Comparison of Repeat Versus Initial Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: A Retrospective Multicenter Matched Cohort Study.

BACKGROUND AND OBJECTIVES: Studies comparing neurological and radiographic outcomes of repeat to initial stereotactic radiosurgery (SRS) intracranial arteriovenous malformations are scarce. Our aim was to perform a retrospective matched comparison of patients initially treated with SRS with those undergoing a second radiosurgical procedure. METHODS: We collected data from arteriovenous malformations managed in 21 centers that underwent initial and repeated radiosurgery from 1987 to 2022. Based on arteriovenous malformations volume, margin dose, deep venous drainage, deep, and critical location, we matched 1:1 patients who underwent an initial SRS for treatment-naive arteriovenous malformations and a group with repeated SRS treatment. RESULTS: After the selection process, our sample consisted of 328 patients in each group. Obliteration in the initial SRs group was 35.8% at 3 and 56.7% at 5 years post-SRS, while the repeat SRS group showed obliteration rates of 33.9% at 3 years and 58.6% at 5 years, without statistically significant differences (P = .75 and P = .88, respectively). There were no statistically significant differences between the 2 groups for obliteration rates (hazard ratio = 0.93; 95% CI, 0.77-1.13; P = .5), overall radiation-induced changes (RIC) (OR = 1.1; 95% CI, 0.75-1.6; P = .6), symptomatic RIC (OR = 0.78; 95% CI, 0.4-1.5; P = .4), and post-SRS hemorrhage (OR = 0.68; 95% CI; P = .3). CONCLUSION: In matched cohort analysis, a second SRS provides comparable outcomes in obliteration and RIC compared with the initial SRS. Dose reduction on repeat SRS may not be warranted.

Improving the Volumetric Capacity of Gallocyanine Flow Battery by Adding a Molecular Spectator.

Gallocyanine (GAL) was recently introduced as a promising aqueous-soluble electroactive molecule for preparing two-electron storage alkaline flow battery (FB) negolytes. The development of a cost-effective GAL FB electrolyte is limited by the unexpectedly low solubility of GAL. In this work, the compound 7-amino-4-hydroxy-2-naphthalenesulfonic acid was introduced as a molecular spectator to modulate the solubility of GAL in KOH; this formulation allowed the preparation of a negolyte with a theoretical volumetric capacity of 32.00 Ah L-1. The cycling stability of an improved GAL electrolyte was demonstrated by operating a FB cell outside of the glovebox (bubbling N2 in the tanks). The cell exhibited a Coulombic efficiency close to 98% and began operating with 72.1% of its theoretical capacity (16.06 Ah L-1), retaining 88% of it after 110 cell cycles. This work demonstrates that significant improvement in electrolyte performance can be obtained with suitable additives and electrolyte engineering.

A Homolog of the Histidine Kinase RetS Controls the Synthesis of Alginates, PHB, Alkylresorcinols, and Motility in Azotobacter vinelandii.

The two-component system GacS/A and the posttranscriptional control system Rsm constitute a genetic regulation pathway in Gammaproteobacteria; in some species of Pseudomonas, this pathway is part of a multikinase network (MKN) that regulates the activity of the Rsm system. In this network, the activity of GacS is controlled by other kinases. One of the most studied MKNs is the MKN-GacS of Pseudomonas aeruginosa, where GacS is controlled by the kinases RetS and LadS; RetS decreases the kinase activity of GacS, whereas LadS stimulates the activity of the central kinase GacS. Outside of the Pseudomonas genus, the network has been studied only in Azotobacter vinelandii. In this work, we report the study of the RetS kinase of A. vinelandii; as expected, the phenotypes affected in gacS mutants, such as production of alginates, polyhydroxybutyrate, and alkylresorcinols and swimming motility, were also affected in retS mutants. Interestingly, our data indicated that RetS in A. vinelandii acts as a positive regulator of GacA activity. Consistent with this finding, mutation in retS also negatively affected the expression of small regulatory RNAs belonging to the Rsm family. We also confirmed the interaction of RetS with GacS, as well as with the phosphotransfer protein HptB.

CaMKII protein expression and phosphorylation in human skeletal muscle by immunoblotting: Isoform specificity.

Calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMKII) is activated during exercise by reactive oxygen species (ROS) and Ca2+ transients initiating muscle contraction. CaMKII modulates antioxidant, inflammatory, metabolic and autophagy signalling pathways. CaMKII is coded by four homologous genes (α, ß, γ, and δ). In rat skeletal muscle, δD, δA, γD, γB and ßM have been described while different characterisations of human skeletal muscle CaMKII isoforms have been documented. Precisely discerning between the various isoforms is pivotal for understanding their distinctive functions and regulatory mechanisms in response to exercise and other stimuli. This study aimed to optimize the detection of the different CaMKII isoforms by western blotting using eight different CaMKII commercial antibodies in human skeletal muscle. Exercise-induced posttranslational modifications, i.e. phosphorylation and oxidations, allowed the identification of specific bands by multitargeting them with different antibodies after stripping and reprobing. The methodology proposed has confirmed the molecular weight of ßM CaMKII and allows distinguishing between γ/δ and δD CaMKII isoforms. The corresponding molecular weight for the CaMKII isoforms resolved were: δD, at 54.2 ± 2.1 kDa; γ/δ, at 59.0 ± 1.2 kDa and 61.6 ± 1.3 kDa; and ßM isoform, at 76.0 ± 1.8 kDa. Some tested antibodies showed high specificity for the δD, the most responsive isoform to ROS and intracellular Ca2+ transients in human skeletal muscle, while others, despite the commercial claims, failed to show such specificity.

Rethinking the role of surgical resection in the management of primary pituitary lymphoma.

BACKGROUND: Primary pituitary lymphoma (PPL) is a rare finding in immunocompetent patients, with only 54 patients reported to date (including ours). It presents most often with headache and hypopituitarism, with MRI findings comparable to more common pituitary tumours, making the diagnosis challenging. There is no consensus on the ideal management for these lesions with the role of surgical resection not clearly established. CASE REPORT: We present here a 49-year-old female who presented with acute vision loss and was found to have PPL of diffuse large B-cell lymphoma, non-germinal centre type. The radiologic findings were distinct from prior cases with haemorrhagic components and perilesional edoema in the bilobed sellar mass. Surgical resection was halted when a diagnosis of lymphoma was suspected. This decision was based on the guidelines for the treatment of primary CNS lymphoma (PCNSL) and the lack of evidence to support surgical resection of PPL specifically. Our patient lacked mutations commonly associated with a poor prognosis in DLBCL, such as TP53 and BCL6. She remains in remission with normal vision nearly two years after treatment with minimal resection, MR-CHOP, and consolidation radiotherapy. CONCLUSION: We highlight here the clinical and diagnostic features of PPL to guide clinicians to early recognition and diagnosis. Surgical resection should be limited to what is necessary to obtain a diagnosis and critical decompression; otherwise, these lesions respond excellently to steroids and typical chemoradiation regimens.

Assessing Leg Blood Flow and Cardiac Output During Running Using Thermodilution.

Cardiac output (Q̇C) and leg blood flow (Q̇LEG) can be measured simultaneously with high accuracy using transpulmonary and femoral vein thermodilution with a single-bolus injection. The invasive measure has offered important insight into leg hemodynamics and blood flow distribution during exercise. Despite being the natural modality of exercise in humans, there has been no direct measure of Q̇LEG while running in humans. We sought to determine the feasibility of the thermodilution technique for measuring Q̇LEG and conductance during high-intensity running, in an exploratory case study. A trained runner (30 years male) completed two maximal incremental tests on a cycle ergometer and motorized treadmill. Q̇LEG and Q̇C were determined using the single-bolus thermodilution technique. Arterial and venous blood were sampled throughout exercise, with continuous monitoring of metabolism, intra-arterial and venous pressure, and temperature. The participant reached a greater peak oxygen uptake (V̇O2peak) during running relative to cycling (74 vs. 68 mL/kg/min) with comparable Q̇LEG (19.0 vs. 19.5 L/min) and Q̇C (27.4 vs. 26.2 L/min). Leg vascular conductance was greater during high-intensity running relative to cycling (82 vs. 70 mL/min/mmHg @ ~80% V̇O2peak). The "beat phenomenon" was apparent in femoral flow while running, producing large gradients in conductance (62-90 mL/min/mmHg @ 70% V̇O2peak). In summary, we present the first direct measure of Q̇LEG and conductance in a running human. Our findings corroborate several assumptions about Q̇LEG during running compared with cycling. Importantly, we demonstrate that using thermodilution in running exercise can be completed effectively and safely.

Activation of macroautophagy and chaperone-mediated autophagy in human skeletal muscle by high-intensity exercise in normoxia and hypoxia and after recovery with or without post-exercise ischemia.

Autophagy is essential for the adaptive response to exercise and physiological skeletal muscle functionality. However, the mechanisms leading to the activation of macroautophagy and chaperone-mediated autophagy in human skeletal muscle in response to high-intensity exercise remain elusive. Our findings demonstrate that macroautophagy and chaperone-mediated autophagy are stimulated by high-intensity exercise in normoxia (PIO2: 143 mmHg) and severe acute hypoxia (PIO2: 73 mmHg) in healthy humans. High-intensity exercise induces macroautophagy initiation through AMPKα phosphorylation, which phosphorylates and activates ULK1. ULK1 phosphorylates BECN1 at Ser15, eliciting the dissociation of BECN1-BCL2 crucial for phagophore formation. Besides, high-intensity exercise elevates the LC3B-II:LC3B-I ratio, reduces total SQSTM1/p62 levels, and induces p-Ser349 SQSTM1/p62 phosphorylation, suggesting heightened autophagosome degradation. PHAF1/MYTHO, a novel macroautophagy biomarker, is highly upregulated in response to high-intensity exercise. The latter is accompanied by elevated LAMP2A expression, indicating chaperone-mediated autophagy activation regardless of post-exercise HSPA8/HSC70 downregulation. Despite increased glycolytic metabolism, severe acute hypoxia does not exacerbate the autophagy signaling response. Signaling changes revert within 1 min of recovery with free circulation, while the application of immediate post-exercise ischemia impedes recovery. Our study concludes that macroautophagy and chaperone-mediated autophagy pathways are strongly activated by high-intensity exercise, regardless of PO2, and that oxygenation is necessary to revert these signals to pre-exercise values. PHAF1/MYTHO emerges as a pivotal exercise-responsive autophagy marker positively associated with the LC3B-II:LC3B-I ratio.

E-cigarette use among Ecuadorian adults: A national cross-sectional study on use rates, perceptions, and associated factors.

INTRODUCTION: Electronic cigarettes (e-cigarettes) have emerged as a new paradigm in nicotine delivery systems. Although they are marketed as safer alternatives to tobacco, public perceptions of their safety and utility vary widely. This study aims to understand the percentage of use, factors associated, perceptions, and attitudes about e-cigarettes among Ecuadorian adults. METHODS: A cross-sectional survey was conducted among the Ecuadorian population aged 18-65 years through a convenience sample, using a structured online questionnaire designed to collect responses from voluntary participants over three months, from February to April 2023. The questionnaire assessed the respondents' attitudes and perceptions towards e-cigarettes. Data were analyzed using descriptive statistics, chi-squared tests, and adjusted logistic regression analyses to identify factors associated with e-cigarette use. RESULTS: Out of a total of 3047 Ecuadorian adults, the percentage of e-cigarette ever use was 27.9% (n=850), with 19.4% being current users and 8.5% former users. A negative stance towards e-cigarettes was predominant, with 66.3% considering e-cigarette use a public health problem in Ecuador. A significant association was observed between e-cigarette use and perceived harmfulness (p<0.001). Among non-users, there was a predominant stance in favor of control measures and disapproval of e-cigarette use among minors (p<0.001). The factors associated with the use of electronic cigarettes included being health personnel (AOR=1.51; 95% CI: 1.26-1.80). Older age (aged >24 years) and a history of tobacco use were associated with lower e-cigarette use (current users, OR=0.31; 95% CI: 0.25-0.38; previous users, OR=0.23; 95% CI: 0.18-0.28). CONCLUSIONS: The findings highlight a significant percentage of e-cigarette use among Ecuadorian adults, especially among younger groups. There is a need for comprehensive public health education about e-cigarettes in Ecuador. There is strong support from the public for control measures, suggesting the potential acceptability of regulations concerning e-cigarettes.

Enhanced electrochemical discharge of Li-ion batteries for safe recycling.

The recycling of spent lithium-ion batteries (LIBs) is crucial to sustainably manage resources and protect the environment as the use of portable electronics and electric vehicles (EVs) increases. However, the safe recycling of spent LIBs is challenging, as they often contain residual energy. Left untreated, this can trigger a thermal runaway and result in disasters during the recycling process. For efficient recycling, it is important to withdraw any leftover energy from LIBs, regardless of the processing method that follows the discharge. The electrochemical discharge method is a quick and inexpensive method to eliminate this hazard. This method works by immersing batteries in an aqueous inorganic salt solution to discharge LIBs completely and efficiently. Previously, research focus has been on different inorganic salt solutions that release toxic or flammable gaseous products during discharge. In contrast, we present an entirely new approach for electrochemical discharge - the utilization of an Fe(ii)-Fe(iii) redox couple electrolyte. We show that this medium can be used for efficient LIB deep discharge to a voltage of 2.0 V after rebound, a level that is low enough for safe discharge. To accomplish this, periodic discharge methods were used. In addition, no corrosion on the battery casing was observed. The pH behavior at the poles was also investigated, and it was found that without convection, gas evolution during discharge cannot be avoided. Finally, it was discovered that the battery casing material plays a vital role in electrochemical discharge, and its industrial standardization would facilitate efficient recycling.

Sex and adrenal hormones in association with insecticide biomarkers among adolescents living in ecuadorian agricultural communities.

BACKGROUND: Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. METHODS: In 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17ß-estradiol, and cortisol. We used general linear models to assess linear (ß = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (ß2 = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. RESULTS: The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (ßboys = 5.88% [1.21%, 10.78%], ßgirls = 4.10% [-0.02%, 8.39%]), and cortisol (ßboys = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (ß2boys = -0.17 (-0.33, -0.003), p = 0.04) and DHEA (ß2boys = -0.49 (-0.80, -0.19), p = 0.001) in boys. The neonicotinoid summary score (ßboys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (ßboys = 3.90% [1.28%, 6.58%]) were positively associated with 17ß-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE. CONCLUSIONS: We observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17ß-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.

Thromboembolic Events After the Coverage of Anterior Cerebral Artery with Flow Diversion: A Single Institution Series and Systematic Review.

BACKGROUND: Advances in the use of flow diversion (FD) now extend to bifurcation aneurysms; herein, we compare thromboembolic events in patients with internal carotid artery (ICA) aneurysms treated with and without exclusion of the anterior cerebral artery (ACA). METHODS: Retrospective analysis of aneurysms in the terminal ICA treated with FD from 2013 to 2023 at a single-center study. Procedures were classified according to the coverage at the origin of the ACA and compared through bivariate-analysis. A review was also carried on PubMed, Web of Science, and EMBASE until April 2024, adhering to the PRISMA reporting guidelines. RESULTS: Ninety-five patients harboring 113 aneurysms treated in 102 procedures were evaluated. Fifty-eight were treated covering the ACA origin. Dual antiplatelet regimens included aspirin-clopidogrel (50%), aspirin-ticagrelor (44.1%), and aspirin-prasugrel (4.9%). Thromboembolic events occurred in 6 patients (5.9%), all of which presented with large vessel occlusion of the ICA, but without reaching statistical difference in the 2 treated cohorts (P = 0.46). At a median clinical follow-up of 5.95 months, there were no differences in the functional outcomes in the 2 groups (P = 0.22). Contralateral angiographic runs post-treatment after covering the ACA origin demonstrated increase in the A1 (median: 0.45 mm; IQR = 0.4-1.2) and ICA diameter (median: 0.55 mm; IQR = 0.1-1.2). After pooling data from literature and our cohort, complete side branch occlusion after the coverage of ACA was seen in 25% of branches (95%CI = 0.16-0.36), and thromboembolic events were observed after 3% (95%CI = 0.01-0.04) of procedures. CONCLUSIONS: Thromboembolic events can occur in distal ICA aneurysms treated with FD, but no significant association was seen with covering the ACA origin.

Acute intoxication with diisopropylfluorophosphate promotes cellular senescence in the adult male rat brain.

Acute intoxication with high levels of organophosphate (OP) cholinesterase inhibitors can cause cholinergic crisis, which is associated with acute, life-threatening parasympathomimetic symptoms, respiratory depression and seizures that can rapidly progress to status epilepticus (SE). Clinical and experimental data demonstrate that individuals who survive these acute neurotoxic effects often develop significant chronic morbidity, including behavioral deficits. The pathogenic mechanism(s) that link acute OP intoxication to chronic neurological deficits remain speculative. Cellular senescence has been linked to behavioral deficits associated with aging and neurodegenerative disease, but whether acute OP intoxication triggers cellular senescence in the brain has not been investigated. Here, we test this hypothesis in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague-Dawley rats were administered DFP (4 mg/kg, s.c.). Control animals were administered an equal volume (300 µL) of sterile phosphate-buffered saline (s.c.). Both groups were subsequently injected with atropine sulfate (2 mg/kg, i.m.) and 2-pralidoxime (25 mg/kg, i.m.). DFP triggered seizure activity within minutes that rapidly progressed to SE, as determined using behavioral seizure criteria. Brains were collected from animals at 1, 3, and 6 months post-exposure for immunohistochemical analyses of p16, a biomarker of cellular senescence. While there was no immunohistochemical evidence of cellular senescence at 1-month post-exposure, at 3- and 6-months post-exposure, p16 immunoreactivity was significantly increased in the CA3 and dentate gyrus of the hippocampus, amygdala, piriform cortex and thalamus, but not the CA1 region of the hippocampus or the somatosensory cortex. Co-localization of p16 immunoreactivity with cell-specific biomarkers, specifically, NeuN, GFAP, S100ß, IBA1 and CD31, revealed that p16 expression in the brain of DFP animals is neuron-specific. The spatial distribution of p16-immunopositive cells overlapped with expression of senescence associated ß-galactosidase and with degenerating neurons identified by FluoroJade-C (FJC) staining. The co-occurrence of p16 and FJC was positively correlated. This study implicates cellular senescence as a novel pathogenic mechanism underlying the chronic neurological deficits observed in individuals who survive OP-induced cholinergic crisis.

Enhancing Image-Guided Radiation Therapy for Pancreatic Cancer: Utilizing Aligned Peak Response Beamforming in Flexible Array Transducers.

To develop ultrasound-guided radiotherapy, we proposed an assistant structure with embedded markers along with a novel alternative method, the Aligned Peak Response (APR) method, to alter the conventional delay-and-sum (DAS) beamformer for reconstructing ultrasound images obtained from a flexible array. We simulated imaging targets in Field-II using point target phantoms with point targets at different locations. In the experimental phantom ultrasound images, image RF data were acquired with a flexible transducer with in-house assistant structures embedded with needle targets for testing the accuracy of the APR method. The lateral full width at half maximum (FWHM) values of the objective point target (OPT) in ground truth ultrasound images, APR-delayed ultrasound images with a flat shape, and images acquired with curved transducer radii of 500 mm and 700 mm were 3.96 mm, 4.95 mm, 4.96 mm, and 4.95 mm. The corresponding axial FWHM values were 1.52 mm, 4.08 mm, 5.84 mm, and 5.92 mm, respectively. These results demonstrate that the proposed assistant structure and the APR method have the potential to construct accurate delay curves without external shape sensing, thereby enabling a flexible ultrasound array for tracking pancreatic tumor targets in real time for radiotherapy.

Surviving the Shocks: A Contemporary of Short-coupled Ventricular Fibrillation.

A young man presented following successful cardiac resuscitation after an out-of-hospital cardiac arrest. During his admission, he had multiple runs of short-coupled ventricular fibrillation with a similar morphology premature ventricular complex (PVC) trigger. He was brought to the electrophysiology laboratory, and, with a high dose of isoprenaline, the PVC was localised to the moderator band. Ablation induced short runs of ventricular tachycardia before elimination of the PVC. He subsequently underwent subcutaneous implantable cardiac defibrillator implantation before his discharge.

Pneumococci isolated from children in community-based practice differ from isolates identified by population and laboratory-based invasive disease surveillance.

BACKGROUND: Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs). METHODS: During 2011-2019, among children aged 6-36 months, pneumococcal serotype distribution and antibiotic non-susceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York were compared with IPD isolates from Active Bacterial Core surveillance (ABCs) across 10 U.S. sites. RESULTS: From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic non-susceptible pneumococcal isolates was generally more common among IPD cases. In 2015-2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic non-susceptibility for both the Rochester AOM and ABCs IPD cases. CONCLUSIONS: Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through U.S. surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD.

Pupil reflex as a marker of activity and prognosis in heart failure: a longitudinal and prospective study.

AIMS: Compensatory mechanisms in heart failure (HF) are triggered to maintain adequate cardiac output. Among them, hyperactivation of the sympathetic nervous system (SNS) is one of the main ones and carries a worse prognosis. The pupillary reflex depends on the SNS, and we can evaluate it through pupillometry. The aim of the study was to compare the differences in pupillary reflex between patients with acute HF and controls and to analyse whether these differences in pupillary reflex may offer a new and easy prognostic factor in such patients. METHODS AND RESULTS: We prospectively and consecutively included 107 patients admitted with decompensated HF. Quantitative pupillometry was performed with the NeuroOptics pupillometry during the first 24 h after admission and prior to discharge. The results were compared with those of a group of 100 healthy volunteers who also underwent pupillometry. The maximum baseline pupil size (MBPS) and the minimum pupil diameter (MPD) were measured. Patients with decompensated HF have a higher MBPS (3.64 ± 0.81) and higher MPD (2.60 ± 0.58) than HF patients at discharge and in the control group (P-value = 0.01 and 0.01, respectively). Also, HF patients presented an improvement in pupillometric values at discharge [MBPS (3.47 ± 0.79) and MPD (2.51 ± 0.58)] and showed no differences compared with the control group [MBPS (3.34 ± 0.82) and MPD (2.40 ± 0.53)] (P-value = 0.19 and 0.14, respectively). In addition, MBPS provides a good independent predictor of in-hospital and 1 month mortality in patients admitted with HF. Six patients (5.61%) died during hospital admission, and 11 patients (10.2%) died in the first month after discharge. Also, four patients (3.74%) were readmitted within 1 month of discharge. The receiver operating characteristic (ROC) curve for predicting in-hospital mortality through MBPS was 0.823. No patient with an MBPS < 3.7 mm died. The ROC curve for predicting combined mortality or readmission within the first month for MBPS was 0.698. CONCLUSIONS: Pupillometry may be a new, non-invasive, and simple tool to determine the status of SNS, help in the prognostic stratification of acute HF patients, and improve therapeutic management.

Process Development and Scale-Up of a Novel Atypical DAT Inhibitor (S)-CE-123.

Large-scale syntheses of small molecules and kilo laboratories are crucial steps in drug development, especially in advanced stages. (S)-5-((Benzhydrylsulfinyl)methyl)thiazole, (S)-CE-123, a potent, selective, and novel atypical DAT inhibitor, has undergone iterative testing as part of the preclinical evaluation step. This required the process transfer, scale-up, and synthesis of a 1 kg preclinical batch. The Kagan protocol for asymmetric sulfide to sulfoxide oxidation was successfully applied within a four-step synthetic process for the successful upscaling of (S)-CE-123. During the scale-up of the last step, several changes were made to the original synthetic procedure, as with every increase in batch size, new problems had to be overcome. These include, among others, the workup optimization of the last step, the simplification of chromatographic purification, elution modification to improve the purity of the product and saving of workup time. Two washing steps were added to the original procedure to enhance both the yield and the enantiomeric excess value of the final product. The modifications introduced allowed access to a 1 kg (S)-CE-123 batch with a purity >99% and an enantiomeric excess value of 95%.

Social determinants of hypertensive disorders of pregnancy trends in Mexican municipalities.

OBJECTIVES: To analyze the hypertensive disorders of pregnancy (HDP) trends in the 2000-2020 period and its association with social determinants of health (SDH) in Mexican municipalities. STUDY DESIGN: This was a retrospective longitudinal study analyzing data from routine information systems on 21,493,076 hospital discharges due to maternal causes and SDH data of 2,439-2,450 municipalities between 2000 and 2020. MAIN OUTCOMES MEASURES: We used joinpoint regression models to analyze HDP trends and hybrid negative binomial regression models to examine the association between SDH and HDP rates at intra- and inter-municipality levels. RESULTS: HDP rate increased from 0.54 in 2000 to 2.42 cases per 100 live births in 2020 (annual average percent change of 7.7 %, 95 % CI 6.6-8.9). Municipalities with higher marginalization index had higher HDP rates (IRR 1.12, 95 % CI 1.01-1.24; 1.36, 95 % CI 1.25-1.47; 1.30, 95 % CI 1.23-1.37, and 1.06, 95 % CI 1.00-1.12, in 2000-2004, 2005-2009, 2010-2014, 2015-2020, respectively). Municipal increases in the percentage of population with high schooling were associated with decreases in HDP rates in 2000-2009. Meanwhile, the role of socioeconomic status at the state level was less consistent, yet the HDP rates were lower in most socially advantaged regions. CONCLUSION: During 21 years, HDP rates increased overall in Mexican municipalities, suggesting an increased maternal morbidity burden due to HDP. The association of municipal marginalization and socioeconomic level with HDP trends indicates a need to ensure equitable interventions to improve maternal health in Mexican municipalities.

Solubility and Thermodynamic Parameters of H2S/CH4 in Ionic Liquids Determined by 1H NMR.

Natural gas remains an important global source of energy. Usually, sour gas from the well or refinery stream contains H2S among other contaminants that should be removed to fulfill permissible standards of use. Despite the use of different gas-liquid sour gas upgrading technologies, ionic liquids (ILs) have been recognized as promising materials to remove H2S from sour gas. However, data concerned with thermodynamic solution functions of H2S in ILs have scarcely been reported in the literature. In this work, solution 1H NMR spectroscopy was employed for quantifying H2S soluble in [BMIM][Cl] and for gaining a better understanding of the H2S-IL interaction. Experiments were carried out in a Young-Tap NMR tube containing a saturated solution of H2S/CH4/[BMIM][Cl] and recording spectra from 298 to 333 K. The thermodynamic solution functions, determined from the Van't Hoff equation, showed that solubility of the H2S in the [BMIM][Cl] is an exothermic gas-liquid physisorption process (ΔsolH° = -66.13 kJmol-1) with a negative entropy change (ΔsolS° = -168.19 JK-1 mol-1). 1H NMR spectra of the H2S/[BMIM][Cl] solution show a feature of strong solute-solvent interactions. However, solubility enthalpy is a fifth of the H-S bond energy value. Results from 1H NMR spectroscopy also agree with those from the bench dynamic experiments.