Exercise-Induced Pulmonary Hypertension: Rationale for Correcting Pressures for Flow and Guide to Non-Invasive Diagnosis.

Exercise-induced pulmonary hypertension (exPHT) is a hemodynamic condition linked to increased morbidity and mortality across various cardiopulmonary diseases. Traditional definitions of exPHT rely on absolute cut-offs, such as mean pulmonary artery pressure (mPAP) above 30 mmHg during exercise. However, recent research suggests that these cut-offs may not accurately reflect pathophysiological changes, leading to false positives and false negatives. Instead, the mPAP over cardiac output (CO) slope, which incorporates both pressure and flow measurements, has emerged as a more reliable indicator. A slope exceeding 3 mmHg/L/min is now considered diagnostic for exPHT and strongly correlates with adverse outcomes. Stress echocardiography serves as a viable alternative to invasive assessment, enabling broader implementation. This review discusses the physiological basis of pulmonary hemodynamics during exercise, the advantages of the mPAP/CO slope over absolute pressure measurements, the evidence supporting its inclusion in clinical guidelines, and provides a practical guide for non-invasive determining the mPAP/CO slope in clinical practice.

The Leicester, Leicestershire and Rutland quality improvement project and integrated chronic kidney disease system: implementation within a primary care network.

BACKGROUND: The optimisation of patients in primary care is a prime opportunity to manage patient care within the community and reduce the burden of referrals on secondary care. This paper presents a quality improvement clinical programme taking place within an NHS Primary Care Network as part of the wider Leicester Leicestershire Rutland integrated chronic kidney disease programme. METHOD: Patients are optimised to guidelines from the National Institute for Health and Care Excellence, by a primary care clinical team who are supported by nephrology consultants and nephrology pharmacists. Multidisciplinary team meetings take place with secondary care specialists and primary care staff. Learning is passed to the community clinicians for better patient treatment locally. RESULTS: A total of 526 patients were reviewed under this project.The total number of referrals to secondary care which were discharged following first outpatient appointment, reduced from 42.9% to 10%. This reduction of 32.9% represents the optimisation of patient cases through this quality improvement project. Patients can be optimised and managed within the community, reducing the number of unnecessary referrals to secondary care. CONCLUSION: This programme has the potential to offer significant improvement in patient outcomes when expanded to a larger patient base. Medicine management and the use of clinical staff are optimised in both primary and secondary care.

The Biochar Amendment Improves Tomato Growth and Yield under Deficit Irrigation in Sandy Loam Soil in Senegal.

Poor agricultural soil management practices and water use optimisation in irrigation are major challenges facing crop production in Senegal. To address these problems, a factorial experiment was conducted in 2021 and 2022 to investigate the effects of biochar on tomato growth and yield in sandy loam soil under different irrigation levels. Treatments included three biochar treatments (B2 = 30 t·ha-1, B1 = 15 t·ha-1, and B0 = 0 t·ha-1) and three irrigation levels (full irrigation, W0 = 8 L·m-2·day-1; medium deficit irrigation, W1 = 6 L·m-2·day-1, which is 75% of W0; and deficit irrigation, W2 = 4 L·m-2·day-1, 50% of W0). The results showed that using biochar at 30 t·ha-1 significantly (P < 0.05) reduced the bulk density of the soil by up to 8.3% under W1. In addition, biochar at 15 t·ha-1 and 30 t·ha-1 enhanced, regardless of the amount of water applied, the growth of tomato plants by at least 14% compared to that in the B0 treatment. Furthermore, the tomatoes' yields in biochar treatments B1 (12.58 t·ha-1) and B2 (12.45 t·ha-1) under W2 were greater than those under B0 (9.27 t·ha-1) under full irrigation. The combinations of biochar and the lowest irrigation water level (W2 and B1 or W2 and B2) can therefore allow a water economy of up to 50% of full irrigation without compromising yield. Our study concluded that biochar could sustainably reduce agricultural water consumption while increasing yields. To further understand the influence of biochar on sandy loam soil, more research is needed on its effects on soil moisture content at permanent wilting points and field capacity.

Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. METHODS AND RESULTS: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e' (exE/e') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/e'<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e'≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e'<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/e'<15 but a high slope had NT-proBNP levels and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope. CONCLUSIONS: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Combined use of long-lasting insecticidal nets and Bacillus thuringiensis israelensis larviciding, a promising integrated approach against malaria transmission in northern Côte d'Ivoire.

BACKGROUND: The recent reduction in malaria burden in Côte d'Ivoire is largely attributable to the use of long-lasting insecticidal nets (LLINs). However, this progress is threatened by insecticide resistance and behavioral changes in Anopheles gambiae sensu lato (s.l.) populations and residual malaria transmission, and complementary tools are required. Thus, this study aimed to assess the efficacy of the combined use of LLINs and Bacillus thuringiensis israelensis (Bti), in comparison with LLINs. METHODS: This study was conducted in the health district of Korhogo, northern Côte d'Ivoire, within two study arms (LLIN + Bti arm and LLIN-only arm) from March 2019 to February 2020. In the LLIN + Bti arm, Anopheles larval habitats were treated every fortnight with Bti in addition to the use of LLINs. Mosquito larvae and adults were sampled and identified morphologically to genus and species using standard methods. The members of the An. gambiae complex were determined using a polymerase chain reaction technique. Plasmodium infection in An. gambiae s.l. and malaria incidence in local people was also assessed. RESULTS: Overall, Anopheles spp. larval density was lower in the LLIN + Bti arm 0.61 [95% CI 0.41-0.81] larva/dip (l/dip) compared with the LLIN-only arm 3.97 [95% CI 3.56-4.38] l/dip (RR = 6.50; 95% CI 5.81-7.29; P < 0.001). The overall biting rate of An. gambiae s.l. was 0.59 [95% CI 0.43-0.75] biting/person/night in the LLIN + Bti arm against 2.97 [95% CI 2.02-3.93] biting/person/night in LLIN-only arm (P < 0.001). Anopheles gambiae s.l. was predominantly identified as An. gambiae sensu stricto (s.s.) (95.1%, n = 293), followed by Anopheles coluzzii (4.9%; n = 15). The human-blood index was 80.5% (n = 389) in study area. EIR was 1.36 infected bites/person/year (ib/p/y) in the LLIN + Bti arm against 47.71 ib/p/y in the LLIN-only arm. Malaria incidence dramatically declined from 291.8‰ (n = 765) to 111.4‰ (n = 292) in LLIN + Bti arm (P < 0.001). CONCLUSIONS: The combined use of LLINs with Bti significantly reduced the incidence of malaria. The LLINs and Bti duo could be a promising integrated approach for effective vector control of An. gambiae for elimination of malaria.

Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis.

BACKGROUND: In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines. OBJECTIVES: The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm2 and peak aortic valve velocity <4.0 m/s. METHODS: All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women. RESULTS: A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women. CONCLUSIONS: Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS.

Mitral regurgitation in heart failure with preserved ejection fraction: The interplay of valve, ventricle, and atrium.

Mitral regurgitation (MR) is highly prevalent among patients with heart failure and preserved ejection fraction (HFpEF). Despite this combination being closely associated with unfavourable outcomes, it remains relatively understudied. This is partly due to the inherent heterogeneity of patients with HFpEF. To address this gap, dissecting HFpEF into mechanism-based phenotypes may offer a promising avenue for advancing our comprehension of these complex intertwined conditions. This review employs the validated CircAdapt model to explore the haemodynamic implications of moderate to severe MR across a well-defined spectrum of myocardial disease, characterized by impaired relaxation and reduced myocardial compliance. Both heart failure and mitral valve disease share overlapping symptomatology, primarily attributed to elevated pulmonary pressures. The intricate mechanisms contributing to these elevated pressures are multifaceted, potentially influenced by diastolic dysfunction, left atrial myopathy, and MR. Accurate evaluation of the haemodynamic and clinical impact of MR necessitates a comprehensive approach, taking into account the characteristics of both the left atrium and left ventricle, as well as their intricate interactions, which may currently be underemphasized in diagnostic practice. This holistic assessment is imperative for enhancing our understanding and refining therapeutic strategies within this patient cohort.

Non-invasive imaging in acute decompensated heart failure with preserved ejection fraction.

Non-invasive imaging plays an increasingly important role in emergency medicine, given the trend towards smaller, portable ultrasound devices, the integration of ultrasound imaging across diverse medical disciplines, and the growing evidence supporting its clinical benefits for the patient. Heart failure with preserved ejection fraction (HFpEF) provides a compelling illustration of the impactful role that imaging plays in distinguishing diverse clinical presentations of heart failure with numerous associated comorbidities, including pulmonary, renal, or hepatic diseases. While a preserved left ventricular ejection fraction might misguide the clinician away from diagnosing cardiac disease, there are several clues provided by cardiac, vascular, and lung ultrasonography, as well as other imaging modalities, to rapidly identify (decompensated) HFpEF. Congestion remains the primary reason why patients with heart failure (irrespective of ejection fraction) seek emergency care. Furthermore, comprehensive phenotyping is becoming increasingly important, considering the development of targeted treatments for conditions exhibiting HFpEF physiology, such as cardiac amyloidosis. Timely recognition in such cases has lasting implications for long-term outcomes.

Colloidal Atomic Layer Deposition on Nanocrystals Using Ligand-Modified Precursors.

Atomic layer deposition (ALD) is a method to grow thin metal oxide layers on a variety of materials for applications spanning from electronics to catalysis. Extending ALD to colloidally stable nanocrystals promises to combine the benefits of thin metal oxide coatings with the solution processability of the nanocrystals. However, challenges persist in applying this method, which relate to finding precursors that promote the growth of the metal oxide while preserving colloidal stability throughout the process. Herein, we introduce a colloidal ALD method to coat nanocrystals with amorphous metal oxide shells using metal and oxygen precursors that act as colloidal stabilizing ligands. Our scheme involves metal-amide precursors modified with solubilizing groups and oleic acid as the oxygen source. The growth of the oxide is self-limiting and proceeds in a layer-by-layer fashion. Our protocol is generalizable and intrinsically scalable. Potential applications in display, light detection, and catalysis are envisioned.

Long live(d) CsPbBr3 superlattices: colloidal atomic layer deposition for structural stability.

Superlattice formation afforded by metal halide perovskite nanocrystals has been a phenomenon of interest due to the high structural order induced in these self-assemblies, an order that is influenced by the surface chemistry and particle morphology of the starting building block material. In this work, we report on the formation of superlattices from aluminum oxide shelled CsPbBr3 perovskite nanocrystals where the oxide shell is grown by colloidal atomic layer deposition. We demonstrate that the structural stability of these superlattices is preserved over 25 days in an inert atmosphere and that colloidal atomic layer deposition on colloidal perovskite nanocrystals yields structural protection and an enhancement in photoluminescence quantum yields and radiative lifetimes as opposed to gas phase atomic layer deposition on pre-assembled superlattices or excess capping group addition. Structural analyses found that shelling resulted in smaller nanocrystals that form uniform supercrystals. These effects are in addition to the increasingly static capping group chemistry initiated where oleic acid is installed as a capping ligand directly on aluminum oxide. Together, these factors lead to fundamental observations that may influence future superlattice assembly design.

Mitral Valve Surgery for Mitral Regurgitation Results in Reduced Left Ventricular Ejection Fraction in Barlow's Disease as Compared with Fibro-Elastic Deficiency.

Surgical correction of severe mitral regurgitation (MR) can reverse left ventricular (LV) remodeling in patients with mitral valve prolapse (MVP). However, whether this process is similar to the case in Barlow's Disease (BD) and Fibro-elastic Deficiency (FED) is currently unknown. The aim of this study is to evaluate post-operative LV reverse remodeling and function in patients with BD versus FED. In this study, 100 MVP patients (BD = 37 and FED = 63) with severe MR who underwent mitral valve surgery at three Belgian centers were retrospectively included. Transthoracic echocardiography was used to assess MR severity, LV volumes and function before surgery and 6 months thereafter. Baseline MR severity, LV ejection fraction (LVEF), indexed LV end-diastolic (LVEDVi) and end-systolic volumes (LVESVi) were not different between the groups. After a median follow-up of 278 days, there was a similar decrease in LVEDVi, but a trend towards a smaller decrease in LVESVi in BD compared to FED (-3.0 ± 11.2 mL/m2 vs. -5.3 ± 9.0 mL/m2; p = 0.154). This resulted in a significantly larger decrease in LVEF in BD (-8.3 ± 9.6%) versus FED (-3.9 ± 6.9%) after adjusting for baseline LVEF (p < 0.001) and type of surgical intervention (p = 0.01). These findings suggest that LV (reverse) remodeling in BD could be affected by other mechanisms beyond volume overload, potentially involving concomitant cardiomyopathy.

Genomic characterisation of bioaerosols within livestock facilities: A systematic review.

Livestock facilities are widely regarded as reservoirs of infectious disease, owing to their abundance in particulate matter (PM) and microbial bioaerosols. Over the past decade, bioaerosol studies have increasingly utilised high throughput sequencing (HTS) to achieve superior throughput, taxonomic resolution, and the detection of unculturable organisms. However, the prevailing focus on amplicon sequencing has limited the identification of viruses and microbial taxa at the species-level. Herein, a literature search was conducted to identify methods capable of overcoming the aforementioned limitations. Screening 1531 international publications resulted in 29 eligible for review. Metagenomics capable of providing rich insights were identified in only three instances. Notably, long-read sequencing was not utilised for metagenomics. This review also identified that sample collection methods lack a uniform approach, highlighted by the differences in sampling equipment, flow rates and durations. Further heterogeneity was introduced by the unique sampling conditions, which makes it challenging to ground new findings within the established literature. For instance, winter was associated with increased microbial abundance and antimicrobial resistance, yet less alpha diversity. Researchers implementing metagenomics into the livestock environment should consider season, the microclimate, and livestock growth stage as influential upon their findings. Considering the increasing accessibility of long-read sequencing, future research should explore its viability within a novel uniform testing protocol for bioaerosol emissions.

Hybrid oxide coatings generate stable Cu catalysts for CO2 electroreduction.

Hybrid organic/inorganic materials have contributed to solve important challenges in different areas of science. One of the biggest challenges for a more sustainable society is to have active and stable catalysts that enable the transition from fossil fuel to renewable feedstocks, reduce energy consumption and minimize the environmental footprint. Here we synthesize novel hybrid materials where an amorphous oxide coating with embedded organic ligands surrounds metallic nanocrystals. We demonstrate that the hybrid coating is a powerful means to create electrocatalysts stable against structural reconstruction during the CO2 electroreduction. These electrocatalysts consist of copper nanocrystals encapsulated in a hybrid organic/inorganic alumina shell. This shell locks a fraction of the copper surface into a reduction-resistant Cu2+ state, which inhibits those redox processes responsible for the structural reconstruction of copper. The electrocatalyst activity is preserved, which would not be possible with a conventional dense alumina coating. Varying the shell thickness and the coating morphology yields fundamental insights into the stabilization mechanism and emphasizes the importance of the Lewis acidity of the shell in relation to the retention of catalyst structure. The synthetic tunability of the chemistry developed herein opens new avenues for the design of stable electrocatalysts and beyond.

Significant reduction of blackfly densities in persistent onchocerciasis area following pilot implementation of an environment friendly approach (Slash and Clear).

The effectiveness of the "Slash and Clear" method in reducing blackfly populations in low transmission areas is established, but its impact in high transmission settings with large rivers and dense vectors is yet to be proven. A community-based intervention study was conducted in the Mbam Valley, Centre Cameroon, involving two sites: Bayomen (control) and Biatsota (intervention). In each arm, baseline blackfly densities were collected over one year using the human landing method. The intervention consisted of destroying the trailing vegetation where blackflies breed. Blackfly densities were collected post-intervention to assess the impact of the intervention. Post-intervention data showed a 50.8% reduction in blackfly density in Biatsota (mean number of collected blackflies from 1936 to 953), while a reduction of 26.7% was observed in Bayomen (mean number of collected blackflies from 2418 to 1774). The reduction rate attributable to the intervention was 32.9%. Statistical analysis confirmed that the reduction in blackfly density was significantly greater in the intervention site. This study demonstrates the feasibility and significant impact of the "Slash and Clear" method in high transmission areas. However, further research is required to assess its long-term effects and determine how this strategy can be scaled up and sustained until onchocerciasis elimination is achieved.

Exercise pulmonary hypertension by the mPAP/CO slope in primary mitral regurgitation.

AIMS: Exercise-induced pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure over cardiac output (mPAP/CO) slope >3 mmHg/L/min, has important diagnostic and prognostic implications. The aim of this study is to investigate the value of the mPAP/CO slope in patients with more than moderate primary mitral regurgitation (MR) with preserved ejection fraction and no or discordant symptoms. METHODS AND RESULTS: A total of 128 consecutive patients were evaluated with exercise echocardiography and cardiopulmonary testing. Clinical outcome was defined as the composite of mitral valve intervention, new-onset atrial fibrillation, cardiovascular hospitalization, and all-cause mortality. The mean age was 63 years, 61% were male, and the mean LVEF was 66 ± 6%. The mPAP/CO slope correlated with peak VO2 (r = -0.52, P < 0.001), while the peak systolic pulmonary artery pressure (sPAP) did not (r = -0.06, P = 0.584). Forty-six per cent (n = 59) had peak exercise sPAP ≥60 mmHg, and 37% (n = 47) had mPAP/CO slope >3 mmHg/L/min. Event-free survival was 55% at 1 year and 46% at 2 years, with reduced survival in patients with mPAP/CO slope >3 mmHg/L/min (hazard ratio, 4.9; 95% confidence interval, 2.9-8.2; P < 0.001). In 53 cases (41%), mPAP/CO slope and peak sPAP were discordant: patients with slope >3 mmHg/L/mmHg and sPAP <60 mmHg (n = 21) had worse outcome vs. peak sPAP ≥60 mmHg and normal slope (n = 32, log-rank P = 0.003). The mPAP/CO slope improved predictive models for outcome, incremental to resting and exercise sPAP, and peak VO2. CONCLUSION: Exercise PH defined by the mPAP/CO slope >3 mmHg/L/min is associated with decreased exercise capacity and a higher risk of adverse events in significant primary MR and no or discordant symptoms. The slope provides a greater prognostic value than single sPAP measures and peak VO2.

Microarray molecular mapping of horses with severe asthma.

BACKGROUND: Severe asthma (SA) in horses, resembling human asthma, is a prevalent, debilitating allergic respiratory condition marked by elevated allergen-specific immunoglobulin E (IgE) against environmental proteins; however, research exploring the exposome's influence on IgE profiles is currently limited but holds paramount significance for diagnostic and therapeutic developments. ANIMALS: Thirty-five sports horses were analyzed, consisting of environmentally matched samples from France (5 SA; 6 control), the United States (6 SA; 6 control), and Canada (6 SEA; 6 control). METHODS: This intentional cross-sectional study investigated the sensitization profiles of SA-affected and healthy horses via serological antigen microarray profiling. Partial least square-discriminant analysis (PLS-DA) was used to identify and rank the importance of allergens for class separation (ie, affected/non-affected) as variable influence of projection (VIP), and allergen with commonality internationally established via frequency analysis. RESULTS: PLS-DA models showed high discriminatory power in predicting SA in horses from Canada (area under the curve [AUC] 0.995) and France (AUC 0.867) but poor discriminatory power in horses from the United States (AUC 0.38). Hev b 5.0101, Cyn D, Der p 2, and Rum cr were the only shared allergens across all geographical groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Microarray profiling can identify specific allergenic components associated with SA in horses, while mathematical modeling of this data can be used for disease classification, highlighting the variability of sensitization profiles between geographical locations and emphasizing the importance of local exposure to the prevalence of different allergens. Frequency scoring analysis can identify important variables that contribute to the classification of SA across different geographical regions.

Anisotropic particle multiphase equilibria in nonuniform fields.

We report a method to predict equilibrium concentration profiles of hard ellipses in nonuniform fields, including multiphase equilibria of fluid, nematic, and crystal phases. Our model is based on a balance of osmotic pressure and field mediated forces by employing the local density approximation. Implementation of this model requires development of accurate equations of state for each phase as a function of hard ellipse aspect ratio in the range k = 1-9. The predicted density profiles display overall good agreement with Monte Carlo simulations for hard ellipse aspect ratios k = 2, 4, and 6 in gravitational and electric fields with fluid-nematic, fluid-crystal, and fluid-nematic-crystal multiphase equilibria. The profiles of local order parameters for positional and orientational order display good agreement with values expected for bulk homogeneous hard ellipses in the same density ranges. Small discrepancies between predictions and simulations are observed at crystal-nematic and crystal-fluid interfaces due to limitations of the local density approximation, finite system sizes, and uniform periodic boundary conditions. The ability of the model to capture multiphase equilibria of hard ellipses in nonuniform fields as a function of particle aspect ratio provides a basis to control anisotropic particle microstructure on interfacial energy landscapes in diverse materials and applications.