Outcomes and complications of heart failure with iron deficiency anemia: a nationwide analysis.

INTRODUCTION: Heart failure is a pressing public health concern, affecting millions in the United States and projected to rise significantly by 2030. Iron deficiency, prevalent in nearly half of ambulatory heart failure patients, contributes to anemia and diminishes patient outcomes. In this study, we aim to evaluate the impact of iron deficiency anemia on acute heart failure hospitalizations outcomes. METHODS: Utilizing the 2019 National Inpatient Sample (NIS) database, a retrospective observational study assessed 112,864 adult patients hospitalized with heart failure and 7,865 cases also had a concomitant diagnosis of iron deficiency anemia (IDA). RESULTS: Among 112,864 heart failure hospitalizations in 2019, approximately 7% had concomitant iron deficiency anemia (IDA). Heart failure patients with IDA exhibited distinct demographic characteristics, with females comprising 51.1% (p < 0.01) and higher rates of complicated hypertension (p < 0.01), complicated diabetes (p < 0.01), and peripheral vascular disease (p < 0.01). Adjusted mean LOS for patients with IDA was significantly longer at 1.31 days (95% CI 0.71-1.47; p < 0.01), persisting in both HFpEF and HFrEF subgroups. While total hospital charges were comparable in HFpEF, HFrEF patients with IDA incurred significantly higher charges ($13427.32, 95% CI: 1463.35-$25391.29, p = 0.03) than those without IDA. Complications such as atrial fibrillation and acute kidney injury were notably more prevalent in HFpEF and HFrEF patients with IDA. CONCLUSION: The study highlighted that iron deficiency in heart failure patients leads to extended hospital stays, increased costs, and heightened risks of specific complications, particularly in HFrEF. Our study emphasized the implications of IDA in patients with heart failure ranging from prolonged hospitalizations and increased costs. Addressing iron deficiency is crucial, given its substantial impact on heart failure hospitalizations and outcomes, emphasizing the need for proactive diagnosis and management.

Effects of the COVID-19 pandemic on senior dental students in Korea: Examining stress, burnout, and depression.

Background/purpose: The COVID-19 pandemic has had a profound and enduring impact on various aspects of society, including medical education and the training of dental students. The field of dentistry, given its nature, is particularly susceptible to the challenges posed by a pandemic. Prolonged exposure to the pandemic is believed to have increased stress and burnout among medical and dental students. This study aimed to investigate and analyze the relationship between COVID-19 and stress, burnout, and depression in Korean dental students. Materials and methods: A cross-sectional survey was conducted among 162 third and fourth-grade students from the School of Dentistry at Seoul National University. The survey comprised four main sections: general information, the Maslach Burnout Inventory (MBI), the Patient Health Questionnaire-9 (PHQ-9), and the Impact of Event Scale-Revised (IES-R). Results: The results indicated significant differences in age, study time, career satisfaction, and counseling needs between third and fourth-grade students. The fourth-grade students exhibited higher scores in the IES-R survey, PHQ-9 total score, emotional exhaustion, and depersonalization subscale items of the MBI. Furthermore, the group with abnormal responses to COVID-19 demonstrated lower levels of career satisfaction. Conclusion: Fourth-grade dental students experienced higher levels of depression, vulnerability to the effects of COVID-19, and burnout. These findings highlight the need for addressing the mental health challenges faced by dental students during the COVID-19 pandemic.

Study protocol of a randomized controlled trial to assess the efficacy of the "PrEPare for Work" intervention to enhance PrEP uptake and optimize adherence for HIV prevention among male sex workers in the U.S.

BACKGROUND: Male sex workers (MSWs), specifically cisgender men who exchange sex for money, goods, drugs, or other items of value with other cisgender men, are at high risk for HIV infection. Compared to men not engaged in sex work, MSWs are more likely to engage in frequent condomless sex with paying and non-paying sexual partners. While MSWs are often included as a subgroup of gay and bisexual men, data show that a large proportion identify as heterosexual; additionally, most MSWs do not identify as "sex workers." This places MSWs in a unique position where they may not engage with traditional HIV prevention programs, and when they do, they may not feel comfortable, leading to poor retention. Thus, HIV prevention interventions that address MSWs' unique life circumstances and provide support in exploring their sexual health options are needed. METHODS: In this protocol paper, we describe the design and procedures for a National Institute of Health-funded, randomized controlled trial testing the efficacy of "PrEPare for Work,"- a theory-based, manualized PrEP uptake and adherence intervention for MSW - using a 2-stage randomization design. Stage 1: MSWs are equally randomized to receive either the "PrEPare for Work Stage 1 intervention" (strength-based case management and facilitated PrEP linkage) or Standard of Care (SOC) to evaluate successful PrEP uptake (prescription filled) within two months post-randomization. Stage 2: Those who initiate PrEP are then equally re-randomized to receive either the "PrEPare for Work Stage 2 intervention" (1-on-1 skills training, problem-solving, and motivational interviewing adherence counseling and personalized, daily text message reminders) or SOC to assess adherence (Tenofovir concentrations in hair) over 12 months of follow up. Planned analyses will examine intervention efficacy, specific conceptual mediators, and hypothesized moderators. DISCUSSION: Based on our extensive preliminary research, multi-component, theory-informed interventions targeting this subpopulation of MSWs' unique life circumstances are urgently needed. In this study, we are evaluating whether "PrEPare for Work" can improve PrEP uptake and adherence among MSWs. If this intervention is efficacious, it would be readily disseminated to diverse community organizations that serve MSWs and possibly other community or clinic-based settings. TRIAL REGISTRATION: ClinicalTrials.gov number NCT05736614, registered February 8, 2023.

The efficacy of non-pharmacological and non-pacing therapies in preventing vasovagal syncope: Tilt training, physical counter pressure maneuvers, and yoga - A systematic review and meta-analysis.

BACKGROUND: Vasovagal syncope (VVS) is a prevalent condition characterized by a sudden drop in blood pressure and heart rate, leading to a brief loss of consciousness and postural control. Recurrent episodes of VVS significantly impact the quality of life and are a common reason for emergency department visits. Non-pharmacological interventions, such as tilt training, physical counter pressure maneuvers, and yoga, have been proposed as potential treatments for VVS. However, their efficacy in preventing VVS remains uncertain. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Web of Science, and Embase were searched up to March 2023 for randomized controlled trials comparing non-pharmacological interventions with control in preventing VVS recurrence. The primary outcome was the recurrence rate of VVS episodes. RESULTS: A total of 1130 participants from 18 studies were included in the meta-analysis. The overall mean effect size for non-pharmacological interventions versus control was 0.245 (95 % CI: 0.128-0.471, p-value <0.001). Subgroup analysis showed that yoga had the largest effect size (odds ratio 0.068, 95 % CI: 0.018-0.250), while tilt training had the lowest effect size (odds ratio 0.402, 95 % CI: 0.171-0.946) compared to control. Physical counter pressure maneuvers demonstrated an odds ratio of 0.294 (95 % CI: 0.165-0.524) compared to control. CONCLUSION: Non-pharmacological interventions show promise in preventing recurrent VVS episodes. Yoga, physical counter pressure maneuvers, and tilt training can be considered as viable treatment options. Further research, including randomized studies comparing pharmacological and non-pharmacological approaches, is needed to evaluate the safety and efficacy of these interventions for VVS treatment.

Design and synthesis of 4th generation EGFR inhibitors against human triple (Del19/T790M/C797S) mutation.

Epidermal growth factor receptor (EGFR)-targeted therapy is used to treat EGFR mutation-induced non-small cell lung cancer (NSCLC). However, its efficacy does not last beyond a certain period due to the development of primary and secondary resistance. First and second-generation inhibitors (e.g., gefitinib, erlotinib, and afatinib) induce EGFR T790M mutations, while third-generation inhibitors (e.g., osimertinib) induce C797S as a major target resistance mutation. Therefore, the C797S mutation is being actively researched. In this study, we investigated the structure-activity relationship of several synthesized compounds as fourth-generation inhibitors against the C797S mutation. We identified a compound 13k that displayed nanomolar potency and high selectivity. Moreover, we used a triple mutant xenograft mouse model to evaluate the in vivo efficacy of 13k in inhibiting EGFR C797S, which demonstrated exceptional profiles and satisfactory EGFR C797S inhibition efficacy. Based on its excellent in vitro and in vivo profiles, compound 13k can be considered a promising candidate for treating EGFR C797S mutations.

In situ photo-crosslinkable hyaluronic acid-based hydrogel embedded with GHK peptide nanofibers for bioactive wound healing.

A versatile hydrogel was developed for enhancing bioactive wound healing by introducing the amphiphilic GHK peptide (GHK-C16) into a photo-crosslinkable tyramine-modified hyaluronic acid (HA-Ty). GHK-C16 self-assembled into GHK nanofibers (GHK NF) in HA-Ty solution, which underwent in situ gelation after the wound area was filled with precursor solution. Blue light irradiation (460-490 nm), with riboflavin phosphate as a photoinitiator, was used to trigger crosslinking, which enhanced the stability of the highly degradable hyaluronic acid and enabled sustained release of the nanostructured GHK derivatives. The hydrogels provided a microenvironment that promoted the proliferation of dermal fibroblasts and the activation of cytokines, leading to reduced inflammation and increased collagen expression during wound healing. The complexation of Cu2+ into GHK nanofibers resulted in superior wound healing capabilities compared with non-lipidated GHK peptide with a comparable level of growth factor (EGF). Additionally, nanostructured Cu-GHK improved angiogenesis through vascular endothelial growth factor (VEGF) activation, which exerted a synergistic therapeutic effect. Furthermore, in vivo wound healing experiments revealed that the Cu-GHK NF/HA-Ty hydrogel accelerated wound healing through densely packed remodeled collagen in the dermis and promoting the growth of denser fibroblasts. HA-Ty hydrogels incorporating GHK NF also possessed improved mechanical properties and a faster wound healing rate, making them suitable for advanced bioactive wound healing applications. STATEMENT OF SIGNIFICANCE: By combining photo-crosslinkable tyramine-modified hyaluronic acid with self-assembled Cu-GHK-C16 peptide nanofibers (Cu-GHK NF), the Cu-GHK NF/HA-Ty hydrogel offers remarkable advantages over conventional non-structured Cu-GHK for wound healing. It enhances cell proliferation, migration, and collagen remodeling-critical factors in tissue regeneration. The incorporation of GHK nanofibers complexed with copper ions imparts potent anti-inflammatory effects, promoting cytokine activation and angiogenesis during wound healing. The Cu-GHK NF/hydrogel's unique properties, including in situ photo-crosslinking, ensure high customization and potency in tissue regeneration, providing a cost-effective alternative to growth factors. In vivo experiments further validate its efficacy, demonstrating significant wound closure, collagen remodeling, and increased fibroblast density. Overall, the Cu-GHK NF/HA-Ty hydrogel represents an advanced therapeutic option for wound healing applications.

Beta IV spectrin inhibits the metastatic growth of melanoma by suppressing VEGFR2-driven tumor angiogenesis.

BACKGROUND: Tumor-associated angiogenesis mediates the growth and metastasis of most solid cancers. Targeted therapies of the VEGF pathways can effectively block these processes but often fail to provide lasting benefits due to acquired resistance and complications. RESULTS: Recently, we discovered ßIV -spectrin as a powerful regulator of angiogenesis and potential new target. We previously reported that ßIV -spectrin is dynamically expressed in endothelial cells (EC) to induce VEGFR2 protein turnover during development. Here, we explored how ßIV -spectrin influences the tumor vasculature using the murine B16 melanoma model and determined that loss of EC-specific ßIV -spectrin dramatically promotes tumor growth and metastasis. Intraperitoneally injected B16 cells formed larger tumors with increased tumor vessel density and greater propensity for metastatic spread particularly to the chest cavity and lung compared to control mice. These results support ßIV -spectrin as a key regulator of tumor angiogenesis and a viable vascular target in cancer.

Increased dental comorbidities in patients with psoriasis: a nationwide population-based cohort study in Korea.

BACKGROUND: Limited data are available regarding the association between psoriasis and common dental conditions. OBJECTIVES: To investigate the risk of potential dental comorbidities in patients with psoriasis. METHODS: We conducted a nationwide population-based cohort study to analyse the claims data of patients with psoriasis (n = 15 165) and age- and sex-matched controls (n = 75 825). The incidence risk of the following potential dental conditions was analysed: dental caries, pulp and periapical disease, periodontal disease, gingival changes and tooth loss. RESULTS: After adjusting for potential cofactors, the adjusted hazard ratios (aHRs) of dental caries [1.105; 95% confidence interval (CI) 1.078-1.132], pulp and periapical disease (1.07; 95% CI 1.044-1.096) and periodontal disease (1.108; 95% CI 1.088-1.129) were significantly higher than those in the control cohort (P < 0.001). However, among the subset of patients with psoriasis who received systemic antipsoriatic treatment (n = 4275), the aHR risk of all potential dental comorbidities was not significantly higher from that of the control cohort. CONCLUSIONS: Patients with psoriasis have an increased risk of dental comorbidities, and systemic antipsoriatic treatment may help mitigate this increased risk.

Endothelial tip/stalk cell selection requires BMP9-induced ßIV-spectrin expression during sprouting angiogenesis.

ßIV-Spectrin is a membrane cytoskeletal protein with specialized roles in the nervous system and heart. Recent evidence also indicates a fundamental role for ßIV-spectrin in angiogenesis as its endothelial-specific gene deletion in mice enhances embryonic lethality due to hypervascularization and hemorrhagic defects. During early vascular sprouting, ßIV-spectrin is believed to inhibit tip cell sprouting in favor of the stalk cell phenotype by mediating VEGFR2 internalization and degradation. Despite these essential roles, mechanisms governing ßIV-spectrin expression remain unknown. Here we identify bone morphogenetic protein 9 (BMP9) as a major inducer of ßIV-spectrin gene expression in the vascular system. We show that BMP9 signals through the ALK1/Smad1 pathway to induce ßIV-spectrin expression, which then recruits CaMKII to the cell membrane to induce phosphorylation-dependent VEGFR2 turnover. Although BMP9 signaling promotes stalk cell behavior through activation of hallmark stalk cell genes ID-1/3 and Hes-1 and Notch signaling cross-talk, we find that ßIV-spectrin acts upstream of these pathways as loss of ßIV-spectrin in neonate mice leads to retinal hypervascularization due to excessive VEGFR2 levels, increased tip cell populations, and strong Notch inhibition irrespective of BMP9 treatment. These findings demonstrate ßIV-spectrin as a BMP9 gene target critical for tip/stalk cell selection during nascent vessel sprouting.

Periodontal disease does not increase the risk of subsequent psoriasis.

Previous studies suggested that chronic periodontitis may be a risk factor for psoriasis. However, no study has confirmed this relationship for all stages of periodontal disease (gingivitis and periodontitis). This nationwide population-based retrospective cohort study aimed to investigate whether periodontal disease is an independent risk factor for the development of subsequent psoriasis. Patients aged ≥ 20 years who underwent both medical and oral checkups from the National Health Screening Program between 2002 and 2007 were selected from a customized database provided by the National Health Insurance Service (NHIS). Then, patients with periodontal disease (n = 3,682,468) and without periodontal disease (control, n = 3,637,128) according to oral examination results were identified. We tracked each patient for subsequent psoriasis diagnosis until the end of 2018 using NHIS database. The incidence rates of psoriasis per 1000 person-years were 0.36 and 0.34 in the periodontal disease group and control groups, respectively. After adjusting for potential cofactors, no significant increase in risk (adjusted hazard ratio, 0.994; 95% confidence interval, 0.974-1.015) was observed. Similar results were observed when analyzing the risk of psoriasis in patients who required scaling or periodontal surgery. In conclusion, periodontal disease is not an independent risk factor of psoriasis.

Substance P Inhibitor Promotes Tendon Healing in a Collagenase-Induced Rat Model of Tendinopathy.

BACKGROUND: The substance P-neurokinin 1 receptor pathway has been proposed as a therapeutic target for tendinopathy. However, there is a lack of evidence regarding its practical applications. PURPOSE: To investigate the therapeutic effects of substance P inhibitor (SPI) on inflamed tenocytes in vitro and in a collagenase-induced rat model of tendinopathy in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: We analyzed the mRNA levels of inflammatory (cyclooxygenase [COX]-2 and interleukin [IL]-6) and tenogenic (Mohawk and scleraxis [SCX]) markers using reverse transcription quantitative polymerase chain reaction to demonstrate the effects of SPI on lipopolysaccharide-treated (inflamed) tenocytes. A collagenase-induced rat model of tendinopathy was created by injecting 20 µL of collagenase into the Achilles tendon. A behavior test using an incapacitance apparatus was performed to detect changes in postural equilibrium. The tendon specimens were obtained, and their gross findings were examined. The tensile strength was measured, and histopathological evaluation was performed (hematoxylin and eosin, alcian blue, and immunohistochemical staining). RESULTS: The mRNA levels of COX-2, IL-6, Mohawk, and SCX differed significantly between inflamed tenocytes and those treated with SPI. SPI improved the weight burden in a rat model of tendinopathy in a behavioral test. The specimens of the SPI group showed a normal tendon-like appearance. In the biomechanical test, the tensile strength of the SPI group was significantly greater than that of the tendinopathy group. In the histopathological evaluation, the degree of collagen matrix breakdown was mild in the SPI group. In alcian blue staining, only small focal depositions of proteoglycans and glycosaminoglycans were observed in the SPI group. The SPI group showed decreased expression of IL-6 and neurokinin 1 receptor. CONCLUSION: This study suggests that SPI has therapeutic effects on tendon healing and restoration in a collagenase-induced rat model of tendinopathy. CLINICAL RELEVANCE: SPI is a promising agent for tendinopathy in humans.

ßIV-spectrin as a stalk cell-intrinsic regulator of VEGF signaling.

Defective angiogenesis underlies over 50 malignant, ischemic and inflammatory disorders yet long-term therapeutic applications inevitably fail, thus highlighting the need for greater understanding of the vast crosstalk and compensatory mechanisms. Based on proteomic profiling of angiogenic endothelial components, here we report ßIV-spectrin, a non-erythrocytic cytoskeletal protein, as a critical regulator of sprouting angiogenesis. Early loss of endothelial-specific ßIV-spectrin promotes embryonic lethality in mice due to hypervascularization and hemorrhagic defects whereas neonatal depletion yields higher vascular density and tip cell populations in developing retina. During sprouting, ßIV-spectrin expresses in stalk cells to inhibit their tip cell potential by enhancing VEGFR2 turnover in a manner independent of most cell-fate determining mechanisms. Rather, ßIV-spectrin recruits CaMKII to the plasma membrane to directly phosphorylate VEGFR2 at Ser984, a previously undefined phosphoregulatory site that strongly induces VEGFR2 internalization and degradation. These findings support a distinct spectrin-based mechanism of tip-stalk cell specification during vascular development.

Regulation of mitochondrial fission by GIPC-mediated Drp1 retrograde transport.

Dynamin-related protein 1 (Drp1) is a key regulator of mitochondrial fission, a large cytoplasmic GTPase recruited to the mitochondrial surface via transmembrane adaptors to initiate scission. While Brownian motion likely accounts for the local interactions between Drp1 and the mitochondrial adaptors, how this essential enzyme is targeted from more distal regions like the cell periphery remains unknown. Based on proteomic interactome screening and cell-based studies, we report that GAIP/RGS19-interacting protein (GIPC) mediates the actin-based retrograde transport of Drp1 toward the perinuclear mitochondria to enhance fission. Drp1 interacts with GIPC through its atypical C-terminal PDZ-binding motif. Loss of this interaction abrogates Drp1 retrograde transport resulting in cytoplasmic mislocalization and reduced fission despite retaining normal intrinsic GTPase activity. Functionally, we demonstrate that GIPC potentiates the Drp1-driven proliferative and migratory capacity in cancer cells. Together, these findings establish a direct molecular link between altered GIPC expression and Drp1 function in cancer progression and metabolic disorders.

Internal Resorption of Multiple Posterior Teeth in a Patient Diagnosed with Hyperparathyroidism: A Case Report.

This case reports a 46-year-old man with end-stage renal disease and internal resorption (IR) affecting multiple posterior teeth. IR involves odontoclast's removal of dentin within pulp chambers and root canal space. Typically, asymptomatic until detected on radiographs, IR is relatively rare, so the etiology and pathogenesis are poorly understood. Patients' radiographs with cone-beam computed tomography revealed extensive IR in multiple premolars and all remaining molar teeth. Blood tests and hormonal assay measured elevated phosphorus and parathyroid hormone levels consistent with secondary hyperparathyroidism. Histopathology showed highly vascularized and inflamed pulp tissues with numerous odontoclast-like multinucleated giant cells along dentinal walls and in resorption lacunae. Immunohistochemistry showed that multinucleated giant cells and adjacent mononuclear precursors stained strongly for tartrate-resistant acid phosphatase like osteoclasts. Extraction of crown-root fractures and endodontic treatment with crown restorations for all IR teeth effectively arrested disease progression at 9 months' follow-up. Elevated parathyroid hormone from secondary hyperparathyroidism that promotes bone osteoclast activity may also stimulate odontoclasts causing IR.

Impact of pre-transplant carbapenem-resistant Enterobacterales colonization and/or infection on solid organ transplant outcomes.

The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.

Conceptualizing the use of the term financial risk by non-academics and academics using twitter messages and ScienceDirect paper abstracts.

A text mining technique, based on an Application Programming Interface (API) request-using narrative data from Twitter™ and ScienceDirect™-was used to identify how non-academics and academics conceptualize and evaluate sentiment indicators associated with the term financial risk in their communications. It was determined that unlike the day-to-day uses of the term-all of which tend to focus predominately on the business and technology aspects of risk taking-the academic definition of the term is expressed broadly. It was also determined that the term was mainly associated with negative emotions in daily conversations, whereas the term tended to be used in a positive way in research paper abstracts. Results from this study suggest that the way financial risk is conceptualized and applied in real-life settings primarily represents negative emotional contexts, while academic papers tend to represent positive emotional contexts. Information presented in this paper can help educators, researchers, and policy makers better understand the way non-academics objectively and subjectively evaluate and describe financial risk. This information may help lead to better investor educational interventions and decision outcomes.

Target-mediated drug disposition modeling of an anti-TFPI antibody (MG1113) in cynomolgus monkeys to predict human pharmacokinetics and pharmacodynamics.

BACKGROUND: MG1113 is a human monoclonal antibody of tissue factor pathway inhibitor (TFPI) under development for prophylaxis for hemophilia patients with or without inhibitors against factor VIII products, which have been used for the treatment of hemophilia. Because TFPI is a negative regulator in the extrinsic coagulation pathway, neutralization of TFPI function by MG1113 can potentially increase coagulation activity by bypassing the intrinsic coagulation pathway, which factor VIII activates. OBJECTIVES: This study aims to determine the correlation between pharmacokinetics (PK) and pharmacodynamics (PD) after administering MG1113 to monkeys and to predict the PK and PD of MG1113 in humans by the Target-Mediated Drug Disposition (TMDD) model using the results from monkeys. METHODS: The PK profile of MG1113 and the PD effect on the free TFPI level were evaluated after intravenous (IV) and subcutaneous (SC) administrations of MG1113 (2.5, 5, and 10 mg/kg) to male cynomolgus monkeys. After setting up the PK/PD model on monkeys, PK parameters on humans were calculated using allometric scaling, and then clinically effective doses were predicted applying the TMDD model. RESULTS AND CONCLUSIONS: MG1113 showed nonlinear PK after both IV and SC administrations at the dosing range from 2.5 to10 mg/kg. The concentrations of MG1113 versus TFPI could be characterized a dose-response relationship using a TMDD model. The TMDD modeling and simulation built in this study were used to simulate various dosage regimens of MG1113 to apply to the first-in-human study design, and moreover expected to be referred to establish the dose for further clinical trials.

High levels of burnout and depression in a population of senior dental students in a school of dentistry in Korea.

BACKGROUND/PURPOSE: Dental students are exposed to highly stressful environments, making them high-risk for burnout and depression. This study intended to investigate the burnout and depression level in senior dental students in Korea. MATERIALS AND METHODS: We conducted a cross-sectional questionnaire study among third- and fourth-year dental students enrolled at Seoul National University. Demographic data, Maslach Burnout Inventory (MBI), Patient Health Questionnaire (PHQ-9), dental education satisfaction, and counseling needs were measured. Statistical analyses included intergroup comparison of MBI subscales (emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA)) to identify the risk factors for burnout. Correlation analyses between MBI subscales and PHQ-9 were also conducted. RESULTS: Among 112 students included in the study, 44.6% had high EE, 36.6% showed high DP, and 51.8% had low PA. There were 20 (17.9%) students who satisfied burnout criteria on all three subscales. There were 19 (17.0%) students with PHQ-9 scores of 10 or greater. There were no significant differences in MBI subscales or PHQ-9 scores according to sex, study year, marital status, funding for studies, or academic grade, but there was a difference according to academic workload. All MBI subscales had significant correlation with PHQ-9 score. Burnout students reported significantly lower satisfaction scores and greater need for counseling compared to non-burnout students. CONCLUSION: Burnout and depression levels among dental students in Korea were relatively high and intercorrelated. Burnout level was significantly associated with high academic workload. Students experiencing burnout were likely to be dissatisfied with their education programs and likely to need counseling.

Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients.

BACKGROUND: Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. METHODS: A single-center, retrospective study of patients who received isavuconazole (September 2015-February 2018) or voriconazole (September 2013-September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. RESULTS: Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005). CONCLUSIONS: Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.

Guidance for dental treatment of patients with disabilities during COVID-19 pandemic.

People with disabilities are challenged managing their oral hygiene and more often burdened with oral diseases. They often require immediate dental treatment for severe pain and greater precautions are needed to cope with COVID-19. The potential for COVID-19 infection can be relatively high in patients with disabilities due to concomitant systemic diseases, unique individual circumstances, relationship with caregivers and the living conditions of long-term care facilities, which make them vulnerable to the virus. For behavior management, dental treatment is often provided under general anesthesia with meticulous preoperative evaluation and the use of high-quality viral filters. In response to COVID-19, additional considerations should be taken for dental procedures on patients with special needs. These recommendations for dental treatment of the disabled are based on 6 months of authors COVID-19 pandemic experience.