Search Results (193)

Glaucoma is recognized as a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. While intraocular pressure (IOP) is considered the only modifiable risk factor, current medical treatments are challenged by issues such as inadequate IOP control and ocular side effects. Rho kinase (ROCK) inhibitors have been developed as a novel pharmacologic class targeting the trabecular meshwork to enhance conventional aqueous humor outflow. In this review, the pharmacokinetics and IOP-lowering efficacy of key ROCK inhibitors are summarized. Beyond IOP reduction, ROCK inhibitors exhibit neuroprotective, anti-inflammatory, antifibrotic, and ocular perfusion-enhancing effects. Finally, we analyzed the limitations and future prospects of ROCK inhibitors in the management of glaucoma. Full article

Background: Iron deficiency (ID) is a prevalent comorbidity of heart failure (HF), affecting up to 59% of patients, regardless of the presence of anaemia. Although its negative impact on left ventricular (LV) function is well documented, its effect on right ventricular (RV) function remains unclear. This study assessed the effects of ID on RV global longitudinal strain (RV-GLS) in patients diagnosed with acute decompensated HF (ADHF). Methods: This study included data from 100 patients hospitalised with ADHF irrespective of LV ejection fraction (LVEF) value. ID was defined according to the European Society of Cardiology HF guidelines as serum ferritin <100 ng/mL or ferritin 100–299 ng/mL, with transferrin saturation <20%. Anaemia was defined according to World Health Organization criteria as haemoglobin level <12 g/dL in women and <13 g/dL in men. RV systolic function was assessed using parameters including RV ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (FAC), peak systolic tissue Doppler velocity of the RV annulus (RV TDI S′), acceleration time of the RV outflow tract, and RV free wall GLS. Results: The mean (±SD) age of the study population (64% male) was 70 ± 10 years. The median LVEF was 35%, with 66% of patients classified with HF with reduced ejection fraction, 6% with HF with mid-range ejection fraction, and 28% with HF with preserved ejection fraction. Fifty-eight percent of patients had ID. There were no significant differences between patients with and without ID regarding demographics, LVEF, RV FAC, RV TDI S′, or systolic pulmonary artery pressure. However, TAPSE (15.6 versus [vs.] 17.2 mm; p = 0.05) and RV free wall GLS (−14.7% vs. −18.2%; p = 0.005) were significantly lower in patients with ID, indicating subclinical RV systolic dysfunction. Conclusions: ID was associated with subclinical impairment of RV systolic function in patients diagnosed with ADHF, as evidenced by reductions in TAPSE and RV-GLS, despite the preservation of conventional RV systolic function parameters. Further research validating these findings and exploring the underlying mechanisms is warranted. Full article

Contemporary evaluation and surgical approaches in congenital aortic valve disease have yielded limited success. The ability to evaluate and understand detailed flow characteristics surrounding surgical repair may be beneficial. This study explores the feasibility and utility of echocardiographic-based blood speckle imaging (BSI) in assessing pre- and post-operative flow characteristics in those with non-stenotic congenital aortic root disease undergoing aortic valve repair or valve-sparing root replacement (VSRR) surgery. Transesophageal echocardiogram was performed during the pre-operative and post-operative assessment surrounding aortic surgery for ten patients with non-stenotic congenital aortic root disease. BSI, utilizing block-matching algorithms, enabled detailed visualization and quantification of flow parameters from the echocardiographic data. Post-operative BSI unveiled enhanced hemodynamic patterns, characterized by quantified changes suggestive of the absence of stenosis and no more than trivial regurgitation. Rectification of an asymmetric jet and the reversal of flow on the posterior aspect of the ascending aorta resulted in a reduced oscillatory shear index ($OSI$) of $0.0543\pm 0.0207$ (pre-op) vs. $0.0275\pm 0.0159$ (post-op) and $p=0.0044$, increased peak wall shear stress of $1.9423\pm 0.6974$ (pre-op) vs. $3.6956\pm 1.4934$ (post-op) and $p=0.0035$, and increased time-averaged wall shear stress of $0.6885\pm 0.8004$ (pre-op) vs. $0.8312\pm 0.303$ (post-op) and $p=0.23$. This correction potentially attenuates cellular alterations within the endothelium. This study demonstrates that children and young adults with non-stenotic congenital aortic root disease undergoing valve-preserving operations experience significant improvements in flow dynamics within the left ventricular outflow tract and aortic root, accompanied by a reduction in $OSI$. These hemodynamic enhancements extend beyond the conventional echocardiographic assessments, offering immediate and valuable insights into the efficacy of surgical interventions. Full article

The Beijing–Tianjin–Hebei (BTH) region is one of China’s most water-scarce yet economically vital areas, facing increasing challenges due to climate change and intensive human activities. This study develops an integrated Water–Food–Energy–Ecology (WFEE) simulation and regulation model to assess the system’s stability under coordinated development scenarios and extreme climate stress. A 500-year precipitation series was reconstructed using historical drought and flood records combined with wavelet analysis and machine learning models (Random Forest and Support Vector Regression). Results show that during the reconstructed historical megadrought (1633–1647), with average precipitation anomalies reaching −20% to −27%, leading to a regional water shortage rate of 16.9%, food self-sufficiency as low as 44.7%, and a critical reduction in ecological river discharge. Under future recommended scenario with enhanced water conservation, reclaimed water reuse, and expanded inter-basin transfers, the region could maintain a water shortage rate of 2.6%, achieve 69.3% food self-sufficiency, and support ecological water demand. However, long-term water resource degradation could still reduce food self-sufficiency to 62.9% and ecological outflows by 20%. The findings provide insights into adaptive water management, highlight the vulnerability of highly coupled systems to prolonged droughts, and support regional policy decisions on resilience-oriented water infrastructure planning. Full article

The Angat Reservoir serves as a major water source for Metro Manila, providing most of the region’s domestic, agricultural, and hydropower needs. However, its dependence on rainfall makes it sensitive to climate variability and future climate change. This study assesses potential long-term impacts of climate change on water availability in the Angat watershed using the Hydrologic Engineering Center–Hydrologic Modeling System (HEC-HMS). Historical rainfall data from 1994 to 2023 and projections under both RCP4.5 (moderate emissions) and RCP8.5 (high emissions) scenarios were analyzed to simulate future hydrologic responses. Results indicate projected reductions in wet-season rainfall and corresponding outflows, with declines of up to 18% under the high-emission scenario. Increased variability during dry-season flows suggests heightened risks of water scarcity. While these projections highlight possible changes in the watershed’s hydrologic regime, the study acknowledges limitations, including assumptions in rainfall downscaling and the absence of direct streamflow observations for model calibration. Overall, the findings underscore the need for further investigation and planning to manage potential climate-related impacts on water resources in Metro Manila. Full article

Blood flow restriction exercise (BFRE), which partially restricts arterial inflow and occludes venous outflow to the limbs, has gained attention for its potential to elevate serum brain-derived neurotrophic factor (BDNF), a key mediator in the muscle–brain crosstalk leading to improvement of neuroplasticity, neurogenesis, and cognitive health. In this systematic review of five studies, participants included healthy young adults, older adults, and individuals with clinical conditions. Most investigations found that BFRE increased serum BDNF, with responses comparable to those elicited by high-intensity exercise. Proposed mechanisms center on the metabolic demands of BFRE, which may increase lactate and thereby trigger BDNF release. However, two studies showed no significant changes, possibly due to short exercise duration, insufficient training intensity, or age-related reductions in BDNF responsiveness. The small sample sizes and varied protocols across studies limit definitive conclusions. Nonetheless, BFRE may provide a valuable alternative for populations who cannot tolerate high mechanical loads, and it shows promise for enhancing neurotrophic support and potentially improving brain health. Larger, well-controlled trials are warranted to refine BFRE protocols and better understand optimal strategies for increasing BDNF and supporting neuroplasticity. Full article

In vitro methods have advanced research on rumen microbiology and fermentation. However, artificial saliva formulation may need adjustments, particularly in urea content, for modern diets, warranting further research. This study investigated the effects of different nitrogen (N) levels in artificial saliva on ruminal fermentation and digestion in diets for dairy cows using a Rusitec^® system. Eighteen fermenters tested three saliva treatments with different N levels: a standard saliva as the control and two treatments with N reduced by 15% and 30%. Data were analyzed as a completely randomized design using the MIXED procedure of SAS (v. 9.4), with linear and quadratic contrasts tested for treatment effects (significance set at p ≤ 0.05). Results showed that altering N content had no significant effect on pH, ammonia concentrations, or NH₃-N outflow, nutrient digestibility (dry matter, crude protein, fiber, and starch), gas and methane production, or volatile fatty acid concentrations. The efficiency of microbial protein synthesis and N flow exhibited quadratic responses, with the lowest values observed at the highest level of N reduction in the saliva (−30%). These findings suggest that although ruminal function and digestion remain stable with reduced N, microbial protein synthesis efficiency may decline beyond a threshold. Full article

Background: Vibrating mesh nebulizers (VMNs) are not only used to deliver typical pulmonary drugs but are also a promising platform for novel formulations and therapeutic applications. Typically, these devices operate continuously or on demand and are directly connected to the outflow interface (mouthpiece or mask) without valving systems that could spare the drug during exhalation. This paper examines the possibility of increasing the delivery of inhaled budesonide aerosol by attaching a valved holding chamber (VHC) to selected VMNs. Methods: A laboratory in vitro study was conducted for seven budesonide (BUD) nebulization products (0.25 mg/mL). The rates of aerosol delivery from VMNs alone or VMN + VHC systems were determined gravimetrically for a simulated breathing cycle, while droplet size distributions in mists were measured by laser diffraction. Results: The VMN + VHC systems increased the amount of aerosol available for inhalation and the fraction of fine particles that could penetrate the pulmonary region. Depending on the VMN and BUD product, a relative increase of 30–300% in the total drug delivery (T) and 50–350% in the pulmonary drug availability (P) was obtained. The results are explained by the reduction in aerosol losses during exhalation (the fugitive emission) by the VHC and the simultaneous elimination of the largest droplets due to coalescence and deposition in the chamber. Both VMN and BUD affected the aerosol’s properties and discharge mass and thus the actual benefits of the VHC. Conclusions: While the results confirm the superiority of VMN + VHC over VMNs alone in nebulizing BUD suspensions, they also show that it is difficult to predict the effects quantitatively without testing the individual nebulizer–chamber–drug combination. Full article

Hypertrophic cardiomyopathy (HCM) is often associated with left ventricular outflow tract (LVOT) obstruction, which affects a substantial proportion of patients. This obstruction results from a range of anatomical abnormalities involving both the valvular and subvalvular structures. Pharmacological therapies play a pivotal role in the management of LVOT obstruction, with a range of drug classes exhibiting distinct mechanisms of action. Beta-blockers, including atenolol and nadolol, are considered the first-line treatment due to their ability to reduce heart rate and myocardial contractility and enhance diastolic filling. Non-dihydropyridine calcium channel blockers, such as verapamil and diltiazem, are utilized as second-line agents when beta-blockers are ineffective or contraindicated. Disopyramid, a Class 1A antiarrhythmic agent, is employed for patients who do not respond to initial therapeutic interventions and can reduce LVOT gradients. Recent advancements in cardiac myosin modulators, such as Mavacamten and Aficamten, offer targeted therapies by modulating myosin–actin interactions to reduce LVOT gradients and improve symptoms, with promising results from clinical trials. Although gene therapy is still in its nascent stages, it has the potential to address the genetic basis of HCM by employing techniques such as genome editing, gene replacement, and the modulation of signaling pathways. For patients exhibiting severe symptoms or demonstrating unresponsiveness to medical treatment, invasive therapies, such as septal reduction therapy and alcohol septal ablation, are considered. Ultimately, the treatment and prevention of atrial fibrillation and sudden cardiac death are two key points of HCM management in both obstructive and non-obstructive forms. This review aims to provide an overview of current pharmacological and invasive strategies, as well as emerging therapies, in the management of HCM. Full article

Background: Idiopathic intracranial hypertension (IIH) is, by definition, of unknown cause. Davson’s equation indicates that the increased intracranial pressure (ICP) found in IIH could be due to an increase in the CSF formation rate (CSF_fr), the CSF outflow resistance (R_out) or the venous sinus pressure. Studies simultaneously measuring the ICP and sagittal sinus pressures in IIH suggest that there is either a reduction in the R_out and/or the CSF_fr. The latter suggests that the increased venous pressure can be the only variable causing this disease process. A study maintaining the ICP at zero showed a significantly elevated CSF_fr in this disease. The purpose of the current study is to define the most feasible explanation for these findings and to suggest a viable pathophysiology for IIH. Methods: A lumped parameter vascular model, originally developed to study normal pressure hydrocephalus, was extended to investigate IIH. The model used the simultaneously obtained ICP and sagittal sinus pressure measurements from five experiments published in the literature to estimate the CSF_fr and the capillary transmural pressure (TMP). The assumptions made during this study were those of a normal mean arterial pressure, a normal total R_out and a normal blood flow rate. Results: When the CSF formation rates were plotted against the estimated capillary transmural pressures, a straight line was returned, suggesting that the CSF_fr and capillary TMP are related. Conclusions: The novel findings of this study suggest that the CSF_fr in IIH varies with the capillary TMP. A reduced capillary TMP in IIH can moderate the ICP if there is net CSF absorption across the capillaries. This would require the blood–brain barrier (BBB) to be disrupted. The model suggests that drugs which stabilise the BBB may trigger IIH by blocking CSF absorption across the capillaries, increasing the apparent CSF formation rate back toward normal and increasing the ICP. Anaemia will promote IIH by increasing the cerebral blood flow, the capillary TMP and the CSF_fr. Full article

Extreme precipitation events are one of the common hazards in eastern Texas, generating a large amount of storm water. Water running off urban areas may carry non-point source (NPS) pollution to natural resources such as rivers and lakes. Urbanization exacerbates this issue by increasing impervious surfaces that prevent natural infiltration. This study evaluated the efficacy of rain gardens, a nature-based best management practice (BMP), in mitigating NPS pollution from urban stormwater runoff. Stormwater samples were collected at inflow and outflow points of three rain gardens and analyzed for various water quality parameters, including pH, electrical conductivity, fluoride, chloride, nitrate, nitrite, phosphate, sulfate, salts, carbonates, bicarbonates, sodium, potassium, aluminum, boron, calcium, mercury, arsenic, copper iron lead magnesium, manganese and zinc. Removal efficiencies for nitrate, phosphate, and zinc exceeded 70%, while heavy metals such as lead achieved reductions up to 80%. However, certain parameters, such as calcium, magnesium and conductivity, showed increased outflow concentrations, attributed to substrate leaching. These increases resulted in a higher outflow pH. Overall, the pollutants were removed with an efficiency exceeding 50%. These findings demonstrate that rain gardens are an effective and sustainable solution for managing urban stormwater runoff and mitigating NPS pollution in eastern Texas, particularly in regions vulnerable to extreme precipitation events. Full article

Amidst the backdrop of rural population decline and the inefficient expansion of construction land, traditional land management models are confronted with the dual challenges of supply–demand mismatch and low efficiency. This paper constructs a three-dimensional analytical framework based on decoupling types, development potential, and driving mechanisms. Initially, using Tapio’s decoupling theory, the study identifies the population–land decoupling types among 224 villages in Yanggao County, Shanxi Province, Northern China. It then evaluates the development potential of rural construction land using a comprehensive index system, and a linkage analysis between the two is conducted. Finally, the study employs the Logarithmic Mean Divisia Index (LMDI) method to conduct an in-depth analysis of the mechanisms driving changes in rural construction land. The results indicate the following: (1) Between 2010 and 2020, the study area exhibited a reverse evolution characterized by rural population loss and the expansion of construction land, with a significant “population–land decoupling” phenomenon. (2) The development potential for rural construction land shows a pattern of being high in the north and south, low in the middle, high in mountainous and hilly areas, low in plains, and high in peripheral areas but low in town centers. (3) Villages in Yanggao County are predominantly of the resource reserve type (49.11%), indicating relatively abundant land resource reserves. (4) In different population migration patterns, the reduction in land-use efficiency represents similar proportions (38% and 36%), with villages experiencing net population inflow performing better in improving land-use efficiency compared to those with net population outflow. Drawing on international governance experiences, the study proposes classification and phased implementation pathways. By revealing the dynamic patterns of rural population–land relationships—construction land potential and change mechanisms—the logic of regulatory path adaptation, the article provides a methodological paradigm for constructing a precise and differentiated land resource allocation system, promoting the transition of rural spatial governance from expansion in scale to an improvement in quality. Full article

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy, caused by either sarcomere protein or other gene mutations. It is a complex and highly heterogeneous disorder, with phenotypes ranging from asymptomatic to severe disease, characterized by asymmetric left ventricular (LV) hypertrophy unexplained by loading conditions, which is also associated with myocardial fiber disarray, and preserved or increased ejection fraction without LV dilation. Comprehensive personal and family history, physical examination, and ECG testing raise suspicion of HCM, and echocardiogram represents the first-line imaging modality for confirming a diagnosis. Moreover, contrast-enhanced cardiac magnetic resonance (CMR) imaging has increasingly emerged as a fundamental diagnostic and prognostic tool in HCM management. This article reviews the role of CMR in HCM identification and differentiation from phenotypic mimics, characterization of HCM phenotypes, monitoring of disease progression, evaluation of pre- and post-septal reduction treatments, and selection of candidates for implantable cardioverter-defibrillator. By providing information on cardiac morphology and function and tissue characterization, CMR is particularly helpful in the quantification of myocardial wall thickness, the detection of hypertrophy in areas blind to echocardiogram, subtle morphologic features in the absence of LV hypertrophy, myocardial fibrosis, and apical aneurysm, the evaluation of LV outflow tract obstruction, and the assessment of LV function in end-stage dilated HCM. Full article

Objectives: The objective of this study is to investigate the two-year continuous efficacy, risk factors, and safety profile of selective laser trabeculoplasty (SLT) in Japanese individuals diagnosed with normal-tension glaucoma (NTG) who underwent SLT as either a first-line or second-line treatment. Methods: A retrospective chart review was conducted of patients with NTG who underwent SLT as either an initial or secondary therapy at 26 medical institutions in Japan between January 2020 and December 2021 with a 2-year follow-up. The primary endpoint was a reduction in the rate of intraocular pressure (IOP) over 2 years after SLT. To estimate the time-varying effect of IOP reduction, a linear mixed-effects model was employed. The secondary endpoints were numerical IOP reduction, treatment success rates shown by a Kaplan–Meier analysis, and complications. Success was defined as an outflow pressure improvement rate (ΔOP) ≥ 20% (definition A) or an IOP reduction rate ≥ 20% (definition B) without further treatment. A Cox proportional hazards regression analysis was used to identify the risk factors to successful SLT treatment. The study was registered with UMIN-CTR (ID: UMIN R000064045). Results: A total of 230 eyes from 230 individuals participated in this study, with 148 eyes receiving SLT as an initial (first-line) therapy and 82 eyes undergoing SLT as a secondary (second-line) intervention. In the first-line group, the mean IOP dropped from 16.7 ± 2.3 mmHg to 13.7 ± 2.4 mmHg at two years post-treatment, reflecting a 16.8% reduction. In the second-line group, the average IOP declined from 15.9 ± 2.5 mmHg to 13.2 ± 2.0 mmHg, marking a 14.4% decrease over the same period. The treatment success rate according to definition A (ΔOP ≥ 20%) was 73.7% at 2 years. Analysis using a linear mixed-effects model identified time (p < 0.001), age (p = 0.044), baseline IOP (p < 0.001), and central corneal thickness (CCT) (p < 0.001) as statistically significant contributors to IOP reduction following SLT. However, neither the Group (first-line vs. second-line) variable (p = 0.386) nor the Time × Group interaction (p = 0.298) reached statistical significance. A lower baseline IOP and a thicker CCT were confirmed as significant predictors of SLT treatment failure. Conclusions: Both initial and secondary SLT treatments for NTG proved to be effective and safe over a two-year period, although the extent of IOP reduction was smaller in cases with a lower baseline IOP. Our findings indicate that the IOP-lowering effect of SLT in NTG is influenced by pretreatment IOP levels, aligning with previous studies on primary open-angle glaucoma and ocular hypertension. However, in contrast to those earlier findings, our research identified pretreatment central corneal thickness as a statistically significant factor influencing SLT efficacy in NTG. These results support the role of SLT as a reliable and safe therapeutic option for managing NTG. Full article

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy marked by increased left ventricular wall thickness, leading in some cases to left ventricular outflow tract (LVOT) obstruction, heart failure, and arrhythmias. Mavacamten, a selective allosteric inhibitor of cardiac myosin, has demonstrated benefits in improving hemodynamics and reducing LVOT obstruction. However, its impact on arrhythmic burden remains unclear, with reports of early atrial fibrillation (AF) risk contrasting with long-term reductions in arrhythmias. This study assesses the temporal patterns of Holter-detected arrhythmias in HCM patients treated with mavacamten. Methods: This retrospective study included HCM patients from three Mayo Clinic sites. Baseline demographic, clinical, and echocardiographic data were collected. Holter monitoring was performed at baseline, short-term (<6 months), and long-term (>6 months) follow-up. Arrhythmic events, including premature atrial contractions (PACs), premature ventricular contractions (PVCs), and supraventricular tachycardia (SVT), were analyzed using standardized rates per 24 h. Statistical comparisons utilized the Wilcoxon signed-rank test. Results: Twenty-seven patients (56% female, median age 66 years) were included. PACs, PVCs, and SVT duration transiently but not significantly increased at short-term follow-up but returned to baseline at long-term follow-up. No sustained or high-risk ventricular arrhythmias were observed. Conclusions: Mavacamten is associated with transient arrhythmic fluctuations early in treatment, followed by stabilization. These findings support its long-term electrophysiological safety and underscore the need for early rhythm monitoring. Further research should explore its role in arrhythmic risk stratification in HCM patients. Full article