Atypical fibroxanthoma and pleomorphic dermal sarcoma: Local recurrence and metastasis in a nationwide population-based cohort of 1118 patients.

BACKGROUND: The prognosis of patients with atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) remains uncertain and no standardized follow-up programs have been established. OBJECTIVE: To recommend a standardized follow-up program of patients with AFX and PDS based on nationwide long-term estimates of local recurrence and metastasis. METHODS: All patients with AFX and PDS in Denmark between 2002 and 2022 were included. Danish National Registries were used to estimate the risks of local recurrence and metastasis for AFX and PDS. RESULTS: The 5-year risk of local recurrence was 10% for AFX and 17% for PDS. The 5-year risk of metastasis was 0.8% for AFX and 16% for PDS. PDS metastasized within 3 years in >90% of the patients with the lungs as the primary metastasis site (50%). Invasion beyond the subcutis, perineural/intravascular infiltration, and increasing age significantly increased the risk of PDS relapse. LIMITATIONS: Risk of misclassification and lack of detailed surgical information. CONCLUSION: The follow-up of patients with AFX can be limited to clinical visits for 4 years. Patients with PDS should be followed with clinical visits and PET/CT twice a year for the first 3 years and once a year for a minimum of 1 year.

Comparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli.

Morphometric estimates of mean or individual glomerular volume (MGV, IGV) have biological implications, over and above qualitative histologic data. However, morphometry is time-consuming and requires expertise limiting its utility in clinical cases. We evaluated MGV and IGV using plastic- and paraffin-embedded tissue from 10 control and 10 focal segmental glomerulosclerosis (FSGS) mice (aging and 5/6th nephrectomy models) using the gold standard Cavalieri (Cav) method versus the 2-profile and Weibel-Gomez (WG) methods and a novel 3-profile method. We compared accuracy, bias and precision, and quantified results obtained when sampling differing numbers of glomeruli. In both FSGS and controls, we identified an acceptable precision for MGV of 10-glomerular sampling versus 20-glomerular sampling using the Cav method, while 5-glomerular sampling was less precise. In plastic tissue, 2- or 3-profile MGVs showed greater concordance with MGV when using Cav, versus MGV with WG. IGV comparisons using the same glomeruli reported a consistent underestimation bias with both 2- or 3-profile methods versus the Cav method. FSGS glomeruli showed wider variations in bias estimation than controls. Our 3-profile method offered incremental benefit to the 2-profile method in both IGV and MGV estimation (improved correlation coefficient, Lin's concordance and reduced bias). In our control animals, we quantified a shrinkage artifact of 52% from tissue processed for paraffin-embedded versus plastic-embedded tissue. FSGS glomeruli showed overall reduced shrinkage albeit with variable artifact signifying periglomerular/glomerular fibrosis. A novel 3-profile method offers slightly improved concordance with reduced bias versus 2-profile. Our findings have implications for future studies using glomerular morphometry.

Factors in nephrologists' decision to treat pre-dialysis CKD patients with vitamin D insufficiency and SHPT: A discrete choice experiment.

Little is known about the most important factors that inform a nephrologist's decision to treat (DTT) pre-dialysis chronic kidney disease (CKD) patients with vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT). The objective of this study was to identify such factors and their relative importance in the DTT with a vitamin D therapy. A web-based, adaptive design conjoint analysis discrete-choice survey was developed to study factors that informed the DTT among a sample of 200 nephrologists located throughout the United States. Based on literature review and clinician input, eight attributes were selected that could influence a provider's DTT: age, race, CKD stage, serum 25-hydroxyvitamin D (25D), parathyroid hormone (PTH), serum calcium (Ca), serum phosphorus (P), and history of comorbidities. Respondents were asked to select one patient profile most suitable for treatment from three profiles with varying attribute levels. Each attribute's relative importance score was computed using hierarchical-Bayesian statistics to measure the influence of each factor where higher scores represented greater DTT consideration. The pooled analysis revealed the four most important factors: serum 25D (31.4%), serum Ca (22.7%), plasma PTH (11.5%) levels, and history of comorbidities (8.5%). Age (8.2%), serum P (7.7%), CKD stage (5.7%), and race (4.4%) were relatively less important. Patients' 25D and Ca levels contributed to more than half of nephrologists' DTT, with the consideration of PTH levels being less of a factor. Further understanding of the driving forces behind the factors that inform the DTT may help to standardize the management of CKD patients with SHPT and VDI and improve outcomes.

Efficacy and Safety of the Bruton's Tyrosine Kinase Inhibitor Evobrutinib in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Trial.

OBJECTIVE: Evobrutinib is a highly selective, orally administered Bruton's tyrosine kinase (BTK) inhibitor. The objective of this phase II, multicenter, randomized, double-blind, placebo-controlled trial was to evaluate the efficacy and safety of evobrutinib in patients with active autoantibody-positive systemic lupus erythematosus (SLE). METHODS: Patients were diagnosed with SLE by either the Systemic Lupus International Collaborating Clinics criteria or at least four American College of Rheumatology criteria 6 months or more prior to screening, had an SLE Disease Activity Index-2000 score of 6 or more, were autoantibody-positive and on standard-of-care therapy. Randomization was 1:1:1:1 to oral evobrutinib 25 mg once daily (QD), 75 mg QD, 50 mg twice daily, or placebo. Primary efficacy endpoints were SLE responder index (SRI)-4 response at week 52 and SRI-6 response at week 52 in the high disease activity subpopulation. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: A total of 469 patients were randomized and received at least one dose of evobrutinib or placebo at the time of primary analysis. Mean (SD) age at baseline was 40.7 (±12.3) years; 94.9% of patients were female. Neither primary efficacy endpoint was met. All doses of evobrutinib were well tolerated, and there was no clear dose effect on the incidence of reported TEAEs, or serious TEAEs, including severe infections. CONCLUSION: This phase II, dose-ranging trial in SLE failed to show a treatment effect of evobrutinib versus placebo at any dose. Evobrutinib was generally well tolerated, with no dose effect observed for TEAEs. These results suggest that BTK inhibition does not appear to be an effective therapeutic intervention for patients with SLE.

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO's and Advanced Virgo's Third Observing Run.

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2 M_{⊙} and 1.0 M_{⊙} in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14 yr^{-1}. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200] Gpc^{-3} yr^{-1}, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2 M_{⊙}

Comparison of product safety data sheet ingredient lists with skin irritants and sensitizers present in a convenience sample of light-curing resins used in additive manufacturing.

Material jetting and vat photopolymerization additive manufacturing (AM) processes use liquid resins to build objects. These resins can contain skin irritants and/or sensitizers but product safety data sheets (SDSs) might not declare all ingredients. We characterized elemental and organic skin irritants and sensitizers present in 39 commercial products; evaluated the influence of resin manufacturer, system, color, and AM process type on the presence of irritants and sensitizers; and compared product SDSs to results. Among all products, analyses identified 23 irritant elements, 54 irritant organic substances, 22 sensitizing elements, and 23 sensitizing organic substances; SDSs listed 3, 9, 4, and 6 of these ingredients, respectively. Per product, the number and total mass (an indicator of potential dermal loading) of ingredients varied: five to 17 irritant elements (8.32-4756.65 mg/kg), one to 17 irritant organics (3273 to 356,000 mg/kg), four to 17 sensitizing elements (8.27-4755.63 mg/kg), and one to seven sensitizing organics (15-382,170 mg/kg). Median numbers and concentrations of irritants and sensitizers were significantly influenced by resin system and AM process type. The presence of undeclared irritants and sensitizers in these resins supports the need for more complete information on product SDSs for comprehensive dermal risk assessments.

Case Report: Giant Paraganglioma of the Skull Base With Two Somatic Mutations in SDHB and PTEN Genes.

Head and neck paragangliomas (HNPGLs) are neuroendocrine tumors. They arise from the parasympathetic ganglia and can be either sporadic or due to hereditary syndromes (up to 40%). Most HNPGLs do not produce significant amounts of catecholamines. We report a case of a giant paraganglioma of the skull base with an unusually severe presentation secondary to excessive release of norepinephrine, with a good outcome considering the severity of disease. A 39-year-old Caucasian woman with no prior medical history was found unconscious and emaciated in her home. In the intensive care unit (ICU) the patient was treated for multi-organ failure with multiple complications and difficulties in stabilizing her blood pressure with values up to 246/146 mmHg. She was hospitalized in the ICU for 72 days and on the 31st day clinical assessment revealed jugular foramen syndrome and paralysis of the right n. facialis. A brain MRI confirmed a right-sided tumor of the skull base of 93.553 cm3. Blood tests showed high amounts of normetanephrine (35.1-45.4 nmol/L, ref <1.09 nmol/L) and a tumor biopsy confirmed the diagnosis of a paraganglioma. Phenoxybenzamine and Labetalol were used in high doses ((Dibenyline®, 90 mg x 3 daily) and labetalol (Trandate®, 200 + 300 + 300 mg daily) to stabilize blood pressure. The patient underwent two tumor embolization procedures before total tumor resection on day 243. Normetanephrine and blood pressure normalized after surgery (0.77 nmol/L, ref: < 1.09 nmol/L). The damage to the cranial nerve was permanent. Our patient was comprehensively examined for germline predisposition to PPGLs, however we did not identify any causal aberrations. A somatic deletion and loss of heterozygosity (LOH) of the short arm (p) of chromosome 1 (including SDHB) and p of chromosome 11 was found. Analysis showed an SDHB (c.565T>G, p.C189G) and PTEN (c.834C>G, p.F278L) missense mutation in tumor DNA. The patient made a remarkable recovery except for neurological deficits after intensive multidisciplinary treatment and rehabilitation. This case demonstrates the necessity for an early tertiary center approach with a multidisciplinary expert team and highlights the efficacy of the correct treatment with alpha-blockade.

Estimation of Serum Ferritin in Mucormycosis Patients and Prognostication Based on the Ferritin Value.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been implicated in a variety of vulnerable bacterial and fungal diseases. Mucormycosis is a life-threatening infection caused by fungi belonging to the class Zygomycetes and the order Mucorales. The aim of the present study is to evaluate the level of serum ferritin level in mucormycosis patients and to prognosticate them based on those values. MATERIALS AND METHODS: This prospective observational study was conducted in the Department of General Medicine, Mahatma Gandhi Memorial Government Hospital, Tiruchirappalli, in 50 diagnosed mucormycosis patients. RESULTS: During the study period, 44 had prior COVID-19 illness (post-COVID). Six patients had mucormycosis with no prior COVID-19 illness. Rhino-orbital involvement was found in 44 of the 50 cases, with three of them having cerebral extension. Forty-one cases recovered and were discharged, six cases remained sick and were hospitalized, and three died. The post-COVID patients (554.13 ± 371.60) have greater serum ferritin levels than non-COVID patients (259.95 ± 110.15), which are statistically significant.  Conclusion: Mucormycosis patients tend to have higher serum ferritin values, especially among non-survivors and sick patients than survivors. For a better chance of recovery and survival, early identification, surgical debridement, and antifungal medications are essential.

Influence of E-Liquid Humectants, Nicotine, and Flavorings on Aerosol Particle Size Distribution and Implications for Modeling Respiratory Deposition.

Electronic cigarette, or vaping, products are used to heat an e-liquid to form an aerosol (liquid droplets suspended in gas) that the user inhales; a portion of this aerosol deposits in their respiratory tract and the remainder is exhaled, thereby potentially creating opportunity for secondhand exposure to bystanders (e.g., in homes, automobiles, and workplaces). Particle size, a critical factor in respiratory deposition (and therefore potential for secondhand exposure), could be influenced by e-liquid composition. Hence, the purposes of this study were to (1) test the influence of laboratory-prepared e-liquid composition [ratio of propylene glycol (PG) to vegetable glycerin (VG) humectants, nicotine, and flavorings] on particle size distribution and (2) model respiratory dosimetry. All e-liquids were aerosolized using a second-generation reference e-cigarette. We measured particle size distribution based on mass using a low-flow cascade impactor (LFCI) and size distribution based on number using real-time mobility sizers. Mass median aerodynamic diameters (MMADs) of aerosol from e-liquids that contained only humectants were significantly larger compared with e-liquids that contained flavorings or nicotine (p = 0.005). Humectant ratio significantly influenced MMADs; all aerosols from e-liquids prepared with 70:30 PG:VG were significantly larger compared with e-liquids prepared with 30:70 PG:VG (p = 0.017). In contrast to the LFCI approach, the high dilution and sampling flow rate of a fast mobility particle sizer strongly influenced particle size measurements (i.e., all calculated MMAD values were < 75 nm). Dosimetry modeling using LFCI data indicated that a portion of inhaled particles will deposit throughout the respiratory tract, though statistical differences in aerosol MMADs among e-liquid formulations did not translate into large differences in deposition estimates. A portion of inhaled aerosol will be exhaled and could be a source for secondhand exposure. Use of laboratory-prepared e-liquids and a reference e-cigarette to standardize aerosol generation and a LFCI to measure particle size distribution without dilution represents an improved method to characterize physical properties of volatile aerosol particles and permitted determination of MMAD values more representative of e-cigarette aerosol in situ, which in turn, can help to improve dose modeling for users and bystanders.

Potential for Exposure to Particles and Gases throughout Vat Photopolymerization Additive Manufacturing Processes.

Vat photopolymerization (VP), a type of additive manufacturing process that cures resin to build objects, can emit potentially hazardous particles and gases. We evaluated two VP technologies, stereolithography (SLA) and digital light processing (DLP), in three separate environmental chambers to understand task-based impacts on indoor air quality. Airborne particles, total volatile organic compounds (TVOCs), and/or specific volatile organic compounds (VOCs) were monitored during each task to evaluate their exposure potential. Regardless of duration, all tasks released particles and organic gases, though concentrations varied between SLA and DLP processes and among tasks. Maximum particle concentrations reached 1200 #/cm3 and some aerosols contained potentially hazardous elements such as barium, chromium, and manganese. TVOC concentrations were highest for the isopropyl alcohol (IPA) rinsing, soaking, and drying post-processing tasks (up to 36.8 mg/m3), lowest for the resin pouring pre-printing, printing, and resin recovery post-printing tasks (up to 0.1 mg/m3), and intermediate for the curing post-processing task (up to 3 mg/m3). Individual VOCs included, among others, the potential occupational carcinogen acetaldehyde and the immune sensitizer 2-hydroxypropyl methacrylate (pouring, printing, recovery, and curing tasks). Careful consideration of all tasks is important for the development of strategies to minimize indoor air pollution and exposure potential from VP processes.

Evaluation of the Effect of Long-term Use of Three Intracanal Medicaments on the Radicular Dentin Microhardness and Fracture Resistance: An in vitro study.

OBJECTIVES: The aim of this research was to evaluate the effect of long-term use of three intracanal medicaments on the radicular dentin microhardness and fracture resistance. MATERIAL AND METHODS: A chemomechanical preparation was done using the Protaper rotary instruments up to F3. The teeth were stored in an incubator at 37°C at 100% humidity and were categorized in three groups by random allocation, namely: Triple Antibiotic Paste (TAP), Calcium hydroxide paste (Apexcal) and Ledermix. Following medicament application, the access openings of all teeth were sealed with 4 mm thickness of cavit. The samples were stored for periods of 1 week, 1 month and 3months. Two dentin cylinders measuring 5mm and 3mm were obtained from each sample. The cervical third was used for fracture resistance and the middle third was used for micro hardness evaluation. The microhardness testing was done using a Knoop microhardness tester, and the fracture resistance testing was done using the universal testing machine. RESULTS: Calcium hydroxide showed maximally negative effect on the physical properties of radicular dentin compared to TAP (p= 0.0100 at one month and Ledermix (p=0.0001 at one month). With an increase in the application time, there was an increased deterioration in the physical properties of radicular dentin. CONCLUSION: Long-term placement of calcium hydroxide, Triple Antibiotic Paste, and Ledermix (p= 0.0001at 3 months) significantly affects the microhardness and fracture resistance of radicular dentin.

AMPK mediates regulation of glomerular volume and podocyte survival.

Herein, we report that Shroom3 knockdown, via Fyn inhibition, induced albuminuria with foot process effacement (FPE) without focal segmental glomerulosclerosis (FSGS) or podocytopenia. Interestingly, knockdown mice had reduced podocyte volumes. Human minimal change disease (MCD), where podocyte Fyn inactivation was reported, also showed lower glomerular volumes than FSGS. We hypothesized that lower glomerular volume prevented the progression to podocytopenia. To test this hypothesis, we utilized unilateral and 5/6th nephrectomy models in Shroom3-KD mice. Knockdown mice exhibited less glomerular and podocyte hypertrophy after nephrectomy. FYN-knockdown podocytes had similar reductions in podocyte volume, implying that Fyn was downstream of Shroom3. Using SHROOM3 or FYN knockdown, we confirmed reduced podocyte protein content, along with significantly increased phosphorylated AMPK, a negative regulator of anabolism. AMPK activation resulted from increased cytoplasmic redistribution of LKB1 in podocytes. Inhibition of AMPK abolished the reduction in glomerular volume and induced podocytopenia in mice with FPE, suggesting a protective role for AMPK activation. In agreement with this, treatment of glomerular injury models with AMPK activators restricted glomerular volume, podocytopenia, and progression to FSGS. Glomerular transcriptomes from MCD biopsies also showed significant enrichment of Fyn inactivation and Ampk activation versus FSGS glomeruli. In summary, we demonstrated the important role of AMPK in glomerular volume regulation and podocyte survival. Our data suggest that AMPK activation adaptively regulates glomerular volume to prevent podocytopenia in the context of podocyte injury.

Comparative Evaluation of Efficacy of Calcium Hydroxide, Propolis, and Glycyrrhiza glabra as Intracanal Medicaments in Root Canal Treatment.

AIM: To evaluate and compare the antimicrobial efficacy of Ca(OH)2, 25% propolis, and 25% Glycyrrhiza glabra as intracanal medicaments in root canal treatment. MATERIALS AND METHODS: Total 60 freshly extracted permanent incisors were decoronated and chemomechanical preparation of root canal was performed. Samples were inoculated with a pure culture of Enterococcus faecalis and incubated for 21 days. Colony-forming units (CFUs) were recorded before medication. Incubated samples were randomly categorized into three groups, namely, Ca(OH)2, propolis, and G. glabra, with 20 samples in each group. Antibacterial activity was assessed by evaluating the variance in the CFUs on Day 7. Paired "t" test and Post-hoc Tukey's test were applied to analyze the data. RESULTS: Reduction of CFUs was noticed in all the groups (p <0.001), however the reduction was more predominant in the propolis group. CONCLUSION: Propolis is more effective against E. faecalis, when compared to G. glabra and Ca(OH)2. CLINICAL SIGNIFICANCE: Propolis could be used as an effective medicament in root canal treatment.

Extra-axial chordoma of the thumb: Report of a rare case with clinicopathologic and molecular analysis.

Chordoma is a very rare malignant tumor, with a phenotype that recapitulates notochord, and is chiefly located in the axial skeleton with only few cases reported in the extra-axial skeleton and soft tissues. The diagnosis can be challenging for both clinicians, radiologists and pathologists because of the rarity of tumor, its unspecific radiological pattern and histomorphological similarities to other tumors like extra-skeletal myxoid chondrosarcoma, soft tissue myoepithelioma and metastatic adenocarcinomas, more so on small biopsies. We present a case of a recurrent extra-axial chordoma with a prominent soft tissue component in the left thumb around proximal phalanx of an 80-year-old man, with detailed report of the histopathological, imaging and most importantly molecular features, which are in conformity with the typical profile of notochordal neoplasms. To the best of our knowledge, we report the first DNA-methylation- and the copy number variation analysis of an extra-axial chordoma with a very rare localization, thumb. With this case study we try to give a better understanding of tumor's specification, lessen the diagnostic confusion by highlighting its extra-axial occurrence, and more importantly present substantial molecular data, which might help in providing more therapeutic opportunities in the future.

Basal Cell Carcinoma of Prostate With MSMB-NCOA4 Fusion and a Probable Basal Cell Carcinoma In Situ: Case Report.

Basal cell carcinomas of prostate (BCCP) are very rare. Most arise in the transition zone and thus are associated with lower urinary tract symptoms and rarely associated with elevated prostate-specific antigen (PSA). These features make diagnosis/early diagnosis difficult because of the routine protocols followed. Basal cell carcinomas have distinctive histopathological, immunohistochemical, and to some extent also different molecular characteristics. Basal cell carcinoma in situ (BCCIS) is a nonexistent histological lesion as per the current literature, but here is an attempt to describe it through this case.A 74-year-old man presented with hematuria and previous diagnosis of prostatic hyperplasia. Based on this history, he underwent a prostatectomy ad modum Freyer. Pathological examination surprisingly revealed a diffusely infiltrative tumor with nonacinar adenocarcinoma morphology and many glandular structures probably representing BCCIS. Tumor was diagnosed as BCCP. Patient presented with metastasis to the abdominal wall 8 months postprostatectomy.BCCP is an aggressive type of prostate cancer, which might be challenging to diagnose based on routine protocols. This results in delayed diagnosis and treatment and thus poor prognosis. Furthermore, patients with this subtype of prostate cancer need appropriately designed, and maybe a totally different follow-up regimen as PSA is of no use for BCCP patients. Finally, diagnosis of BCCIS, if agreed upon its existence needs to be studied in larger cohorts as a precursor lesion.

Sarcomas with sclerotic epithelioid phenotype harboring novel EWSR1-SSX1 fusions.

Undifferentiated sarcomas remain difficult to classify. Despite the remarkable advances in sarcoma classification made by the increased application of RNA sequencing in clinical practice, the unexpected result of a novel gene fusion raises further questions regarding the tumor histogenesis and subclassification. In this study, we present two high grade sarcomas with epithelioid phenotype occurring in the deep-soft tissues (shoulder, thigh) of young adults which based on the non-specific pathologic findings were deemed unclassified and subjected to targeted RNA sequencing for further diagnostic interpretation. The results showed an identical EWSR1 exon 7-SSX1 exon 5 fusion. The breakpoints in both genes represent similar hot spots as seen in Ewing sarcoma and synovial sarcoma, generating a fusion transcript predicted to be in frame, and to retain the same protein domains within the fusion oncoprotein. These results were further confirmed by FISH analysis for both break-apart and fusion come-together assays in both genes. Both tumors showed a round to epithelioid morphology associated with extensive stromal hyalinization and necrosis. One case showed scattered psammomatous calcifications. The tumors shared a similar immunoprofile, including reactivity for EMA, CK, TLE1, BCOR, and CD99, while negative for S100, SOX10, CD34, SMA, and desmin. Both cases showed MUC4 positivity (one diffuse, one patchy), while one case showed patchy ALK positivity. One patient developed lymph node metastases, while the other showed no evidence of disease at 6-month follow-up. Neither case fit in any known pathologic categories. Larger series are needed to interrogate if the presence of EWSR1-SSX1 fusion defines a novel pathologic entity of a sarcoma with epithelioid cytomorphology, sclerotic stroma, and epithelial differentiation immunohistochemically.

Toxicology of flavoring- and cannabis-containing e-liquids used in electronic delivery systems.

Electronic cigarettes (e-cigarettes) were introduced in the United States in 2007 and by 2014 they were the most popular tobacco product amongst youth and had overtaken use of regular tobacco cigarettes. E-cigarettes are used to aerosolize a liquid (e-liquid) that the user inhales. Flavorings in e-liquids is a primary reason for youth to initiate use of e-cigarettes. Evidence is growing in the scientific literature that inhalation of some flavorings is not without risk of harm. In this review, 67 original articles (primarily cellular in vitro) on the toxicity of flavored e-liquids were identified in the PubMed and Scopus databases and evaluated critically. At least 65 individual flavoring ingredients in e-liquids or aerosols from e-cigarettes induced toxicity in the respiratory tract, cardiovascular and circulatory systems, skeletal system, and skin. Cinnamaldehyde was most frequently reported to be cytotoxic, followed by vanillin, menthol, ethyl maltol, ethyl vanillin, benzaldehyde and linalool. Additionally, modern e-cigarettes can be modified to aerosolize cannabis as dried plant material or a concentrated extract. The U.S. experienced an outbreak of lung injuries, termed e-cigarette, or vaping, product use-associated lung injury (EVALI) that began in 2019; among 2,022 hospitalized patients who had data on substance use (as of January 14, 2020), 82% reported using a delta-9-tetrahydrocannabinol (main psychoactive component in cannabis) containing e-cigarette, or vaping, product. Our literature search identified 33 articles related to EVALI. Vitamin E acetate, a diluent and thickening agent in cannabis-based products, was strongly linked to the EVALI outbreak in epidemiologic and laboratory studies; however, e-liquid chemistry is highly complex, and more than one mechanism of lung injury, ingredient, or thermal breakdown product may be responsible for toxicity. More research is needed, particularly with regard to e-cigarettes (generation, power settings, etc.), e-liquids (composition, bulk or vaped form), modeled systems (cell type, culture type, and dosimetry metrics), biological monitoring, secondhand exposures and contact with residues that contain nicotine and flavorings, and causative agents and mechanisms of EVALI toxicity.

Preoperative Embolization of a Solitary Fibrous Tumor Originating from External Auditory Meatus: A Case Report with Literature Review.

Solitary fibrous tumors (SFTs) are mesenchymal, fibroblastic tumors with mostly favorable, but still unpredictable prognosis. Their rarity and occurrence at a variety of locations coupled with variable histological appearance make the diagnosis a challenge. This can be resolved by histological and immunohistochemical analysis on the histologic material eventually coupled with demonstration of NAB2-STAT6 gene fusion by next generation sequencing (NGS) analysis. Tumor removal with clear surgical margins is sufficient for complete cure in most cases. Percutaneous transcatheter embolization in well-vascularized lesions may minimize the risk of bleeding during subsequent removal. In this article we present a rare case of SFT arising from the external auditory canal and treated with preoperative endovascular arterial embolization. A literature review with focus on diagnostics and treatment of this entity in the head and neck region is following.

Comparative Evaluation of Cytotoxic and Genotoxic Effects of Three Resin-Based Sealers by 3,(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide Assay and Comet Assay - An In Vitro Study.

BACKGROUND AND AIM: The complete sealing of the pulpal space contributes to the better healing potential after an root canal treatment, and root canal sealers are an integral part of this treatment which comes in contact with the periodontal tissue. Biocompatibility of an endodontic sealer plays an important role in the root canal treatment procedure. Hence, the aim of the study was to compare and evaluate the cytotoxicity and genotoxicity effect of three resin-based sealers on human periodontal fibroblast cells. SETTINGS AND DESIGN: This in vitro study was conducted in Dr. Prabhakar Kore's Basic Science and Research Center and K. L. E V. K. Institute of Dental Sciences, Belagavi. MATERIALS AND METHODS: Human periodontal fibroblasts were incubated with 15 specimens of Group 1 - AH Plus Group 2 - MTA Fillapex, and Group 3 - GuttaFlow 2, respectively. Cytotoxicity was assessed by 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and genotoxicity was assessed by Comet assay at time intervals at 24 h and 48 h. STATISTICAL ANALYSIS: Data were analyzed by the Kruskal-Wallis and Mann-Whitney U-test. RESULTS: AH Plus and GuttaFlow 2 did not show any cytotoxicity or genotoxicity. MTA Fillapex was slightly cytotoxic throughout the time interval, and it also showed low genotoxicity throughout the time periods for which it was tested. CONCLUSION: AH Plus and GuttaFlow 2 did not show any cytotoxic and genotoxic effect; however, MTA Fillapex showed cytotoxic and genotoxic effect throughout the time interval.

MutT Homolog1 has multifaceted role in glioma and is under the apparent orchestration by Hypoxia Inducible factor1 alpha.

AIMS: The study focused on the expression and role of a recent potential cancer therapeutic target protein, MutT Homolog1 (MTH1). MTH1 gets activated in an increased reactive oxygen species (ROS) environment and removes the oxidized nucleotides from the cell. The study aimed to check the role of MTH1 in DNA damage and apoptosis, migration and angiogenesis and also to examine its regulation in glioma. MAIN METHODS: The experiments were carried out in human glioma tissue samples and brain tissues of epilepsy patients (non-tumor control). We used two human glioblastomas cell lines, U87MG and U251MG cells. In order to study the role of MTH1 in glioma and to analyze the relation of MTH1 with Hif1α, we have used MTH1 siRNA and Hif1α siRNA respectively. KEY FINDINGS: We found an increased expression of MTH1 in glioma tissues compared to the non-tumor brain tissues. Correlation analysis revealed that those samples showing reduced expression of MTH1 also had high levels of DNA damage and apoptotic markers, while diminished expression of angiogenesis regulators and levels of migration. MTH1 knockdown in vitro by siRNA in tumor cell lines corroborates the above observation. This justifies the emergence of MTH1 inhibitors as potential first-in-class drugs. Mechanistically, our observations suggest that Hif1α may modulate MTH1 expression. SIGNIFICANCE: We found elevated MTH1 expression in glioma irrespective of their grades, while its inhibition affects multiple tumor progression pathways, and that targeting Hif1α could simulate the same.