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There are significant sex and age differences in left ventricular (LV) remodeling that may lead to disparity in outcomes when used to inform the timing of aortic regurgitation (AR) intervention. The aim of this study was to examine whether left atrial (LA) parameters might represent better criteria than LV parameters to inform the timing of AR intervention. Using data on patients with moderate to severe or severe AR with serial echocardiography (2010-2016), the longitudinal trends in left atrial volume index (LAVI) and left atrial reservoir strain (LAr) were evaluated by sex and age. The incremental utility of these parameters in predicting adverse events over LV parameters was also determined. In 525 patients (25.7% women) with 1,687 echocardiograms over a median follow-up period of 2.0 years (Q1-Q3: 1.0-3.6 years), there was significant increase in LAVI (1.0 mL/m2 per year [95% CI: 0.76-1.2 mL/m2 per year]) and decrease in LAr (−1.3% per year [95% CI: −1.6% to −0.92%]), without a significant interaction by sex or age category (P for interaction ≥ 0.17). In addition, both LAVI and LAr were significant predictors of adverse events independent of LV parameters. The optimal discriminatory thresholds were 37 mL/m2 for LAVI and 35% for LAr. These thresholds were similar across categories of sex and age. Within the relatively short-term follow-up, surgery was associated with survival benefit among patients with LAVI ≥37 mL/m2 (HR: 0.33 [95% CI: 0.15-0.72]; P = 0.006) but was not statistically significant among patients with LAVI <37 mL/m2 (HR: 0.46 [95% CI: 0.18-1.17]; P = 0.09). Similarly, surgery was associated with survival for the subgroup with LAr ≤35% but not among those with LAr >35%. Unlike LV remodeling, LA remodeling demonstrates a similar rate of progression between categories of sex and age among patients with AR. In addition, LA parameters provide incremental prognostic value over LV parameters. [Display omitted] [ABSTRACT FROM AUTHOR]

Thoracic endovascular aortic repair (TEVAR) represents optimal therapy for complicated acute type B aortic dissection (aTBAD). Persistent knowledge gaps remain, including the optimal length of aortic coverage, impact on distal aortic remodeling, and fate of the dissected abdominal aorta. Review of the Emory Aortic Database identified 92 patients who underwent TEVAR for complicated aTBAD from 2012 to 2018. Standard TEVAR covered aortic zones 3 and 4 (from the left subclavian to the mid-descending thoracic aorta). Extended TEVAR fully covered aortic zones 3 though 5 (from the left subclavian to the celiac artery). Long-term imaging, clinical follow-up, and overall and aortic-specific mortality were reviewed. Extended TEVAR (n = 52) required a greater length of coverage vs standard TEVAR (n = 40) (240 ± 32 mm vs 183 ± 23 mm; P <.01). In-hospital mortality occurred in 5.4% of patients (7.7% vs 2.5%; P =.27) owing to mesenteric malperfusion (n = 3) or rupture (n = 2). The overall incidences of postoperative stroke, transient paraparesis, paraplegia, and dialysis were 5.4% (3.9% vs 7.5%; P =.38), 3.2% (5.8% vs 0%; P =.18), 0%, and 0% respectively, equivalent between groups. Follow-up was 96.6% complete to a mean of 6.1 years (interquartile range, 3.5-8.6 years). There were significantly higher rates of complete thrombosis or obliteration of the entire thoracic false lumen after Extended TEVAR (82.2% vs 51.5%; P =.04). Distal aortic reinterventions were less frequent after extended TEVAR (5.8% vs 20%; P =.04). Late aorta-specific survival was 98.1% after extended TEVAR vs 92.3% for standard TEVAR (P =.32). Extended TEVAR for complicated aTBAD is safe, results in a high rate of total thoracic false lumen thrombosis/obliteration, and reduces distal reinterventions. Longer-term follow-up will be needed to demonstrate a survival benefit compared to limited aortic coverage. [ABSTRACT FROM AUTHOR]

More than a hundred genetic loci have been associated with atrial fibrillation (AF). But the exact mechanism remains unclear and the treatment needs to be improved. This study aimed to investigate the mechanism and potential treatment of NPPA mutation–associated AF. Nppa knock-in (KI, p.I137T) rats were generated, and cardiac function was evaluated. Blood pressure was recorded using a tail-cuff system. The expression levels were measured using real-time polymerase chain reaction, enzyme-linked immunosorbent assay or Western blot analysis, and RNA-sequence analysis. Programmed electrical stimulation, patch clamp, and multielectrode array were used to record the electrophysical characteristics. Mutant rats displayed downregulated expression of atrial natriuretic peptide but elevated blood pressure and enlarged left atrial end-diastolic diameter. Further, gene topology analysis suggested that the majority of differently expressed genes in Nppa KI rats were related to inflammation, electrical remodeling, and structural remodeling. The expression levels of C-C chemokine ligand 5 and galectin-3 involved in remodeling were higher, while there were declined levels of Na v 1.5, Ca v 1.2, and connexin 40. AF was more easily induced in KI rats. Electrical remodeling included abbreviated action potentials, effective refractory period, increased late sodium current, and reduced calcium current, giving rise to conduction abnormalities. These electrophysiological changes could be reversed by the late sodium current blocker ranolazine and the Na v 1.8 blocker A-803467. Our findings suggest that structural remodeling related to inflammation and fibrosis and electrical remodeling involved in late sodium current underly the major effects of the Nppa (p.I137T) variant to induce AF, which can be attenuated by the late sodium current blocker and Na v 1.8 blocker. [Display omitted] [ABSTRACT FROM AUTHOR]

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Left ventricular noncompaction (LVNC) is commonly described as a congenital cardiomyopathy characterized by prominent myocardial trabeculae and deep intertrabecular recesses extending in the left ventricular chamber. Clinical presentation can differ considerably from asymptomatic individuals to those presenting with heart failure and other serious complications. Diagnosis is usually made by two-dimensional transthoracic echocardiography or cardiac magnetic resonance. Moreover, even if strain parameters are significantly reduced in patients with LVNC, they are not routinely investigated. Here, we report the case of a previously symptomless patient admitted to the hospital for pulmonary edema. Two-dimensional transthoracic echocardiography showed severe valvular heart disease and left ventricle pronounced trabeculation and remodeling, although speckle tracking echocardiography (STE) demonstrated only mild strain reduction. We, therefore, explore the possibility that STE may be useful to differentiate LVNC cardiomyopathy from LVNC phenotype due to severe remodeling. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PHT) is a devastating disease with low survival rates. In PHT, chronic pressure overload leads to right ventricle (RV) stiffening; thus, impeding diastolic filling. Multiple mechanisms may contribute to RV stiffening, including wall thickening, microstructural disorganization, and myocardial stiffening. The relative importance of each mechanism is unclear. Our objective is to use a large animal model to untangle these mechanisms. Thus, we induced pulmonary arterial hypertension (PAH) in sheep via pulmonary artery banding. After eight weeks, the hearts underwent anatomic and diffusion tensor MRI to characterize wall thickening and microstructural disorganization. Additionally, myocardial samples underwent histological and gene expression analyses to quantify compositional changes and mechanical testing to quantify myocardial stiffening. Finally, we used finite element modeling to disentangle the relative importance of each stiffening mechanism. We found that the RVs of PAH animals thickened most at the base and the free wall and that PAH induced excessive collagen synthesis, increased cardiomyocyte cross-sectional area, and led to microstructural disorganization, consistent with increased expression of fibrotic genes. We also found that the myocardium itself stiffened significantly. Importantly, myocardial stiffening correlated significantly with collagen synthesis. Finally, our computational models predicted that myocardial stiffness contributes to RV stiffening significantly more than other mechanisms. Thus, myocardial stiffening may be the most important predictor for PAH progression. Given the correlation between myocardial stiffness and collagen synthesis, collagen-sensitive imaging modalities may be useful for estimating myocardial stiffness and predicting PAH outcomes. Ventricular stiffening is a significant contributor to pulmonary hypertension-induced right heart failure. However, the mechanisms that lead to ventricular stiffening are not fully understood. The novelty of our work lies in answering this question through the use of a large animal model in combination with spatially- and directionally sensitive experimental techniques. We find that myocardial stiffness is the primary mechanism that leads to ventricular stiffening. Clinically, this knowledge may be used to improve diagnostic, prognostic, and therapeutic strategies for patients with pulmonary hypertension. [Display omitted] [ABSTRACT FROM AUTHOR]

Spiral artery remodeling is the process by which the uterine vessels become large bore low resistance conduits, allowing delivery of high volumes of maternal blood to the placenta to nourish the developing fetus. Failure of this process is associated with the pathophysiology of most of the major obstetric complications, including late miscarriage, fetal growth restriction and pre-eclampsia. However, the point at which remodeling 'fails' in these pathological pregnancies is not yet clear. Spiral artery remodeling has predominantly been described in terms of its morphological features, however we are starting to understand more about the cellular and molecular triggers of the different aspects of this process. This review will discuss the current state of knowledge of spiral artery remodeling, in particular the processes involved in loss of the vascular smooth muscle cells, and consider where in the process defects would lead to a pathological pregnancy. • Spiral artery remodeling is key for a successful pregnancy. • The morphological aspects of spiral artery remodeling are well described. • Understanding of the cellular and molecular mediators is becoming clearer. [ABSTRACT FROM AUTHOR]

Genomewide association studies have associated >100 genetic loci with atrial fibrillation (AF), but establishing causal genes contributing to AF remains challenging. The purpose of this study was to determine candidate novel causal genes and mechanistic pathways associated with AF risk loci by incorporating gene expression and coexpression analyses and to provide a resource for functional studies and targeting of AF-associated genes. Cis-expression quantitative trait loci were identified for candidate genes near AF risk variants in human left atrial tissues. Coexpression partners were identified for each candidate gene. Weighted gene coexpression network analysis (WGCNA) identified modules and modules with overrepresentation of candidate AF genes. Ingenuity pathway analysis (IPA) was applied to the coexpression partners of each candidate gene. IPA and gene set over representation analysis were applied to each WGCNA module. One hundred sixty-six AF-risk single nucleotide polymorphisms were located in 135 loci. Eighty-one novel genes not previously annotated as putative AF risk genes were identified. IPA identified mitochondrial dysfunction, oxidative stress, epithelial adherens junction signaling, and sirtuin signaling as the most frequent significant pathways. WGCNA characterized 64 modules (candidate AF genes overrepresented in 8), represented by cell injury, death, stress, developmental, metabolic/mitochondrial, transcription/translation, and immune activation/inflammation regulatory pathways. Candidate gene coexpression analyses suggest significant roles for cellular stress and remodeling in AF, supporting a dual risk model for AF: Genetic susceptibility to AF may not manifest until later in life, when cellular stressors overwhelm adaptive responses. These analyses also provide a novel resource to guide functional studies on potential causal AF genes. [ABSTRACT FROM AUTHOR]

The collagen molecular family is the result of nearly one billion years of evolution. It is a unique family of proteins, the majority of which provide general mechanical support to biological tissues. Fibril forming collagens are the most abundant collagens in vertebrate animals and are generally found in positions that resist tensile loading. In animals, cells produce fibril-forming collagen molecules that self-assemble into larger structures known as collagen fibrils. Collagen fibrils are the fundamental, continuous, load-bearing elements in connective tissues, but are often further aggregated into larger load-bearing structures, fascicles in tendon, lamellae in cornea and in intervertebral disk. We know that failure to form fibrillar collagen is embryonic lethal, and excessive collagen formation/growth (fibrosis) or uncontrolled enzymatic remodeling (type II collagen: osteoarthritis) is pathological. Collagen is thus critical to vertebrate viability and instrumental in maintaining efficient mechanical structures. However, despite decades of research, our understanding of collagen matrix formation is not complete, and we know still less about the detailed mechanisms that drive collagen remodeling, growth, and pathology. In this perspective, we examine the known role of mechanical force on the formation and development of collagenous structure. We then discuss a mechanochemical mechanism that has the potential to unify our understanding of collagenous tissue assembly dynamics, which preferentially deposits and grows collagen fibrils directly in the path of mechanical force, where the energetics should be dissuasive and where collagen fibrils are most required. We term this mechanism: Mechanochemical force-structure causality. Our mechanochemical-force structure causality postulate suggests that collagen molecules are components of mechanochemically-sensitive and dynamically-responsive fibrils. Collagen molecules assemble preferentially in the path of applied strain, can be grown in place by mechanical extension, and are retained in the path of force through strain-stabilization. The mechanisms that drive this behavior operate at the level of the molecules themselves and are encoded into the structure of the biomaterial. The concept might change our understanding of structure formation, enhance our ability to treat injuries, and accelerate the development of therapeutics to prevent pathologies such as fibrosis. We suggest that collagen is a mechanochemically responsive dynamic element designed to provide a substantial "material assist" in the construction of adaptive carriers of mechanical signals. [Display omitted] [ABSTRACT FROM AUTHOR]

The benefit of an anterior mitral line (AML) in patients with persistent atrial fibrillation (AF) and anterior atrial scar undergoing ablation has never been investigated. The purpose of this study was to evaluate the outcomes of AML in addition to standard treatment compared to standard treatment alone (no AML) in this subset of patients. Patients with persistent AF and anterior low-voltage zone (LVZ) treated with AML in 3 centers were retrospectively enrolled. The patients were matched in 1:1 fashion with patients having persistent AF and anterior LVZ who underwent conventional ablation in the same centers. Matching parameters were age, LVZ burden, and repeated ablation. Primary endpoint was AF/atrial tachycardia (AT) recurrence. One hundred eight-six patients (age 66 ± 9 years; 34% women) were selected and divided into 2 matched groups. Bidirectional conduction block was achieved in 95% of AML. After median follow-up of 2 years, AF/AT recurrence occurred in 29% of the patients in the AML group vs 48% in the no AML group (log-rank P =.024). On Cox regression multivariate analysis, left atrial volume (hazard ratio [HR] 1.03; P =.006) and AML (HR 0.46; P =.003) were significantly associated with the primary endpoint. On univariate logistic regression, lower body mass index, older age, extensive anterior LVZ, and position of the left atrial activation breakthrough away from the AML were associated with first-pass AML block. In this retrospective matched analysis of patients with persistent AF and anterior scar, AML in addition to standard treatment was associated with improved AF/AT-free survival compared to standard treatment alone. [Display omitted] [ABSTRACT FROM AUTHOR]

To investigate the clinical effect of acupuncture among patients with dysphagia after cerebral infarction, and the nerve remodeling of acupuncture using diffusion tensor imaging. One hundred and twenty patients with dysphagia after cerebral infarction were randomly assigned to either acupuncture group or sham-acupuncture group with a 1:1 ratio. All patients received usual care and swallowing function training of neurology department. Additionally, acupuncture was applied at Sìshéncōng (四神聪EX-HN1), Băihuì (百会GV20), Tàiyáng (太阳EX-HN5), Fēngchí (风池GB20) and Shésānzhēn (舌三针three-tongue needling points, Extra) in acupuncture group. The needles were retained for 30 min each time, and five times a week for three weeks as a course of treatment. Two courses of treatments were required in total. In sham-acupuncture group, the blunt needles were put into the needle sleeve, and the top of needle was fixed on the skin. During treatment the blunt needle tip only had slight contact with the skin without any penetration. The blunt needle tips were placed on EX-HN1, GV20, EX-HN5, GB20 and three-tongue needling points, respectively. The duration of treatment in sham-acupuncture group was the same as that in acupuncture group. Before and after treatment, all patients underwent Kubota water swallowing test to evaluate the clinical effect. Using diffusion tensor image (DTI), the nerve remodeling was detected. Clinical effect: After treatment and assessed by water swallowing test, there were 38 cases of normal swallowing function in acupuncture group, higher than 15 cases in sham-acupuncture group (P < 0.05). Nerve remodeling: (1) apparent diffusion coefficient (ADC): before treatment, ADC in acupuncture group and sham acupuncture group were 1.76 ± 0.45 mm/s and 1.68 ± 0.51 mm/s, respectively. After treatment, ADC were 0.66 ± 0.15 mm/s and 0.74 ± 0.11 mm/s, respectively. The difference in ADC had no statistical significance between two groups after treatment (P > 0.05); (2) fractional anisotropy (FA): after treatment, FA of acupuncture group was 0.57 ± 0.06, which was significantly higher than that of sham-acupuncture group (P < 0.05); (3) observation of different infarct lesions: after treatment, ADC of temporal lobe infarction in acupuncture group was (0.57 ± 0.11) mm/s, lower than 0.82 ± 0.24 mm/s of sham acupuncture group, while FA in acupuncture group was 0.61 ± 0.07, higher than 0.45 ± 0.10 in sham-acupuncture group, both with statistical significance (both P < 0.05). Regarding the changes of FA maps for temporal lobe infarction before and after treatment, the transverse bundles of the white matter fibers increased remarkably in infarct lesions and on the healthy side of temporal lobe. Acupuncture could improve the swallowing function of patients with dysphagia after cerebral infarction. It reduced ADC and increased FA, especially among patients with temporal lobe infarction after treatment. Acupuncture may have a remodeling effect on transverse cortical fibers after temporal lobe infarction. [ABSTRACT FROM AUTHOR]

Due to the increasing incidence rate of obesity worldwide and the associated complications such as type 2 diabetes and cardiovascular diseases, research on the adipose tissue physiology and the role of the extracellular matrix (ECM) has gained tremendous attention. The ECM, one of the most crucial components in body tissues, undergoes remodeling and regeneration of its constituents to guarantee normal tissue function. There is a crosstalk between fat tissue and various body organs, including but not limited to the liver, heart, kidney, skeletal muscle, and so forth. These organs respond to fat tissue signals through changes in ECM, function, and their secretory products. Obesity can cause ECM remodeling, inflammation, fibrosis, insulin resistance, and disrupted metabolism in different organs. However, the mechanisms underlying the reciprocal communication between various organs during obesity are still not fully elucidated. Gaining a profound knowledge of ECM alterations during the progression of obesity will pave the way toward developing potential strategies to either circumvent pathological conditions or open an avenue to treat complications associated with obesity. [ABSTRACT FROM AUTHOR]

To evaluate the axial and dimensional changes of the condylar head after orthognathic surgery, including Le Fort I and bilateral sagittal split ramus osteotomies, and to assess condylar remodeling through three-dimensional (3D) surface superimposition. Twenty-four patients (15 females, 9 males; mean age: 32.22 ± 6.92 years) with skeletal Class III deformity were included in the study. Cone-beam computed tomography data obtained in the preoperative (T0) and postoperative (T1) periods were examined using Mimics and 3-Matic software. The height, depth, and width of the condylar head and its angular changes were measured. The volumes of the 3D reconstructed models were calculated, and remodeling amounts were evaluated through regional surface superimposition. Statistical significance was set at P <.05. Following the surgery, there was a significant decrease in the size of condyles (P <.05). An inward rotation of the condyles was found in the axial plane (T0: 79.60 ± 6.01°, T1: 76.6 ± 6.48°, P <.05). The maximum resorption, maximum apposition, mean remodeling, and mean absolute remodeling were −2.63 ± 1.23 mm, 1.15 ± 0.4 mm, −0.30 ± 0.34 mm, and 0.73 ± 0.43 mm, respectively. No correlation was found between the angular changes and remodeling parameters or linear and volumetric changes of the condylar head (P >.05). Condyles undergo a remodeling process with a resorptive character following orthognathic surgery, without clinically significant effects in the present study. [ABSTRACT FROM AUTHOR]

Background: Pacing at sites of longest interventricular delay has been associated with greater reverse remodeling in cardiac resynchronization therapy (CRT). However, the effects of pacing at such sites on clinical outcomes is less well studied.Objective: To assess the association between interventricular delay and clinical outcomes in CRT patients implanted with quadripolar left ventricular (LV) leads.Methods: RALLY-X4 was a registry study of the Acuity X4 quadripolar LV leads. Interventricular delay was measured during unpaced basal rhythm from the right ventricular (RV) lead to the LV lead electrode (E1 to E4) chosen for CRT pacing. Patients were stratified by median RV-LV delay (80 ms) into short and long delay groups, and they were also analysed by multivariable modelling. The primary composite outcome measure was all-cause mortality and heart failure hospitalization (HFH) at 18 months.Results: There were 581 patients with complete RV-LV delay data. The mean LV ejection fraction (EF) was 27% and 73% had a typical left bundle branch block. Predictors of long RV-LV delay included female sex, LBBB and QRS duration >150ms. Survival free of the primary outcome at 18 months follow up was 87% in the long activation delay group compared with 77% in the short delay group (p=0.0042). Multivariate analysis showed that RV-LV delay was a, independent predictor of survival free of HFH (p=0.028).Conclusions: Among CRT patients with quadripolar LV pacing leads, longer baseline interventricular activation delay was significantly associated with the composite endpoint of all-cause mortality and heart failure hospitalization. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this paper is to investigate the efficacy of filler applications which were evaluated in terms of nasal deformity and quality of life of the patients, and to review the fillers around the nose. PATIENTS AND METHODS: Forty patients who underwent filler application were included into the study and were divided into Group 1 (Deep Radix), Group 2 (Minor irregularities due to rhinoplasty), Group 3 (Shallow dorsum) and Group 4 (Dorsal irregularity). There were 10 patients in each of the groups. In all groups, nasal deformity score was evaluated with a 1 to 5 scale as following: 1- No deformity, 2- Hardly visible deformity, 3- Visible deformity, 4- Moderate deformity, 5- Apparent deformity. Quality of life was evaluated by a 1 to 10 scale, 1 showing very low and 10 showing very high. RESULTS: Our results showed that there were statistically significant improvements (decreased) in nasal deformity evaluation scores after the procedure compared to the before the procedure scores in Group 1 (Deep Radix), Group 3 (Shallow dorsum) and Group 4 (Dorsal irregularity) (p<0.05) However in Group 2 (Minor irregularities due to rhinoplasty), there were no significant differences between the nasal deformity evaluation scores after and before the procedure (p>0.05). For nasal deformity evaluation after the procedure, Group 1 (Deep Radix), Group 3 (Shallow dorsum) and Group 4 (Dorsal irregularity) scores were significantly lower (better) than Group 2 (Minor irregularities due to rhinoplasty) scores (padjusted <0.0125). In all four groups (Deep Radix, Minor irregularities due to rhinoplasty, Shallow dorsum, Dorsal irregularity), quality of life scores were significantly improved (increased) after the procedure compared to before the procedure (p<0.05). For Quality of life (VAS) before the procedure, Group 3 (Shallow dorsum) scores were significantly higher (improved, increased) than Group 1 (Deep Radix) and Group 4 (Dorsal irregularity) (p adjusted <0.0125). CONCLUSIONS: Filler applications improved (decreased) nasal deformity evaluation scores and improved (increased) quality of life scores. Fillers can be applied for deep radix, minor irregularities due to rhinoplasty, shallow dorsum and dorsal irregularity. It is essential to choose carefully appropriate materials and procedures for patients to obtain optimum results. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) response stratified by left ventricular (LV) remodeling revealed differing mortality profiles for distinct patient cohorts. Measuring functional endpoints, as well as mortality, may better assess CRT efficacy and inform patient management. However, the association between LV remodeling and functional outcomes after CRT is not well understood.Objective: To evaluate long-term CRT outcomes by extent of LV remodeling.Methods: REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (NCT00271154) was a prospective, double-blind, randomized CRT trial. Patients were classified based on LV end-systolic volume (LVESV) change from baseline to 6-months post-CRT: Worsened (increase); Stabilized (0 to ≤15% reduction); Responder (>15 to < 30% reduction); and Super-responder (≥30% reduction). Subjects were evaluated annually for 5 years.Results: The analyses included 353 patients randomized to CRT-ON arm. All-cause mortality was higher in the worsened group compared with the 3 other response groups (29.8% vs 8.0%, p<0.0001), with no difference in survival among those groups (p=0.87). A significant interaction between LVESV group and time was observed for health status and quality of life (both p=0.02). The interaction was not significant for 6-minute hall walk (p=0.79); however, super-responders had increased walk distance compared to the 3 other response groups (p=0.03).Conclusion: Preventing further increase in LVESV with CRT was associated with reduced mortality, whereas functional measure improvement was associated with LV remodeling magnitude. These results support consideration of functional and mortality endpoints to assess CRT efficacy and provide further evidence the dichotomous 'responder and non-responder' classification should be modified. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the osteolysis rate, graft remodeling, and risk factors for osteolysis at the 1-year threshold after an arthroscopic Latarjet procedure with double-button fixation. In this multicenter, retrospective study, postoperative computed tomography scans obtained after an arthroscopic Latarjet procedure with double-button fixation to treat anterior shoulder instability were analyzed at 15 days and at 3, 6, and 12 months. Graft volume, dimensions, and morphologic remodeling were analyzed. Twenty-seven patients were included (mean age, 26 years). At 1 year, osteolysis occurred in 19 of 27 patients (70%). The volume initially decreased until 6 months' follow-up (−35%; range, −75% to +26%) and then increased until our last follow-up. At 1 year, the graft volume decreased by 17% (range, −61% to +56%) compared with the immediate postoperative volume. In multivariate analysis, the rate of osteolysis was inversely associated with an unhealed graft at 3 months (P =.02; β coefficient = −44.50 [95% confidence interval, −81 to −8]). The maximal height of the graft significantly grew 0.2 cm (range, −55 to +124 mm) (P =.015). In the sagittal plane, osteolysis occurred in the superior part in 100% of patients (27 of 27) whereas bone formation occurred in the inferior part. In the axial plane, osteolysis occurred in the anterior part whereas bone formation occurred in the posterior part. In the articular part, the observed remodeling was aimed to obtain a new anatomic and congruent glenoid. At 1 year after an arthroscopic Latarjet procedure with double-button fixation, osteolysis occurred in 70% of patients. The rate of osteolysis was 17% of the initial volume. Osteolysis occurred mainly during the first 6 months, in the anterior and superior parts. Remodeling led to a circular anatomic glenoid. This osteolysis did not cause any recurrence of instability or require revision surgery. [ABSTRACT FROM AUTHOR]

Background: Wall stiffness of the abdominal aorta is an important factor in the cardiovascular risk assessment. We investigated abdominal aortic wall stiffness divided in direct and cross-coupled stiffness components with respect to sex and age. Methods: Thirty healthy adult males (n = 15) and females were recruited and divided into three age groups: young, middle aged and elderly. Pulsatile diameter changes were determined noninvasively by an echo-tracking system, and intra-aortic pressure was measured simultaneously. A mechanical model was used to compute stress and stiffness in circumferential and longitudinal directions. Results: Circumferential stretch had a higher impact on longitudinal wall stress than longitudinal stretch had on circumferential wall stress. Furthermore, there were an age-related and sex-independent increase in circumferential and longitudinal direct and cross-coupled stiffnesses and a decrease in circumferential and longitudinal stretch of the abdominal aortic wall. For the young group, females had a stiffer wall compared to males, while the male aortic wall grew stiffer with age at a higher rate, reaching a similar level to that of the females in the elderly group. Conclusion: Temporal changes in aortic stiffness suggest an age-related change in wall constituents that is expressed in terms of circumferential remodeling impacting longitudinal stress. These mechanisms may be active in the development of aortic tortuosity. We observed an age-dependent increase in circumferential and longitudinal stiffnesses as well as decrease in stretch. A possible mechanism related to the observed changes could act via chemical alterations of wall constituents and changes in the physical distribution of fibers. Furthermore, modeling of force distribution in the wall of the human abdominal aorta may contribute to a better understanding of elastin--collagen interactions during remodeling of the aortic wall. [ABSTRACT FROM AUTHOR]

Background: Wall stiffness of the abdominal aorta is an important factor in the cardiovascular risk assessment. We investigated abdominal aortic wall stiffness divided in direct and cross-coupled stiffness components with respect to sex and age. Methods: Thirty healthy adult males (n = 15) and females were recruited and divided into three age groups: young, middle aged and elderly. Pulsatile diameter changes were determined noninvasively by an echo-tracking system, and intra-aortic pressure was measured simultaneously. A mechanical model was used to compute stress and stiffness in circumferential and longitudinal directions. Results: Circumferential stretch had a higher impact on longitudinal wall stress than longitudinal stretch had on circumferential wall stress. Furthermore, there were an age-related and sex-independent increase in circumferential and longitudinal direct and cross-coupled stiffnesses and a decrease in circumferential and longitudinal stretch of the abdominal aortic wall. For the young group, females had a stiffer wall compared to males, while the male aortic wall grew stiffer with age at a higher rate, reaching a similar level to that of the females in the elderly group. Conclusion: Temporal changes in aortic stiffness suggest an age-related change in wall constituents that is expressed in terms of circumferential remodeling impacting longitudinal stress. These mechanisms may be active in the development of aortic tortuosity. We observed an age-dependent increase in circumferential and longitudinal stiffnesses as well as decrease in stretch. A possible mechanism related to the observed changes could act via chemical alterations of wall constituents and changes in the physical distribution of fibers. Furthermore, modeling of force distribution in the wall of the human abdominal aorta may contribute to a better understanding of elastin–collagen interactions during remodeling of the aortic wall. [ABSTRACT FROM AUTHOR]

Aging is a primary risk factor for degenerative tendon injuries, yet the etiology and progression of this degeneration are poorly understood. While aged tendons have innate cellular differences that support a reduced ability to maintain mechanical tissue homeostasis, the response of aged tendons to altered levels of mechanical loading has not yet been studied. To address this question, we subjected young and aged murine flexor tendon explants to various levels of in vitro tensile strain. We first compared the effect of static and cyclic strain on matrix remodeling in young tendons, finding that cyclic strain is optimal for studying remodeling in vitro. We then investigated the remodeling response of young and aged tendon explants after 7 days of varied mechanical stimulus (stress deprivation, 1%, 3%, 5%, or 7% cyclic strain) via assessment of tissue composition, biosynthetic capacity, and degradation profiles. We hypothesized that aged tendons would show muted adaptive responses to changes in tensile strain and exhibit a shifted mechanical setpoint, at which the remodeling balance is optimal. Interestingly, we found that 1% cyclic strain best maintains native physiology while promoting extracellular matrix (ECM) turnover for both age groups. However, aged tendons display fewer strain-dependent changes, suggesting a reduced ability to adapt to altered levels of mechanical loading. This work has a significant impact on understanding the regulation of tissue homeostasis in aged tendons, which can inform clinical rehabilitation strategies for treating elderly patients. [ABSTRACT FROM AUTHOR]

The performance of small-diameter vascular grafts adapted to vascular replacement is commonly hindered by stenosis. To address this issue, a graft featuring rapid remodeling with degradation is warranted. In this work, a 1.8-mm-diameter graft was constructed by fabricating a decellularized human amniotic membrane (HAM) with polycaprolactone (PCL)/silk fibroin (SF) around it through electrospinning, namely, an HPS graft, and applied in a rat aortic grafting model for comparison to a decellularized porcine small intestinal submucosa (SIS)-integrated PCL/SF (SPS) graft and an autologous aorta. In vitro studies demonstrated that HAM provided a bioactive milieu for rapid endothelial cell proliferation and resisting fibroblast-induced collagen secretion. PCL/SF provides a biocompatible microenvironment for cellular infiltration with mechanical properties resembling those of the rat aorta. In vivo studies showed that the HPS graft induced functional endothelialization more rapidly, along with less intensive ECM deposition than the SPS graft upon the histologically weaker inflammatory response and foreign body reaction 4 weeks after implantation, and maintained patency by progressively stabilizing the remodeling structure approximating the native counterparts over 24 weeks. The bioengineered graft expands the applicability of allogeneic matrices with degradable electrospun polymers for long-term in situ vascular applications. An orchestrated remodeling of the vascular graft, featuring rapid endothelialization and resisting extracellular matrix (ECM) deposition on the luminal surface, with a mechanically stable structure, is requisite for long-term vascular patency. Nevertheless, off-the-shelf grafts might not fulfil the criteria under abdominal aortic pressure. Herein, we fabricated a 1.8-mm-diameter vascular graft through the integration of a decellularized human amniotic membrane (HAM) with electrospun polycaprolactone (PCL)/silk fibroin (SF). In a rat aortic grafting model, the graft is capable of rapid endothelialization and resisting collagen deposition and provides a native-like mechanical structure for stabilizing the remodeling process towards that of the native aorta. This bioengineered graft has potential for small-diameter vascular regeneration, and provides advanced strategies to facilitate full-remodeling tissue applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Long-term voice abuse or sudden vocal fold microvascular disruption may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and also in various otolaryngological diseases. The aim of this article was to investigate the expression and the role of periostin in the formation of vocal fold polyps. The expression patterns of periostin in 59 surgical specimens of vocal fold polyps from 54 patients were investigated immunohistochemically. Normal vocal fold mucosa specimens from 5 patients who had undergone total laryngectomy were used as the control group. Retrospective study with planned data collection was conducted at Tohoku Medical and Pharmaceutical University. Expression of periostin was detected in 43 (72.9%) samples and four patterns of periostin expression were observed in vocal fold polyps: negative type, superficial type, infiltrative type, and diffuse type. An association was observed between periostin expression patterns and the histological subtypes of vocal fold polyps. The infiltrative pattern of periostin expression was significantly dominant in vascular-hyaline types. Expression of transforming growth factor-ß (TGF-ß) was also detected in the vocal fold polyps. Our results confirmed that periostin might be involved in certain pathological changes in vocal fold polyps, such as extracellular matrix accumulation, local fibrosis, and formation and development of vocal fold polyps. [ABSTRACT FROM AUTHOR]

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Background: Despite interest in left ventricular (LV) recovery, there is an absence of data on the relationship between intrinsic LV hemodynamics and both reverse remodeling on a continuous flow LV assist device (CF-LVAD) therapy. We hypothesized that the markers of intrinsic LV function would be associated with remodeling, optimization, and outcomes.Methods and Results: Patients with continuous flow LVADs between 2015 and 2019 who underwent combined left and right heart catheterization ramp protocol at a single institution were enrolled. Patients were stratified by response to continuous flow LV assist device therapy: full responders, partial responders, or nonresponders per the Utah-Inova criteria. Hemodynamic data, including LV hemodynamics of peak LV dP/dt and tau (τ) were obtained at each phase. The 1-year heart failure hospitalization-free survival was the primary end point. Among 61 patients included in the current study 38 (62%) were classified as nonresponders, 14 as partial responders (23%), and 9 as full responders (15%). The baseline LV dP/dt and τ varied by response status (P ≤ .02) and generally correlated with reverse remodeling on linear regression. Biventricular filling pressures varied with τ and there was an interaction effect of speed on the relationship between τ and pulmonary capillary wedge pressure (P = .04). Last, τ was a prognostic marker and associated with 1-year HF hospital-free survival (odds ratio 1.04, 95% confidence interval 1.00-1.07, P = .02 per millisecond increase).Conclusions: Significant correlations between τ and LV dP/dt and reverse remodeling were noted, with τ serving as a prognostic marker. A higher LVAD speed was associated with a greater reliance on LVAD for unloading. Future work should focus on defining the optimal level of LVAD support in relation to LV recovery. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) reduces mortality and improves outcomes in appropriately selected patients with heart failure (HF); however, response may vary.Objective: We sought to correlate 6-month CRT response assessed by clinical composite score (CCS) and left ventricular end-systolic volume index (LVESVi) with longer-term mortality and HF-related hospitalizations.Methods: Individual patient data from 5 prospective CRT studies-Multicenter InSync Randomized Clinical Evaluation (MIRACLE), Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD), InSync III Marquis, predictors of response to cardiac resynchronization therapy (PROSPECT), and Adaptive CRT-were pooled. Classification of CRT response status using CCS and LVESVi were made at 6 months. Kaplan-Meier analyses were used to assess time to mortality. Cox proportional hazards regression models were used to compute hazard ratios (HRs) for the 3 levels of CRT response: improved, stabilized, and worsened. Adjusted models controlled for baseline factors known to influence both CRT response and mortality. HF-related hospitalization was compared between CRT response categories using incidence rate ratios.Results: Among a total of 1603 patients, 1426 and 1165 were evaluated in the CCS and LVESVi outcome assessments, respectively. Mortality was significantly lower for patients in the improved (CCS: HR 0.22; 95% confidence interval [CI] 0.15-0.31; LVESVi: HR 0.40; 95% CI 0.27-0.60) and stabilized (CCS: HR 0.38; 95% CI 0.24-0.61; LVESVi: HR 0.41; 95% CI 0.25-0.68) groups than in the worsened group for both measures after adjusting for potential confounders.Conclusion: Patients with a worsened CRT response status have a high mortality rate and HF-related hospitalizations. Stabilized patients have a more favorable prognosis than do worsened patients and thus should not be considered CRT nonresponders. [ABSTRACT FROM AUTHOR]

Objectives: Excessive left ventricular mass (LVM) results in inefficient LV work with energy waste leading to a negative prognostic effect. We aimed at investigating the presence of inappropriate LVM and calculating the myocardial mechano-energetic efficiency index (MEEi) in former pre-eclamptic (PE) women (with or without HELLP syndrome) compared to women who experienced HELLP syndrome without PE.Study Design: In this cross-sectional study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent echocardiography as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity.Main Outcome Measures: LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was considered as the ratio between stroke work and "double product" (to approximate energy consumption), indexed to LVM.Results: LV hypertrophy was present in 8-14% and concentric remodeling in 31-42% of women, without intergroup difference. LVM was inappropriate in one-third of normotensive former HELLP and in about one-half of PE with or without HELLP, with no difference among groups. Accordingly, without nominal difference, MEEi showed a tendency towards lower values in former pre-eclamptic individuals.Conclusions: Women with a history of HELLP syndrome, independently from the presence/absence of PE, showed inappropriate LVM in the first 4 years after delivery, which may partially explain the elevated CV risk in these women compared to the general female population. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to determine the most appropriate timing for thoracic endovascular aortic repair (TEVAR) of type B aortic dissection (TBAD) in terms of remodeling of the aorta. A total of 41 patients who had undergone TEVAR for the treatment of aortic dissection were included in the present study. The patients were divided into two groups: those who had undergone TEVAR in the acute or subacute phase (group A) and those who had undergone TEVAR in the chronic phase (group B). The indications for TEVAR as the treatment of TBAD were the presence of aortic rupture or malperfusion of the aortic branches, a maximum aortic diameter of ≥40 mm on the initial diagnostic computed tomography scan, and/or expansion of the aorta of ≥5 mm within 3 months for acute and subacute TBAD. The indication was a maximum aortic diameter of ≥50 mm or expansion of the aorta of ≥5 mm within 1 year for chronic TBAD. The diameters of the aorta, true lumen, and false lumen were measured at the level of the most dilated part of the descending aorta (level M) and at the diaphragm (level D) on the computed tomography scan obtained before TEVAR and at the 2-year follow-up examination. The median interval between TEVAR and the onset of TBAD was 0.2 month (interquartile range, 0.03-0.7 month) in group A (n = 21) and 32 months (interquartile range, 4.7-35.2 months) in group B (n = 20). Except for the aortic diameter at level D in group B, favorable remodeling was obtained at both levels in both groups. The diameter change ratio of the aorta at level D was significantly greater in group A than in group B (P =.02). Receiver operating characteristic curve analysis of the interval for a significant decrease in the aortic diameter at level D yielded 4.2 months as the optimal threshold for performing TEVAR (area under the curve, 0.859; 95% confidence interval, 0.7-1.0). TEVAR for TBAD will result in favorable outcomes, irrespective of the timing of the procedure. However, it might be more effective to perform TEVAR within 4.2 months of the onset of TBAD, provided that the TEVAR procedure can be performed safely. [ABSTRACT FROM AUTHOR]

Background: Electrophysiological (EP) properties have been studied mainly in the monocrotaline model of pulmonary arterial hypertension (PAH). Findings are confounded by major extrapulmonary toxicities, which preclude the ability to draw definitive conclusions regarding the role of PAH per se in EP remodeling.Objective: The purpose of this study was to investigate the EP substrate and arrhythmic vulnerability of a new model of PAH that avoids extracardiopulmonary toxicities.Methods: Sprague-Dawley rats underwent left pneumonectomy (Pn) followed by injection of the vascular endothelial growth factor inhibitor Sugen-5416 (Su/Pn). Five weeks later, cardiac magnetic resonance imaging was performed in vivo, optical action potential (AP) mapping ex vivo, and molecular analyses in vitro.Results: Su/Pn rats exhibited right ventricular (RV) hypertrophy and were highly prone to pacing-induced ventricular tachycardia/fibrillation (VT/VF). Underlying this susceptibility was disproportionate RV-sided prolongation of AP duration, which promoted formation of right-sided AP alternans at physiological rates. While propagation was impaired at all rates in Su/Pn rats, the extent of conduction slowing was most severe immediately before the emergence of interventricular lines of block and onset of VT/VF. Measurement of the cardiac wavelength revealed a decrease in Su/Pn relative to control. Nav1.5 and total connexin 43 expression was not altered, while connexin 43 phosphorylation was decreased in PAH. Col1a1 and Col3a1 transcripts were upregulated coinciding with myocardial fibrosis. Once generated, VT/VF was sustained by multiple reentrant circuits with a lower frequency of RV activation due to wavebreak formation.Conclusion: In this pure model of PAH, we document RV-predominant remodeling that promotes multiwavelet reentry underlying VT. The Su/Pn model represents a severe form of PAH that allows the study of EP properties without the confounding influence of extrapulmonary toxicity. [ABSTRACT FROM AUTHOR]

Progressive displacement of diaphyseal clavicle fractures has been observed in adult patients, at times necessitating a change from nonoperative to operative treatment. Whether this occurs in adolescent patients has not been well investigated. The purpose of this study was to assess the rate and extent of progressive clavicle fracture displacement in adolescent patients following injury and during the early stages of healing. This was a multicenter study evaluating prospective data that had previously been collected as part of a larger study evaluating the functional outcomes of adolescent clavicle fractures. A consecutive series of completely displaced diaphyseal clavicle fractures in patients aged 10-18 years treated at 1 of 3 tertiary-care pediatric trauma centers was included; all fractures underwent standardized imaging within 2 weeks of the date of injury and during the course of healing (5-20 weeks after injury). Measurements of clavicle shortening, superior displacement, and angulation were performed using validated techniques. Progressive displacement and/or interval improvement in fracture alignment, as well as the subsequent need for surgical intervention, was noted. Patient demographic and radiographic parameters were assessed as possible risk factors for interval displacement. One hundred patients met the inclusion criteria. Mean end-to-end shortening, cortex-to-cortex shortening, superior displacement, and angulation at the time of injury were 24 mm, 15 mm, 15 mm, and 7°, respectively. At a mean of 10 weeks after injury, the fracture alignment improved across all 4 measurements for the overall cohort, with mean improvements of 3.5 mm in end-to-end shortening, 3.3 mm in cortex-to-cortex shortening, 2.1 mm in superior displacement, and 2° in angulation. By use of a clinical threshold of a change in shortening or displacement of 10 mm or change in angulation of 10°, 26% of fractures improved, 4% worsened, and 70% remain unchanged. Patients with more severe fractures were more likely to have improved alignment than were patients with less displaced fractures (P <.001). No patient underwent surgical intervention for progressive displacement. Significant early improvements in fracture alignment were observed in a substantial percentage of adolescent patients with completely displaced clavicle fractures. Among the most severely displaced fractures, shortening improved approximately 6 mm and angulation improved approximately 9°. In 4% of cases, increased displacement was observed, but this tended to be mild, and in no cases did it prompt surgical intervention. This finding indicates that the true final deformity after an adolescent clavicle fracture is commonly less than that present at the time of injury. [ABSTRACT FROM AUTHOR]

Background: Aortic elasticity creates a cushion that protects the heart from pressure injury, and a recoil that helps perfuse the coronary arteries. TEVAR has become first-line therapy for many aortic pathologies including trauma, but stent-grafts stiffen the aorta and likely increase LV afterload. Objective: Test the hypothesis that trauma TEVAR is associated with LV mass increase and adverse off-target aortic remodeling. Methods: Computed Tomography Angiography (CTA) scans of 20 trauma TEVAR patients (17 M/3 F) at baseline [age 34.9 ± 18.5 (11.4–71.5) years] and 5.1 ± 3.1 (1.1–12.3) years after repair were used to measure changes in LV mass, LV mass index, and diameters and lengths of the ascending thoracic aorta (ATA). Measurements were compared with similarly-aged control patients without aortic repair (21 M/21 F) evaluated at similar follow-ups. Results: LV mass and LV mass index of TEVAR patients increased from 138.5 ± 39.6 g and 72.35 ± 15.17 g/m2 to 173.5 ± 50.1 g and 85.48 ± 18.34 g/m2 at the rate of 10.03 ± 12.79 g/yr and 6.25 ± 10.28 g/m2/yr, whereas in control patients LV characteristics did not change. ATA diameters of TEVAR patients increased at a rate of 0.60 ± 0.80 mm/yr, which was 2.4-fold faster than in controls. ATA length in both TEVAR and control patients increased at 0.58 mm/yr. Half of TEVAR patients had hypertension at follow-up compared to only 5% at baseline. Conclusions: TEVAR is associated with LV mass increase, development of hypertension, and accelerated expansile remodeling of the ascending aorta. Although younger trauma patients may adapt to these effects, these changes may be even more important in older patients with other aortic pathologies and diminished baseline cardiac function. [ABSTRACT FROM AUTHOR]

The treatment of complicated chronic aortic dissection remains controversial. We previously reported encouraging early results with the stent-assisted balloon-induced intimal disruption and relamination of aortic dissection (STABILISE) technique for treating complicated acute aortic dissections. However, to date there have been no specific reports on the treatment of complicated chronic aortic dissections with this technique. The aim of this study was to assess the results of the STABILISE technique to treat complicated chronic aortic dissection. A single-center prospectively maintained database enrolled all patients hospitalized for aortic dissection at our institution. Inclusion criteria for the STABILISE procedure at the chronic stage of dissection (>3 months) were postdissection aneurysm with a diameter >55 mm or rapid aortic diameter growth >5 mm/6 months. We reviewed all patients treated for complicated chronic aortic dissection with the STABILISE technique. Patients were monitored at 3, 6, and 12 months and annually thereafter with clinical, imaging, and laboratory studies. Outcome analyses included survival, rupture, spinal cord ischemia, endoleak, morbidity (cardiac, renal, or pulmonary), reinterventions, false lumen patency, and aneurysm growth. Between September 2015 and December 2018, 17 patients underwent a STABILISE procedure for complicated chronic aortic dissection of the descending aorta. Fifteen patients were treated for remaining chronic distal thoracoabdominal aortic dissection after acute DeBakey type I aortic dissection repair, and 2 patients were treated for chronic type B aortic dissection. The median patient age was 61 years (range, 46-67 years). The median interval between the onset of acute symptoms and the procedure was 9 months (range, 3-67 months). Indications for the STABILISE procedure were a rapidly growing dissected aortic diameter >5 mm/6 months in 13 patients and aneurysmal evolution of the descending thoracic aorta >55 mm in 4 patients. There were no cases of in-hospital death, stroke, spinal cord ischemia, ischemic colitis, or renal failure necessitating dialysis. The median duration of follow-up was 17 months (range, 5-28.5 months). At the last computed tomography scan, 15 patients (88%) had complete false lumen thrombosis of the treated thoracoabdominal aorta down to the renal arteries. None of the patients had aortic growth at treated thoracoabdominal aorta level. One patient developed a proximal type 1 endoleak and required reintervention. Regarding the untreated aortoiliac level below the renal arteries, 11 patients had persistent false lumen patency, and 1 patient developed a common iliac artery aneurysm. All the other patients had stable infrarenal aortoiliac diameters. No late deaths were reported during follow-up. The STABILISE technique is a safe and effective means of performing immediate, complete aortic remodeling of the thoracoabdominal aorta in patients with complicated chronic aortic dissection, stabilizing the diameter of the dissected aorta. [ABSTRACT FROM AUTHOR]

Superior capsule reconstruction (SCR) has been developed to improve shoulder function and relieve pain in the treatment of irreparable rotator cuff tears. Previous studies have reported that graft healing can enhance favorable outcomes after SCR. On the other hand, graft tears often lead to less desirable outcomes and sometimes require additional surgical procedures. However, the healing process underlying this remains unclear. In this study, we aimed to investigate histologic changes occurring during the healing process associated with autologous fascia lata graft after SCR in vivo. We hypothesized that (1) autologous fascia lata graft can regenerate the fibrocartilaginous insertion into both the greater tuberosity and superior glenoid and (2) the midsubstance of the grafted fascia gradually remodels into tendon- and/or ligament-like tissue after SCR. Irreparable supraspinatus tendon defects were created in 24 mature Japanese white rabbits (age, 6 months; mean weight, 3.2 kg). Four weeks after creation of the defects, the right shoulders were subjected to SCR using autologous fascia lata grafts. The left shoulders were left untreated. Samples from the shoulders were harvested at 4, 8, 12, and 16 weeks after surgery to undergo histologic and immunohistochemical examinations. Macroscopically, we did not observe graft tears after SCR in our experiments. Histologically, the number of chondrocyte-like cells gradually increased, and the extracellular matrices around those cells contained glycosaminoglycan at the fascia-bone junction after SCR. The unmineralized fibrocartilage, mineralized fibrocartilage, and tidemark were observed 16 weeks after SCR. The distribution of type II collagen presented a pattern similar to that of a normal tendon and ligament insertion. The cells and collagen fiber gradually oriented parallelly to the long axis in the midsubstance of the grafted fascia lata. Additionally, type III collagen was replaced with type I collagen in the midsubstance of the grafted fascia lata after SCR. SCR using fascia lata autograft regenerated the fibrocartilaginous insertion at both the greater tuberosity and superior glenoid. The midsubstance of the grafted fascia gradually remodeled into tendon- and/or ligament-like tissue. These results suggest that the fascia lata autograft has the capacity for graft-to-bone healing and remodeling after SCR. [ABSTRACT FROM AUTHOR]

Background: The cardiac muscle has the ability to adapt to different loading conditions. We analyzed the associations of the age-related decreasing handgrip strength (HGS), a marker of muscular fitness, on cardiac structure and function in a community-based sample.Methods: We performed cross-sectional analyses of 4646 subjects (2554 women; 55.0%) aged 20 to 93 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the associations of HGS with structural and functional left and right ventricular (LV and RV) and left atrial (LA) parameters as determined by echocardiography and magnetic resonance imaging (MRI) as well with log-transformed NT-proBNP values using multivariable-adjusted linear regression models.Results: MRI data showed that a 1 kg lower HGS was associated with a 0.40 mL (95% confidence interval: 0.26 to 0.54; p < 0.001) lower LV end-diastolic volume, a 0.011 mm (0.005 to 0.018; p = 0.001) lower LV wall-thickness, a 0.59 g (0.43 to 0.75; p < 0.001) lower LV mass, a 0.58 mL/beat (0.43 to 0.74; p < 0.001) lower LV stroke volume, a 0.03 L/min (0.02 to 0.04; p < 0.001) lower LV cardiac output, a 0.48 mL (0.27 to 0.68; p < 0.001) lower LA end-diastolic volume, and a 1.02 mL (0.71 to 1.32) lower RV end-diastolic volume. Similar findings were observed for echocardiographic parameters. Moreover, lower HGS was associated with higher echocardiographic LV diastolic stiffness and NT-proBNP levels.Conclusions: In this large population-based sample, lower muscular fitness as assessed by HGS was associated with lower LV wall thickness and mass as well as with smaller chamber size, stroke volume and cardiac output of the LV, LA and RV. Moreover, HGS was inversely related to LV diastolic stiffness and NT-proBNP values. These outcomes might demonstrate the effects of an aging-related decrease in physical activity and lower muscular fitness on the heart - "the sedentary's heart". [ABSTRACT FROM AUTHOR]

Background: The heart has the capacity to adapt to different demands. The pathophysiological mechanisms involved with sedentarism are not fundamentally the opposite of those related with physical activity and regular exercise. We investigated the impact of lower cardiorespiratory fitness (CRF) on heart's plasticity and function in a population-based setting.Methods: We used data from 1165 participants (539 women; 46.3%) aged 21-81 years from two independent cohorts of the Study of Health in Pomerania (SHIP-2 and SHIP-TREND-0). We analyzed the cross-sectional associations of peak oxygen uptake (VO2peak), determined by symptom-limited cardiopulmonary exercise testing, with structural and functional left ventricular (LV) and left atrial (LA) parameters determined by magnetic resonance imaging (MRI) using multivariable- adjusted linear regression models.Results: A 1 L/min lower VO2peak was associated with a 10.5 g (95% confidence interval: 8.00 to 12.9; p < 0.001) lower LV mass, a 14.8 mL (10.9 to 18.6; p < 0.001) lower LV end-diastolic volume, a 0.29 mm (0.19 to 0.40; p < 0.001) lower LV wall-thickness, a 8.85 mL/beat (6.53 to 11.2; p < 0.001) lower LV stroke volume, a 0.42 L/min (0.25 to 0.60; p < 0.001) lower LV cardiac output and a 7.51 mL (3.88 to 11.1; p < 0.001) lower LA end-diastolic volume. Moreover, there were no associations with a concentric or eccentric remodeling and LV and LA ejection fraction.Conclusions: Lower CRF was associated with a smaller heart, LV wall-thickness and mass, LV and LA stroke volume and cardiac output. Conversely, there was no association with LA and LV ejection fraction. Our cross-sectional observations are consistent with cardiac adaptations reflecting reduced volume loading demands of a sedentary lifestyle - "the sedentary's heart". [ABSTRACT FROM AUTHOR]

In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success. We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics. We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV 1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort. Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin). FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring. [Display omitted] [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic T H 2 disorder complicated by tissue fibrosis and loss of esophageal luminal patency. The fibrostenotic esophagus does not respond well to therapy, but profibrotic therapeutic targets are largely unclear. Our aim was to utilize proteomics and primary cells as a novel approach to determine relevant profibrotic factors. We utilized primary esophageal EoE and normal fibroblasts, their derivative extracellular matrixes (ECMs), an approach of fibroblast culture on autologous versus nonautologous ECM, and proteomics to elucidate EoE ECM proteins that dysregulate cellular function. We cultured esophageal fibroblasts from normal esophagi and esophagi from patients with severe EoE on autologous versus nonautologous ECM. The EoE ECM proteome shifted normal esophageal fibroblast protein expression. Proteomic analysis demonstrated that thrombospondin-1 is detected only in the EoE ECM, is central in the EoE ECM protein-protein interactome, is found at significantly elevated levels in biopsy specimens from patients with active EoE, and induces fibroblast collagen I production. Fibroblasts from patients with EoE secrete a unique ECM proteome that reflects their in vivo state and induces collagen I and α-smooth muscle actin protein expression from normal fibroblasts. Thrombospondin-1 is a previously unappreciated profibrotic molecule in EoE. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Alterations in myocardial mitochondrial function and metabolism have been implicated in the pathophysiology of heart failure with reduced ejection fraction (HFrEF). The impact of mechanical dyssynchrony and its alleviation through cardiac resynchronization therapy (CRT) on myocardial mitochondrial function and metabolism remain poorly understood.Methods: HFrEF patients with an indication for CRT underwent targeted metabolomic analysis of 84 energetic substrates at baseline (coronary sinus and peripheral venous blood). Mitochondrial membrane potential (Ψm) as an indicator of mitochondrial function was assessed non-invasively through 99mTC-sestamibi myocardial washout. Changes in peripheral metabolism and Ψm were assessed 6-months after CRT and their association with left ventricular remodeling and peakVO2 was assessed. Principle component analysis (PCA) was used as dimension reduction strategy for metabolic analysis.Results: Forty-five HFrEF-patients underwent CRT-implant (76% male, ejection fraction 29±6%). At baseline, PCA of coronary (CS) vs peripheral blood (PB) illustrated preferred cardiac uptake of β-hydroxybutyrate (CS vs PB-ratio=-78%; p<0.005) together with anaplerotic amino-acids, and glycolytic pyruvate breakdown to lactate. Baseline Ψm-dysfunction was associated with shift away from free fatty acids oxidation (FAO). Myocardial β-hydroxybutyrate extraction strongly associated with peakVO2 (-0.836; p<0.001). CRT improved Ψm (25±5% vs 18±6%; p=0.002), in parallel with metabolic remodeling, with increased reliance on FAO, and less reliance on β-hydroxybutyrate and glycolytic pyruvate breakdown to lactate. Changes in myocardial mitochondrial function and metabolism were associated with left ventricular reverse remodeling.Conclusion: HFrEF-patients exhibit baseline mitochondrial dysfunction, which is associated with alterations in myocardial substrate utilization, including less FAO, more reliance on ketone bodies, anaplerotic amino-acids and the breakdown of glycolytic pyruvate to lactate. CRT is capable of inducing mitochondrial and metabolic reverse remodeling which is associated with cardiac morphology changes. [ABSTRACT FROM AUTHOR]

This study investigated the anti-remodeling and anti-fibrotic and effect of quercetin (QUR) in the remote non-infarcted of rats after myocardial infarction (MI). Rats were divided as control, control + QUR, MI, and MI + QUR. MI was introduced to the rats by ligating the eft anterior descending (LAD) coronary artery. All treatments were given for 30 days, daily. QUR persevered the LV hemodynamic parameters and prevented remote myocardium damage and fibrosis. Also, QUR supressed the generation of ROS, increased the nuclear levels of Nrf2, and enhanced SOD and GSH levels in the LVs of the control and MI model rats. It also reduced angiotensin II, nuclear level/activity of the nuclear factor NF-κβ p65, and protein expression of TGF-β1, α-SMA, and total/phospho-smad3 in the LVs of both groups. Concomitantly, QUR upregulated LV smad7 and BMP7. In conclusion, QUR prevents MI-induced LV remodeling by antioxidant, anti-inflammatory, and anti-fibroticα effects mediated by ROS scavenging, suppressing NF-κβ, and stimulating Nrf-2, Smad7, and BMP7. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated right atrial (RA) remodeling in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to characterize the RA remodeling in HFpEF and to determine its prognostic significance.Methods and Results: Patients with HFpEF were classified based on the presence of RA enlargement (RA volume index >39 mL/m2 in men and >33 mL/m2 in women). Compared with patients with normal RA size (n = 234), patients with RA dilation (n = 67) showed a higher prevalence of atrial fibrillation (AF), worse right ventricular systolic function, more severe pulmonary hypertension, and a greater prevalence of mild tricuspid regurgitation, as well as impaired RA reservoir function, with increased hepatobiliary enzyme levels. AF was strongly associated with the presence of RA dilation (odds ratio [OR] 10.2, 95% confidence interval [CI] 4.00-26.1 in current AF vs no AF and odds ratio 3.38, 95% CI 1.26-9.07, earlier AF vs no AF). Patients with RA dilation had more than a two-fold increased risk of composite outcomes of all-cause mortality or HF hospitalization (adjusted hazard ratio 2.01, 95% CI 1.09-3.70, P = .02). The presence of RA dilation also displayed an additive prognostic value over left atrial dilation alone.Conclusions: These data demonstrate that HFpEF with RA remodeling is associated with distinct echocardiographic features characterizing advanced right heart dysfunction with an increased risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo. Then, we demonstrated that PM2.5 induced up-regulation of collagen-I and alpha-smooth muscle actin (α-SMA) expression in rat and human ASMCs in vitro. Next, we found PM2.5 led to rat and human ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP) by autophagy-induced GATA4/TRAF6/NF-κB signaling, which contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. Together, our results provided evidence that SASP induced by PM2.5 in airway smooth muscle cells prompted airway remodeling. [Display omitted] • Inhaled particular matter induced airway smooth muscle remodeling. • PM2.5 led to ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP). • SASP contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. • Inhibition of SASP prevented PM2.5-induced airway remodeling. [ABSTRACT FROM AUTHOR]

To evaluate the results after selective sinus replacement (SSR) for aortic root remodeling in bicuspid aortopathy. Among 662 patients who underwent root repair using SSR between 2005 and 2020, there were 114 with bicuspid aortopathy. SSR was performed either as an isolated procedure (31) or as an adjunct to aortic valve repair (83) and was adjusted to the existing aortic annulus diameter rather than a downsized diameter. In valves with asymmetrical commissural orientation, the repair aimed for the achievement of a 180°-commissural orientation. Abolishment of aortic insufficiency (AI) ≥2+ using root repair alone was only possible in 2 patients with acute-dissection-related AI, yet isolated root repair was also performed in 29 further patients with no/mild AI. All remaining patients with AI ≥2+ presented cusp-related regurgitation and necessitated an additional valve repair. During the mean follow-up of 91 months (range, 13-196), a relevant valve defect (AI ≥3+ in 8, stenosis in 2) occurred in 10 patients (all after combined repair) resulting in an estimated freedom from a relevant aortic valve defect and/or reoperation of 96 ± 2%, 89 ± 4%, and 82 ± 6% at 5, 10, and 12 years, respectively. Echocardiographically, no patient revealed a considerable change of form or size of the repaired root nor was any root reintervention necessary. Patient-tailored root repair using SSR is a very effective and durable valve-sparing approach for bicuspid aortopathy. Aortic cusp repair is decisive for both abolishment of AI in bicuspid aortopathy and for the functional durability of the repaired aortic valve. [Display omitted] [ABSTRACT FROM AUTHOR]

Patients with severe asthma can present with eosinophilic type 2 (T2), neutrophilic, or mixed inflammation that drives airway remodeling and exacerbations and represents a major treatment challenge. The common β (βc) receptor signals for 3 cytokines, GM-CSF, IL-5, and IL-3, which collectively mediate T2 and neutrophilic inflammation. To determine the pathogenesis of βc receptor–mediated inflammation and remodeling in severe asthma and to investigate βc antagonism as a therapeutic strategy for mixed granulocytic airway disease. βc gene expression was analyzed in bronchial biopsy specimens from patients with mild-to-moderate and severe asthma. House dust mite extract and Aspergillus fumigatus extract (ASP) models were used to establish asthma-like pathology and airway remodeling in human βc transgenic mice. Lung tissue gene expression was analyzed by RNA sequencing. The mAb CSL311 targeting the shared cytokine binding site of βc was used to block βc signaling. βc gene expression was increased in patients with severe asthma. CSL311 potently reduced lung neutrophils, eosinophils, and interstitial macrophages and improved airway pathology and lung function in the acute steroid-resistant house dust mite extract model. Chronic intranasal ASP exposure induced airway inflammation and fibrosis and impaired lung function that was inhibited by CSL311. CSL311 normalized the ASP-induced fibrosis-associated extracellular matrix gene expression network and strongly reduced signatures of cellular inflammation in the lung. βc cytokines drive steroid-resistant mixed myeloid cell airway inflammation and fibrosis. The anti-βc antibody CSL311 effectively inhibits mixed T2/neutrophilic inflammation and severe asthma-like pathology and reverses fibrosis gene signatures induced by exposure to commonly encountered environmental allergens. [ABSTRACT FROM AUTHOR]

As a daily physiological mechanism in bone, microdamage accumulation dissipates energy and helps to prevent fractures. However, excessive damage accumulation might bring adverse effects to bone mechanical properties, which is especially problematic among the osteoporotic and osteopenic patients treated by bisphosphonates. Some pre-clinical studies in the literature applied forelimb loading models to produce well-controlled microdamage in cortical bone. Ovariectomized animals were also extensively studied to assimilate human conditions of estrogen-related bone loss. In the present study, we combined both experimental models to investigate microdamage accumulation in the context of osteopenia and zoledronate treatment. Three-month-old normal and ovariectomized rats treated by saline or zoledronate underwent controlled compressive loading on their right forelimb to create in vivo microdamage, which was then quantified by barium sulfate contrast-enhanced micro-CT imaging. Weekly in vivo micro-CT scans were taken to evaluate bone (re)modeling and to capture microstructural changes over time. After sacrifice, three-point-bending tests were performed to assess bone mechanical properties. Results show that the zoledronate treatment can reduce cortical microdamage accumulation in ovariectomized rats, which might be explained by the enhancement of several bone structural properties such as ultimate force, yield force, cortical bone area and volume. The rats showed increased bone formation volume and surface after the generation of microdamage, especially for the normal and the ovariectomized groups. Woven bone formation was also observed in loaded ulnae, which was most significant in ovariectomized rats. Although all the rats showed strong correlations between periosteal bone formation and microdamage accumulation, the correlation levels were lower for the zoledronate-treated groups, potentially because of their lower levels of microdamage. The present study provides insights to further investigations of pharmaceutical treatments for osteoporosis and osteopenia. The same experimental concept can be applied in future studies on microdamage and drug testing. [ABSTRACT FROM AUTHOR]

Background: There is still an unmet need for pharmacologic treatment of atrial fibrillation (AF) with few effects on ventricular electrophysiology. Ranolazine is an antiarrhythmic drug reported to have strong atrial selectivity.Objective: The purpose of this study was to investigate the electrophysiological effects of ranolazine in atria with AF-induced electrical remodeling in a model of lone AF in awake goats.Methods: Electrode patches were implanted on the atrial epicardium of 8 Dutch milk goats. Experiments were performed at baseline and after 2 and 14 days of electrically maintained AF. Several electrophysiological parameters and AF episode duration were measured during infusion of vehicle and different doses of ranolazine (target plasma levels 4, 8, and 16 μM, respectively).Results: The highest dose of ranolazine significantly prolonged atrial effective refractory period and decreased atrial conduction velocity at baseline and after 2 days of AF. After 2 weeks of AF, ranolazine prolonged the p5 and p50 of AF cycle length distribution in a dose-dependent manner but was not effective in restoring sinus rhythm. No adverse ventricular arrhythmic events (eg, premature ventricular beats or signs of hemodynamic instability) were observed during infusion of ranolazine at any point in the study.Conclusion: The lowest investigated dose of ranolazine, which is expected to block both late INa and atrial peak INa, had no effect on the investigated electrophysiological parameters. The highest dose affected both atrial and ventricular electrophysiological parameters at different stages of AF-induced remodeling but was not efficacious in cardioverting AF to sinus rhythm in a goat model of lone AF. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy and clinical outcomes of endovascular treatment for superior mesenteric artery dissection (SMAD) and its effect on superior mesenteric artery (SMA) remodeling compared with medical management alone after successful initial medical management. In this retrospective analysis, all patients with spontaneous SMAD at a single institution were identified from March 2007 to August 2019. The primary outcomes were freedom from major adverse events (MAEs, a composite of dissection-related death, the recurrence of mesenteric ischemia symptoms, and a requirement for intervention). The secondary outcomes were morphologic remodeling of the dissections and stenosis or occlusion of the SMA. A total of 94 patients with SMAD who underwent successful initial medical management (91 males; mean age, 50.4 ± 6.3 years) were enrolled in the study. Fifty-seven (60.6%) received medical management alone, and 37 (39.4%) underwent endovascular repair after initial medical management. In the endovascular group, the technical success rate was 86.5% (32 of 37). During a mean follow-up period of 33.6 ± 26.2 months (range, 1-120 months), nine (9.6%) patients experienced a recurrence of abdominal pain, and six had additional interventions for SMAD. The patients in the endovascular group showed more complete or partial remodeling (22 [81.1%] vs 24 [44.4%]; P <.0001) or unchanged dissections (5 [13.5%] vs 23 [42.6%]; P =.0001) than those in the conservative group. Survival analysis showed that the estimated MAE-free survival rates were 95.6%, 88.9%, and 85.4% at 1, 3, and 5 years, respectively. There was a higher freedom from SMA stenosis or occlusion in the endovascular group (log rank P =.046). Endovascular treatment and medical management alone result in similar MAE-free survival for patients with SMAD after successful initial medical management. Moreover, endovascular therapy is associated with a higher complete remodeling rate and greater freedom from SMA stenosis or occlusion. [ABSTRACT FROM AUTHOR]

The authors sought to characterize the functional and structural myocardial phenotypes of patients with moderate-to-severe aortic stenosis (AS) and to determine whether severe paradoxical low-gradient AS (LG-AS) is specifically associated with left ventricular (LV) remodeling and fibrosis. Recently, it was suggested that severe paradoxical LG-AS is a more advanced form of AS, with greater reduction of longitudinal deformation, adverse LV remodeling, and more interstitial fibrosis. The study population includes 147 patients with moderate-to-severe AS and a normal LV ejection fraction, and 75 normal control subjects. They prospectively underwent 2-dimensional speckle-tracking echocardiography and cardiac magnetic resonance to evaluate myocardial deformation, LV remodeling, and age- and sex-adjusted extravascular volume fraction (ECV, %). Among AS patients, 18 had moderate AS, 74 had severe high-gradient AS (HG-AS), and 55 had severe paradoxical LG-AS. Reduced longitudinal and circumferential deformation was observed in 21% and 6% of the AS patients, respectively. Multivariate analyses identified increased ECV (ß = 1.99; p = 0.001) and the absence of normal LV geometry (ß = −1.37; p = 0.007) and as independent predictors of reduced longitudinal deformation. Increased ECV was an independent predictor of reduced circumferential deformation (ß = 2.19; p = 0.001). Over a median follow-up of 29 months, reduced longitudinal deformation (hazard ratio: 0.82; p = 0.023) and higher transvalvular gradients (hazard ratio: 1.05; p < 0.001) increased the risk of death or need for aortic valve replacement. LV hypertrophy was more frequently observed among patients with severe HG-AS (65%) than among the other AS patients (14%; p < 0.001). On average, ECV was within normal limits and did not differ among gradient-area subgroups. When present, increased ECV was associated with reduced longitudinal deformation. This study's data show that patients with severe paradoxical LG-AS less frequently display reduced longitudinal deformation, LV hypertrophy, or myocardial fibrosis than patients with HG-AS. Also, interstitial fibrosis only occurs when reduced longitudinal deformation and severe HG-AS are present together. Finally, this study suggests that reduced longitudinal deformation and higher transvalvular gradients adversely affect patients' outcomes. [ABSTRACT FROM AUTHOR]

Background: According to recent epidemiologic studies, exposure to fine particulate matter (particulate matter 2.5 ≤ µm [PM2.5]) in the air increases the incidence and severity of allergic rhinitis (AR). Ursolic acid (UA) has activities in immune regulation and anti-inflammatory. However, the role of UA intervention on PM2.5-exposed AR remains unknown. In this study, we investigated the effects of UA on tissue remodeling and mucus hypersecretion in a rat model of AR after PM2.5 exposure. Methods: AR was induced in rats with ovalbumin (OVA) and they were exposed to ambient PM2.5(200 µg/m3) via a PM2.5 inhalation exposure system for 30 days(ARE group). Ursolic acid intervention was administrated in the AR model after PM2.5 exposure (UA group). Hyperplasia of goblet cells was detected by periodic acid-Schiff (PAS) staining and collagen deposition in the nasal mucosa was detected by Masson trichrome (MT) staining.MUC5AC expression was measured by immunohistochemistry. Results: UA group showed reduced goblet cell hyperplasia and collagen deposition in the nasal mucosa which exacerbated after PM2.5 exposure, as reflected by PAS and MT staining when compared with the ARE group. Immunohistochemical results showed that the expression of MUC5AC in the UA group was lower than that in the ARE group. Conclusion: Analysis of our data indicated that UA could attenuate nasal remodeling and mucus hypersecretion in aggravation of AR after PM2.5 exposure, which may be the pathophysiologic mechanisms for the prevention of AR exacerbated by exposure to PM2.5. [ABSTRACT FROM AUTHOR]

Hypertension (HT) confers the highest population-attributable risk among factors leading to atrial fibrillation (AF). Data also are accumulating regarding the association between pre-HT, aortic stiffness, and increased incident AF or AF recurrence. Atrial remodeling due to HT is progressive but also reversible. Although inhibition of the renin-angiotensin-aldosterone system has shown the greatest promise in improving AF outcomes, optimal blood pressure targets in individuals with HT and AF remain elusive. AF management demands an integrated care approach. HT is best treated alongside a comprehensive risk factor management program where other AF risk factors are targeted, with involvement of a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Physiologic pH is maintained in a narrow range through multiple systemic buffering systems. Metabolic Acidosis (MA) is an acid-base disorder clinically characterized by a decrease in systemic pH and bicarbonate (HCO 3 −) levels. Acidosis affects millions annually, resulting in decreased bone mineral density and bone volume and an increased rate of fracture. We developed an adult murine model of diet-induced metabolic acidosis via graded NH 4 Cl administration that successfully decreased systemic pH over a 14 day period to elucidate the effects of acidosis on the skeletal system. Blood gas analyses measured an increase in blood calcium and sodium levels indicating a skeletal response to 14 days of acidosis. MA also significantly decreased femur ultimate strength, likely due to modifications in bone morphology as determined from decreased microcomputed tomography values of centroid distance and area moment of inertia. These structural changes may be caused by aberrant remodeling based on histological data evidencing altered OCL activity in acidosis. Additionally, we found that acidosis significantly decreased bone CO 3 content in a site-specific manner similar to the bone phenotype observed in human MA. We determined that MA decreased bone strength thus increasing fracture risk, which is likely caused by alterations in bone shape and compounded by changes in bone composition. Additionally, we suggest the temporal regulation of cell-mediated remodeling in MA is more complex than current literature suggests. We conclude that our model reliably induces MA and has deleterious effects on skeletal form and function, presenting similarly to the MA bone phenotype in humans. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Chronic wounds are still an intractable medical problem for both clinicians and researchers and cause a substantial social and medical burden. Current clinical approaches can only manage wounds but have limited capacity to promote the regeneration of chronic wounds. As a type of natural nanovesicle, extracellular vesicles (EVs) from multiple cell types (e.g. , stem cells, immune cells, and skin cells) have been shown to participate in all stages of skin wound healing including inflammation, proliferation, and remodeling, and display beneficial roles in promoting wound repair. Moreover, EVs can be further re-engineered with genetic/chemical or scaffold material-based strategies for enhanced skin regeneration. In this review, we provide an overview of EV biology and discuss the current findings regarding the roles of EVs in chronic wound healing, particularly in immune regulation, cell proliferation and migration, angiogenesis, and extracellular matrix remodeling, as well as the therapeutic effects of EVs on chronic wounds by genetic modification, in combination with functionalized biomaterials, and as drug carriers. We also discuss the challenges and perspectives of translating EV-based therapies into clinical wound care in the future. Image, graphical abstract [ABSTRACT FROM AUTHOR]