Strain surveillance during chemotherapy to improve cardiovascular outcomes: the SUCCOUR-MRI trial.

BACKGROUND AND AIMS: The detection of cancer therapy-related cardiac dysfunction (CTRCD) by reduction of left ventricular ejection fraction (LVEF) during chemotherapy usually triggers the initiation of cardioprotective therapy. This study addressed whether the same approach should be applied to patients with worsening of global longitudinal strain (GLS) without attaining thresholds of LVEF. METHODS: Strain sUrveillance during Chemotherapy for improving Cardiovascular Outcomes (SUCCOUR-MRI) was a prospective multicentre randomized controlled trial involving 14 sites. Of 355 patients receiving anthracyclines with normal baseline LVEF, 333 patients (age 59±13 years, 79% women) with at least one other CTRCD risk factor, able to undergo magnetic resonance imaging (MRI), GLS and 3D echocardiography were tracked over 12 months. A total of 105 patients (age 59±13 years, 75% women, 69% breast cancer) developing GLS-CTRCD (>12% relative reduction of GLS without a change in LVEF) between cardioprotection with neurohormonal antagonists versus usual care were randomized. The primary endpoint was 12-month change in MRI-LVEF; the secondary endpoint was MRI LVEF-defined CTRCD. RESULTS: During follow-up, 2 patients died and 2 developed heart failure. Most patients were randomized at 3 months (62%). Median doses of angiotensin inhibition/blockade and beta-blockade were 75% and 50% of respective targets; 21 (43%) had side-effects attributed to cardioprotection. Due to a smaller LVEF change from baseline with cardioprotection than usual care (-2.5±5.4% vs -5.6±5.9%, p=0.009), follow-up LVEF was higher after cardioprotection (59±5% vs 55±6%, p<0.0001). After adjustment for baseline LVEF, the mean (95% confidence interval) difference in the change in LVEF between the two groups was -3.6% (-1.8% to -5.5%, p<0.001). After cardioprotection, 1/49 patients developed 12-month LVEF-CTRCD, compared to 6/56 in usual care (p=0.075). GLS improved at 3 months post-randomization in the cardioprotection group, with little change with usual care. CONCLUSIONS: In patients with isolated GLS reduction after anthracyclines, cardioprotection is associated with better preservation of 12-month MRI-LVEF compared with usual care.

Left Atrial Strain to Predict Postoperative Atrial Fibrillation in Patients Undergoing Off-pump Coronary Artery Bypass Graft.

OBJECTIVE: Postoperative atrial fibrillation (POAF) is associated with increased morbidity, mortality, and length of hospital stay. The objective of this study was to assess the utility of left atrial strain (LAS) to predict POAF in patients undergoing off-pump coronary artery bypass grafting (OPCABG). DESIGN: Retrospective observational study. SETTING: Tertiary care hospital. PARTICIPANTS: 103 patients undergoing OPCABG. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: In addition to comprehensive transthoracic echocardiography, LAS was measured for reservoir (R), conduction (CD), and contraction (CT) components. POAF was defined as new electrocardiographic evidence of AF requiring treatment. Logistic regression was done to assess factors associated with POAF. The diagnostic accuracy of variables in predicting POAF was assessed by receiver operating characteristic analysis. POAF was documented in 24 (23.3%) patients. There was no difference in ejection fraction, average global longitudinal strain, or proportion of left ventricular diastolic dysfunction grades between patients with POAF and patients without POAF. All three components of LAS: LAS R (19.2 ± 4.7 v 23.5 ± 4.8, p < 0.001), LAS CD (8.9 ± 3.7 v 12.3 ± 4.8, p = 0.1), and LAS CT (10.3 ± 3.9 v 12.1 ± 4.1, p = 0.04), were significantly lower among patients with POAF compared with patients without POAF, respectively. According to univariate analysis, all components of LAS were statistically significant predictors of POAF. In multivariate analysis, only age (odds ratio = 1.08, p = 0.025) and LAS R (odds ratio = 0.84, p = 0.004) were independently associated with POAF. LAS R was a better predictor of POAF, with an area under the curve (AUC) of 0.758, than LAS CD (AUC = 0.67) and LAS CT (AUC = 0.62). LAS R had an optimal cutoff of 23% with sensitivity of 95.8% (confidence interval: 78.9-99.9%) and specificity of 49.4% (37.9-60.9%) to predict POAF. CONCLUSIONS: LAS R is a significant predictor of POAF, and its use can be recommended for screening of OPCABG patients at high risk of POAF.

Serial Changes in Ventricular Strain in Symptomatic Obstructive Hypertrophic Cardiomyopathy Treated With Mavacamten: Insights From the VALOR-HCM Trial.

BACKGROUND: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy, VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) demonstrated that mavacamten reduces the need for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function. In VALOR-HCM, we assessed serial changes in LV and right ventricular (RV) strain. METHODS: VALOR-HCM included 112 patients with symptomatic obstructive hypertrophic cardiomyopathy (mean, 60 years; 51% male; LV ejection fraction, 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo (n=52) transitioned to mavacamten from weeks 16 to 56 (40-week exposure). LV-GLS and RV-GLS assessment was performed using a vendor-neutral software. Non-foreshortened apical (4-, 3-, and 2-chamber) views were used to obtain peak LV-GLS. RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. RESULTS: At baseline, the mean LV-GLS, RV 4-chamber, and free wall strain values were -14.7%, -22.2%, and -16.8%, respectively (all worse than reported normal means). In the total study sample, LV-GLS significantly improved from baseline to week 56 (P=0.02). Twelve patients had transient reduction in LV ejection fraction (<50%) requiring temporary drug interruption (including 3 permanent discontinuations). The LV-GLS in this subgroup was worse at baseline versus total study population (-11.4%), with no significant worsening from baseline through week 56 (P=0.64). Both free wall and 4-chamber RV-GLS remained unchanged from baseline to week 56 (P=0.62 and P=0.56, respectively). CONCLUSIONS: In VALOR-HCM, treatment with mavacamten improved LV-GLS from baseline through week 56 (with no significant worsening of LV-GLS in patients with a reduction in LV ejection fraction ≤50%), suggesting a favorable long-term impact on regional LV systolic function. Additionally, there was no detrimental impact on RV systolic function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072.

Myocardial work in idiopathic premature ventricular contractions: Assessing left ventricular function and prognosis.

BACKGROUND: Premature ventricular contractions (PVCs) can lead to impairment of left ventricular function. The noninvasive myocardial work technique, which incorporates left ventricular afterload, represents a new method for assessing left ventricular functional. AIM: The aim of this study is to explore the value of noninvasive myocardial work technique in assessing left ventricular systolic function in patients with PVCs. METHODS: Compare the clinical data, two-dimensional echocardiography parameters, and myocardial work parameters of 66 patients with PVCs and 35 healthy volunteers and explore the relevant risk factors for postoperative recurrence in patients with PVCs. RESULTS: In patients with PVCs compared to the control group, they exhibit enlargement of left atrial diameter (LAD) and left ventricular internal dimension in diastole (LVIDd), as well as thickening of the left ventricular wall. The global work waste (GWW) increases, while the global work efficiency (GWE) decreases. There is a significant negative correlation between the PVC burden and GWE (r = -0.70, p <0.01), and a significant positive correlation between the PVC burden and GWW (r = 0.58, p <0.01). GWE is a sensitive indicator for predicting the recurrence of PVCs after radiofrequency ablation. Patients with GWE <91.5%, global longitudinal strain (GLS) <15.5%, and ejection fraction (EF) <62.5% have a higher postoperative recurrence rate. CONCLUSION: PVCs can cause impairment of left ventricular systolic function. GWE is the most sensitive indicator for predicting postoperative recurrence in patients with PVCs. Patients with GWE <91.5%, GLS <15.5%, and EF <62.5% have a higher postoperative recurrence rate.

Myocardial Mechanics in Acromegaly: A Meta-Analysis of Echocardiographic Studies.

INTRODUCTION: Evidence on myocardial deformation, detected by speckle tracking echocardiography (STE), in patients with acromegaly is scanty. AIM: The aim of the present meta-analysis was to provide an updated information on left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) in patients with acromegaly and preserved LVEF. METHODS: Following the PRISMA guidelines, systematic searches were conducted across bibliographic databases (Pub-Med, OVID, EMBASE and Cochrane library) to identify eligible studies from inception up to June 30-2024. Clinical studies published in English reporting data on LV mechanics in patients with acromegaly and controls were included. The statistical difference of the echocardiographic variables of interest between groups such as LVEF and global longitudinal strain (GLS) was calculated by standardized mean difference (SMD) with 95% confidence interval (CI) by using random-effects models. RESULTS: Seven studies including 288 patients with acromegaly and 294 healthy individuals were considered for the analysis. Pooled average LVEF values were 64.6 ± 1.5% in the healthy control group and 64.0 ± 1.3% in the acromegaly group (SMD: - 0.21 ± 0.22, CI -0.62/0.22, p = 0.34); the corresponding values of GLS were - 19.1.1 ± 1.2% and - 17.5 ± 1.2% (SMD: -0.52 ± 0.27, CI - 1.05/0.01, p = 0.05). No difference was found between the two groups for both global circumferential strain (GCS) and global radial strain (GRS). CONCLUSIONS: Our findings suggest that patients with acromegaly in which LVEF is completely comparable to healthy controls show an impairment in GLS of borderline statistical significance. Whether GLS assessment can actually unmask early alterations of systolic function in patients with acromegaly better than LVEF will need to be investigated by future studies.

Recombinant Marek's disease virus type 1 provides full protection against H9N2 influenza A virus in chickens.

The H9N2 subtype of the avian influenza virus (AIV) poses a significant threat to the poultry industry and human health. Recombinant vaccines are the preferred method of controlling H9N2 AIV, and Marek's disease virus (MDV) is the ideal vector for recombinant vaccines. During this study, we constructed two recombinant MDV type 1 strains that carry the hemagglutinin (HA) gene of AIV to provide dual protection against both AIV and MDV. To assess the effects of different MDV insertion sites on the protective efficacy of H9N2 AIV, the HA gene of H9N2 AIV was inserted in UL41 and US2 of the MDV type 1 vector backbone to obtain recombinant viruses rMDV-UL41/HA and rMDV-US2/HA, respectively. An indirect immunofluorescence assay showed sustained expression of HA protein in both recombinant viruses. Additionally, the insertion of the HA gene in UL41 and US2 did not affect MDV replication in cell cultures. After immunization of specific pathogen-free chickens, although both the rMDV-UL41/HA and rMDV-US2/HA groups exhibited similar levels of hemagglutination inhibition antibody titers, only the rMDV-UL41/HA group provided complete protection against the H9N2 AIV challenge, and also offered complete protection against challenge with MDV. These results demonstrated that rMDV-UL41/HA could be used as a promising bivalent vaccine strain against both H9N2 avian influenza and Marek's disease in chickens.

Strain-Mediated Defect Engineering toward Rapid Atomic Migration in Fe-Al Diffusion Couples.

In the pursuit of rapid atomic migration in lightweight Fe-Al diffusion couples, rationally designing short-circuit diffusion paths has become paramount. Herein, a strain-mediated defect engineering strategy was proposed for reducing the vacancy activation energy and enhancing diffusion behaviors along dislocations (DLs) and grain boundaries (GBs). Combining the modified Arrhenius-type relationship, an interfacial apparent activation energy of 139 kJ mol-1 was acquired utilizing defect engineering, which was decreased by about 49%. This was closely related to high-density vacancies, DLs, and GBs formed in strained Fe and Al materials, which provided more low activation energy paths for atomic migration. First-principles calculations indicated that the lattice diffusion barrier mediated by monovacancy was reduced with strain incorporation, attributed to the weakened atom-vacancy bond as a consequence of less electron transport. The synergistic effect of abnormal electron-charge distribution in the bulk and strong attraction force at the Al/Fe interface radically resulted in rapid atomic migration, collectively regulating the "breaking-forming bond" process.

Effects of Fe addition on the mechanical and corrosive properties of biomedical Co-Cr-W-Ni alloys for balloon-expandable stents.

Co-20Cr-15W-10Ni (mass%, CCWN) alloy is extensively used as a platform material for balloon-expandable stents. In this study, the mechanical properties of CCWN alloy are improved following the addition of Fe, and the effects of Fe addition on the mechanical and corrosive properties of the alloy are investigated. As-cast specimens were fabricated by adding pure Fe to a commercially available CCWN alloy (base alloy) such that the resulting alloys contained 4, 6, and 8 mass% Fe. The as-cast specimens were subjected to homogenization heat treatment at 1523 K for 7.2 ks and then hot-forged at 1473 K (as-forged specimens). The as-forged specimens were cold-rolled at a reduction rate of 30% and heat-treated at 1473 K for 300 s (recrystallized specimens). The matrix of the recrystallized base- and Fe-containing alloys consisted of a single γ (face-centered cubic)-phase. The Fe-added alloys revealed precipitates composed of the η-phase (M6X-M12X-type phase, M: metallic element, X: C and/or N). The average grain size of the recrystallized base and Fe-added alloy specimens was approximately 34 µm and the amount of added Fe had no significant effect on the static recrystallization behavior of the resulting alloys. Alloys containing 6 mass% or more Fe showed improvements in strength and ductility compared with the base alloy. When the Fe-added alloys were compared, their strength decreased whereas their ductility increased when the added Fe increased. Because Fe acts as a γ-phase-stabilizing element for Co, Fe addition increases the stacking fault energy of the base alloy, resulting in the formation of the ε (hexagonal close-packed)-phase owing to the suppression of strain-induced martensitic transformation (SIMT), and improvements in ductility. No deterioration in corrosion resistance was observed following the addition of up to 8 mass% Fe to the base alloy. Based on these results, the addition of Fe to CCWN alloy may be considered an effective method to improve its mechanical properties, especially ductility, without impairing its corrosion resistance. The results of this study will be useful for the future development of Ni-free Co-Cr alloys for next-generation, small-diameter stents.

Highly accurate and sensitive absolute quantification of bacterial strains in human fecal samples.

BACKGROUND: Next-generation sequencing (NGS) approaches have revolutionized gut microbiome research and can provide strain-level resolution, but these techniques have limitations in that they are only semi-quantitative, suffer from high detection limits, and generate data that is compositional. The present study aimed to systematically compare quantitative PCR (qPCR) and droplet digital PCR (ddPCR) for the absolute quantification of Limosilactobacillus reuteri strains in human fecal samples and to develop an optimized protocol for the absolute quantification of bacterial strains in fecal samples. RESULTS: Using strain-specific PCR primers for L. reuteri 17938, ddPCR showed slightly better reproducibility, but qPCR was almost as reproducible and showed comparable sensitivity (limit of detection [LOD] around 104 cells/g feces) and linearity (R2 > 0.98) when kit-based DNA isolation methods were used. qPCR further had a wider dynamic range and is cheaper and faster. Based on these findings, we conclude that qPCR has advantages over ddPCR for the absolute quantification of bacterial strains in fecal samples. We provide an optimized and easy-to-follow step-by-step protocol for the design of strain-specific qPCR assays, starting from primer design from genome sequences to the calibration of the PCR system. Validation of this protocol to design PCR assays for two L. reuteri strains, PB-W1 and DSM 20016 T, resulted in a highly accurate qPCR with a detection limit in spiked fecal samples of around 103 cells/g feces. Applying our strain-specific qPCR assays to fecal samples collected from human subjects who received live L. reuteri PB-W1 or DSM 20016 T during a human trial demonstrated a highly accurate quantification and sensitive detection of these two strains, with a much lower LOD and a broader dynamic range compared to NGS approaches (16S rRNA gene sequencing and whole metagenome sequencing). CONCLUSIONS: Based on our analyses, we consider qPCR with kit-based DNA extraction approaches the best approach to accurately quantify gut bacteria at the strain level in fecal samples. The provided step-by-step protocol will allow scientists to design highly sensitive strain-specific PCR systems for the accurate quantification of bacterial strains of not only L. reuteri but also other bacterial taxa in a broad range of applications and sample types. Video Abstract.

Presbyopia, Dry Eye, and Retinal Thickness in the Middle-Aged Population: Focusing on Sex Differences.

Purpose: Risk factors for presbyopia have not been fully determined although previous studies suggested presbyopia was associate with age, dry eye, and retinal ganglion cell complex thickness (GCC). We accessed these signs and common ocular symptoms in the middle-aged population focusing on sex differences when women have drastic hormonal change. Methods: This cohort study consecutively enrolled 2743 patients aged 36-45 years (n=1000), 46-55 years (n=1000), and 56-65 years (n=743). All underwent ocular surface tests and had near add power and GCC measured. Common ocular symptoms were asked using questionnaire. Results: Among female participants, visual symptoms (eye strain and photophobia) were more prevalent in the age group 46-55, whereas non-visual symptoms (dryness, irritation, and pain) were not. We identified symptomatic presbyopia (near add power ≥ 1.5D) in 14.4%, 73.8%, and 97.8%, positive corneal staining in 29.1%, 23.8%, and 23.9%, and a mean GCC of 98.2 µm, 105.3 µm, and 89.6 µm in the age groups 36-45, 46-55, and 56-65, respectively. Mean tear break-up time were 3.3, 3.5, and 3.3 seconds, respectively. Results indicated a large progression of presbyopia (P<0.01) from the period of 36-45 years onward and significantly increased GCC (P<0.01) in women of age group 46-55. No notable tendency was observed in symptoms and GCC for male participants. Conclusion: Visual symptoms in women were worse between 46 and 55 years than before or after these ages. The increase of symptomatic presbyopia and GCC may be contributing to visual symptoms in addition to menopausal transition symptoms in this age group.

High-Performance Stretchable Strain Sensors Based on Auxetic Fabrics for Human Motion Detection.

Wearable strain sensors play a pivotal role in real-time human motion detection and health monitoring. Traditional fabric-based strain sensors, typically with a positive Poisson's ratio, face challenges in maintaining sensitivity and comfort during human motion due to conflicting resistance changes in different strain directions. In this work, high-performance stretchable strain sensors are developed based on graphene-modified auxetic fabrics (GMAF) for human motion detection in smart wearable devices. The proposed GMAF sensors, with a negative Poisson's ratio achieved through commercially available warp-knitting technology, exhibit an 8-fold improvement in sensitivity compared to conventional plain fabric sensors. The unique auxetic fabric structure enhances sensitivity by synchronizing resistance changes in both wale and course directions. The GMAF sensors demonstrate excellent washability, showing only slight degradation in auxeticity and an acceptable increase in resistance after 10 standard wash cycles. The GMAF sensors maintain stability under different strain levels and various motion frequencies, emphasizing their dynamic performance. The sensors exhibit superior conformability to joint movements, which effectively monitor a full range of motions, including joint bending, sports activities, and subtle actions like coughing and swallowing. The research underscores a promising approach to achieve industrial-scale production of wearable sensors with improved performance and comfort through fabric structure design.

Occupational heat stress and its health impacts- an overview of research status and need for further research in Southeast Asia with special emphasis on mitigation strategies in North East India.

The Intergovernmental Panel on Climate Change, IPCC predicts that hot seasons will get even hotter due to global climate change. There exists a critical dependence of human metabolic processes on temperature. Changes in thermal balance therefore, have an adverse effect on health because they raise body temperature, cause excessive sweating, and accelerate the rate of dehydration. Different nations and professional groups use different techniques to measure heat strain. This paper aims to review previous research conducted in the area of heat strain due to heat exposure among workers in Southeast Asia and also to profile mitigation strategies in North East India. Studies conducted between the years 2011 to 2023 in the evaluation of the health impacts of occupational heat stress were searched systematically using several sources of databases like PubMed, Google Scholar, Science Direct, Web of Science, Scopus, etc. It was noted that a greater proportion of previous research on evaluating physiological effects was carried out in controlled environments as opposed to real-world field settings. While such studies give us valuable insights into the relationship, applying the same methodology in the workplace may not be feasible. In India, very few research has been carried out on workplace heat stress, and even fewer have been done in North East India using physiological indicators. North East India is also affected by global climate change leading top more hotter days than before. The region of Northeast India, particularly Guwahati (Assam), has recently seen extreme heat waves during the sweltering summer months. With less literature available in this geographical location, studies with actual field-based settings are much needed to understand the occupational health impacts in this region. This review can formulate a suitable methodology for assessing the health impacts in working environment. This can also help the local health professionals to recognize the heat strain parameters that are acceptable worldwide, and use as pertinent indicators to scrutinize worker's health and develop preventive agendas as climate change advances.

Mavacamten-Associated Temporal Changes in Left Atrial Function in Obstructive HCM: Insights From the VALOR-HCM Trial.

BACKGROUND: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) trial showed that mavacamten reduced the eligibility for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients. Mavacamten also resulted in favorable cardiac remodeling, including improvement in biomarkers (eg, N-terminal pro-B-type natriuretic peptide and troponin T). However, the impact of mavacamten on left atrial (LA) function is unknown. OBJECTIVES: The aim of this study was to assess serial changes in LA strain measures in patients enrolled in the VALOR-HCM trial. METHODS: VALOR-HCM included 112 symptomatic patients with obstructive HCM (mean age 60 years; 51% male). Patients assigned to receive mavacamten at baseline (n = 56) continued therapy for 56 weeks and those assigned to placebo transitioned to mavacamten (n = 52) from week 16 to week 56. Echocardiographic LA strain (reservoir, conduit, and contraction) was measured by using a vendor-neutral postprocessing software. RESULTS: At baseline, the mean LA volume index (LAVI) and LA strain values (conduit, contraction, and reservoir) were 41.3 ± 16.5 mL/m2, -11.8% ± 6.5%, -8.7% ± 5.0%, and 20.5% ± 8.7%, respectively (all worse than reported normal). LAVI significantly improved by -5.6 ± 9.7 mL/m2 from baseline to week 56 (P < 0.001). There was a significant (P < 0.05) improvement in absolute LA strain values from baseline to week 56 (conduit [-1.7% ± 6%], contraction [-1.2% ± 4.5%], and reservoir [2.8% ± 7.7%]). Patients originally receiving placebo had no differences in LA measurements up to week 16. There was no significant improvement in LA strain values (conduit [-0.9% ± 3.8%], contraction [-0.4% ± 3.4%], and reservoir [1.4% ± 6.1%]; all; P = NS) from baseline to week 56 in patients with history of atrial fibrillation. CONCLUSIONS: In VALOR-HCM, mavacamten resulted in an improvement in LAVI and LA strain at week 56, suggesting sustained favorable LA remodeling and improved function, except in the atrial fibrillation subgroup. Whether the advantageous LA remodeling associated with long-term treatment with mavacamten results in a favorable impact on the observed high burden of atrial tachyarrhythmias in HCM remains to be proven. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072).

NanoMGT: Marker gene typing of low complexity mono-species metagenomic samples using noisy long reads.

Rapid advancements in sequencing technologies have led to significant progress in microbial genomics, yet challenges persist in accurately identifying microbial strain diversity in metagenomic samples, especially when working with noisy long-read data from platforms like Oxford Nanopore Technologies (ONT). In this article, we introduce NanoMGT, a tool designed to enhance marker gene typing in low-complexity mono-species samples, leveraging the unique properties of long reads. NanoMGT excels in its ability to accurately identify mutations amidst high error rates, ensuring the reliable detection of multiple strain-specific marker genes. Our tool implements a novel scoring system that rewards mutations co-occurring across different reads and penalizes densely grouped, likely erroneous variants, thereby achieving a good balance between sensitivity and precision. A comparative evaluation of NanoMGT, using a simulated multi-strain sample of seven bacterial species, demonstrated superior performance relative to existing tools and the advantages of using a threshold-based filtering approach to calling minority variants in ONT's sequencing data. NanoMGT's potential as a post-binning tool in metagenomic pipelines is particularly notable, enabling researchers to more accurately determine specific alleles and understand strain diversity in microbial communities. Our findings have significant implications for clinical diagnostics, environmental microbiology, and the broader field of genomics. The findings offer a reliable and efficient approach to marker gene typing in complex metagenomic samples.

Gender-related differences in left atrial strain mechanics and exercise capacity in hypertrophic cardiomyopathy: a propensity-score matched study from the Cleveland Clinic.

Background: Male and female patients with hypertrophic cardiomyopathy (HCM) differ in physiologic characteristics and hemodynamics. Little is known about gender-related differences in left atrial (LA) strain and exercise capacity. The aim of this study was to assess the gender-related differences in the relationship between exercise capacity and cardiac function including LA function in patients with HCM. Methods: Five hundred and thirty-two patients with HCM undergoing exercise stress echocardiography and cardiopulmonary exercise testing (CPET) were prospectively recruited between October 2015 and April 2019 as part of a cohort study in a quaternary referral center. To reduce potential confounding factors, propensity score (PS) matching was performed in 420 patients. LA strain mechanics were evaluated using speckle-tracking echocardiography. Results: The majority of patients were male, comprising 58% of the total. Female HCM patients were older (54±14 vs. 50±15 years, P=0.002). After PS matching, percent-predicted peak VO2 was similar between the genders (67.5%±20.7% vs. 65.8%±21.8%, P=0.41), even though female HCM patients had lower peak VO2 (17.7±5.9 vs. 24.1±8.3 mL/kg/min, P<0.001). Left ventricular (LV) diastolic function was worse for female HCM patients. This is shown by worse E/e' ratio (15.0±5.9 vs. 12.9±6.4, P<0.001) and larger LA volume in respect to LV (0.88±0.35 vs. 0.74±0.31, P<0.001), compared with male HCM patients. The gender-related differences in LA reservoir strain were more evident for patients aged 60 years and older (27.5%±8.8% vs. 30.9%±9.1%, P=0.03). LA reservoir strain was found to have a significant association with exercise capacity in both male and female HCM patients (for females, ß=0.27, P=0.001; for males, ß=0.27, P<0.001), independent of LV diastolic dysfunction and stroke volume. Conclusions: Gender-related differences in LA reservoir strain were increasingly evident for older HCM patients aged 60 years and older. LA reservoir strain was an independent determinant of percent-predicted peak VO2 in male and female patients, underpinning the importance of LA function in determining exercise capacity in HCM.

Preoperative right ventricular longitudinal strain as a prognosticator of postoperative residual or recurrent tricuspid regurgitation in Ebstein anomaly: a cardiovascular magnetic resonance study.

Background: The preoperative predictors of residual or recurrent tricuspid regurgitation (TR) after cone reconstruction (CR) remains unclear in patients with Ebstein anomaly (EA). We aimed to determine the predictive value of right ventricular longitudinal strain, assessed using cardiac magnetic resonance (CMR) imaging, for residual or recurrent TR after CR in patients with EA. Methods: This single-centre, retrospective study analysed data from 48 patients with EA [mean ± standard deviation (SD), age, 35.0±13.6 years; 13 males] who underwent CMR before CR between January 2017 and February 2023. Two-dimensional colour Doppler echocardiography was performed before CR and mid-term (>6 months) after CR to evaluate the degree of TR in patients with EA. Thirty healthy volunteers served as controls. Univariate and multivariate logistic regression analyses were performed to identify CMR predictors of moderate or severe TR >6 months after CR. Results: Mid-term postoperative results revealed severe, moderate, and mild TR in 8 (17%), 7 (15%), and 33 (69%) patients, respectively. For patients with EA and moderate or severe TR after CR, left ventricular global longitudinal strain (GLS), left ventricular ejection fraction, right ventricular global longitudinal strain (RVGLS), and right ventricular ejection fraction (RVEF) were significantly worse compared to patients with mild TR (all P<0.05). Multivariate logistic regression analyses revealed that RVGLS was independently associated with moderate or severe TR >6 months after CR [odds ratio (OR) 1.193, 95% confidence interval (CI): 1.025-1.388; P=0.02]. Conclusions: RVGLS was a significant predictor of moderate or severe TR >6 months after CR. This finding emphasizes that early and accurate measurement of RV function may help to identify patients at high risk for severe residual or recurrent TR.

Inflammatory response and parasite regulation in acute toxoplasmosis: the role of P2X7 receptor in controlling virulent atypical genotype strain of Toxoplasma gondii.

Toxoplasmosis is a globally significant disease that poses a severe threat to immunocompromised individuals, especially in Brazil, where a high prevalence of virulent and atypical strains of Toxoplasma gondii is observed. In 1998, the EGS strain, exhibiting a unique infection phenotype, was isolated in Brazil, adding to the complexity of strain diversity. The P2X7 receptor is critical in inflammation and controlling intracellular microorganisms such as T. gondii. However, its genetic variability can result in receptor dysfunction, potentially worsening susceptibility. This study investigates the role of the P2X7 receptor during acute infection induced by the EGS atypical strain, offering insight into the mechanisms of T. gondii infection in this context. We infected the female C57BL/6 (WT) or P2X7 knockout (P2X7-/-) by gavage. The EGS infection causes intestinal inflammation. The P2X7-/- mice presented higher parasite load in the intestine, spleen, and liver. The absence of the P2X7 receptor disrupts inflammatory cell balance by reducing NLRP3, IL-1ß, and Foxp3 expression while increasing IFN-γ expression and production in the intestine. In the liver, P2X7-/- animals demonstrate diminished inflammatory infiltrate within the portal and lobular regions concurrent with an enlargement of the spleen. In conclusion, the infection of mice with the EGS strain elicited immune alterations, leading to acute inflammation and cytokine dysregulation, while the P2X7 receptor conferred protection against parasitic proliferation across multiple organs.

The association between leisure-time physical activity and cardiorespiratory and muscular fitness and job strain-Study with a Northern Finland birth cohort of 1966.

Job strain is a major concern in the workplace. Work-related stress is an increasing challenge worldwide as it is the leading cause of long-term sickness absences, disability pensions and lower productivity. Rarely studied simultaneously, both leisure-time physical activity (LTPA) and physical fitness (PF), which comprises cardiorespiratory fitness (CRF) and muscular fitness (MF), may have potential in preventing and managing job strain. The current study aimed to investigate whether LTPA, CRF and MF predict perceived job strain. In addition, the study examines reverse associations, that is, whether job strain predicts LTPA, CRF and MF. We used longitudinal population-based data from a Northern Finland birth cohort of 1966 (n = 5363) to analyse LTPA, CRF and MF as well as job strain and its components, job demands and job control, at age 31 years (1997) and 46 years (2012). Leisure-time physical activity was measured with a self-reported questionnaire whereas CRF and MF were measured as part of clinical examination. Linear regression analyses were used to analyse the data. In both men (n = 2548) and women (n = 2815), higher baseline MF predicted lower job strain and job demands 15 years later. In women, higher baseline total LTPA predicted higher job demands, whereas in men, higher CRF predicted lower job strain and higher job control. These associations remained significant, also when adjusted for education and occupational status. In the analyses on reverse associations, higher job control and higher job demands were linked to higher leisure-time moderate-to-vigorous physical activity (MVPA) and total LTPA 15 years later among both men and women, except for the association between job demands and total LTPA among women. These associations remained significant after adjustment for education and occupational status, except for the association of job control with MVPA and total LTPA among men. The association of higher job demands and total LTPA became significant in women. We conclude that LTPA and PF seem beneficial in preventing and managing job strain.

Association of left atrial function with frailty: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Frailty is common in people with cardiovascular disease. Worse left atrial (LA) function is an independent risk factor for cardiovascular disease. However, whether worse LA function is associated with frailty is unclear. METHODS: We included 3292 older adults from the Atherosclerosis Risk in Communities study who were non-frail at baseline (visit 5, 2011-2013) and had LA function (reservoir, conduit, and contractile strain) measured from two-dimensional speckle-tracking echocardiography. LA stiffness index was calculated as a ratio of E/e' to LA reservoir strain. Frailty was defined using the validated Fried frailty phenotype. Incident frailty was assessed between 2016 and 2019 during two follow-up visits. LA function was analyzed as quintiles. Multivariable logistic regression examined odds of incident frailty. RESULTS: Median (interquartile range [IQR]) age was 74 (71-77) years, 58% were female, and 214 (7%) participants developed frailty during a median (IQR) follow-up of 6.3 (5.6-6.8) years. After adjusting for baseline confounders and incident cardiovascular events during follow-up, the odds of developing frailty was 2.42 (1.26-4.66) times greater among participants in the lowest (vs highest) quintile of LA reservoir strain and 2.41 (1.11-5.22) times greater among those in the highest (vs lowest) quintile of LA stiffness index. Worse LA function was significantly associated with the development of exhaustion, but not the other components of the Fried frailty phenotype. CONCLUSIONS: Worse LA function is associated with higher incidence of frailty and exhaustion component independent of LA size and left ventricular function. Future studies are needed to elucidate the underlying mechanisms that drive the observed association.

[Determining the risk of maladaptation using an electroencephalogram to prevent mental strain]. / Opredelenie riska dezadaptatsii po elektroentsefalogramme dlya preduprezhdeniya psikhicheskogo perenapryazheniya.

OBJECTIVE: To identify criteria for electroencephalogram (EEG) synchronization in patients with post-traumatic stress disorder (PTSD) exhibiting high levels of functional stress and signs of maladaptation. MATERIAL AND METHODS: Two groups of male subjects aged 23-38 years were examined: a group of subjects receiving therapy for PTSD at a medical center; and a group of healthy subjects who regularly practiced psychophysical relaxation sessions. EEG, an innovative method for analyzing brain synchronizing currents, and the Spielberger State-Trait Anxiety Inventory were used. RESULTS: Criteria for the formation of patterns of synchronization of neural networks were found in subjects of the therapy group, who have a high level of psychofunctional stress and signs of maladaptation against the background of PTSD in combination with severe anxiety and impaired cognitive abilities. CONCLUSION: Alpha wave synchronization analysis can be used to more accurately diagnose the level of psychofunctional stress in individuals at risk of developing psychophysical disorders. The results of the work suggest the use of technologies that increase the ability to synchronize brain biocurrents to develop programs for correcting psychophysical status, such as relaxation exercises.