern and eastern) Amazon relative to the wet Amazon.

Scalable synthesis of [8]cycloparaphenyleneacetylene carbon nanohoop using alkyne metathesis.

Large scale synthesis of cycloparaphenyleneacetylenes has been challenging due to low macrocyclization yields and harsh aromatization methods that often decompose strained alkynes. Herein, a cis-stilbene-based building block is subjected to alkyne metathesis macrocylization. The following sequence of alkene-selective bromination and dehydrobromination afforded a [8]cycloparaphenyleneacetylene derivative in high yield with good scalability. X-Ray crystal structure and computational analysis revealed a unique same-rim conformation for the eight methyl groups on the nanohoop.

Cardiovascular risk profiles and outcomes of Chinese living inside and outside China.

AIM: To assess whether cardiovascular risk differs among the Chinese living inside and outside mainland China. METHODS AND RESULTS: Three thousand, four hundred and eighty-two East Asians were enrolled in the REduction of Atherothrombosis for Continued Health Registry in mainland China, Hong Kong/Singapore/Taiwan, Western Europe, and North America. Baseline demographics, medication use, risk factor control, and 30-month cardiovascular outcomes of the 2938 patients with atherothrombotic disease were compared. Rates of hypertension, hypercholesterolemia, diabetes, abdominal obesity, and body mass index ≥25 kg/m² were lowest in mainland China, were increased in Hong Kong/Singapore/Taiwan, and were highest in Western Europe and North America. Diabetes prevalence was 23% in mainland China, approximately two-fold lower than the other regions. Antihypertensive, antidiabetic, and antiplatelet agent use was similar in all regions. Risk factor control was significantly poorer in Western Europe and, except for glucose control, significantly better in North America. Thirty-month nonfatal stroke rates were highest in mainland China and fell in a stepwise manner in more westernized societies. Conversely, nonfatal myocardial infarction rates increased in more westernized societies. CONCLUSION: Obesity and other risk factors progressively worsen as patients move from mainland China to Hong Kong/Singapore/Taiwan and overseas. Despite similar medication use, risk factor control and cardiovascular outcomes were significantly different. The magnitude of these changes is larger than formerly estimated, suggesting population differences in cardiovascular risk and disease prevalence, likely to be more closely associated with lifestyle and cultural habits than genetic differences.

Hypertension Canada's 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children.

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

Functional-Optical Coherence Tomography: A Non-invasive Approach to Assess the Sympathetic Nervous System and Intrinsic Vascular Regulation.

Sympathetic nervous system dysregulation and vascular impairment in neuronal tissue beds are hallmarks of prominent cardiorespiratory diseases. However, an accurate and convenient method of assessing SNA and local vascular regulation is lacking, hindering routine clinical and research assessments. To address this, we investigated whether spectral domain optical coherence tomography (OCT), that allows investigation of retina and choroid vascular responsiveness, reflects sympathetic activity in order to develop a quick, easy and non-invasive sympathetic index. Here, we compare choroid and retina vascular perfusion density (VPD) acquired with OCT and heart rate variability (HRV) to microneurography. We recruited 6 healthy males (26 ± 3 years) and 5 healthy females (23 ± 1 year) and instrumented them for respiratory parameters, ECG, blood pressure and muscle sympathetic nerve microneurography. Choroid VPD decreases with the cold pressor test, inhaled hypoxia and breath-hold, and increases with hyperoxia and hyperpnea suggesting that sympathetic activity dominates choroid responses. In contrast, retina VPD was unaffected by the cold pressor test, increased with hypoxia and breath hold and decreases with hyperoxia and hyperpnea, suggesting metabolic vascular regulation dominates the retina. With regards to integrated muscle sympathetic nerve activity, HRV had low predictive power whereas choroid VPD was strongly (inversely) correlated with integrated muscle sympathetic nerve activity (R = -0.76; p < 0.0001). These data suggest that Functional-OCT may provide a novel approach to assess sympathetic activity and intrinsic vascular responsiveness (i.e., autoregulation). Given that sympathetic nervous system activity is the main determinant of autonomic function, sympathetic excitation is associated with severe cardiovascular/cardiorespiratory diseases and autoregulation is critical for brain health, we suggest that the use of our new Functional-OCT technique will be of broad interest to clinicians and researchers.

Prognostic impact of familial hypercholesterolemia on long-term outcomes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Patients with familial hypercholesterolemia (FH) are at increased risk for premature and subsequent cardiovascular disease. Data on long-term major adverse cardiovascular events (MACE) in patients with FH after percutaneous coronary intervention (PCI) in the era of high-intensity statins are scarce. OBJECTIVE: We assessed the prognostic impact of clinically diagnosed FH on long-term MACE, a composite of all-cause death, myocardial infarction, and ischemic stroke in patients admitted for stable coronary artery disease (SCAD) or acute coronary syndromes (ACSs) undergoing PCI. METHODS: FH was diagnosed according to the Dutch Lipid Clinic Network diagnosis criteria: "Unlikely FH" diagnosis was defined as 0 to 2 points, "possible FH" as 3 to 5 points, and "probable/definite FH" diagnosis as 6 or higher. RESULTS: From a total of 1550 eligible patients (47.4% were admitted for SCAD and 52.6% for ACS), 77 (5.0%) were classified as probable/definite FH, 332 (21.4%) as possible FH, and 1141 (73.6%) as unlikely FH. Mean follow-up was 6.0 ± 2.4 years. After adjustment for possible confounders, patients classified with probable or definite FH (hazard ratio [HR] 1.922 [95% confidence interval (CI) 1.220-2.999]; P = .004), but not patients with possible FH (HR 1.105 [95% CI 0.843-1.447]; P = .470) faced a significant, approximately 2-fold increased risk of MACE compared with patients with unlikely FH. CONCLUSION: After adjustment for confounders, patients with probable or definite FH faced an approximate 2-fold increased risk for long-term MACE compared with patients without FH despite the widespread use of high-intensity statins. The new option of proprotein convertase subtilisin/kexin type 9 gene inhibitors in addition to other current optimal lipid-lowering strategies might help to further improve clinical outcome in patients with probable/definite FH.

Initial diagnostic hypotheses bias analytic information processing in non-visual domains.

CONTEXT: Previous studies have shown that an initial diagnostic hypothesis biases automatic information processing. It is unclear if an initial hypothesis has a similar effect on analytic information processing. Our first objective was to study the effect of an initial diagnostic hypothesis on analytic processing. Our second objective was to assess the effect of clinical experience on analytic processing by evaluating the effect of clinical frequency and urgency of an alternative diagnosis on diagnosis selection. METHODS: During a 12-minute objective structured clinical examination station, 19 subspecialty medical residents diagnosed the cause of 3 clinical presentations: dyspnoea; headache, and chest pain. Subjects were randomly allocated cases for which the suggested initial hypothesis was either correct or incorrect. For cases with an incorrect initial hypothesis, the alternative diagnoses varied in the frequency with which they are encountered in clinical practice, and their clinical urgency, relative to the initial diagnostic hypothesis. RESULTS: All correct initial hypotheses were retained, compared with 10.9% of incorrect hypotheses. All cases with a correct initial hypothesis were diagnosed correctly, compared with 65.2% of cases with an incorrect hypothesis (risk ratio 1.5 [95% confidence interval 1.2-1.9], P = 0.02). Clinical frequency and urgency were not associated with alternative diagnosis selection. DISCUSSION: Our results suggest that an initial diagnostic hypothesis biases analytic processing. The data used to reject an initial hypothesis appear to drive selection of an alternative hypothesis. Further studies aimed at finding strategies for increasing the likelihood of generating a correct initial hypothesis or debiasing an initial hypothesis are needed.

Uric acid is associated with long-term adverse cardiovascular outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Evidence links uric acid (UA) with the promotion of cardiovascular disease. We assessed the prognostic value of UA on long-term major adverse outcomes (MACE) in patients with acute coronary syndrome (ACS), undergoing percutaneous coronary intervention (PCI). METHODS: As primary endpoint, we assessed the association of UA (continuous and dichotomized) with MACE, including cardiovascular death, myocardial infarction (MI) and stroke, using Cox regression and propensity matching. As secondary endpoints, the influence of hyperuricemia (defined as UA levels > 6.0 mg/dl in women, and >7.0 mg/dl in men) was analysed separately for cardiovascular death, MI, and stroke. The incremental prognostic value of UA was tested using the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). RESULTS: We included 1215 patients. Hyperuricemia was present in 356 (29.3%) patients. Mean follow-up was 5.5 years. UA (HR 1.091 [1.035-1.150]; p = 0.001) and hyperuricemia (HR 1.750 [1.388-2.207]; p < 0.001) were significantly associated with MACE. Results were consistent between Cox regression and propensity matched analysis. Patients with hyperuricemia had a 1.6-fold increased relative risk for cardiovascular death (p = 0.005) and a 1.5-fold increased risk for MI (p = 0.032). For stroke, hyperuricemia only constituted a confounder (HR 1.104; p = 0.970). The prognostic accuracy of an established risk prediction model was significantly increased by adding UA (continuous NRI p = 0.004; categorical NRI p = 0.029; IDI p = 0.002). CONCLUSIONS: Our data suggest an independent association of elevated UA with long-term MACE in ACS patients undergoing PCI. Whether lowering UA might be beneficial remains to be elucidated in large clinical trials.

Hypertension Canada's 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children. This year, the adult and pediatric guidelines are combined in one document. The new 2018 pregnancy-specific hypertension guidelines are published separately. For 2018, 5 new guidelines are introduced, and 1 existing guideline on the blood pressure thresholds and targets in the setting of thrombolysis for acute ischemic stroke is revised. The use of validated wrist devices for the estimation of blood pressure in individuals with large arm circumference is now included. Guidance is provided for the follow-up measurements of blood pressure, with the use of standardized methods and electronic (oscillometric) upper arm devices in individuals with hypertension, and either ambulatory blood pressure monitoring or home blood pressure monitoring in individuals with white coat effect. We specify that all individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure. Finally, an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in individuals with heart failure (with ejection fraction < 40%) who are symptomatic despite appropriate doses of guideline-directed heart failure therapies. The specific evidence and rationale underlying each of these guidelines are discussed.

The molecular identities of the Caenorhabditis elegans intraflagellar transport genes dyf-6, daf-10 and osm-1.

The Caenorhabditis elegans genes dyf-6, daf-10, and osm-1 are among the set of genes that affect chemotaxis and the ability of certain sensory neurons to take up fluorescent dyes from the environment. Some genes in this category are known to be required for intraflagellar transport (IFT), which is the bidirectional movement of raft-like particles along the axonemes of cilia and flagella. The cloning of dyf-6, daf-10, and osm-1 are described here. The daf-10 and osm-1 gene products resemble each other and contain WD and WAA repeats. DYF-6, the product of a complex locus, lacks known motifs, but orthologs are present in flies and mammals. Phenotypic analysis of dyf-6 mutants expressing an OSM-6::GFP reporter indicates that the cilia of the amphid and phasmid dendritic endings are foreshortened. Consistent with genetic mosaic analysis, which indicates that dyf-6 functions in neurons of the amphid sensilla, DYF-6::GFP is expressed in amphid and phasmid neurons. Movement of DYF-6::GFP within the ciliated endings of the neurons indicates that DYF-6 is involved in IFT. In addition, IFT can be observed in dauer larvae.