Extending the lifetime of lithium metal batteries requires electrolyte strategies that coordinate Li[+] solvation with interfacial chemistry. Here, we introduce hydrogen-bond-mediated cross-sheath molecular association as a design principle for an ether-based localized high-concentration electrolyte. Spectroscopic analyses, noncovalent-interaction calculations and ab initio molecular dynamics simulations indicate that 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) and fluoroethylene carbonate (FEC) reside predominantly in the outer solvation environment, whereas 1,2-diethoxyethane (DEE) remains an important inner-shell solvent. The pre-associated FEC-TTE motif exhibits a stronger overall association with DEE than isolated TTE, providing a plausible molecular bridge between the outer and primary solvation environments. This cross-sheath association contributes to weaker average Li[+]-DEE coordination and increased participation of bis(fluorosulfonyl)imide (FSI[-]) and isosorbide dinitrate (ISDN), yielding a compact, anion-enriched local solvation structure. At the electrode interface, the reconstructed solvation environment cooperates with the reduction chemistry of FEC, FSI[-] and ISDN to suppress excessive solvent decomposition and promote a homogeneous LiNxOy/LiF-rich solid electrolyte interphase. Consequently, Li||Li symmetric cells sustain stable plating/stripping for approximately 1354 h at 1 mA cm[-2] and 1 mAh cm[-2], while high-loading Li||LiFePO4 cells cycle for approximately 1188 cycles at 1 C. Unlike conventional approaches focused primarily on direct regulation of the first Li[+] solvation shell, this work demonstrates that engineering molecular associations across solvation environments offers an effective route to couple solvation redistribution with interfacial film formation.

Heart failure is a major contributor to maternal morbidity and mortality. Pregnancy is a state of hemodynamic stress, and normal physiologic changes of pregnancy may mimic signs of heart failure. Prepregnancy counseling, multidisciplinary care, and referral to a center with expertise in managing pregnant patients with heart failure can help optimize outcomes. The option for abortion care should be available to all patients with heart failure, regardless of the severity of the disease, and is an essential component of individualized counseling. In this Consult, we provide guidance for managing patients with heart failure with reduced ejection fraction who are continuing pregnancy. The following are Society for Maternal-Fetal Medicine (SMFM) recommendations: (1) we recommend that all patients with right heart failure due to pulmonary arterial hypertension receive counseling about high rates of maternal morbidity and mortality; if pregnancy is pursued, the patient should be referred to a center with expertise in this condition to guide management during pregnancy and postpartum (GRADE 1C); (2) we recommend considering referral to a genetics provider with expertise in heritable cardiac disease for people with peripartum cardiomyopathy (PPCM), particularly when the index of suspicion is high and no other contributing factors are identified (GRADE 1C); (3) we recommend that other causes of heart failure be ruled out before making a diagnosis of PPCM (Best Practice); (4) for acute left ventricular heart failure during pregnancy, we recommend hydralazine or isosorbide dinitrate for afterload reduction and furosemide for diuresis. For acute left ventricular failure postpartum, we recommend afterload reduction with angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), or angiotensin receptor/neprilysin inhibitor (ARNi) unless contraindicated (e.g., renal failure) (GRADE 1B); (5) we recommend against inotropic blockade (i.e., beta-blockers) in the setting of acute decompensated left ventricular heart failure (GRADE 1B); (6) we recommend prophylactic anticoagulation administration in hospitalized pregnant patients with acute left ventricular heart failure (GRADE 1C); (7) in patients who are pursuing pregnancy or pregnant, we recommend discontinuing spironolactone, ACEi, ARB, and ARNi and continuing beta-blockers (metoprolol, carvedilol, bisoprolol) (GRADE 1C); (8) for pregnant patients with left ventricular failure and ejection fraction < 35%, we recommend pharmacologic thromboprophylaxis during pregnancy and for six weeks postpartum (GRADE 1C); (9) for patients with chronic left ventricular failure, we recommend starting or continuing guideline-directed medical therapy when medically able, in consultation with experts in cardiology (GRADE 1C); (10) we recommend fetal echocardiography when maternal heart failure is a result of an underlying congenital cardiac defect (GRADE 1C); (11) we recommend serial growth ultrasounds in pregnancies complicated by maternal heart failure (GRADE 1C); (12) we recommend continuous fetal heart rate monitoring during anesthesia administration, labor, and delivery for pregnant patients with heart failure (GRADE 1B); (13) in the case of maternal cardiovascular changes prompting inpatient assessment or treatment, we recommend continuous or intermittent fetal heart rate monitoring, taking into consideration the gestational age and any relevant maternal or fetal factors that may impact fetal viability or the maternal clinical status (GRADE 1C); (14) we recommend planned vaginal delivery at term in patients with heart failure in the absence of hemodynamic compromise or obstetric indications for cesarean (GRADE 1C); (15) we recommend the use of neuraxial anesthesia in most patients with heart failure to provide appropriate analgesia and to limit the effects of labor on cardiac parameters (GRADE 1C); (16) we recommend considering a limited or assisted second stage for some patients after input from cardiology about each individual patient's cardiac risk (GRADE 1C); (17) we recommend that postpartum patients with heart failure undergo routine counseling regarding infant feeding. We recommend reviewing all medications for compatibility with breastfeeding and using shared decision-making in the absence of robust data (GRADE 1B).

Nitric oxide (NO) can effectively combat periodontitis by disrupting biofilms and suppressing inflammation; however, its clinical translation has been limited by the lack of a controllable delivery strategy. This study aimed to develop an ultrasound-controlled NO delivery platform based on a clinically approved NO donor for precise periodontitis treatment. A clinically approved NO donor, isosorbide dinitrate (ISDN), was identified that can be efficiently activated by low-intensity ultrasound (2 W/cm[2]) in the presence of vitamin B2 tetrabutyrate (TBR) by generating ·OH free radicals, thereby releasing NO in an on-demand and spatiotemporally controlled manner. Thereafter, ISDN-loaded nanoparticles were synthesized, and a miniaturized intraoral ultrasonic transducer for localized NO generation was developed. The reaction between NO and the reactive oxygen species (ROS) produced from TBR formed peroxynitrite, which exerted strong antibacterial and anti-biofilm effects (the bacterial survival rate within the biofilm during the formation stage was less than 10%) and inhibited NLRP3-mediated inflammation. In a rat model of periodontitis, the treatment significantly decreased bacterial load and mitigated inflammation, resulting in a reduction of inflammatory gene expression by approximately 2.4-fold, while maintaining the integrity of alveolar bone structure. Overall, this study presents a highly promising clinical application for ultrasound-controlled NO delivery strategy for precision therapy of periodontitis.

This study addresses a critical challenge in delivering a drug to prevent angina in the early morning hours, aligning with the heart's circadian rhythm. For this purpose, we formulated Isosorbide dinitrate (ISDN) - loaded spherules for delayed release (DR) followed by sustained release (SR) using ethyl cellulose by spheronization technique. DOE-led optimisation is done to develop the design of space for optimized spherules. The DR-coated spherules exhibit possible surface modifications, indicating the presence of a coating layer that can influence the release profile and provide marginally better flow characteristics (Angle of repose 31.38 ± 0.02, Carr's index 10 ± 0.35%, Hausner's Ratio 1.11 ± 0.037) compared to granules and SR spherules. In vitro drug release in pH 1.2 is 4.8% indicating negligible drug release due to DR coating, whereas, under colonic pH (7.4) conditions, initially 40% is released as a burst release and approximately 60% of ISDN is released over 24 h, which indicates that DR coating modifies the drug release profile. Following the successful modulation of release behaviour via engineering the delivery system, spherules coated with ethyl cellulose and Eudragit S-100 exhibit negligible release in pH 1.2, confirming strong resistance for release in the gastric environment. The design of space (DOS), optimized through JMP software using the Design of Experiments (DOE) approach, confirms the targeted performance. The results of the DOE to experimental validated results were within 5% deviation.

Chagasic esophagopathy, resulting from Trypanosoma cruzi-induced myenteric plexus denervation, leads to lower esophageal sphincter hypertonia, esophageal body hypertrophy, and dilation (megaesophagus), manifesting as progressive dysphagia and regurgitation that impair nutritional status and quality of life. This case report aims to describe chronic esophageal dysphagia in a patient from an endemic area in northeastern Brazil, highlighting diagnostic and therapeutic challenges within the public health system, including delays due to COVID-19 restrictions and resource limitations. A 67-year-old female from Rio Grande do Norte, with prior Chagas disease diagnosis (2004, etiologically treated), hypertension, and dyslipidemia, presented in 2019 with solid-food dysphagia and nocturnal regurgitation. Initial tests (chest X-ray, ECG, and echocardiography) were normal, but contrast studies (barium esophagogram, and colon) were delayed until 2022, revealing 7 cm esophageal dilation (Rezende Group III), cardia narrowing, and retained contrast/food residues. Symptoms worsened, with a 5 kg weight loss and liquid-only diet. Videolaparoscopic Heller-Pinotti cardiomyotomy was performed in September 2023 after clinical optimization (isosorbide dinitrate and domperidone). The 2 h procedure was uneventful; discharge occurred within 24 h on zero diet, progressing to normal intake by 5 weeks. By February 2024, she was asymptomatic, with a 2 kg weight gain (from 66 kg). This case confirms laparoscopic cardiomyotomy's efficacy (90% success in Rezende I-III) for symptom resolution in nonadvanced chagasic megaesophagus. Public health insights underscore Chagas underreporting, late diagnosis, and public health system barriers in vulnerable populations, advocating early serological screening and etiological treatment in acute phases to prevent chronic digestive forms in endemic regions.

Poly(1,3-dioxolane) (PDOL)-based electrolytes are promising candidates for lithium-sulfur (Li-S) batteries due to their high ionic conductivity and low cost. However, their poor interfacial compatibility with lithium metal impedes the formation of a stable solid electrolyte interphase (SEI). This challenge is further exacerbated by the fact that conventional nitrate additives (e.g., LiNO3) inhibit 1,3-dioxolane (DOL) polymerization. Herein, we propose isosorbide dinitrate (ISDN), a covalent organic nitrate, as a multifunctional additive that not only promotes DOL polymerization but also enables the formation of an inorganic-rich hybrid SEI (Li3N and LiNxOy), as verified through X-ray photoelectron spectroscopy (XPS) analysis and theoretical calculations. The reinforced SEI enhances interfacial ion transport and mechanical robustness, thereby achieving uniform and dendrite-free lithium deposition. Density functional theory (DFT) calculations further reveal strong chemical interactions between ISDN and PDOL, which effectively enhance the adsorption of polysulfide onto PDOL to suppress the shuttle effect. Benefiting from these synergistic functions, Li|PDOL@ISDN|Li symmetric cells achieve stable cycling exceeding 1000 h without short-circuit failure. Quasi-solid-state Li-S batteries also demonstrate excellent cycling stability, with a capacity retention of 84.7% after 100 cycles at 0.2C. This work offers a promising strategy for designing high-performance solid-state Li-S batteries based on PDOL electrolytes.

To analyze Isosorbide Mononitrate in human plasma, a highly sensitive and accurate LC–MS/MS bioanalytical method was developed and validated using Isosorbide mononitrate-[13]C6 as the internal standard. Validate a suitable analytical method for the estimation of unknown drug concentrations in plasma. It can be used for the quantitation of isosorbide mononitrate in K2EDTA human plasma for bioequivalence and bioavailability studies. The method was found to be specific, sensitive, linear, precise, accurate, and reproducible for the extraction and analysis of isosorbide mononitrate in K2EDTA human plasma samples over the investigated concentration range of 5.000 ng/mL to 1800.000 ng/mL using a processing volume of 0.100 mL. Chromatographic separation was achieved using a 2 mM ammonium acetate (acidified) mobile phase with acetonitrile containing 0.1% acetic acid in a ratio of 55:45 (v/v) at a flow rate of 0.5 mL/min. Detection was carried out using multiple reaction monitoring with transitions (m/z) of 249.90 → 59.00 for isosorbide mononitrate and 255.90 → 58.90 for the internal standard. The analytes were detected using tandem mass spectrometry (LC–MS/MS). The proposed method was comprehensively validated in terms of linearity, accuracy, precision, specificity, sensitivity, recovery, and stability, with results meeting the acceptance criteria. The developed and validated method was found to be simpler, faster, more specific, precise, and cost-effective compared with previously reported methods.

We report a 54-year-old woman with stable angina who exhibited heterogeneous responses of tandem left anterior descending artery (LAD) plaques to intensive lipid-lowering therapy. Coronary CT angiography performed at another hospital suggested diffuse disease, and she presented to our clinic for a second opinion. Intravascular ultrasound revealed a lipid-rich proximal LAD lesion and a fibrous-predominant distal lesion, along with a smaller intermediate lesion. Fractional flow reserve (FFR) pullback showed distal LAD FFR of 0.50, increasing to 0.73 across the distal lesion (ΔFFR + 0.23) and to 0.95 across the proximal lesion (ΔFFR + 0.22). Although PCI was considered, in accordance with the patient's preference and guideline recommendations, medical therapy with high-intensity statin, ezetimibe, aspirin, nebivolol, and isosorbide dinitrate was initiated. LDL-C decreased to < 35 mg/dL and remained consistently suppressed. After 2 years, serial CT and intravascular ultrasound (IVUS) demonstrated near-complete regression of the lipid-rich proximal lesion with lumen enlargement, a marked reduction in IVUS features consistent with a lipid-rich core, and attenuation of its lesion-specific physiological contribution (ΔFFR + 0.02), whereas the distal fibrous lesion remained stable (ΔFFR + 0.20) (lesion-specific functional improvement defined as attenuation of lesion-specific ΔFFR contribution on FFR pullback). The intermediate lesion also regressed morphologically, although it was not assessed functionally. The patient remained asymptomatic with preserved exercise capacity. This case suggests that plaque morphology may influence the response to lipid-lowering therapy and highlights the value of multimodality imaging with lesion-specific physiological assessment in individualized management of stable coronary disease.