Interrogation of a fluoropolymer dispersion manufactured with a non-fluorinated polymerization aid for targeted and non-targeted fluorinated residuals by liquid chromatography high resolution mass spectrometry.

Recent advances in fluoropolymer polymerization have focused on replacing perfluorinated polymerization aids (PAs) with hydrocarbon-based alternatives. Hydrocarbon PAs are vulnerable to fluorinated radicals during polymerization, leading to the creation of hundreds of process-specific polyfluorinated residuals. These residuals, which include low molecular weight extractable or leachable impurities, are challenging to detect at trace levels. This study investigates a polytetrafluoroethylene (PTFE) dispersion prepared with a hydrocarbon-based surfactant (DOSS) to measure these process-specific fluorinated residues. Liquid chromatography high resolution mass spectrometry is one of the few analytical methods that offers the sensitivity and selectivity required to detect these residuals in complex matrices at concentrations as low as parts per billion. The results indicate that using a hydrocarbon PA during emulsion polymerization produces numerous polyfluorinated residuals. These must be identified and monitored to develop effective abatement strategies, ensuring responsible fluoropolymer manufacturing.

Acute Metabolic Stress Induces Lymphatic Dysfunction Through KATP Channel Activation.

Lymphatic dysfunction is an underlying component of multiple metabolic diseases, including diabetes, obesity, and metabolic syndrome. We investigated the roles of KATP channels in lymphatic contractile dysfunction in response to acute metabolic stress induced by inhibition of the mitochondrial electron transport chain. Ex vivo popliteal lymphatic vessels from mice were exposed to the electron transport chain inhibitors antimycin A and rotenone, or the oxidative phosphorylation inhibitor/protonophore, CCCP. Each inhibitor led to a significant reduction in the frequency of spontaneous lymphatic contractions and calculated pump flow, without a significant change in contraction amplitude. Contraction frequency was restored by the KATP channel inhibitor, glibenclamide. Lymphatic vessels from mice with global Kir6.1 deficiency or expressing a smooth muscle-specific dominant negative Kir6.1 channel were resistant to inhibition. Antimycin A inhibited the spontaneous action potentials generated in lymphatic muscle and this effect was reversed by glibenclamide, confirming the role of KATP channels. Antimycin A, but not rotenone or CCCP, increased dihydrorhodamine fluorescence in lymphatic muscle, indicating ROS production. Pretreatment with tiron or catalase prevented the effect of antimycin A on wild-type lymphatic vessels, consistent with its action being mediated by ROS. Our results support the conclusion that KATP channels in lymphatic muscle can be directly activated by reduced mitochondrial ATP production or ROS generation, consequent to acute metabolic stress, leading to contractile dysfunction through inhibition of the ionic pacemaker controlling spontaneous lymphatic contractions. We propose that a similar activation of KATP channels contributes to lymphatic dysfunction in metabolic disease.

Connexin-45 is expressed in mouse lymphatic endothelium and required for lymphatic valve function.

The expression and functional relevance of the gap junction molecule connexin-45 (Cx45; GJC1) in lymphatic endothelium were not previously known. We found that Cx45 was expressed widely in the endothelium of murine lymphatics, in both valve and nonvalve regions. Cell-specific deletion of Cx45, driven by a constitutive Cre line (Lyve1-Cre) or an inducible Cre line (Prox1-CreERT2), compromised the function of lymphatic valves, as assessed by physiological tests (back leak and closure) of isolated, single-valve vessel segments. The defects were comparable to those previously reported for loss of Cx43, and as with Cx43, deletion of Cx45 resulted in shortening or increased asymmetry of lymphatic valve leaflets, providing an explanation for the compromised valve function. In contrast with Cx43, lymphatic endothelial cell-specific (LEC-specific) deletion of Cx45 did not alter the number of valves in mesenteric or dermal lymphatic networks or the expression patterns of the canonical valve-associated proteins PROX1, ITGA9, or CLAUDIN5. Constitutive deletion of Cx45 from LECs resulted in increased backflow of injected tracer in popliteal networks in vivo and compromised the integrity of the LEC permeability barrier in a subset of collecting vessels. These findings provide evidence for an unexpected role of Cx45 in the development and maintenance of lymphatic valves.

Twins in rotational spectroscopy: Does a rotational spectrum uniquely identify a molecule?

Rotational spectroscopy is the most accurate method for determining structures of molecules in the gas phase. It is often assumed that a rotational spectrum is a unique "fingerprint" of a molecule. The availability of large molecular databases and the development of artificial intelligence methods for spectroscopy make the testing of this assumption timely. In this paper, we pose the determination of molecular structures from rotational spectra as an inverse problem. Within this framework, we adopt a funnel-based approach to search for molecular twins, which are two or more molecules, which have similar rotational spectra but distinctly different molecular structures. We demonstrate that there are twins within standard levels of computational accuracy by generating rotational constants for many molecules from several large molecular databases, indicating that the inverse problem is ill-posed. However, some twins can be distinguished by increasing the accuracy of the theoretical methods or by performing additional experiments.

Galleria mellonella as a superficial model for Malassezia globosa and its treatment.

Introduction. Malassezia globosa is a yeast species that belongs to the mycobiota of humans and animals, associated with dermatological disorders, such as dandruff. This is a chronic scalp skin disorder characterized by flaking and itching. Treatments include commercial shampoo with different formulations that contain antifungal activities like zinc pyrithione (ZPT) or piroctone olamine (PO). The effectiveness of these formulations has been evaluated for decades for dandruff symptom relief of volunteers. To date, non-mammalian, in vivo methods exist to test formulations of these actives. Aim. To evaluate in vivo in Galleria mellonella larva, two commercial antifungal shampoos (shampoo with 1 % ZPT and 1.6 % zinc Carbonate and shampoo with 0.5 % PO) against this species. Methodology. G. mellonella larvae were inoculated with M. globosa on abraded cuticular surface. Then, integument cell viability, histological changes, and fungal burden were evaluated. Results. Larvae inoculated with M. globosa showed higher lesion melanization and tissue damage. In addition, M. globosa population showed to increase over time. Concerning the shampoo's effectiveness, both formulations significantly reduced M. globosa burden and tissue damage. Conclusion. G. mellonella larvae were allowed to evaluate M. globosa superficial infection and antifungal effectiveness. Shampoos with ZPT and PO showed a positive effect on inoculated larvae.

Shared decision making for perioperative antibiotic use during Mohs micrographic surgery on the lower extremities.

Background: While there is a higher risk of surgical site infection (SSI) on the lower extremities following Mohs micrographic surgery (MMS), antibiotic prophylaxis (AP) is debated. Objective: To determine the role of shared decision making (SDM) in guiding AP usage during MMS on the lower extremities. Materials and methods: A prospective observational study was conducted whereby patients received a standardized SDM discussion or routine counseling. Patient satisfaction quantified by the shared decision-making questionnaire (SDMQ9) survey, rate of SSI, and rate of AP prescription were recorded. Results: In total, 51 patients were included. While there were less antibiotics prescribed in the treatment group (20% versus 50%, P = .025), this did not affect incidence of SSI (8% in treatment group versus 7.7% in control group, P = .668). Patient satisfaction was statistically greater in SDM group (4.73 versus 2.18 in control (P < .001). Conclusion: Patient satisfaction scores were higher among the patients who received SDM. While the usage of AP was lower in the SDM group, this did not affect incidence of SSI. This study allows the opportunity to apply SDM in the setting of MMS, which to our knowledge has not yet been attempted in the field of dermatologic surgery.

The Aconitate Decarboxylase 1/Itaconate Pathway Modulates Immune Dysregulation and Associates with Cardiovascular Disease Markers and Disease Activity in Systemic Lupus Erythematosus.

The Krebs cycle enzyme aconitate decarboxylase 1 (ACOD1) mediates itaconate synthesis in monocytes and macrophages. Previously, we reported that administration of 4-octyl itaconate to lupus-prone mice abrogated immune dysregulation and clinical features. In this study, we explore the role of the endogenous ACOD1/itaconate pathway in the development of TLR7-induced lupus (imiquimod [IMQ] model). We found that, in vitro, ACOD1 was induced in mouse bone marrow-derived macrophages and human monocyte-derived macrophages following TLR7 stimulation. This induction was partially dependent on type I IFN receptor signaling and on specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1-/-) displayed disruptions of the splenic architecture, increased serum levels of anti-dsDNA and proinflammatory cytokines, and enhanced kidney immune complex deposition and proteinuria, when compared with the IMQ-treated wild-type mice. Consistent with these results, Acod1-/- bone marrow-derived macrophages treated in vitro with IMQ showed higher proinflammatory features. Furthermore, itaconate serum levels in systemic lupus erythematosus patients were decreased compared with healthy individuals, in association with disease activity and specific perturbed cardiometabolic parameters. These findings suggest that the ACOD1/itaconate pathway plays important immunomodulatory and vasculoprotective roles in systemic lupus erythematosus, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.

A Multiomic Analysis to Identify Drivers of Subclinical Vascular Disease in Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) increases cardiovascular disease (CVD) risk, and this is not explained by traditional risk factors. Characterization of blood immunologic signatures that associate with subclinical CVD and predict its progression has been challenging and may help identify subgroups at risk. METHODS: Patients with SLE (n = 77) and healthy controls (HCs) (n = 27) underwent assessments of arterial stiffness, vascular wall inflammation, and coronary atherosclerosis burden with cardio-ankle vascular index (CAVI); fluorodeoxyglucose-positron emission tomography/computed tomography (CT) (target-to-background ratio [TBR]); and coronary CT angiography. Whole blood bulk RNA sequencing was performed in a subset of study participants (HC n = 10, SLE n = 20). In a partially overlapping subset (HC n = 24, SLE n = 64), serum inflammatory protein biomarkers were quantified with an Olink platform. RESULTS: CAVI, TBR, and noncalcified coronary plaque burden (NCB) were increased in patients with SLE compared to HCs. When comparing patients with SLE with high CAVI scores to those with low CAVI scores or to HCs, there was a down-regulation of genes in pathways involved in the cell cycle and differentially regulated pathways related to metabolism. Distinct serum proteins associated with increased CAVI (CCL23, colony-stimulating factor 1, latency-activating peptide transforming growth factor ß1, interleukin 33 [IL-33], CD8A, and IL-12B), NCB (monocyte chemotactic protein 4 and FMS-like tyrosine kinase 3 ligand [Flt3L]), and TBR (CD5, IL-1α, AXIN1, cystatin D [CST5], and tumor necrosis factor receptor superfamily 9; P < 0.05). CONCLUSION: Blood gene expression patterns and serum proteins that associate with worse vascular phenotypes suggest dysregulated immune and metabolic pathways linked to premature CVD. Cytokines and chemokines identified in associations with arterial stiffness, inflammation, and NCB in SLE may allow for characterization of new CVD biomarkers in lupus.

Analysis of PM2.5, black carbon, and trace metals measurements from the Kansas City Transportation and Local-Scale Air Quality Study (KC-TRAQS).

Communities near transportation sources can be impacted by higher concentrations of particulate matter (PM) and other air pollutants. Few studies have reported on air quality in complex urban environments with multiple transportation sources. To better understand these environments, the Kansas City Transportation and Local-Scale Air Quality Study (KC-TRAQS) was conducted in three neighborhoods in Southeast Kansas City, Kansas. This area has several emissions sources including transportation (railyards, vehicles, diesel trucks), light industry, commercial facilities, and residential areas. Stationary samples were collected for 1-year (October 24, 2017, to October 31, 2018) at six sites using traditional sampling methods and lower-cost air sensor packages. This work examines PM less than 2.5 µm in diameter (PM2.5), black carbon (BC), and trace metals data collected during KC-TRAQS. PM2.5 filter samples showed the highest 24-h mean concentrations (9.34 µg/m3) at the sites located within 20-50 m of the railyard. Mean 24-h PM2.5 concentrations, ranging from 7.96 to 9.34 µg/m3, at all sites were lower than that of the nearby regulatory site (9.83 µg/m3). Daily maximum PM2.5 concentrations were higher at the KC-TRAQS sites (ranging from 25.31 to 43.76 µg/m3) compared to the regulatory site (20.50 µg/m3), suggesting short-duration impacts of localized emissions sources. Across the KC-TRAQS sites, 24-h averaged PM2.5 concentrations from the sensor package (P-POD) ranged from 3.24 to 5.69 µg/m3 showing that, out-of-the-box, the PM sensor underestimated the reference concentrations. KC-TRAQS was supplemented by elemental and organic carbon (EC/OC) and trace metal analysis of filter samples. The EC/OC data suggested the presence of secondary organic aerosol formation, with the highest mean concentrations observed at the site within 20 m of the railyard. Trace metals data showed daily, monthly, and seasonal variations for iron, copper, zinc, chromium, and nickel, with elevated concentrations occurring during the summer at most of the sites.Implications: This work reports on findings from a year-long air quality study in Southeast Kansas City, Kansas to understand micro-scale air quality in neighborhoods impacted by multiple emissions sources such as transportation sources (including a large railyard operation), light industry, commercial facilities, and residential areas. While dozens of studies have reported on air quality near roadways, this work will provide more information on PM2.5, black carbon, and trace metals concentrations near other transportation sources in particular railyards. This work can also inform additional field studies near railyards.

Murdering the person closest to you: Similarities and differences between intimate partner sexual homicide and non-intimate partner sexual homicide.

Sexual homicides (SHs) demand nuanced research for effective prevention, treatment, risk assessment and theoretical insights. Intimate-partner sexual homicides (IPSHs), comprising approximately 20% of SHs, have received limited attention. This study compares IPSHs (n = 56) and non-intimate partner sexual homicides (NIPSHs) (n = 236) in Australia and New Zealand by investigating offender, victim, and crime-scene characteristics. While IPSH perpetrators were typically older, separated, and had prior domestic violence convictions, victims were more often non-white with histories of domestic violence and substance use. Although crime-scene locations and post-offence behaviours differed, similar crime scene behaviours were displayed across offender groups, which seemed to be routed in different underlying motives. Whereas drivers of IPSH commonly were grievance and anger, associated with offences occurring after arguments, drivers for NIPSH were more often sexual deviance and sadism. Overall, IPSH encompasses aspects of domestic violence, homicide, and sexual violence, distinguishing it from SH.

Comparing child and adult sexual homicides in Australia and New Zealand: A retrospective study.

The present study examined distinctions between child (n = 30) and adult (n = 212) sexual homicide offenders (SHOs) in Australia and New Zealand, contributing to the limited international research on the subject. Data, primarily sourced from judges' sentencing comments on AustLII and New Zealand Legal Information Institute, revealed significant differences. Child SHOs displayed elevated rates of pedophilia, sexual deviance, and adverse childhood experiences, including sexual abuse. They were more likely to be married, cohabitate, and target familial victims. Their crimes were more often committed during daylight and outdoors, involving tactics such as victim conning, restraints, strangulation, and hiding victim's bodies. No significant group differences emerged regarding offenders' psychopathy or sexual sadism scores. Results were interpreted in line with child SHOs' deviant sexual preferences and the routine activity theory. The study, as the first investigating child sexual homicides in Australia and New Zealand, sets the foundation for an evidence-based approach to policy and practice.

A Biomimetic Leaflet Scaffold for Aortic Valve Remodeling.

Heart valve disease poses a significant clinical challenge, especially in pediatric populations, due to the inability of existing valve replacements to grow or respond biologically to their microenvironment. Tissue-engineered heart valves (TEHVs) provide a solution by facilitating patient-specific models for self-repair and remodeling. In this study, a 3D-bioprinted TEHV is designed to emulate the trilayer leaflet structure of an aortic valve. A cell-laden hydrogel scaffold made from gelatin methacrylate and polyethylene glycol diacrylate (GelMA/PEGDA) incorporates valvular interstitial-like (VIC-like) cells, being reinforced with a layer of polycaprolactone (PCL). The composition of the hydrogel scaffold remains stable over 7 days, having increased mechanical strength compared to pure GelMA. The scaffold maintains VIC-like cell function and promotes extracellular matrix (ECM) protein expression up to 14 days under two dynamic culture conditions: shear stress and stretching; replicating heart valve behavior within a more physiological-like setting and suggesting remodeling potential via ECM synthesis. This TEHV offers a promising avenue for valve replacements, closely replicating the structural and functional attributes of a native aortic valve, leading to mechanical and biological integration through biomaterial-cellular interactions.

The aconitate decarboxylase 1/itaconate pathway modulates immune dysregulation and associates with cardiovascular disease markers in SLE.

Objective: The Krebs cycle enzyme Aconitate Decarboxylase 1 (ACOD1) mediates itaconate synthesis in myeloid cells.. Previously, we reported that administration of 4-octyl itaconate abrogated lupus phenotype in mice. Here, we explore the role of the endogenous ACOD1/itaconate pathway in the development of murine lupus as well as their relevance in premature cardiovascular damage in SLE. Methods: We characterized Acod1 protein expression in bone marrow-derived macrophages and human monocyte-derived macrophages, following a TLR7 agonist (imiquimod, IMQ). Wild type and Acod1-/- mice were exposed to topical IMQ for 5 weeks to induce an SLE phenotype and immune dysregulation was quantified. Itaconate serum levels were quantified in SLE patients and associated to cardiometabolic parameters and disease activity. Results: ACOD1 was induced in mouse bone marrow-derived macrophages (BMDM) and human monocyte-derived macrophages following in vitro TLR7 stimulation. This induction was partially dependent on type I Interferon receptor signaling and specific intracellular pathways. In the IMQ-induced mouse model of lupus, ACOD1 knockout (Acod1-/-) displayed disruptions of the splenic architecture, increased serum anti-dsDNA and proinflammatory cytokine levels, enhanced kidney immune complex deposition and proteinuria, when compared to the IMQ-treated WT mice. Consistent with these results, Acod1-/- BMDM exposed to IMQ showed higher proinflammatory features in vitro. Itaconate levels were decreased in SLE serum compared to healthy control sera, in association with specific perturbed cardiometabolic parameters and subclinical vascular disease. Conclusion: These findings suggest that the ACOD1/itaconate pathway plays important immunomodulatory and vasculoprotective roles in SLE, supporting the potential therapeutic role of itaconate analogs in autoimmune diseases.

Pinch Grafting: A Systematic Review of Modern Perspectives and Applications in Dermatologic Surgery and Wound Healing.

BACKGROUND: Pinch grafting has experienced a resurgence in interest in recent years, stemming from its simplicity, safety, and potential in restoring tissue integrity. While historically employed for chronic nonhealing wounds, pinch grafts have shown promise following surgical procedures, particularly those involving the lower extremities. OBJECTIVE: To systematically review the literature and present an updated overview of the current applications of pinch grafting. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In collaboration with a medical reference librarian, the PubMed, Embase, Scopus, and Web of Science databases were searched for studies reporting on the use of pinch grafting from 2000 onward. The references of each included article were also screened. RESULTS: Ten articles met final inclusion criteria. In total, 300 patients underwent pinch grafting for treatment of skin ulceration, while an additional 35 cases were performed as an alternative to primary closure following skin cancer resection. Overall, pinch grafting was safe and well tolerated, with minimal adverse outcomes reported. CONCLUSION: Pinch grafting is a safe, straightforward, and effective technique to promote the healing of chronic wounds. While the procedure shows early promise in emerging applications within dermatologic surgery, only about 10% of the reported cases involved this indication, reflecting a need for further research in this area.

Determination of Ploidy Levels and Nuclear DNA Content in Cryptococcus neoformans by Flow Cytometry: Drawbacks with Variability.

Flow cytometry is commonly employed for ploidy determination and cell cycle analysis in cryptococci. The cells are subjected to fixation and staining with DNA-binding fluorescent dyes, most commonly with propidium iodide (PI), before undergoing flow cytometric analysis. In ploidy determination, cell populations are classified according to variations in DNA content, as evidenced by the fluorescence intensity of stained cells. As reported in Saccharomyces cerevisiae, we found drawbacks with PI staining that confounded the accurate analysis of ploidy by flow cytometry when the size of the cryptococci changed significantly. However, the shift in the fluorescence intensity, unrelated to ploidy changes in cells with increased size, could be accurately interpreted by applying the ImageStream system. SYTOX Green or SYBR Green I, reported to enable DNA analysis with a higher accuracy than PI in S. cerevisiae, were nonspecific for nuclear DNA staining in cryptococci. Until dyes or methods capable of reducing the variability inherent in the drastic changes in cell size or shape become available, PI appears to remain the most reliable method for cell cycle or ploidy analysis in Cryptococcus.

Myocardial Matrix Hydrogels Mitigate Negative Remodeling and Improve Function in Right Heart Failure Model.

This study evaluates the effectiveness of myocardial matrix (MM) hydrogels in mitigating negative right ventricular (RV) remodeling in a rat model of RV heart failure. The goal was to assess whether a hydrogel derived from either the right or left ventricle could promote cardiac repair. Injured rat right ventricles were injected with either RV-or left ventricular-derived MM hydrogels. Both hydrogels improved RV function and morphology and reduced negative remodeling. This study supports the potential of injectable biomaterial therapies for treating RV heart failure.

ChatGPT Yields a Passing Score on a Pediatric Board Preparatory Exam but Raises Red Flags.

Objectives: We aimed to evaluate the performance of a publicly-available online artificial intelligence program (OpenAI's ChatGPT-3.5 and -4.0, August 3 versions) on a pediatric board preparatory examination, 2021 and 2022 PREP® Self-Assessment, American Academy of Pediatrics (AAP). Methods: We entered 245 questions and answer choices from the Pediatrics 2021 PREP® Self-Assessment and 247 questions and answer choices from the Pediatrics 2022 PREP® Self-Assessment into OpenAI's ChatGPT-3.5 and ChatGPT-4.0, August 3 versions, in September 2023. The ChatGPT-3.5 and 4.0 scores were compared with the advertised passing scores (70%+) for the PREP® exams and the average scores (74.09%) and (75.71%) for all 10 715 and 6825 first-time human test takers. Results: For the AAP 2021 and 2022 PREP® Self-Assessments, ChatGPT-3.5 answered 143 of 243 (58.85%) and 137 of 247 (55.46%) questions correctly on a single attempt. ChatGPT-4.0 answered 193 of 243 (79.84%) and 208 of 247 (84.21%) questions correctly. Conclusion: Using a publicly-available online chatbot to answer pediatric board preparatory examination questions yielded a passing score but demonstrated significant limitations in the chatbot's ability to assess some complex medical situations in children, posing a potential risk to this vulnerable population.