Medico-Legal Complaints Against Dermatologists: Data From the Canadian Medical Protective Association, 2013 to 2022.

BACKGROUND: Medico-legal complaints against physicians are a significant source of anxiety and could be associated with defensive medical practices that may correlate with poor patient outcomes. Little is known about patient concerns brought to regulatory bodies and courts against dermatologists in Canada. OBJECTIVE: To characterize factors contributing to medico-legal complaints brought against dermatologists in Canada. METHODS: The Canadian Medical Protective Association (CMPA) repository was queried for all closed cases involving dermatologists over the past decade. Aggregate, anonymized data was reviewed and case outcomes, patient harm, and contributing factors were extracted. RESULTS: Nearly one-fifth of all dermatologists who are CMPA members have been named in at least one medico-legal case between 2013 to 2022. A total of 396 civil-legal actions or College complaint cases involving dermatologists were closed at the CMPA during this timeframe. The most common patient allegations were deficient assessment (34%), diagnostic error (28%), and unprofessional manner (22%). Nearly half of patients experienced a harmful event, the majority of which were asymptomatic or mild. The most frequently identified contributing factors related to providers were poor clinical decision making (n = 73), lack of situational awareness (n = 67), and conduct and boundary issues (n = 59). Team factors included a breakdown of communication with patients (n = 124). CONCLUSIONS: Improved communication with patients for informed consent, treatment plans, clinical follow-up, and documentation of thorough clinical patient assessments can improve patient satisfaction and health outcomes, and mitigate dermatologists' medico-legal risk.

Anti-inflammatory Effect of Symplocos prunifolia Extract in an In Vitro Model of Acute Pneumonia.

Acute pneumonia is a respiratory disease characterized by inflammation within the lung tissue, exhibiting higher morbidity rates and mortality rates among immunocompromised children and older adults. Symplocos species have been traditionally used as herbal remedies for conditions like dysentery, skin ulcers, diarrhea, and dyspepsia. Contemporary research has employed various Symplocos species in the study of diverse diseases. However, the exact efficacy and mechanisms of action of Symplocos Prunifolia remain unknown. Therefore, this study investigated the anti-inflammatory mechanism of S. prunifolia extract (SPE) in A549 and RAW264.7 cells stimulated by lipopolysaccharide (LPS). SPE significantly reduced nitric oxide (NO) production and the protein expression levels of like inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 cells. Furthermore, it reduced the protein expression levels of iNOS, COX-2 and the levels of pro-inflammatory cytokines in LPS-stimulated A549 cells. The mechanism underlying the anti-inflammatory effect of SPE was associated with the inhibition of LPS stimulated the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) and Mitogen-activated protein kinase (MAPK) phosphorylation. Moreover, we confirmed that SPE decreased the nuclear translocation of nuclear factor-κB (NF-κB)/p65 stimulated by LPS. In conclusion, these results demonstrate that SPE alleviates inflammatory responses by deactivating the PI3K/Akt, MAPK, and NF-κB signaling pathways. Our findings suggest that SPE is a potential candidate for acute pneumonia prevention.

Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism. We found that overexpressing Tau in glia disrupts LDs in flies and rat neuron-astrocyte co-cultures, sensitizing the glia to toxic, neuronal LPOs. Using a new fly tau loss-of-function allele and RNA-mediated interference, we found that endogenous Tau is required for glial LD formation and protection against neuronal LPOs. Similarly, endogenous Tau is required in rat astrocytes and human oligodendrocyte-like cells for LD formation and the breakdown of LPOs. Behaviorally, flies lacking glial Tau have decreased lifespans and motor defects that are rescuable by administering the antioxidant N-acetylcysteine amide. Overall, this work provides insights into the important role that Tau has in glia to mitigate ROS in the brain.

Effects of L-Ornithine-L-Aspartate on Angiogenesis and Perfusion in Subacute Hind Limb Ischemia: Preliminary Study.

The current treatment options for peripheral arterial disease (PAD) are limited due to a lack of significant high-level evidence to inform clinical decisions and unfavorable outcomes in terms of cost-effectiveness and amputation rates. In order to suggest the use of the commercially available L-Ornithine-L-Aspartate (LOLA) for treating PAD, we induced hind limb ischemia (HLI) by unilaterally ligating the femoral artery in a rat model. The rats were randomly divided into three groups, with seven rats assigned to each group: group 1 (control), group 2 (sorbitol), and group 3 (LOLA). Intraperitoneal injections were administered five times on post-operative days (PODs) 3, 5, 7, 10, and 12. Perfusion imaging was conducted on PODs 7 and 14 and compared to pre-operative perfusion imaging. Immunohistochemistry staining and Western blotting were performed after the final perfusion imaging. Group 3 showed a significant increase in perfusion, high CD31-positive capillary lumen density, and substantial overexpression of VEGF in the ischemic limb during the subacute phase of HLI. In conclusion, this study provides the first documented evidence of angiogenesis and perfusion recovery in the subacute phase of the HLI model following the administration of LOLA. With LOLA readily available on the commercial market, the implementation of LOLA treatment for PAD in humans can be expedited compared to other therapies still in the developmental stage.

Corrigendum: Nocebo effects in systemic therapies for adult plaque psoriasis: a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fmed.2024.1373520.].

An interdisciplinary framework of youth participatory action research informed by curricula, youth, adults, and researchers.

Rarely are youth voices incorporated into program and policy development. Youth participatory action research (YPAR) is an opportunity for adolescents to develop research skills by completing projects relevant to their lives and allows participation and decision-making at systems and organizational levels. Attention to YPAR implementation detail, especially a curricular focus, is lacking in the literature. Specifically absent is an all-encompassing YPAR framework, a gap the current study addresses. The current study includes a review of existing YPAR curricula to develop the Youth Researcher Empowerment Framework, including research components, social emotional competencies, and assumptions necessary for completing a YPAR project that centers youth voice and shared power. The study includes a quantitative assessment of the YPAR curricula and qualitative reviews by adult practitioners. In addition, focus group data from youth and teacher audiences across multiple settings confirmed and clarified terms and concepts related to the framework. The study provides empirical evidence to support a revised framework for YPAR curricular implementation. Implications are discussed in terms of aspects of the research process needed for YPAR projects, attention to specific youth developmental skills as outcomes, and underlying principles needed to create a welcoming, contextual space allowing for empowerment, youth voice, and choice.

High-purity 1,2-dimyristoyl-sn-glycero-3-phosphocholine: synthesis and emulsifying performance evaluation.

Introduction: 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) is a promising emulsifier for bioactive delivery systems, but its industrial applications are limited by the lack of cost-effective and scalable synthetic routes. The purpose of this study was to economically produce high-purity DMPC by replacing commonly used column chromatography methods and to evaluate the emulsifying performance. Methods: DMPC was synthesized from sn-glycero-3-phosphocholine using Steglich esterification followed by sequential recrystallization from ethyl acetate and acetone. The structure of DMPC was identified and its purity was confirmed using various spectroscopy and chromatography techniques. The emulsifying performance was evaluated by examining the effects of storage on the properties of o/w emulsions prepared using soybean oil with (i) soy PC, (ii) soy PC + DMPC (1:1, w/w), and (iii) DMPC as emulsifiers. Results: The chemical impurities formed during the synthesis of DMPC was removed, and its final purity was 96%, and the melt transition temperature was 37.6°C. No visible difference between the three emulsions (soy PC, soy PC+DMPC, and DMPC) was observed during two-week storage, and the DMPC-based emulsion was more stable than soy PC emulsion, showing smaller particle size distribution during 6 months. Discussion: The highly pure DMPC was synthesized by an economical method, and DMPC-based emulsions demonstrated physicochemical stable, highlighting its potential for food and pharmaceutical industry-related applications. Our findings suggest that DMPC holds promise as an emulsifier with broad applications in the food industry.

Multimodal Imaging-Assisted Intravascular Theranostic Photoactivation on Atherosclerotic Plaque.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution. METHODS: We fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence-emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks. RESULTS: The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-ß/CTGF (connective tissue growth factor) pathway. CONCLUSIONS: Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1-targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-ß-dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.

Rationally Designed Li-Ag Alloy with In-Situ-Formed Solid Electrolyte Interphase for All-Solid-State Lithium Batteries.

All-solid-state lithium batteries (ASSLBs) with sulfide-based solid electrolytes have attracted significant attention as promising energy storage devices, owing to their high energy density and enhanced safety. However, the combination of a lithium metal anode and a sulfide solid electrolyte results in performance degradation, owing to lithium dendrite growth and the side reactions of lithium metal with the solid electrolyte. To address these issues, a Ag-based Li alloy with a favorable solid electrolyte interphase (SEI) was prepared using electrodeposition and applied to the ASSLB as an anode. The electrochemically formed SEI layer on the Li-Ag alloy primarily comprised LiF and Li2O with high mechanical strength and Li3N with high ionic conductivity, which suppressed the formation of lithium dendrites and short-circuiting of the cell. The symmetric cell with the Li-Ag alloy achieved a critical current density of 1.6 mA cm-2 and maintained stable cycling for over 2000 h at a current density of 0.6 mA cm-2. Consequently, the all-solid-state lithium cell assembled with the Li-Ag alloy anode with SEI, Li6PS5Cl solid electrolyte, and LiNi0.78Co0.10Mn0.12O2 cathode delivered a high discharge capacity of 185 mAh g-1 and exhibited good cycling performance in terms of cycling stability and rate capability at 25 °C.

Effects of NF-κB Inhibitor on Sepsis Depend on the Severity and Phase of the Animal Sepsis Model.

Hyperinflammation occurs in sepsis, especially in the early phase, and it could have both positive and negative effects on sepsis. Previously, we showed that a new concept of NF-κB inhibitor, exosome-based super-repressor IκBα (Exo-srIκB) delivery, has a beneficial effect on sepsis. Here, we further investigate the therapeutic effects of Exo-srIκB at different severities and phases of sepsis using an animal polymicrobial intra-abdominal infection model. We used a rat model of fecal slurry polymicrobial sepsis. First, we determined the survival effects of Exo-srIκB on sepsis according to the severity. We used two different severities of the animal sepsis model. The severe model had a mortality rate of over 50%. The mild/moderate model had a less than 30% mortality rate. Second, we administered the Exo-srIκB at various time points (1 h, 6 h, and 24 h after fecal slurry administration) to determine the therapeutic effect of Exo-srIκB at different phases of sepsis. Lastly, we determined the effects of the Exo-srIκB on cytokine production, arterial blood gas, electrolyte, and lactate. The survival gain was statistically significant in the severe sepsis model when Exo-srIκB was administered 6 h after sepsis. Interleukin 6 and interleukin-10 were significantly decreased in the kidney when administered with Exo-srIκB. The laboratory data showed that lactate, glucose, and potassium levels were significantly lowered in the NF-κB inhibitor group. In conclusion, Exo-srIκB exhibited a beneficial therapeutic effect when administered 6 h post fecal slurry administration in a severe sepsis model.

HIF-1α and MIF enhance neutrophil-driven type 3 immunity and chondrogenesis in a murine spondyloarthritis model.

The hallmarks of spondyloarthritis (SpA) are type 3 immunity-driven inflammation and new bone formation (NBF). Macrophage migration inhibitory factor (MIF) was found to be a key driver of the pathogenesis of SpA by amplifying type 3 immunity, yet MIF-interacting molecules and networks remain elusive. Herein, we identified hypoxia-inducible factor-1 alpha (HIF1A) as an interacting partner molecule of MIF that drives SpA pathologies, including inflammation and NBF. HIF1A expression was increased in the joint tissues and synovial fluid of SpA patients and curdlan-injected SKG (curdlan-SKG) mice compared to the respective controls. Under hypoxic conditions in which HIF1A was stabilized, human and mouse neutrophils exhibited substantially increased expression of MIF and IL-23, an upstream type 3 immunity-related cytokine. Similar to MIF, systemic overexpression of IL-23 induced SpA pathology in SKG mice, while the injection of a HIF1A-selective inhibitor (PX-478) into curdlan-SKG mice prevented or attenuated SpA pathology, as indicated by a marked reduction in the expression of MIF and IL-23. Furthermore, genetic deletion of MIF or HIF1A inhibition with PX-478 in IL-23-overexpressing SKG mice did not induce evident arthritis or NBF, despite the presence of psoriasis-like dermatitis and blepharitis. We also found that MIF- and IL-23-expressing neutrophils infiltrated areas of the NBF in curdlan-SKG mice. These neutrophils potentially increased chondrogenesis and cell proliferation via the upregulation of STAT3 in periosteal cells and ligamental cells during endochondral ossification. Together, these results provide supporting evidence for an MIF/HIF1A regulatory network, and inhibition of HIF1A may be a novel therapeutic approach for SpA by suppressing type 3 immunity-mediated inflammation and NBF.

Dosimetric analysis of six whole-breast irradiation techniques in supine and prone positions.

In breast cancer radiation therapy, minimizing radiation-related risks and toxicity is vital for improving life expectancy. Tailoring radiotherapy techniques and treatment positions can reduce radiation doses to normal organs and mitigate treatment-related toxicity. This study entailed a dosimetric comparison of six different external beam whole-breast irradiation techniques in both supine and prone positions. We selected fourteen breast cancer patients, generating six treatment plans in both positions per patient. We assessed target coverage and organs at risk (OAR) doses to evaluate the impact of treatment techniques and positions. Excess absolute risk was calculated to estimate potential secondary cancer risk in the contralateral breast, ipsilateral lung, and contralateral lung. Additionally, we analyzed the distance between the target volume and OARs (heart and ipsilateral lung) while considering the treatment position. The results indicate that prone positioning lowers lung exposure in X-ray radiotherapy. However, particle beam therapies (PBTs) significantly reduce the dose to the heart and ipsilateral lung regardless of the patient's position. Notably, negligible differences were observed between arc-delivery and static-delivery PBTs in terms of target conformity and OAR sparing. This study provides critical dosimetric evidence to facilitate informed decision-making regarding treatment techniques and positions.

PHGDH: a novel therapeutic target in cancer.

Serine is a key contributor to the generation of one-carbon units for DNA synthesis during cellular proliferation. In addition, it plays a crucial role in the production of antioxidants that prevent abnormal proliferation and stress in cancer cells. In recent studies, the relationship between cancer metabolism and the serine biosynthesis pathway has been highlighted. In this context, 3-phosphoglycerate dehydrogenase (PHGDH) is notable as a key enzyme that functions as the primary rate-limiting enzyme in the serine biosynthesis pathway, facilitating the conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate. Elevated PHGDH activity in diverse cancer cells is mediated through genetic amplification, posttranslational modification, increased transcription, and allosteric regulation. Ultimately, these characteristics allow PHGDH to not only influence the growth and progression of cancer but also play an important role in metastasis and drug resistance. Consequently, PHGDH has emerged as a crucial focal point in cancer research. In this review, the structural aspects of PHGDH and its involvement in one-carbon metabolism are investigated, and PHGDH is proposed as a potential therapeutic target in diverse cancers. By elucidating how PHGDH expression promotes cancer growth, the goal of this review is to provide insight into innovative treatment strategies. This paper aims to reveal how PHGDH inhibitors can overcome resistance mechanisms, contributing to the development of effective cancer treatments.

Dose-toxicity surface histogram-based prediction of radiation dermatitis severity and shape.

Objective.This study aimed to develop a new approach to predict radiation dermatitis (RD) by using the skin dose distribution in the actual area of RD occurrence to determine the predictive dose by grade.Approach.Twenty-three patients with head and neck cancer treated with volumetric modulated arc therapy were prospectively and retrospectively enrolled. A framework was developed to segment the RD occurrence area in skin photography by matching the skin surface image obtained using a 3D camera with the skin dose distribution. RD predictive doses were generated using the dose-toxicity surface histogram (DTH) calculated from the skin dose distribution within the segmented RD regions classified by severity. We then evaluated whether the developed DTH-based framework could visually predict RD grades and their occurrence areas and shapes according to severity.Main results.The developed framework successfully generated the DTH for three different RD severities: faint erythema (grade 1), dry desquamation (grade 2), and moist desquamation (grade 3); 48 DTHs were obtained from 23 patients: 23, 22, and 3 DTHs for grades 1, 2, and 3, respectively. The RD predictive doses determined using DTHs were 28.9 Gy, 38.1 Gy, and 54.3 Gy for grades 1, 2, and 3, respectively. The estimated RD occurrence area visualized by the DTH-based RD predictive dose showed acceptable agreement for all grades compared with the actual RD region in the patient. The predicted RD grade was accurate, except in two patients.Significance. The developed DTH-based framework can classify and determine RD predictive doses according to severity and visually predict the occurrence area and shape of different RD severities. The proposed approach can be used to predict the severity and shape of potential RD in patients and thus aid physicians in decision making.

Development and evaluation of hot-melt-extruded diquafosol tetrasodium formulations for ophthalmic inserts: A design of experiments approach.

This study aimed to develop, optimize, and evaluate hot-melt-extruded ophthalmic inserts capable of sustained release of diquafosol tetrasodium (DQS) via a design of experiments approach. DQS, a tear stimulant for dry eye management, faces challenges of frequent administration and low bioavailability. The developed insert uses biodegradable polymers in varied proportions to achieve sustained release. Optimized through mixture design, the insert completely dissolved within 24 h and maintained a stable drug content, thickness, and surface pH over three months at room temperature. In vitro corneal permeation studies on excised rabbit corneas demonstrated increased bioavailability, suggesting a reduced dosing frequency compared with conventional eye drops. Therefore, this insert has potential to enhance treatment outcomes by improving patient compliance and providing sustained drug effects.

Nocebo effects in systemic therapies for adult plaque psoriasis: A systematic review and meta-analysis.

Introduction: The nocebo effect is defined as adverse outcomes secondary to negative patient expectations rather than the pharmacologic activity of an intervention. Nocebo effects can reduce treatment adherence and/or persistence. Therefore, nocebo effects in psoriasis need to be defined. Methods: A Cochrane systematic review was updated with a search of MEDLINE, Embase, and the CENTRAL Register of Controlled Trials for phase II - IV RCTs comparing systemic therapy versus placebo for patients with moderate-to-severe plaque psoriasis. Estimates were pooled using a random effects model, and heterogeneity was evaluated using the I2 statistic. The primary outcome was the pooled proportion of any adverse event (AE) and corresponding risk difference (RD) in patients randomized to placebo versus systemic therapy. Results: A total of 103 unique trials were identified enrolling 43,189 patients. The overall pooled AE rate in patients randomized to systemic therapy was 57.1% [95% CI: 54.7-59.5%] compared to 49.8% [95% CI: 47.1-52.4%] for placebo [RD 6.7% (95% CI: 4.6-8.9%), p < 0.00001, I2 = 75%]. Both biologic and non-biologic systemic therapy groups had a higher proportion of infectious AEs compared to placebo. No statistically significant RD in serious AEs or AEs leading to discontinuation was identified between systemic therapy and placebo groups. Discussion: Half of patients exposed to inert placebo in clinical trials of systemic psoriasis therapies experienced AEs, which may be explained by nocebo effects. These findings have important implications when counseling patients and designing future studies.

Epidemiology and Healthcare Expenditure for Skin Disease in Emergency Departments in Alberta, Canada.

BACKGROUND: There are limited data on the epidemiology and costs associated with managing dermatologic conditions in emergency departments (EDs). OBJECTIVE: To assess the incidence and mean cost per case of skin diseases in EDs in Alberta. METHODS: Alberta Health Services' Interactive Health Data Application was used to determine the epidemiology and costs associated with nonneoplastic dermatologic diseases in EDs in the province of Alberta, Canada, from 2018 to 2022. Skin conditions were identified using the International Classification of Disease 10th edition diagnostic groupings. RESULTS: Skin disease represented 3.59% of all ED presentations in Alberta in 2022. The total costs associated with managing dermatologic conditions have remained stable over time at approximately 15 million Canadian Dollars (CAD) annually, but the mean cost per case has risen from 188.88 (SD 15.42) in 2018 to 246.25 CAD (SD 27.47) in 2022 (7.59%/year). Infections of skin and subcutaneous tissue were the most expensive diagnostic grouping. The most common dermatologic diagnostic groupings presenting to the ED were infections of skin and subcutaneous tissue [mean age-standardized incidence rate (ASIR) of 143.67 per 100,000 standard population (SD 241.99)], urticaria and erythema [mean ASIR 33.57 per 100,000 standard population (SD 59.13)], and dermatitis and eczema [mean ASIR 18.59 per 100,000 standard population (SD 23.65)]. Cellulitis was both the most common and the costliest individual diagnosis. The majority of patients were triaged as less urgent or nonurgent. CONCLUSIONS: Skin disease represents a substantial public health burden in EDs. Further research into drivers of cost change and areas for cost savings is essential.