Professionalism in Physician Assistant Education as a Predictor of Future Licensing Board Disciplinary Actions.

PURPOSE: The purpose of this study was to evaluate associations between postgraduate disciplinary actions (PGDA) by state licensing boards and physician assistant (PA) school documented professionalism violations (DPV) and academic probation. METHODS: This was a retrospective cohort study comprising PA graduates from 2001 to 2011 at 3 institutions (n = 1364) who were evaluated for the main outcome of PGDA and independent variable of DPV and academic probation. Random-effects multiple logistic regression and accelerated failure time parametric survival analysis were used to investigate the association of PGDA with DPV and academic probation. RESULTS: Postgraduate disciplinary action was statistically significant and positively associated with DPV when unadjusted (odds ratio [OR] = 5.15; 95% CI: 1.62-16.31; P = .01) and when adjusting for age, sex, overall PA program GPA (GPA), and Physician Assistant National Certifying Exam Score (OR = 5.39; 95% CI: 1.54-18.85; P = .01) (fully adjusted). Academic probation increased odds to 8.43 times (95% CI: 2.85-24.92; P < .001) and 9.52 times (95% CI: 2.38-38.01; P < .001) when fully adjusted. CONCLUSION: Students with professionalism violation or academic probation while in the PA school had significant higher odds of receiving licensing board disciplinary action compared with those who did not. Academic probation had a greater magnitude of effect and could represent an intersection of professionalism and academic performance.

Diagnosing Midline Neck Masses: Comparing Clinical Exam, the SIST Score, and the 4S Algorithm.

OBJECTIVE: To validate and compare novel ultrasound scoring systems for dermoid cysts and thyroglossal duct cysts among pediatric patients. STUDY DESIGN: Retrospective study. SETTING: Tertiary care children's hospital. METHODS: An electronic medical record query of patients younger than 18 years old who underwent primary excision of a neck mass between January 2005 and February 2022, who underwent preoperative ultrasound, and had final histopathologic diagnosis of either thyroglossal duct cysts or dermoid cysts. This generated 260 results, of which 134 patients met the inclusion criteria. Charts were reviewed for demographic data, clinical impressions, and radiographic studies. Radiologists blindly reviewed ultrasound for SIST score (septae + irregular walls + solid components = thyroglossal), and 4S algorithm (Septations, depth relative to Strap muscles, Shape, Solid parts). Statistical analyses were performed to determine the accuracy of each diagnostic modality. RESULTS: Of 134 patients, 90 (67%) had a final histopathologic diagnosis of thyroglossal duct cysts, and 44 (33%) were dermoid cysts. The accuracy of clinical diagnosis was 52%, and preoperative ultrasound report accuracy was 31%. The 4S and SIST accuracies were each 84%. CONCLUSION: Both the 4S algorithm and SIST score provide increased accuracy of diagnosis relative to standard preoperative ultrasound assessment. Neither scoring modality was determined to be superior. Further research is warranted in improving the accuracy of preoperative assessments for pediatric congenital neck masses.

Sesquiterpenes from Artemisia princeps regulate inflammatory responses in RAW 264.7 macrophages.

Four sesquiterpenoids were isolated from an ethyl acetate-soluble fraction of A. princeps ethanolic extract: seco-tanapartholide B (5-epi-seco-tanapartholide A) (1), 4-epi-seco-tanapartholide A (2), 11,13-dehydrodesacetylmatricarin (3) and desacetylmatricarin (4). Compounds 1 - 3 dose-dependently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages. These compounds also decreased mRNA and protein expression levels of inducible NO synthase and cyclooxygenase-2 as well as mRNA levels of pro-inflammatory cytokines (interleukin-1ß and tumour necrosis factor-α) in LPS-stimulated RAW 264.7 macrophages. Moreover, compound 3 effectively enhanced the expression of heme oxygenase-1 (HO-1) in macrophages in the presence or absence of LPS. Additionally, the exocyclic methylene of α-methylene-γ-lactone moiety of compound 3 was found to be essential for the activation of the NF erythroid 2-related factor 2 (Nrf2)/HO-1 pathway. Here, we firstly report the isolation of compounds 3 and 4 from A. princeps and the anti-inflammatory activity of compound 3 by up-regulation of Nrf2/HO-1 pathway.

Semi-subterranean environment and soil metagenomic datasets of the Gyeongju Seokbinggo (stone ice storage) in South Korea.

The Seokbinggo is an ice cellar made of stone to store ice in the 1700s. The Seokbinggo, a traditional Korean stone architecture, can keep ice collected in winter until summer because the semi-subterranean structure utilizes the natural environment, and the insulation design is effective. However, these structures and scientific designs are not used as ice storage and are easily damaged by biological contamination. We present the environmental data of the inside and the metagenomic dataset of the soil samples from the Seokbinggo. Next-generation sequencing was carried out on an Illumina MiSeq platform. The raw sequence data used for analysis is available in NCBI under the Sequence Read Archive (SRA) with BioProject No. PRJNA727939 and SRA accession Nos. SRX10976613, SRX10976614, SRX10976615, SRX10976616, SRX10976617, SRX10976618, SRX10976619, SRX10976620. Environmental data, including data from Korea Meteorological Administration, is available in the Mendeley data repository with DOI: 10.17632/2r8gpg7pxn.1.

The proximal tubular α7 nicotinic acetylcholine receptor attenuates ischemic acute kidney injury through Akt/PKC signaling-mediated HO-1 induction.

Activation of the α7 nicotinic acetylcholine receptor (α7nAChR) has been shown to attenuate excessive inflammation by inhibiting proinflammatory cytokines during ischemia-reperfusion (IR) injury; however, the underlying kidney-specific molecular mechanisms remain unclear. The protective action of α7nAChR against renal IR injury was investigated using a selective α7nAChR agonist and antagonist. α7nAChR activation reduced plasma creatinine levels and tubular cell damage, whereas α7nAChR inhibition aggravated the IR-induced phenotype. α7nAChR activation decreased neutrophil infiltration and proinflammatory cytokine expression, increased heme oxygenase-1 (HO-1) expression, and reduced proximal tubular apoptosis after IR as shown by terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and caspase-3 cleavage. In this study, we first showed that α7nAChR activation in the proximal tubules induced HO-1 expression through the phosphoinositide 3-kinase (PI3K)/Akt and protein kinase C (PKC) signaling pathway in vivo in renal IR mice and in vitro in proximal tubular cells. Chemical inhibitors of PKC or PI3K/Akt and small interfering RNA-mediated PKC silencing confirmed the signal specificity of α7nAChR-mediated HO-1 induction in the proximal tubular cells. α7nAChR activation inhibited high-mobility group box 1 release by inducing HO-1 expression and reduced proinflammatory cytokine gene expression and apoptotic cell death in tumor necrosis factor α-stimulated proximal tubular cells. Taken together, we conclude that α7nAChR activation in proximal tubular cells directly protects cells against renal IR injury by inducing HO-1 expression through PI3K/Akt and PKC signaling.

Bactericidal effect of 266 to 279nm wavelength UVC-LEDs for inactivation of Gram positive and Gram negative foodborne pathogenic bacteria and yeasts.

Recently, UVC-LED technology has been validated as an alternative to irradiation with conventional mercury UV lamps. In this study, we sought to determine primary factors affecting reduction trends shown in several microorganisms. Four major foodborne pathogens (Escherichia coli O157:H7, Salmonella spp. Listeria monocytogenes, Staphylococcus aureus) and spoilage yeasts (Saccharomyces pastorianus, Pichia membranaefaciens), important to the brewing industry, were inoculated onto selective and non-selective media in order to investigate reduction tendencies at 4 different peak wavelengths (266 to 279nm). As irradiation dose increased, inactivation levels for every microorganism were enhanced, but there were different UV-sensitivities in Gram positive bacteria (GP), Gram negative bacteria (GN), and yeasts (Y). Loss of membrane integrity measured by propidium iodide (PI) increased as peak wavelength increased for every microorganism studied. Similar results were observed in membrane potential measured by DiBAC4(3). However, there were contrasting results which showed that greater DNA damage occurred at a lower peak wavelength as measured by Hoechst 33,258. The level of DNA damage was strongly related to trends of microbial inactivation. This study showed that even though membrane damage was present in every microorganism studied, DNA damage was the primary factor for inactivating microorganisms through UVC-LED treatment.

Small and big Hodgkin-Reed-Sternberg cells of Hodgkin lymphoma cell lines L-428 and L-1236 lack consistent differences in gene expression profiles and are capable to reconstitute each other.

The hallmark of classical Hodgkin lymphoma (cHL) is the presence of giant, mostly multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Whereas it has recently been shown that giant HRS cells evolve from small Hodgkin cells by incomplete cytokinesis and re-fusion of tethered sister cells, it remains unsolved why this phenomenon particularly takes place in this lymphoma and what the differences between these cell types of variable sizes are. The aim of the present study was to characterize microdissected small and giant HRS cells by gene expression profiling and to assess differences of clonal growth behavior as well as susceptibility toward cytotoxic intervention between these different cell types to provide more insight into their distinct cellular potential. Applying stringent filter criteria, only two differentially expressed genes between small and giant HRS cells, SHFM1 and LDHB, were identified. With looser filter criteria, 13 genes were identified to be differentially overexpressed in small compared to giant HRS cells. These were mainly related to energy metabolism and protein synthesis, further suggesting that small Hodgkin cells resemble the proliferative compartment of cHL. SHFM1, which is known to be involved in the generation of giant cells, was downregulated in giant RS cells at the RNA level. However, reduced mRNA levels of SHFM1, LDHB and HSPA8 did not translate into decreased protein levels in giant HRS cells. In cell culture experiments it was observed that the fraction of small and big HRS cells was adjusted to the basic level several days after enrichment of these populations via cell sorting, indicating that small and big HRS cells can reconstitute the full spectrum of cells usually observed in the culture. However, assessment of clonal growth of HRS cells indicated a significantly reduced potential of big HRS cells to form single cell colonies. Taken together, our findings pinpoint to strong similarities but also some differences between small and big HRS cells.

Inactivation modeling of human enteric virus surrogates, MS2, Qß, and ΦX174, in water using UVC-LEDs, a novel disinfecting system.

In order to assure the microbial safety of drinking water, UVC-LED treatment has emerged as a possible technology to replace the use of conventional low pressure (LP) mercury vapor UV lamps. In this investigation, inactivation of Human Enteric Virus (HuEV) surrogates with UVC-LEDs was investigated in a water disinfection system, and kinetic model equations were applied to depict the surviving infectivities of the viruses. MS2, Qß, and ΦX 174 bacteriophages were inoculated into sterile distilled water (DW) and irradiated with UVC-LED printed circuit boards (PCBs) (266nm and 279nm) or conventional LP lamps. Infectivities of bacteriophages were effectively reduced by up to 7-log after 9mJ/cm2 treatment for MS2 and Qß, and 1mJ/cm2 for ΦX 174. UVC-LEDs showed a superior viral inactivation effect compared to conventional LP lamps at the same dose (1mJ/cm2). Non-log linear plot patterns were observed, so that Weibull, Biphasic, Log linear-tail, and Weibull-tail model equations were used to fit the virus survival curves. For MS2 and Qß, Weibull and Biphasic models fit well with R2 values approximately equal to 0.97-0.99, and the Weibull-tail equation accurately described survival of ΦX 174. The level of UV-susceptibility among coliphages measured by the inactivation rate constant, k, was statistically different (ΦX 174 (ssDNA)>MS2, Qß (ssRNA)), and indicated that sensitivity to UV was attributed to viral genetic material.

AhR activation by 6-formylindolo[3,2-b]carbazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibit the development of mouse intestinal epithelial cells.

The intestinal epithelium plays a central role in immune homeostasis in the intestine. AhR, a ligand-activated transcription factor, plays an important role in diverse physiological processes. The intestines are exposed to various exogenous and endogenous AhR ligands. Thus, AhR may regulate the intestinal homeostasis, directly acting on the development of intestinal epithelial cells (IEC). In this study, we demonstrated that 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibited the in vitro development of mouse intestinal organoids. The number of Paneth cells in the small intestine and the depth of crypts of the small and large intestines were reduced in mice administrated with FICZ. Immunohistochemical and flow cytometric assays revealed that AhR was highly expressed in Lgr5(+) stem cells. FICZ inhibited Wnt signaling lowering the level of ß-catenin protein. Gene expression analyses demonstrated that FICZ increased expression of Lgr5, Math1, BMP4, and Indian Hedgehog while inhibiting that of Lgr4.

Designing Peptide Bunches on Nanocage for Bispecific or Superaffinity Targeting.

Ferritin cage nanoparticles are promising platforms for targeted delivery of imaging and therapeutic agents because their cage structure can accommodate small molecules and their surfaces can be decorated with multiple functionalities. However, selective targeting is still a challenge for translating ferritin-based nanomedicines into the clinic, especially for heterogeneous diseases such as cancer. Targeting peptides can be genetically fused onto the surface of a ferritin cage, forming peptide bunches on nanocages (PBNCs) that offer synergistic increases in binding avidity. Here, we utilized two sites of the ferritin monomer, the N-terminus and the loop between the fourth and fifth helices, which are exposed on the surface of the assembled 24-subunit ferritin cage, to ligate one or two types of peptides to achieve "super affinity" and bispecificity, respectively. PBNCs formed by ligation of the IL-4 receptor-targeting peptide, AP1, to both sites (48AP1-PBNCs) tethered IL-4R, expressing tumor cells with greater affinity than did PBNCs with AP1 ligated to a single site (24AP1-PBNCs). Moreover, bispecific PBNCs containing 24 RGD peptides and 24 AP1 peptides (24RGD/24AP1-PBNCs) were capable of independently targeting cells expressing the corresponding receptors. Bispecific and superaffinity PBNCs could be useful for efficient targeting of ferritin-based therapeutic/diagnostic agents in a clinical setting.

Using UVC Light-Emitting Diodes at Wavelengths of 266 to 279 Nanometers To Inactivate Foodborne Pathogens and Pasteurize Sliced Cheese.

UVC light is a widely used sterilization technology. However, UV lamps have several limitations, including low activity at refrigeration temperatures, a long warm-up time, and risk of mercury exposure. UV-type lamps only emit light at 254 nm, so as an alternative, UV light-emitting diodes (UV-LEDs) which can produce the desired wavelengths have been developed. In this study, we validated the inactivation efficacy of UV-LEDs by wavelength and compared the results to those of conventional UV lamps. Selective media inoculated with Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes were irradiated using UV-LEDs at 266, 270, 275, and 279 nm in the UVC spectrum at 0.1, 0.2, 0.5, and 0.7 mJ/cm(2), respectively. The radiation intensity of the UV-LEDs was about 4 µW/cm(2), and UV lamps were covered with polypropylene films to adjust the light intensity similar to those of UV-LEDs. In addition, we applied UV-LED to sliced cheese at doses of 1, 2, and 3 mJ/cm(2). Our results showed that inactivation rates after UV-LED treatment were significantly different (P < 0.05) from those of UV lamps at a similar intensity. On microbiological media, UV-LED treatments at 266 and 270 nm showed significantly different (P < 0.05) inactivation effects than other wavelength modules. For sliced cheeses, 4- to 5-log reductions occurred after treatment at 3 mJ/cm(2) for all three pathogens, with negligible generation of injured cells.

Fundamental Characteristics of Deep-UV Light-Emitting Diodes and Their Application To Control Foodborne Pathogens.

Low-pressure mercury UV (LP-UV) lamps have long been used for bacterial inactivation, but due to certain disadvantages, such as the possibility of mercury leakage, deep-UV-C light-emitting diodes (DUV-LEDs) for disinfection have recently been of great interest as an alternative. Therefore, in this study, we examined the basic spectral properties of DUV-LEDs and the effects of UV-C irradiation for inactivating foodborne pathogens, including Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes, on solid media, as well as in water. As the temperature increased, DUV-LED light intensity decreased slightly, whereas LP-UV lamps showed increasing intensity until they reached a peak at around 30°C. As the irradiation dosage and temperature increased, E. coli O157:H7 and S. Typhimurium experienced 5- to 6-log-unit reductions. L. monocytogenes was reduced by over 5 log units at a dose of 1.67 mJ/cm(2). At 90% relative humidity (RH), only E. coli O157:H7 experienced inactivation significantly greater than at 30 and 60% RH. In a water treatment study involving a continuous system, 6.38-, 5.81-, and 3.47-log-unit reductions were achieved in E. coli O157:H7, S. Typhimurium, and L. monocytogenes, respectively, at 0.5 liter per minute (LPM) and 200 mW output power. The results of this study suggest that the use of DUV-LEDs may compensate for the drawbacks of using LP-UV lamps to inactivate foodborne pathogens.

Comparison of a Four-Section Spindle and Stomacher for Efficacy of Detaching Microorganisms from Fresh Vegetables.

This study was undertaken to compare the effect of the spindle and stomacher for detaching microorganisms from fresh vegetables. The spindle is an apparatus for detaching microorganisms from food surfaces, which was developed in our laboratory. When processed with the spindle, food samples were barely disrupted, the original shape was maintained, and the diluent was clear, facilitating further detection analysis more easily than with stomacher treatment. The four-section spindle consists of four sample bag containers (A, B, C, and D) to economize time and effort by simultaneously processing four samples. The aerobic plate counts (APC) of 50 fresh vegetable samples were measured following spindle and stomacher treatment. Correlations between the two methods for each section of the spindle and stomacher were very high (R(2) = 0.9828 [spindle compartment A; Sp A], 0.9855 [Sp B], 0.9848 [Sp C], and 0.9851 [Sp D]). One-tenth milliliter of foodborne pathogens suspensions was inoculated onto surfaces of food samples, and ratios of spindle-to-stomacher enumerations were close to 1.00 log CFU/g between every section of the spindle and stomacher. One of the greatest features of the spindle is that it can treat large-sized samples that exceed 200 g. Uncut whole apples, green peppers, potatoes, and tomatoes were processed by the spindle and by hand massaging by 2 min. Large-sized samples were also assayed for aerobic plate count and recovery of the three foodborne pathogens, and the difference between each section of the spindle and hand massaging was not significant (P > 0.05). This study demonstrated that the spindle apparatus can be an alternative device for detaching microorganisms from all fresh vegetable samples for microbiological analysis by the food processing industry.

Lipopolysaccharide directly stimulates Th17 differentiation in vitro modulating phosphorylation of RelB and NF-κB1.

Toll-like receptors (TLRs) recognize a wide range of pathogen-associated molecular patterns (PAMP) and are preferentially expressed in innate immune cells. TLR-mediated activation of these cells activates the adaptive immune system. However, it has become clear that TLRs are not only expressed but also functionally active in CD4 T cells. The intestines are continuously exposed to TLR ligands, including lipopolysaccharide (LPS), a TLR4 ligand, and TLR4 is expressed higher in Th17 cells than Th1 and Th2 cells. In addition, development of Th17 cells in the gut mucosa is more dependent on gut microbiota than Th1, Th2, and Treg. Thus, we examined whether LPS directly regulates Th17 differentiation. LPS directly stimulated Th17 differentiation in vitro. In Th17 cells, LPS increased phosphorylation of NF-κB1, resulting in an increase of p50, the processed form of NF-κB1, whereas it decreased phosphorylation of RelB, leading to the up-regulation of RelB. Subcutaneous injection of LPS increased the frequency of IL-17 producing cells in inguinal lymph nodes, worsening experimental autoimmune encephalomyelitis (EAE). Additionally, expression of TLR1, TLR2, TLR4, and TLR5 was reduced upon T cell activation and LPS showed modest effect on TLR4 expression. These findings provide the first evidence that TLR4 activation directly regulate Th17 differentiation.

3,3'-Diindolylmethane Inhibits Flt3L/GM-CSF-induced-bone Marrow-derived CD103(+) Dendritic Cell Differentiation Regulating Phosphorylation of STAT3 and STAT5.

The intestinal immune system maintains oral tolerance to harmless antigens or nutrients. One mechanism of oral tolerance is mediated by regulatory T cell (Treg)s, of which differentiation is regulated by a subset of dendritic cell (DC)s, primarily CD103(+) DCs. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays an important role in regulating immunity. The intestines are exposed to various AhR ligands, including endogenous metabolites and phytochemicals. It was previously reported that AhR activation induced tolerogenic DCs in mice or in cultures of bone marrow-derived DCs. However, given the variety of tolerogenic DCs, which type of tolerogenic DCs is regulated by AhR remains unknown. In this study, we found that AhR ligand 3,3'-diindolylmethane (DIM) inhibited the development of CD103(+) DCs from mouse bone marrow cells stimulated with Flt3L and GM-CSF. DIM interfered with phosphorylation of STAT3 and STAT5 inhibiting the expression of genes, including Id2, E2-2, IDO-1, and Aldh1a2, which are associated with DC differentiation and functions. Finally, DIM suppressed the ability of CD103(+) DCs to induce Foxp3(+) Tregs.