Insulin-like growth factor (IGF) and hepatocyte growth factor (HGF) in follicular fluid cooperatively promote the oncogenesis of high-grade serous carcinoma from fallopian tube epithelial cells: Dissection of the molecular effects.

Incessant ovulation is believed to be a potential cause of epithelial ovarian cancer (EOC). Our previous investigations have shown that insulin-like growth factor (IGF2) and hepatocyte growth factor (HGF) in the ovulatory follicular fluid (FF) contributed to the malignant transformation initiated by p53 mutations. Here we examined the individual and synergistic impacts of IGF2 and HGF on enhancing the malignant properties of high-grade serous carcinoma (HGSC), the most aggressive type of EOC, and its precursor lesion, serous tubal intraepithelial carcinoma (STIC). In a mouse xenograft co-injection model, we observed that FF co-injection induced tumorigenesis of STIC-mimicking cells, FE25. Co-injection with IGF2 or HGF partially recapitulated the tumorigenic effects of FF, but co-injection with both resulted in a higher tumorigenic rate than FF. We analyzed the different transformation phenotypes influenced by these FF growth signals through receptor inhibition. The IGF signal was necessary for clonogenicity, while the HGF signal played a crucial role in the migration and invasion of STIC and HGSC cells. Both signals were necessary for the malignant phenotype of anchoring-independent growth but had little impact on cell proliferation. The downstream signals responsible for these HGF activities were identified as the tyrosine-protein kinase Met (cMET)/mitogen-activated protein kinase and cMET/AKT pathways. Together with the previous finding that the FF-IGF2 could mediate clonogenicity and stemness activities via the IGF-1R/AKT/mammalian target of rapamycin and IGF-1R/AKT/NANOG pathways, respectively, this study demonstrated the cooperation of the FF-sourced IGF and HGF growth signals in the malignant transformation and progression of HGSC through both common and distinct signaling pathways. These findings help develop targeted prevention of HGSC.

Effect of ovulation IGF and HGF signaling on the oncogenesis of murine epithelial ovarian cancer cell ID8.

The incidence and mortality of epithelial ovarian cancer (EOC) are increasing in Taiwan and worldwide. The prognosis of this disease has improved little in the last few decades due to insufficient knowledge of the etiology. Previous studies on the role of ovulation in the development of EOC have unveiled IGF2, HGF, and other carcinogens in ovulatory follicular fluid (FF) that exert transformation activities on the exposed fallopian tube fimbria epithelium. However, an orthotopic proof in an animal model is lacking. By using the murine ID8 EOC cells and the syngenic transplantation model, this study explored the effect of FF on the oncogenesis of mouse ovarian cancer. We found FF promoted clonogenicity and anchorage-independent growth of ID8 cells, largely through the IGF-1R and cMET signaling. In contrast, FF modestly promoted cell proliferation independent of the two signals and did not affect cell migration and invasion. Transplantation of ID8 cells into the ovarian bursa of C57BL6/J mice orthotopically grew ovarian tumors and metastasized to the peritoneum with ascites formation. The tumorigenic rate and severity of the disease were positively correlated with the level of IGF-1R and cMET receptors on the cell surface. Our data demonstrated that ovulation, through the signaling of IGF/IGF-1R and HGF/cMET, promotes oncogenic phenotypes in a murine EOC model. The results provide further proof of the carcinogenic effect of ovulation in the development of EOC.

Application of Deep Learning Techniques for Detection of Pneumothorax in Chest Radiographs.

With the advent of Artificial Intelligence (AI) and even more so recently in the field of Machine Learning (ML), there has been rapid progress across the field. One of the prominent examples is image recognition in the medical category, such as X-ray imaging, Computed Tomography (CT), and Magnetic Resonance Imaging (MRI). It has the potential to alleviate a doctor's heavy workload of sifting through large quantities of images. Due to the rising attention to lung-related diseases, such as pneumothorax and nodules, ML is being incorporated into the field in the hope of alleviating the already strained medical resources. In this study, we proposed a system that can detect pneumothorax diseases reliably. By comparing multiple models and hyperparameter configurations, we recommend a model for hospitals, as its focus on minimizing false positives aligns with the precision required by medical professionals. Through our cooperation with Poh-Ai Hospital, we acquired a total of over 8000 X-ray images, with more than 1000 of them from pneumothorax patients. We hope that by integrating AI systems into the automated process of scanning chest X-ray images with various diseases, more resources will be available in the already strained medical systems. Our proposed system showed that the best model that is used for transfer learning from our dataset performed with an AP of 51.57 and an AP75 of 61.40, with accuracy at 93.89%, a false positive of 1.12%, and a false negative of 4.99%. Based on the feedback from practicing doctors, they are more wary of false positives. For their use case, we recommend another model due to the lower false positive rate and higher accuracy compared with other models, which in our test shows a rate of only 0.88% and 95.68%, demonstrating the feasibility of the research. This promising result showed that it could be utilized in other types of diseases and expand to more hospitals and medical organizations, potentially benefitting more people.

Methicillin-resistant Staphylococcus aureus nasal colonization among HIV-infected patients in Taiwan: prevalence, molecular characteristics and associated factors with nasal carriage.

BACKGROUND: To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan. METHODS: From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized. RESULTS: Of 553 patients surveyed, methicillin-susceptible S. aureus (MSSA) was detected in 119 subjects (21.5%) and MRSA in 19 subjects (3.4%). Female gender, injection drug use, smoking, hepatitis C virus carrier, cancer and antibiotic use within 1 year were positively associated with MRSA colonization. By multivariate analysis, only cancer (adjust odds ratio (aOR) 7.78, [95% confidence interval (CI), 1.909-31.731]) and antibiotic use within 1 year (aOR 3.89, [95% CI, 1.219-12.433]) were significantly associated with MRSA colonization. Ten isolates were characterized as sequence type (ST) 59/staphylococcal chromosome cassette (SCC) IV or VT, endemic community strains in Taiwan, four isolates as ST 8/SCCmec IV (USA 300) and one isolate as ST 239/SCCmec IIIA, a hospital strain. All the community-associated MRSA isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). CONCLUSIONS: Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroquinolones. Cancer and antibiotic use within 1 year were associated with MRSA colonization.

Clinical utility of FDG PET/CT in acute complicated pyelonephritis-results from an observational study.

BACKGROUND: Acute complicated pyelonephritis (ACP) is an upper urinary tract infection associated with coexisting urinary tract abnormalities or medical conditions that could predispose to serious outcomes or treatment failures. Although CT and magnetic resonance imaging (MRI) are frequently used in patients with ACP, the clinical value of 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) has not been systematically investigated. This single-center retrospective study was designed to evaluate the potential usefulness of FDG PET/CT in patients with ACP. METHODS: Thirty-one adult patients with ACP who underwent FDG PET/CT were examined. FDG PET/CT imaging characteristics, including tracer uptake patterns, kidney volumes, and extrarenal imaging findings, were reviewed in combination with clinical data and conventional imaging results. RESULTS: Of the 31 patients, 19 (61%) showed focal FDG uptake. The remaining 12 study participants showed a diffuse FDG uptake pattern. After volumetric approximation, the affected kidneys were found to be significantly enlarged. Patients who showed a focal uptake pattern had a higher frequency of abscess formation requiring drainage. ACP patients showing diffuse tracer uptake patterns had a more benign clinical course. Seven patients had suspected extrarenal coinfections, and FDG PET/CT successfully confirmed the clinical suspicion in five cases. FDG PET/CT was as sensitive as CT in identifying the six patients (19%) who developed abscesses. Notably, FDG PET/CT findings caused a modification to the initial antibiotic regimen in nine patients (29%). CONCLUSIONS: FDG PET/CT may be clinically useful in the assessment of patients with ACP who have a progressive disease course.

Characterization of two novel variants of staphylococcal cassette chromosome mec elements in oxacillin-resistant Staphylococcus lugdunensis.

OBJECTIVES: Staphylococcus lugdunensis, a species of CoNS, has become an important hospital pathogen because of increasing resistance to ß-lactam antibiotics such as methicillin and oxacillin. Methicillin resistance is mainly due to the acquisition of the staphylococcal cassette chromosome (SCC) mec (SCCmec). Little is known about the structure of SCCmec in methicillin- or oxacillin-resistant CoNS. METHODS: WGS was performed to determine the structure of SCCmec elements of two clinical S. lugdunensis isolates: CMUH-22 and CMUH-25. RESULTS: These elements were found to be flanked by DRs and IRs with unique mosaic structures and a common integration site in the 3' end of the rlmH gene. The sequences of the regions located between rlmH and the ISSau4-like transposase genes of both elements were similar to those of SCCmec Vt of Staphylococcus aureus PM1. The SCCmec (type V, 5C2&4) of CMUH-25 harboured a novel ccrC complex and a C2-like mec complex in opposite orientations, similar to the type V SCCmec of S. aureus WIS. The sequences of the ccrA4B4 genes and J1 and J2 regions of CMUH-25 were similar to those of the SCC element of Staphylococcus haemolyticus NCTC 11042. In contrast, portions of the sequence of the J1 region of type Vt (5C2) SCCmec in strain CMUH-22 were highly similar to portions of those of Staphylococcus epidermidis RP62A and the composite SCCmec type V of S. aureus WAMRSA40. CONCLUSIONS: These observations suggest that the SCCmec elements of CMUH-25 and CMUH-22 evolved separately and assembled through different recombination events.

Development of carbapenem resistance in Pseudomonas aeruginosa is associated with OprD polymorphisms, particularly the amino acid substitution at codon 170.

Objectives: Pan-susceptible Pseudomonas aeruginosa (PSPA) clinical isolates carrying an OprD with loop 7 shortening (the group-1A allele) were found to rapidly develop carbapenem resistance under continuous selection pressure. We further studied whether OprD polymorphisms are associated with the potential to develop carbapenem resistance. Methods: OprD amino acid sequences of 126 PSPA clinical isolates were analysed to determine their STs using P. aeruginosa strain PAO1 as the control strain. Site-directed mutagenesis was performed in PAO1 to generate polymorphisms of interest. A disc diffusion method was used to select carbapenem-resistant variants from the mutant strains. Expression levels of oprD were determined by quantitative RT-PCR. MICs of carbapenems were determined by Etest. Results: Forty-eight (38.1%) of the tested isolates carried the group-1A allele. Another two major STs, C1 and C2, both of which harboured an F170L polymorphism, were found in 21 (16.7%) and 39 (31.0%) isolates, respectively. The PAO1 type was also found in 14 (11.1%) isolates. Under continuous selective pressure, isolates of most STs developed carbapenem resistance at different numbers of passaging events; only those belonging to the PAO1 type remained susceptible. However, PAO1 mutants carrying either the oprD group-1A allele or the OprD-F170L polymorphism were able to develop carbapenem resistance. Reduced oprD expression triggered by continuous imipenem challenge was found in PAO1 mutants, but not in the PAO1 WT strain. Conclusions: OprD polymorphisms, particularly the F170L substitution and the specific shortening in loop 7, appear to determine the potential for P. aeruginosa to develop carbapenem resistance.

Influence of borderline cefepime MIC on the outcome of cefepime-susceptible Pseudomonas aeruginosa bacteremia treated with a maximal cefepime dose: a hospital-based retrospective study.

BACKGROUND: We assessed the influence of current cefepime minimal inhibitory concentration (MIC) breakpoints and the maximal cefepime dose on treatment outcomes in patients with bacteremia caused by cefepime-susceptible Pseudomonas aeruginosa. METHODS: Adult patients hospitalized between July 2010 and June 2014 with a positive blood culture for cefepime-susceptible P. aeruginosa and receipt of cefepime as the primary therapy throughout the course were reviewed. Cefepime Etest® MICs and clinical outcomes for P. aeruginosa bacteremia were reviewed to identify the MIC breakpoint influencing treatment outcomes. RESULTS: Of the 90 patients enrolled, 49 (54.4%) were male (mean age = 66.8 years). The mean Acute Physiology and Chronic Health Evaluation II score was 22.01. Sixty patients (66.7%) received a maximal cefepime dose, and the 30-day crude mortality rate was 36.7%. MIC90 of cefepime for P. aeruginosa was 8 mg/L. The cumulative survival rate at 30 days revealed that a lower cefepime MIC (<4 mg/L) for P. aeruginosa was associated with a higher survival rate than a higher MIC (≥4 mg/L) (72.6% vs. 23.5%, p < 0.0001). A cefepime MIC of ≥4 mg/L and age were independent risk factors for mortality, whereas the maximal cefepime dose was the independent protective factor. The use of a maximal cefepime dose did not improve the outcomes of patients with P. aeruginosa bacteremia at a MIC of ≥4 mg/L. CONCLUSIONS: A cefepime MIC of 4 mg/L may predict an unfavorable outcome among patients with serious infections caused by P. aeruginosa, even the MICs still within the CLSI susceptibility breakpoint.

Early surgery with antibiotics treatment had better clinical outcomes than antibiotics treatment alone in patients with pyogenic spondylodiscitis: a retrospective cohort study.

BACKGROUND: Pyogenic spondylodiscitis is a form of spinal infection that can result in severe back pain and even death. However, information is lacking on the relative effectiveness of various therapies. A retrospective chart review was conducted to investigate whether early surgical treatment of pyogenic spondylodiscitis coupled with intravenous antibiotics results in better patient prognoses than intravenous antibiotics therapy alone. METHODS: All patients treated for pyogenic spondylodiscitis at a single medical center from July 2006 to July 2011 were retrospectively reviewed. The inclusion criteria consisted of diagnosis of an early stage infection without neurological deficit, and patients without severe sepsis who were suitable candidates for early surgery as determined by a Pittsburgh bacteremia score < 4, and patients with delayed diagnosis and lost to outpatient follow-up were excluded. Clinical outcomes included patient demographic data, kyphosis angle, length of treatment, Oswestry Disability Index and visual analogue pain scale were analyzed. RESULTS: Of 90 enrolled patients, Group 1 (n = 47) received only antibiotic therapy and Group 2 (n = 43) received early surgery with post-surgery antibiotics for 2 to 4 weeks. Group 2 exhibited significantly better results than Group 1 for mean antibiotic administration period, mean hospitalization period, kyphotic angle correction. Of 61 patients who participated in telephone follow-up after discharge, Group 2 (n = 26) had significant lower mean ODI score, and mean back pain score than Group 1 (n = 35). CONCLUSIONS: While infection control was similar for both groups, patients treated with early surgery and antibiotics were hospitalized for fewer days and required less antibiotics than those treated with antibiotics alone, also having better functional outcomes. In short, early surgical treatment of pyogenic spondylodiscitis typically achieves a better prognosis, shorter hospitalization period, and subsequent significant improvement in kyphotic deformity and quality of life.

Tigecycline-based versus sulbactam-based treatment for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex.

BACKGROUND: The treatment options for pneumonia involving multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (MDR Acb) complex are limited, and the optimal treatment has not been established. METHODS: To compare the efficacy of tigecycline-based with sulbactam (or ampicillin/sulbactam)-based therapy for pneumonia involving MDR Acb complex, we conducted a retrospective study comparing 84 tigecycline-treated adult patients during the period August 2007 to March 2010 with 84 sulbactam or ampicillin/sulbactam-treated adult patients during the period September 2004 to July 2007. Both groups had the matched Acute Physiology and Chronic Health Evaluation (APACHE) II score and received treatment for at least 7 days. RESULTS: The mean APACHE II score was 20.1 for both groups. More patients in sulbactam group had ventilator use (89.3 % versus 69.0 %), bilateral pneumonia (79.8 % versus 60.7 %) and combination therapy (84.5 % versus 53.6 %), particularly with carbapenems (71.4 % versus 6.0 %), while more patients in tigecycline group had delayed treatment (41.7 % versus 26.2 %) (P <0.05). At the end of treatment, more patients in sulbactam group had airway MDR Acb complex eradication (63.5 % versus 33.3 %, P <0.05). The clinical resolution rate was 66.7 % for both groups. The mortality rate during treatment was 17.9 % in sulbactam group, and 25.0 % in tigecycline group (P = 0.259). The multivariate analysis showed that bilateral pneumonia was the only independent predictor for mortality during treatment (adjusted odds ratio, 2.717; 95 % confidence interval, 1.015 to 7.272). CONCLUSIONS: Patients treated with either tigecycline-based or sulbactam-based therapy had a similar clinical outcome, but tigecycline group had a lower microbiological eradiation rate.

Agreement assessment of tigecycline susceptibilities determined by the disk diffusion and broth microdilution methods among commonly encountered resistant bacterial isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2008 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n = 736), and Acinetobacter baumannii (n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC(90) values of tigecycline against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 µg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

Trends in susceptibility of vancomycin-resistant Enterococcus faecium to tigecycline, daptomycin, and linezolid and molecular epidemiology of the isolates: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006 to 2010.

Among the 219 vancomycin-resistant Enterococcus faecium isolates collected in 20 Taiwanese hospitals from 2006 to 2010, all were susceptible to linezolid and daptomycin, and 98.6% were susceptible to tigecycline. There was a shift toward higher tigecycline MIC values (MIC(90)s) from 2006-2007 (0.06 µg/ml) to 2008-2010 (0.12 µg/ml). The MIC(90)s of daptomycin and linezolid remained stationary. Although pulsotypes among the isolates from the 20 hospitals varied, intrahospital spreading of several clones was identified in 13 hospitals.

Trends in the susceptibility of clinically important resistant bacteria to tigecycline: results from the Tigecycline In Vitro Surveillance in Taiwan study, 2006 to 2010.

The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) (n = 1,834), penicillin-resistant Streptococcus pneumoniae (PRSP) (n = 423), vancomycin-resistant enterococci (VRE) (n = 219), extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (n = 1,141), ESBL-producing Klebsiella pneumoniae (n = 1,330), Acinetobacter baumannii (n = 1,645), and Stenotrophomonas maltophilia (n = 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC(90), 0.03 µg/ml), and only one MRSA isolate (MIC(90), 0.5 µg/ml) and three VRE isolates (MIC(90), 0.125 µg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producing E. coli (MIC(90), 0.5 µg/ml) and 96.32% for ESBL-producing K. pneumoniae (MIC(90), 2 µg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate for A. baumannii (MIC(90), 4 µg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptible A. baumannii isolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptible A. baumannii isolates. In Taiwan, tigecycline continues to have excellent in vitro activity against several major clinically important drug-resistant bacteria, with the exception of A. baumannii.

Influence of teicoplanin MICs on treatment outcomes among patients with teicoplanin-treated methicillin-resistant Staphylococcus aureus bacteraemia: a hospital-based retrospective study.

OBJECTIVES: Higher vancomycin MIC values (≥1.5 mg/L via Etest) may be associated with vancomycin treatment failure among patients with serious methicillin-resistant Staphylococcus aureus (MRSA) infections. As there were limited similar data for teicoplanin, this retrospective cohort study intended to determine the predictive value of teicoplanin MICs for treatment failure among patients with MRSA bacteraemia. PATIENTS AND METHODS: All patients with at least one blood culture positive for MRSA admitted to the hospital between January 2010 and January 2011 were reviewed. Patients with an age ≥18 years and receipt of teicoplanin therapy throughout the course or receipt of <72 h of vancomycin therapy and then teicoplanin for >3 days were enrolled. Teicoplanin Etest(®) MICs and treatment outcomes for MRSA bacteraemia were reviewed to identify the breakpoint of teicoplanin MICs influencing treatment outcomes. RESULTS: Of the 101 patients enrolled, 56 had a lower teicoplanin MIC (≤1.5 mg/L) for MRSA and 45 had a higher MIC (>1.5 mg/L) for MRSA. A lower teicoplanin MIC was associated with a favourable outcome [37 (66.1%) versus 13 (28.9%); P<0.001] and a lower rate of bloodstream infection-related mortality [15 (26.8%) versus 22 (48.9%); P=0.022]. Patients with chronic obstructive pulmonary disease, bacteraemic pneumonia or higher Pittsburgh bacteraemia score had an unfavourable outcome (P=0.028, 0.022 and <0.001, respectively). Multivariate analysis showed that teicoplanin MIC >1.5 mg/L, higher Pittsburgh bacteraemia score and bacteraemic pneumonia were independent risk factors for unfavourable outcome. CONCLUSIONS: A higher teicoplanin MIC value (>1.5 mg/L) may predict an unfavourable outcome and higher mortality rate among teicoplanin-treated MRSA bacteraemic patients.

Disseminated Mycobacterium peregrinum and Mycobacterium avium infection in a patient with AIDS: A case report and review of literature.

Disseminated nontuberculous mycobacterial infections are frequently recognized in patients living with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS) and Mycobacterium avium-intracellulare complex (MAIC) is the most common species. Mycobacterium peregrinum is a rapidly growing mycobacterium that accounts for 1-2% of community-acquired and healthcare-associated infections. It mainly causes skin and soft tissue infection. Disseminated infection by M. peregrinum has never been reported in patients with AIDS. We describe a case of disseminated co-infection of M. peregrinum and M. avium in a 33-year-old male with newly diagnosed AIDS, and review the literature regarding M. peregrinum infection. The patient's bone marrow culture grew M. peregrinum and his blood culture grew M. avium. The diagnosis of disseminated co-infection of M. peregrinum and M. avium was confirmed. Disseminated infection due to M. peregrinum is rare and diagnosis can be challenging. Due to limited case numbers, there is no treatment guideline for M. peregrinum nowadays. Further study is warranted for better understanding M. peregrinum related infections.

Exploiting the Nanostructural Anisotropy of ß-Ga2O3 to Demonstrate Giant Improvement in Titanium/Gold Ohmic Contacts.

Here we demonstrate a dramatic improvement in Ti/Au ohmic contact performance by utilizing the anisotropic nature of ß-Ga2O3. Under a similar doping concentration, Ti/Au metallization on (100) Ga2O3 shows a specific contact resistivity 5.11 × 10-5 Ω·cm2, while that on (010) Ga2O3 is as high as 3.29 × 10-3 Ω·cm2. Temperature-dependent contact performance and analyses suggest that field emission or thermionic field emission is the dominant charge transport mechanism across the Ti/Au-(100) Ga2O3 junction, depending on whether reactive ion etching was used prior to metallization. Cross-sectional high-resolution microscopy and elemental mapping analysis show that the in situ-formed Ti-TiOx layer on (100) Ga2O3 is relatively thin (2-2.5 nm) and homogeneous, whereas that on (010) substrates is much thicker (3-5 nm) and shows nanoscale facet-like features at the interface. The anisotropic nature of monoclinic Ga2O3, including anisotropic surface energy and mass diffusivity, is likely to be the main cause of the differences observed under microscopy and in electrical properties. The findings here provide direct evidence and insights into the dependence of device performance on the atomic-scale structural anisotropy of ß-Ga2O3. Moreover, the investigative strategy here─combining comprehensive electrical and materials characterization of interfaces on different semiconductor orientations─can be applied to assess a variety of other anisotropic oxide junctions.

Acute encephalitis after COVID-19 vaccination: A case report and literature review.

Vaccine-related immune responses are one of the causes of encephalitis. Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) have been administered worldwide due to the ongoing global pandemic; cases of SARS-CoV-2 vaccination-related encephalitis were scarcely reported. An 82-year-old female was diagnosed with acute encephalitis following her first dose of vaccination with mRNA-1273 against SARS-CoV-2. The patient presented with fever and headache five days after vaccination, followed by behavior change 17 days after vaccination. Electroencephalographic recordings revealed focal slow waves in the right frontoparietal regions. Brain MRI revealed the signal change in the right middle and posterior temporal lobe. Cerebrospinal fluid analysis showed mildly elevated protein. She responded well to steroid pulse therapy and made a full recovery. The severity of the immune response following COVID-19 vaccination may be alleviated if adequate treatment is achieved. Physicians must be alert for encephalitis after vaccination to help ensure a favorable outcome.

Coexistence of fatal disseminated invasive aspergillosis and pyoderma gangrenosum: a case report.

OBJECTIVE: To report an unusual case of disseminated aspergillosis involving the lymph nodes, lungs, and skin in a patient with pyoderma gangrenosum (PG) and myelodysplastic syndrome (MDS). CASE PRESENTATION AND INTERVENTION: A 46-year-old man presented with productive cough of 2 weeks' duration. Besides, several painless, fixed lymph nodes were palpated at his left neck. He had PG and MDS diagnosed in June 2004 with regular use of oral dapsone and prednisolone. His skin lesions healed with scar formation and no purulent discharge. A computed tomography scan of the head, neck and chest showed bilateral lung consolidation and abscesses at the left neck, right upper lung and right pleura. The neck abscess culture grew Aspergillus species. Dark reddish macules developed over the right arm, chest and abdominal wall, and the left lower limb 2 weeks after initiation of amphotericin B. The histology of the right arm skin biopsy showed invasive aspergillosis. Caspofungin was started then for suspicion of poor response to amphotericin B. He expired despite 35 days of antifungal therapy. CONCLUSION: This report highlights the rarity of coexistence of disseminated aspergillosis and PG, and should alert physicians to the possibility of invasive fungal infection superimposed on a chronic skin lesion.

Insuline-Like Growth Factor-2 (IGF2) and Hepatocyte Growth Factor (HGF) Promote Lymphomagenesis in p53-null Mice in Tissue-specific and Estrogen-signaling Dependent Manners.

Background: Trp53-/- mice are prone to develop lymphomas at old ages. Factors promoting this tumorigenesis are unknown. Here, we showed human ovulatory follicular fluid (FF) largely promotes lymphomagenesis in Trp53-/- mice at earlier ages. Meanwhile, we clarified that IGF2 and HGF are important cell transforming factors within FF. Methods: To induce tumor formation, 5% FFs, 100 ng/ml IGF2, 20 ng/ml HGF, or both IGF2 and HGF in a volume of 200 µl PBS, was injected into 8-wk-old female Trp53 -/- mice at the mammary fat pad. The injection was repeated weekly for up to 7 weeks or extending to 13 weeks to observe the accumulative incidence of lymphomagenesis. Immunohistochemistry staining and gene rearrangement analysis were used to identify the tumor type. Results: By injecting FF into the mammary fat pad weekly, lymphomas developed in 8/16 (50%) of mice by seven weeks. We identified IGF2 and HGF in FF is largely responsible for this activity. The same weekly injection of IGF2, HGF, and their combination induced lymphomas in 4/11 (36%), 3/8 (38%), and 6/9 (67%) mice, respectively. Interestingly, tumorigenesis was induced only when those were injected into the adipose tissues in the mammary gland, but not when injected into non-adipose sites. We also found this tumor-promoting activity is estradiol (E2)-dependent and relies on estrogen receptor (ER) α expression in the adipose stroma. No tumor or only tiny tumor was yielded when the ovaries were resected or when ER is antagonized. Finally, an extension of the weekly FF-injection to 13 weeks did not further increase the lymphomagenesis rate, suggesting an effect on pre-initiated cancer cells. Conclusions: Taken together, the study disclosed a robust tumor-promoting effect of IGF2 and HGF in the p53 loss-initiated lymphomagenesis depending on an adipose microenvironment in the presence of E2. In light of the clarity of this spontaneous tumor promotion model, we provide a new tool for studying p53-mediated lymphomagenesis and suggest that, as a chemoprevention test, this is a practical model to perform.

Ovulation sources coagulation protease cascade and hepatocyte growth factor to support physiological growth and malignant transformation.

The fallopian tube fimbrial epithelium, which is exposed to the follicular fluid (FF) contents of ovulation, is regarded as the main origin of ovarian high-grade serous carcinoma. Previously, we found that growth factors in FF, such as IGF2, are responsible for the malignant transformation of fallopian tube epithelium. However, ovulation is a monthly transient event, whereas carcinogenesis requires continuous, long-term exposure. Here, we found the transformation activity of FF sustained for more than 30 days after drainage into the peritoneal fluid (PF). Hepatocyte growth factor (HGF), activated through the ovulation injury-tissue factor-thrombin-HGF activator (HGFA)-HGF cleavage cascade confers a sustained transformation activity to fallopian tube epithelium, high-grade serous carcinoma. Physiologically, the high reserve of the coagulation-HGF cascade sources a sustained level of HGF in PF, then to the blood circulation. This HGF axis promotes the growth of the corpus luteum and repair of tissue injury after ovulation.