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22 pages, 1420 KB  
Review
Current Management of Resistant Hypertension in Patients with Intracerebral Hemorrhage
by Michelle Nguyen, Sookyung Oh, Matthew King, Wengui Yu and Ahmad Riad Ramadan
Int. J. Mol. Sci. 2026, 27(6), 2716; https://doi.org/10.3390/ijms27062716 - 16 Mar 2026
Viewed by 215
Abstract
Approximately 795,000 people experience new or recurrent strokes in the United States each year; between 10 to 20% of these are spontaneous intracerebral hemorrhages (ICH). Uncontrolled hypertension is not only the most common cause of ICH but also a major risk factor for [...] Read more.
Approximately 795,000 people experience new or recurrent strokes in the United States each year; between 10 to 20% of these are spontaneous intracerebral hemorrhages (ICH). Uncontrolled hypertension is not only the most common cause of ICH but also a major risk factor for hematoma expansion. Resistant hypertension, defined as persistently elevated blood pressure despite the use of three or more antihypertensives of different classes, is common in patients with ICH. A long-acting calcium channel blocker, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), and a thiazide diuretic are generally considered the mainstay for the treatment of resistant hypertension. However, due to the risk of hyponatremia and worsening cerebral edema, thiazide diuretics should be avoided during the first few weeks of ICH. Recent evidence supports the use of a mineralocorticoid receptor antagonist. While resistant hypertension may be idiopathic, a workup of secondary causes should be pursued. Adequate and timely control of elevated blood pressure remains one of the main cornerstones of treatment in patients with ICH. Previous studies have revealed that resistant hypertension in patients with ICH is associated with longer ICU stays, a higher risk of recurrent stroke, and can contribute to renal, cardiac, and neurologic complications. This emphasizes the need for early initiation of oral antihypertensives and adequate blood pressure control at hospital discharge. Landmark studies have shown that early lowering of SBP to 130–150 mm Hg with smooth, sustained BP control is safe and may improve functional outcomes in patients with mild to moderate ICH. After initiating oral antihypertensives with a calcium channel blocker, an ACEi or ARB beta-blocker, and a mineralocorticoid receptor antagonist to maximally tolerated doses, the next line of antihypertensive treatment should be tailored to the patient’s co-morbidities, and may include a beta-blocker, central alpha agonist, hydralazine, and minoxidil. In this review, we discuss the epidemiology of resistant hypertension in ICH and its molecular basis, diagnostic workup, and acute and long-term treatment. We present novel mechanisms implicated in hypertensive ICH, including ferroptosis, neuroinflammation, the CNS–gut microbiome axis, and novel therapeutics. We also propose a simple algorithm for the optimal pharmacological management of resistant hypertension in ICH. Full article
(This article belongs to the Special Issue Recent Research on Hypertension and Related Complications)
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15 pages, 2887 KB  
Article
Survey of Antimicrobial-Resistant Bacteria Isolated from Rivers in Japan, Indonesia and Nepal
by Kayo Osawa, Ryohei Nomoto, Takashi Suzuki, Taishi Maeda, Ganesh Rai, Shouhiro Kinoshita, Noriko Nakanishi, Dadik Raharjo, Masanori Kameoka, Masato Fujisawa, Shiba Kumar Rai, Kuntaman Kuntaman and Toshiro Shirakawa
Pathogens 2026, 15(3), 317; https://doi.org/10.3390/pathogens15030317 - 15 Mar 2026
Viewed by 177
Abstract
The threat of antimicrobial resistance in aquatic environments, particularly riverine systems, is escalating, in part due to effluents discharged from healthcare facilities. This issue has been recognized not only in Japan but also in other Asian countries such as Indonesia and Nepal. Nevertheless, [...] Read more.
The threat of antimicrobial resistance in aquatic environments, particularly riverine systems, is escalating, in part due to effluents discharged from healthcare facilities. This issue has been recognized not only in Japan but also in other Asian countries such as Indonesia and Nepal. Nevertheless, existing research remains limited, prompting an investigation into the prevalence of antimicrobial-resistant bacteria in the upstream and downstream sites of environmental rivers. In 2024, six samples were collected from three rivers in Hyogo Prefecture, Japan; five samples from five river sites in Indonesia; and three samples from downstream sites of rivers in Kathmandu, Nepal. These samples were subjected to selective culture–based Next Generation Sequencing and resistome analyses, based exclusively on the selective culture of bacteria propagated on CHROMagar ESBL plates. In Japan and Indonesia, Pseudomonas, Stenotrophomonas and Acinetobacter were frequently detected, whereas Klebsiella was overwhelmingly predominant in Nepal. Significant differences in the similarity of bacterial community composition among sampling sites across the three countries were observed (p < 0.001). Notably, Nepal exhibited the highest abundance level of antimicrobial resistance genes among the three countries, largely consisting of β-lactam resistance genes. In conclusion, these analyses elucidated substantial differences in bacterial community composition and degrees of environmental contamination. Full article
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29 pages, 2080 KB  
Review
Transmission and Evolution of Antibiotic Resistance Genes and Antibiotic-Resistant Bacteria in Animals, Food, Humans and the Environment
by Linjuan Li, Jie Zhu, Yuxin Yan, Zhangheng Li and Hong Du
Microorganisms 2026, 14(3), 634; https://doi.org/10.3390/microorganisms14030634 - 11 Mar 2026
Viewed by 282
Abstract
Antimicrobial resistance (AMR) constitutes one of the most severe and pressing threats to global public health, food security, and environmental integrity. This review synthesizes current evidence across interconnected One Health domains—humans, animals, food, and the environment—to delineate the scope, mechanisms, and drivers of [...] Read more.
Antimicrobial resistance (AMR) constitutes one of the most severe and pressing threats to global public health, food security, and environmental integrity. This review synthesizes current evidence across interconnected One Health domains—humans, animals, food, and the environment—to delineate the scope, mechanisms, and drivers of AMR transmission. Our analysis reveals three principal findings. First, the scope of AMR is alarmingly extensive, with antibiotic-resistant bacteria (ARB) and genes (ARGs) now pervasive across all four ecological compartments, transcending traditional clinical boundaries. Second, this widespread distribution is critically facilitated by horizontal gene transfer mechanisms, particularly via mobile genetic elements such as plasmids, which enable ARGs to disseminate rapidly between diverse bacterial populations across different ecosystems. Third, we identify multiple interconnected drivers that actively promote this cross-ecosystem spread, encompassing both evolutionary and transmission drivers. By characterizing these critical transmission pathways and underlying drivers, this review provides an integrated framework to identify critical transmission risks and inform integrated strategies for mitigating antimicrobial resistance across One Health domains. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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20 pages, 6748 KB  
Article
Two-Year Implementation, Adherence, and Outcomes of Quadruple Guideline-Directed Medical Therapy in Newly Diagnosed HFrEF: Insights from the Prospective CaRD Registry
by Ivana Jurin, Daniel Lovrić, Karlo Gjuras, Šime Manola, Irzal Hadžibegović, Mario Udovičić, Diana Rudan, Anica Milinković, Jasmina Ćatić, Marija Križanović and Marin Pavlov
J. Clin. Med. 2026, 15(6), 2127; https://doi.org/10.3390/jcm15062127 - 11 Mar 2026
Viewed by 186
Abstract
Background: Contemporary guidelines recommend rapid initiation of four classes of guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF); however, real-world persistence, adherence, and dose optimization remain suboptimal. Methods: We analysed a predefined subregistry within the prospective [...] Read more.
Background: Contemporary guidelines recommend rapid initiation of four classes of guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF); however, real-world persistence, adherence, and dose optimization remain suboptimal. Methods: We analysed a predefined subregistry within the prospective Cardiology Research Dubrava (CaRD) registry, a real-world HF registry at a tertiary centre that includes patients across the ejection-fraction spectrum in whom contemporary HF therapy, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), is introduced or optimised in routine practice. For this analysis, we included patients with newly diagnosed HFrEF (left ventricular ejection fraction (LVEF) ≤ 40%) who were discharged on all four GDMT classes; 167 of 179 patients with newly diagnosed HFrEF during the study period had an available 6-month medication assessment and comprised the final analytic cohort. The four GDMT pillars (beta-blocker; angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), or angiotensin receptor-neprilysin inhibitor (ARNI); mineralocorticoid receptor antagonist (MRA); and SGLT2i) were initiated within 4 days when clinically feasible. Medication adherence and target-dose attainment were assessed at 6, 12, and 24 months using a structured self-report questionnaire. Major adverse events (MAE) and all-cause mortality were recorded over 24 months. Patients were classified as adherent if they reported regular intake (≥80% of prescribed doses) of all four drug classes at 6 months; otherwise, they were classified as nonadherent. Results: Among the 167 analysed patients (median age 64 years, 74% men, median LVEF 30%), regular adherence at 6, 12, and 24 months was 65%, 55%, and 59% for beta-blockers; 66%, 50%, and 49% for ACEi/ARB/ARNI; 62%, 52%, and 49% for MRAs; and 84%, 57%, and 68% for SGLT2i. Target doses were achieved in 25–33% for beta-blockers, 42–50% for ACEi/ARB/ARNI, and 73–78% for MRAs. At 24 months, 56 survivors (37%) were adherent to all four drug classes. Over 24 months, all-cause mortality was 9.0% and MAE 18.6%, occurring less frequently in adherent vs. nonadherent patients (mortality 0% vs. 13.5%; MAE 8.9% vs. 23.4%). Conclusions: In this real-world, non-randomized HFrEF subregistry, in-hospital initiation of quadruple GDMT was feasible, yet maintaining long-term adherence and achieving target doses remained challenging. These data underscore the gap between guideline recommendations and routine practice and support structured follow-up and protocol-driven titration to optimize implementation. Full article
(This article belongs to the Special Issue Therapies for Heart Failure: Clinical Updates and Perspectives)
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17 pages, 272 KB  
Article
Retinal Dysfunction in Hypertensive Patients with Atherosclerotic Plaque Detected by Carotid Doppler Ultrasound: An Optical Coherence Tomography Angiography Assessment
by Irina Barca, Vasile Potop and Stefan Sorin Arama
Life 2026, 16(3), 436; https://doi.org/10.3390/life16030436 - 9 Mar 2026
Viewed by 213
Abstract
Background: Our study aimed to evaluate whether OCTA can detect retinal dysfunction in hypertensive patients with atherosclerotic plaque in order to improve early detection of vascular changes and to better adjust treatment protocols. Therefore, we can potentially reduce the rate of ocular, [...] Read more.
Background: Our study aimed to evaluate whether OCTA can detect retinal dysfunction in hypertensive patients with atherosclerotic plaque in order to improve early detection of vascular changes and to better adjust treatment protocols. Therefore, we can potentially reduce the rate of ocular, cardiovascular and cerebral complications of hypertension and of dyslipidemia. Methods: We performed a study on hypertensive patients with dyslipidemia undergoing specific treatment. Ten OCTA parameters, the presence of carotid plaque on carotid Doppler ultrasound and three types of antihypertensive drugs were analyzed. An increased carotid intima-media thickness (IMT) (≥1.0 mm) or the presence of carotid plaque was defined as subclinical atherosclerosis. We correlated classes of medication with OCTA parameters and with Doppler assessment. Results: In the final study, we included 196 eyes of 98 patients; 51 subjects had carotid plaques. Three groups were formed: antihypertensive monotherapy, including Angiotensin-converting enzyme inhibitor (ACEI) or Calcium channel blocker (CCB) + statins, and combined antihypertensive therapy, including ACEI/Angiotensin Receptor Blocker (ARB) + statins. We found statistically significant results in the presence of atherosclerotic plaques as follows: increased avascular zone (FAZ) and decreased vascular flow area (VFA) in the ACEI group, increased FAZ Circularity and a reduction in Density Total in the CCB lot, higher values of non-flow area (NFA), FAZ Area and decreased Density Total in the ACEI/ARB group. Conclusions: The strongest correlations we found were between increased hypertension, decreased retinal microcirculation and the presence of atherosclerotic plaques in patients using combined antihypertensive therapy and statins. The results indicate that subjects with multiple therapies, advancing hypertensive retinopathy and atherosclerotic carotid plaques display a deficit in retinal vascularization. OCTA can provide early detection of microvascular changes in hypertension associated with dyslipidemia and carotid plaques. Thus, by correlating OCTA and carotid Doppler ultrasound, antihypertensive and statin therapy can be adjusted and disease risk stratification can be obtained. Full article
(This article belongs to the Special Issue Research on Glaucoma Diseases)
17 pages, 51918 KB  
Article
Effects of Cold Rolling on the Microstructure and Properties of Al/TiB2 Laminated Composites Fabricated by Accumulative Roll Bonding
by Wenchao Sun, Zhilei Xiang, Jihao Li, Zian Yang, Yang Han and Ziyong Chen
Materials 2026, 19(5), 1031; https://doi.org/10.3390/ma19051031 - 8 Mar 2026
Viewed by 226
Abstract
Al/TiB2 aluminum alloy laminates were fabricated using a combination of accumulative roll bonding (ARB) and cold rolling processes. The Al/TiB2 interface and microstructure were meticulously characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The mechanical properties of the [...] Read more.
Al/TiB2 aluminum alloy laminates were fabricated using a combination of accumulative roll bonding (ARB) and cold rolling processes. The Al/TiB2 interface and microstructure were meticulously characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The mechanical properties of the laminates were assessed through tensile testing. The experimental results demonstrate that with an increasing cold rolling reduction, a laminated composite sheet with a nanocrystalline structure was successfully produced. The critical strain for the onset of plastic instability was also investigated. The findings indicate that as the cold rolling reduction increases, severe necking occurs in the Al12Zn2.2Mg1.7Cu3TiB2 layer. At a reduction of 80%, the necking region approaches fracture. Tensile results reveal that this pronounced necking has a detrimental effect on the strength of the laminate. It is proposed that the plastic instability originates from shear bands, and the mechanical property mismatch between the constituent layers is identified as the primary reason for the localized preferential deformation. Full article
(This article belongs to the Section Metals and Alloys)
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17 pages, 4760 KB  
Article
MD + QC Methodology for Studying the Interaction of Bioactive Molecules with Amino Acids: The Case of Arbidol Interaction with Aromatic Amino Acids and Its Spectral-Luminescent Validation
by Sophia S. Borisevich, Edward M. Khamitov, Gulshat A. Masyagutova, Olga I. Yarovaya and Sergey L. Khursan
Sci. Pharm. 2026, 94(1), 20; https://doi.org/10.3390/scipharm94010020 - 4 Mar 2026
Viewed by 242
Abstract
A comprehensive MD + QC methodology was developed and applied to evaluate various aspects of Arbidol interactions with functional amino acids of surface proteins of influenza virus and SARS-CoV-2. The spatial structure, solvation features, conformational behavior of Arb AA (AA–Trp, Tyr, Phe, and [...] Read more.
A comprehensive MD + QC methodology was developed and applied to evaluate various aspects of Arbidol interactions with functional amino acids of surface proteins of influenza virus and SARS-CoV-2. The spatial structure, solvation features, conformational behavior of Arb AA (AA–Trp, Tyr, Phe, and Val) complexes were established, and the statistics of intermolecular interactions in the complex were described. It was found that Arb can participate in strong and long-lived π-π stacking interactions with aromatic amino acids. The binding energy (BE) of Arbidol and amino acids in aqueous solution was estimated using an explicit solvation model, QTAIM analysis and correlation of BE vs. total electron density at the bond critical points of the complex. Theoretical calculations were validated by experimental studies of fluorescence (FL) quenching of aromatic AA by Arbidol. Spectral-fluorescent properties of Arbidol hydrochloride in aqueous solutions were studied, and the luminescence quantum yield for the electronically excited state of Arb was determined. Full article
(This article belongs to the Special Issue Computer-Aided Drug Design and Molecular Synthesis)
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11 pages, 435 KB  
Article
Can Certain Antihypertensives Prolong the Efficacy of Hyaluronic Acid Injections in Patients with Osteoarthritis of the Knee? Post Hoc Analysis of a Prospective Observational Trial (PRESAGE)
by Arthur Dollinger, Thomas Lohse, Clara Dolci, Charles Rapp, Charlotte Bourgoin, Anne Lohse and Thierry Conrozier
J. Clin. Med. 2026, 15(5), 1935; https://doi.org/10.3390/jcm15051935 - 4 Mar 2026
Viewed by 201
Abstract
Background: Arterial hypertension (AH) is a frequent comorbidity in patients with osteoarthritis (OA). Among antihypertensive agents, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), and beta-blockers (βBs) have been suggested to influence OA progression and symptomatology. The aim [...] Read more.
Background: Arterial hypertension (AH) is a frequent comorbidity in patients with osteoarthritis (OA). Among antihypertensive agents, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), and beta-blockers (βBs) have been suggested to influence OA progression and symptomatology. The aim of this study was to assess whether the duration of effectiveness (DE) of viscosupplementation (VS) differs between patients with knee OA who are receiving antihypertensive treatment and those who are not. Methods: This post hoc analysis was conducted using data from a cross-sectional clinical trial (ClinicalTrials.gov Identifier: NCT04988698). The study included consecutive patients with knee OA who came for consultation at the Rheumatology Department and had received intra-articular hyaluronic acid injections within the past three years. The primary outcome was DE, self-reported by patients as the number of weeks of symptom relief. Associations between DE and various factors, including demographics, disease duration, radiographic OA severity (Kellgren–Lawrence grade and affected compartments), comorbidities, OA treatment history, antihypertensive therapy, physical activity level, and prior VS sessions, were analyzed using bivariate and multivariate models. Results: A total of 105 patients (65 women, 149 treated knees) were included. The mean age was 66.1 ± 13.2 years, and the mean body mass index (BMI) was 27.5 kg/m2. Thirty-eight percent of patients were receiving antihypertensive treatment (mean number of agents: 1.9; range: 1–4), including CCBs (n = 15), ACE inhibitors (n = 13), ARBs (n = 7), βBs (n = 6), and diuretics (n = 2). The overall mean DE of VS was 48.2 ± 24.8 weeks, with a trend toward longer DE in hypertensive patients compared to non-hypertensive patients (53.1 ± 31.3 vs. 45.4 ± 19.8 weeks, p = 0.06). Bivariate analysis identified significantly longer DE in patients with BMI < 27.5 kg/m2 (p = 0.002), Kellgren–Lawrence grade < 4 (p = 0.008), an active lifestyle (p = 0.005), unicompartmental OA (p = 0.01), medial tibiofemoral joint space narrowing (p = 0.046), and fewer than four prior VS sessions (p = 0.02). In multivariate analysis, AH was strongly associated with prolonged DE (p < 0.001), despite AH patients having a higher BMI (29.8 ± 5.5 vs. 25.2 ± 5.2 kg/m2, p = 0.001) and being more frequently sedentary (25.5% vs. 13.8%, p = 0.07). A trend toward longer DE was observed in patients treated with βBs and ARBs but not with CCBs or ACE inhibitors. Additional independent predictors of longer DE included BMI < 27.5 kg/m2 (p < 0.001), unicompartmental OA (p = 0.02), fewer than four prior VS sessions (p = 0.02), and an active lifestyle (p = 0.027). Conclusions: These findings suggest that antihypertensive treatment may extend the effectiveness of viscosupplementation in knee OA. However, the sample size was insufficient to determine whether specific classes of antihypertensive agents provide greater benefits. Further large-scale, prospective studies are warranted to clarify the potential impact of antihypertensive medications on viscosupplementation outcomes in knee OA. Full article
(This article belongs to the Section Orthopedics)
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15 pages, 10515 KB  
Review
Emerging Challenges from Plastics-Driven Climate Change and Microplastics
by Sung Hee Joo
Microplastics 2026, 5(1), 37; https://doi.org/10.3390/microplastics5010037 - 26 Feb 2026
Viewed by 340
Abstract
Greenhouse gas emissions associated with plastic production and disposal span the entire plastic life cycle, establishing a direct link between plastic pollution and climate change. This review demonstrates that micro- and nanoplastics (MNPs) also function as active components of climate feedback systems by [...] Read more.
Greenhouse gas emissions associated with plastic production and disposal span the entire plastic life cycle, establishing a direct link between plastic pollution and climate change. This review demonstrates that micro- and nanoplastics (MNPs) also function as active components of climate feedback systems by disrupting marine trophic structures, altering microbial assemblages, and diminishing the ocean’s capacity for carbon storage. Synthesized evidence further indicates that environmental degradation of polymers enhances surface reactivity, facilitating the sorption and transport of persistent contaminants, including per- and polyfluoroalkyl substances (PFAS) and antibiotic-resistant bacteria (ARB). These interactions amplify combined risks to ecosystems and public health under climate change scenarios. This review also reveals that many existing remediation strategies prioritize waste reduction or physical removal while failing to account for contaminant–plastic–climate interactions, thereby limiting their long-term effectiveness. By integrating climate-related processes, polymer transformation, and contaminant dynamics, this review identifies critical knowledge gaps and underscores the need for mitigation strategies that jointly address plastic pollution, climate feedbacks, and emerging public health threats. Full article
(This article belongs to the Collection Feature Papers in Microplastics)
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22 pages, 6457 KB  
Article
A Digital Twin of the Angiotensin II Receptor Blocker Losartan: Physiologically Based Modeling of Blood Pressure Regulation
by Ennie Tensil, Mariia Myshkina and Matthias König
Pharmaceutics 2026, 18(2), 262; https://doi.org/10.3390/pharmaceutics18020262 - 19 Feb 2026
Viewed by 469
Abstract
Background/Objectives: Losartan, an angiotensin II receptor blocker (ARB) used to treat hypertension and heart failure, shows significant variability in pharmacokinetics (PK) and pharmacodynamics (PD) among individuals. Methods: In this study, we developed a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model of losartan and its active [...] Read more.
Background/Objectives: Losartan, an angiotensin II receptor blocker (ARB) used to treat hypertension and heart failure, shows significant variability in pharmacokinetics (PK) and pharmacodynamics (PD) among individuals. Methods: In this study, we developed a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model of losartan and its active metabolite, E3174, using curated data from 25 clinical trials. The model mechanistically describes the processes of absorption, hepatic metabolism, renal and fecal excretion, and pharmacodynamic blood pressure regulation. Simulation studies examined the effects of dose, hepatic and renal impairment, and genetic polymorphisms in cytochrome p450 2C9 (CYP2C9) and P-glycoprotein 1, also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1), on the model. Results: The model successfully reproduced key PK/PD observations, including dose-dependent receptor blockade, attenuated responses with hepatic impairment, modest enhancement with renal impairment, and substantial variability in E3174 formation dependent on CYP2C9; the effects of ABCB1 were minimal. Specifically, dose dependency simulations confirmed the saturable nature of CYP2C9 metabolism, predicting a decreasing E3174-to-losartan ratio and a stronger, sustained suppression of blood pressure and aldosterone at higher doses. Hepatic impairment was predicted to lead to elevated losartan plasma concentrations (increased AUC) and attenuated metabolite formation, confirming the clinical need for dose reduction. Renal impairment simulations predicted stable losartan AUC but showed an overestimation of E3174 accumulation compared to observed data, where E3174 exposure remained stable. Genetic variability (CYP2C9) was the major determinant of response, with simulations confirming that reduced-function alleles lead to a 1.6- to 3-fold increase in losartan AUC and diminished blood pressure reduction. ABCB1 variability resulted in only minor modulation of systemic exposure and blood pressure effects. Conclusions: This mechanistic digital twin framework provides a quantitative basis for understanding variability in losartan therapy and supports its application in individualized dosing strategies. Full article
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14 pages, 728 KB  
Article
PBBQ: Plug-In Balanced Binary Quantization for LLMs
by Zhangming Li, Weifan Guan, Zhengwei Chang, Linghao Zhang and Qinghao Hu
Electronics 2026, 15(4), 819; https://doi.org/10.3390/electronics15040819 - 13 Feb 2026
Viewed by 273
Abstract
In recent years, the expansion of large-model parameters has substantially increased storage and inference overhead. Consequently, post-training quantization has become a key technique for reducing model size and inference-time energy consumption. However, we observe that, under extremely low bit-width settings, mainstream error-compensation-based algorithms [...] Read more.
In recent years, the expansion of large-model parameters has substantially increased storage and inference overhead. Consequently, post-training quantization has become a key technique for reducing model size and inference-time energy consumption. However, we observe that, under extremely low bit-width settings, mainstream error-compensation-based algorithms tend to overfit the calibration data. To mitigate this issue, we propose Plug-in Balanced Binary Quantization for LLMs (PBBQ), which reduces the excessive emphasis on subsequent channels via block-wise dropout and layer-wise reordering. PBBQ can be integrated into GPTQ-style frameworks and ultra-low-bit methods such as BiLLM and ARB-LLM. Experimental results show that PBBQ significantly improves the performance of multiple error-compensation quantization algorithms. When combined with the state-of-the-art methods BiLLM and ARB-LLM, the perplexity (ppl) on WikiText-2 is reduced by 21.46% (from 32.48 to 25.51) and 22.02% (from 16.44 to 12.82), respectively. Full article
(This article belongs to the Special Issue Emerging Computing Paradigms for Efficient Edge AI Acceleration)
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15 pages, 246 KB  
Article
Genetic Syndromes and Multimorbidity in Adults with Congenital Heart Disease and Heart Failure: Insights from the PATHFINDER-CHD Registry
by Ann-Sophie Kaemmerer-Suleiman, Fritz Mellert, Stephan Achenbach, Pinar Bambul-Heck, Robert Cesnjevar, Oliver Dewald, Helena Dreher, Andreas Eicken, Anna Engel, Peter Ewert, Annika Freiberger, Jürgen Hörer, Christopher Hohmann, Stefan Holdenrieder, Michael Huntgeburth, Harald Kaemmerer, Renate Kaulitz, Frank Klawonn, Christian Meierhofer, Steffen Montenbruck, Nicole Nagdyman, Rhoia C. Neidenbach, Robert D. Pittrow, Christoph R. Sinning, Fabian von Scheidt, Pelagija Zlatic, Frank Harig and Mathieu N. Suleimanadd Show full author list remove Hide full author list
J. Clin. Med. 2026, 15(3), 1290; https://doi.org/10.3390/jcm15031290 - 6 Feb 2026
Viewed by 638
Abstract
Background/Objectives: Progress in diagnostic and therapeutic strategies has resulted in an increasing prevalence of adults with congenital heart disease (ACHD), including those involving genetically determined syndromes. This study aimed to characterize prevalence, congenital phenotypes, heart failure (HF) stages, comorbidity burden, and current medical [...] Read more.
Background/Objectives: Progress in diagnostic and therapeutic strategies has resulted in an increasing prevalence of adults with congenital heart disease (ACHD), including those involving genetically determined syndromes. This study aimed to characterize prevalence, congenital phenotypes, heart failure (HF) stages, comorbidity burden, and current medical management of ACHD and concomitant genetically determined syndromes enrolled in a prospective HF-focused registry. Methods: The PATHFINDER-CHD Registry is a German-based (est. 2022) multicenter observational registry. This web-based platform consecutively tracks ACHD patients across the heart failure spectrum, including those with current or prior HF, as well as those at high structural or functional risk. HF stage was classified using a modified ACC/AHA scheme adapted for CHD; functional capacity was graded according to the Perloff classification. Baseline demographics, CHD anatomy, prior surgical/interventional treatment, cardiac and extracardiac comorbidities, and medication were collected from medical records. Results: Among 1987 enrolled ACHD, 107 (5.4%) had a genetic syndrome (n = 65, 60.7% women; mean age 33.5 ± 9.4 years; range 18–68). Most common syndromes were trisomy 21 (n = 49; 45.8%) and 22q11.2 deletion (n = 27; 25.2%); 31 patients (30.0) had rarer syndromes. Predominant CHD diagnoses were atrioventricular septal defect (n = 42, 39.3%), tetralogy of Fallot (n = 19, 17.8%), and pulmonary atresia with ventricular septal defect (n = 7, 6.5%). A systemic left ventricle was present in 102 (95.3%); 40 (37.4%) had primarily cyanotic CHD, and 7 (6.5%) an Eisenmenger physiology. Most patients (n = 71; 66.4%) had undergone definite surgical repair; 25 patients (23.3%) had at least one catheter intervention, including transcatheter valve implantation in 17 cases (15.9%). HF stage was mainly B (n = 30, 28.0%) or C (n = 75, 70.1%). Perloff functional class I/II was present in 97 (90.7%). Leading cardiac comorbidities included intrinsic aortopathy (n = 49, 45.8%), pulmonary arterial hypertension (n = 12, 11.2%), and arrhythmias (n = 10, 9.3%). Frequent extracardiac comorbidities were thyroid dysfunction (n = 34, 31.8%), kidney disease (n = 16, 15.0%), hyperuricemia (n = 13, 12.1%), and depression (n = 15, 14.0%). Pharmacotherapy was used in 66 patients (61.7%). Beta-blockers (n = 25, 23.4%) were common, while ACEi/ARB (n = 9, 8.4%), diuretics (n = 10, 9.3%), MRAs (n = 8, 7.5%), and SGLT2 inhibitors (n = 3; 2.8%) were infrequently prescribed; no patient received ARNI or digitalis. For targeted treatment of pulmonary arterial hypertension, phosphodiesterase-5 inhibitors (n = 7, 6.5%), endothelin receptor antagonists (n = 6, 5.6%), or prostacyclin analogues (n = 1, 0.9%) were used. As oral anticoagulants, vitamin K antagonists or direct oral anticoagulants (DOACs) were prescribed in 17 cases (15.9%). Forty-one patients (38.3%) received thyroid hormone replacement. Conclusions: Syndromic ACHD constitute a small but clinically high-risk subgroup within an HF-oriented registry, marked by complex CHD, substantial cardio–extracardiac multimorbidity (notably aortopathy, PAH, thyroid disease, renal dysfunction, depression), and low utilization of contemporary HF therapies. These data support specialized, interdisciplinary, longitudinal care pathways and prospective studies addressing outcomes and evidence-based HF management in syndromic ACHD. Full article
(This article belongs to the Section Cardiology)
18 pages, 447 KB  
Article
Understanding Cardio-Oncology: A Survey-Based Study Conducted by the Heart Failure Association of the Polish Cardiac Society and the Polish Society of Clinical Oncology
by Sebastian Szmit, Jarosław Kępski, Marcin Książczyk, Maciej Krzakowski and Małgorzata Lelonek
J. Clin. Med. 2026, 15(3), 1240; https://doi.org/10.3390/jcm15031240 - 4 Feb 2026
Viewed by 442
Abstract
Background: The European Society of Cardiology (ESC) published the first guidelines on cardio-oncology in 2022. Implementing the 272 proposed recommendations into everyday clinical practice has become a mandatory challenge for countries belonging to the ESC community. Methods: The study aimed to [...] Read more.
Background: The European Society of Cardiology (ESC) published the first guidelines on cardio-oncology in 2022. Implementing the 272 proposed recommendations into everyday clinical practice has become a mandatory challenge for countries belonging to the ESC community. Methods: The study aimed to assess cardio-oncology knowledge and the degree of implementation of ESC guidelines among cardiologists registered with the Heart Failure Association of the Polish Cardiac Society and oncologists from the Polish Society of Clinical Oncology. Physicians were invited via email and voluntarily chose to participate by completing a 20-question questionnaire. Results: Among the 104 respondents, half (50%) were cardiologists, and the majority (80%) had more than ten years of clinical experience. A total of 38.8% of specialists practiced outpatient medicine, while 41.7% worked in academic centres. The majority (58.3%) consult fewer than ten cardio-oncology patients per week, with less than 8% of specialists having the greatest experience (>25 consultations per week). Most physicians were familiar with the ESC guidelines on cardio-oncology. Cardiologists more frequently indicated heart failure as the main problem in cancer patients (OR = 5.82; 95% CI: 2.08–16.22; p = 0.0007), ordered echocardiography and ECG together with cardiovascular risk factors control (OR = 4.01; 95% CI: 1.74–9.25; p = 0.001) during long-term follow-up, chose angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB) combined with calcium channel blocker (CCB) for treating hypertension (OR = 3.9; 95% CI: 1.56–9.75; p = 0.003), and rarely monitored lipid profile based on the type of cancer therapy (OR = 0.09; 95% CI: 0.03–0.26; p = 0.000009). Oncologists more often observed cardiovascular issues in lung cancer (OR = 3.78; 95% CI: 1.58–9.05; p = 0.002), recognized venous thromboembolism as the most common problem in cardio-oncology (OR = 6.52; 95% CI: 2.7–15.73; p = 0.00002), opted for ACEI/ARB monotherapy in the management of high blood pressure (OR = 11.76; 95% CI: 2.49–55.54; p = 0.002), and significantly more often chose low-molecular-weight heparin in the treatment of asymptomatic incidental pulmonary embolism (OR = 5.93; 95% CI: 2.47–14.24; p = 0.00006). Conclusions: The understanding of cardio-oncology varies significantly between cardiologists and oncologists. Although the survey was conducted only in one country (Poland), its results may serve as a reference point for structural reforms with building implementation strategies of ESC guidelines in daily practice in other countries. Full article
(This article belongs to the Section Oncology)
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11 pages, 452 KB  
Article
Evolution of Hemodynamic Parameters After Tooth Extraction and Infiltration of Local Anesthetic with Vasoconstrictor in Healthy and Hypertensive Patients Controlled with Different Antihypertensive Drugs
by Francisco Javier Silvestre, Cecilia Fabiana Márquez-Arrico, Javier Silvestre-Rangil and Belén García-López
Oral 2026, 6(1), 15; https://doi.org/10.3390/oral6010015 - 2 Feb 2026
Viewed by 443
Abstract
Background: The progressive aging of the population has led to an increased prevalence of chronic diseases and polypharmacy, with arterial hypertension representing one of the most frequent conditions. Consequently, the management of vital signs during dental interventions, such as tooth extractions, has [...] Read more.
Background: The progressive aging of the population has led to an increased prevalence of chronic diseases and polypharmacy, with arterial hypertension representing one of the most frequent conditions. Consequently, the management of vital signs during dental interventions, such as tooth extractions, has acquired particular clinical relevance. The present study aimed to analyze the hemodynamic impact of vasoconstrictors (VAs) used in local anesthesia (LA) at different procedural stages in patients with pharmacologically controlled hypertension, as well as to compare these effects with those observed in normotensive individuals. Additionally, the study evaluated the influence of antihypertensive medication on hemodynamic responses during dental extraction. Methods: A case–control study was conducted at Dr. Peset University Hospital (Valencia, Spain), including 254 patients—148 hypertensive (controlled with type 1 and 2 antihypertensive therapy) and 106 normotensive controls. Hemodynamic parameters—systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and oxygen saturation (SO2)—were recorded at four time points: baseline (T1), five minutes post anesthesia with 4% articaine and epinephrine (T2), upon completion of extraction (T3), and one week postoperatively (T4). Results: The SBP remained more stable in normotensive patients, while both groups exhibited a slight DBP decrease at T2, with recovery by T3. In hypertensive patients treated with angiotensin receptor blockers (ARBs), DBP decreased further. Tooth extraction under controlled hypertension conditions caused a mild, clinically insignificant increase in HR. Conclusions: Significant fluctuations in SBP, DBP, and SO2 occurred during dental extraction, underscoring the necessity for vigilant intraoperative monitoring and individualized management of hypertensive patients. Full article
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9 pages, 339 KB  
Article
ACE Inhibitor/ARB Therapy and Other Risk Factors for COVID-19 Infection in Elderly Hypertensive Patients: Sub-Group Analysis Based on a Single-Center, Retrospective, Observational Study in Japan
by Kazuhiro Furumachi, Akari Higuchi, Tatsuki Kagatsume, Mariko Kozaru, Tsutomu Nakamura, Etsuko Kumagai and Keiko Hosohata
Pharmacy 2026, 14(1), 22; https://doi.org/10.3390/pharmacy14010022 - 2 Feb 2026
Viewed by 350
Abstract
Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are often used in hypertensive patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, binds the ACE2 receptor on the cell surface. This [...] Read more.
Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are often used in hypertensive patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, binds the ACE2 receptor on the cell surface. This study aimed to identify the risk factors influencing COVID-19 infection in hypertensive patients. Methods: This is a part of a single-center, retrospective, observational study investigating patients ≥ 20 years old at Kenwakai Hospital (Nagano, Japan). COVID-19 was diagnosed by polymerase chain reaction. All patients received antihypertensive drugs. Results: Among 316 patients (mean age, 75.0 ± 13.4 years; men, 55.1%), COVID-19 was diagnosed in 39 (12.3%). Multiple logistic regression analysis after adjustment for age, sex, and smoking status identified increased serum creatinine (Scr) as a significant risk factor for COVID-19 (odds ratio [OR] 1.10; 95% confidence interval [CI] 1.00–1.20; p = 0.046). Conversely, lower serum chloride was associated with COVID-19 (OR 0.92; 95% CI 0.85–0.99; p = 0.047). There was no significant association between COVID-19 and the use of ACEIs and ARBs. Conclusions: Scr was independently associated with COVID-19 risk, whereas ACEI/ARB use was not associated with COVID-19 risk in Japanese hypertensive patients, suggesting that these users need not discontinue or change their treatment. The study population included a very high proportion of patients with advanced chronic kidney disease, which makes the cohort substantially different from the general hypertensive population. However, our results can help guide targeted treatment strategies, improving patient outcomes in healthcare settings. Full article
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