MicroRNA-320a enhances LRWD1 expression through the AGO2/FXR1-dependent pathway to affect cell behaviors and the oxidative stress response in human testicular embryonic carcinoma cells.

BACKGROUND: Testicular cancer is fairly rare but can affect fertility in adult males. Leucine-rich repeats- and WD repeat domain-containing protein 1 (LRWD1) is a sperm-specific marker that mainly affects sperm motility in reproduction. Our previous study demonstrated the impact of LRWD1 on testicular cancer development; however, the underlying mechanisms remain unclear. METHODS: In this study, various plasmids associated with LRWD1 and miR-320a manipulation were used to explore the roles and regulatory effects of these molecules in NT2D1 cellular processes. A Dual-Glo luciferin-luciferase system was used to investigate LRWD1 transcriptional activity, and qRT-PCR and western blotting were used to determine gene and protein expression. RESULTS: The results suggested that miR-320a positively regulated LRWD1 and positively correlated with NT2D1 cell proliferation but negatively correlated with cell migration and invasion ability. In addition, the miRNA-ribonucleoprotein complex AGO2/FXR1 was shown to be essential in the mechanism by which miR-320a regulates LRWD1 mRNA expression. As miR-320a was required to regulate LRWD1 expression through the AGO2 and FXR1 complex, eEF2 and eLF4E were also found to be involved in miR-320a increasing LRWD1 expression. Furthermore, miR-320a and LRWD1 were responsive to oxidative stress, and NRF2 was affected by the presence of miR-320a in response to ROS stimulation. CONCLUSIONS: This is the first study showing the role of miR-320a in upregulating the testicular cancer-specific regulator LRWD1 and the importance of the AGO2/FXR1 complex in miR-320a-mediated upregulation of LRWD1 during testicular cancer progression.

Causative microbes and antibiotic susceptibility of acute appendicitis in adults and children.

BACKGROUND: In recent years, some studies have found that acute uncomplicated appendicitis can be treated with antibiotics alone. Because of the lack of relevant research on treating acute appendicitis in Taiwan, this study investigated the microbiological characteristics of acute appendicitis to permit accurate empirical antibiotic use for uncomplicated appendicitis. METHODS: In this single-center retrospective cohort study, patients listed in the Taiwan National Health Insurance Research Database with a discharge diagnosis of acute appendicitis were identified. Data for bacterial specimens and antibiotic susceptibility tests among patients treated at Tri-Service General Hospital between January 2016 and December 2021 were analyzed. RESULTS: Among 2805 patients diagnosed with acute appendicitis, 167 (6%) were <18 years old. The culture positivity rates among children and adults were 33% and 18%, respectively. In total, 367 aerobes and 207 anaerobes were isolated. The predominant aerobic gram-positive coccus was viridans group streptococci (8.9%), the most common aerobic gram-negative bacillus was Escherichia coli (27.9%), and the most common anaerobic microorganism was Bacteroides spp. (27.7%). The results of antibiotic susceptibility testing of the predominant microorganisms revealed that 86.3% of gram-positive aerobes were susceptible to ampicillin, 76.3% of gram-negative aerobes were susceptible to gentamicin, and all anaerobic isolates were susceptible to metronidazole. CONCLUSION: Triple first-line antibiotic combination therapy, including ampicillin, gentamicin, and metronidazole, remains highly effective against the pathogens that cause acute appendicitis.

The risk factors, antimicrobial resistance patterns, and outcomes associated with extended-spectrum ß-lactamases-Producing pathogens in pediatric urinary tract infection.

BACKGROUND: Extended-spectrum ß-lactamases-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (ESBL-producing-EKP) are an increasingly common cause of childhood urinary tract infection (UTI) worldwide. Recognizing the risk factors and antimicrobial resistance patterns may guide new management in this population. METHODS: This is a retrospective cohort study of over 5 years in Taiwan (2017-2021). Inclusion criteria are hospitalized pediatric patients with the discharge diagnosis of UTI caused by E. coli, Klebsiella pneumoniae, or Proteus mirabilis. ESBL-producing-EKP and non-ESBL-producing-EKP UTI cases were reviewed for characteristics, urinary isolate antibiotics resistance, and clinical outcomes. RESULTS: The incidence rate of ESBL-producing-EKP UTI increased over the study period (Overall incidence rate: 14.1 %, 46/327 patients). Recent antibiotic therapy in ≤6 months (X2 = 11.83, p < 0.01) and a preterm gestational history (X2 = 8.11, p < 0.05) were associated with an increased risk. The proportion of patients with these two risk factors for ESBL acquisition were 37.5 % (X2 = 9.08, p < 0.05). The co-resistance rate of ESBL-producing-EKP to other antimicrobial agents was 63.0 % for gentamicin, 56.5 % for trimethoprim-sulfamethoxazole, 52.2 % for ciprofloxacin, 4.3 % for amikacin, and 2.2 % for imipenem. The generalized linear model analysis identified a significantly longer length of stay (ß: 2.85; 95 % confidence interval [CI]: 1.14-4.56; p < 0.01) and intensive care unit duration (ß: 5.86; 95 % CI: 1.59-10.12; p < 0.01) among patients with ESBL-producing-EKP UTI. CONCLUSION: Amikacin should be considered as an alternative antimicrobial choice beyond carbapenems for ESBL-producing-EKP UTI, especially in the context of carbapenem-resistant E. coli/Klebsiella pneumoniae (CRE/CRKP) emergence.

Critical pediatric neurological illness associated with COVID-19 (Omicron BA.2.3.7 variant) infection in Taiwan: immunological assessment and viral genome analysis in tertiary medical center.

OBJECTIVES: Since April 2022, another wave of the Omicron epidemic has struck Taiwanese society, and children with severe neurological complications have been reported frequently. A few cases even developed acute fulminant encephalitis. To investigate the possible causes of the increased incidence of such complications in Taiwan, we reviewed several cases of pediatric patients with severe neurological symptoms. METHODS: We collected the medical records of pediatric patients with COVID-19 infection who presented with severe neurological symptoms. The COVID-19 infection was diagnosed by nasal swab reverse transcriptase-polymerase chain reaction. The remaining samples were sent for whole genome sequencing and spike (S) protein amino acid variation mapping. RESULTS: The increase of several inflammatory markers was observed in all patients included in this study. However, none of the cerebrospinal fluid samples tested positive for SARS-CoV-2. The result of whole genome sequencing showed that all the sequences belonged to the lineage BA.2.3.7. However, the sequences had a K97E mutation in the S protein that differed from other BA.2.3.7 lineage strains, which was located at the S protein N-terminal domain. CONCLUSION: The new mutation in the S protein, which had not previously been observed but was discovered in this study, potentially explains the sudden increase in incidence of extremely adverse neurological symptoms in pediatric patients.

Spindle cell oncocytoma of the pituitary tumor: A rare case report and literature reviews.

Introduction: Spindle cell oncocytoma (SCO) of the pituitary gland is increasingly established with improvements in histological and immunohistochemical examination. However, the diagnosis was often mistaken based on imaging studies and nonspecific clinical manifestations. Purpose: This case is presented to provide an overview of the characteristics of the rare tumor as well as to demonstrate the difficulties in diagnosis and current treatments. Clinical discussion: The pathogenesis of SCO remains unclear, and a possible origin was described. Further research is needed to optimize pre-operative diagnosis and surgical strategy. Conclusion: SCO should be considered when images indicate some features. Gross total resection (GTR) after surgery seems to have better long-term tumor control, and radiotherapy may help decrease tumor progression in patients with non-GTR. Regular follow-up is advised because of the higher recurrence rate.

The Effect of Far-Infrared Therapy on the Peritoneal Expression of Glucose Degradation Products in Diabetic Patients on Peritoneal Dialysis.

Peritoneal dialysis (PD) is a treatment modality for end-stage renal disease (ESRD) patients. Dextrose is a common osmotic agent used in PD solutions and its absorption may exacerbate diabetes mellitus, a common complication of ESRD. PD solutions also contain glucose degradation products (GDPs) that may lead to encapsulating peritoneal sclerosis (EPS), a severe complication of PD. A previous study showed that far-infrared (FIR) therapy improved a patient's gastrointestinal symptoms due to EPS. Due to limited literature on the matter, this study aims to investigate dialysate GDPs and peritoneal function in diabetic patients on PD. Thirty-one PD patients were enrolled and underwent 40 min of FIR therapy twice daily for six months. We demonstrated the effect of FIR therapy on the following: (1) decrease of methylglyoxal (p = 0.02), furfural (p = 0.005), and 5-hydroxymethylfurfural (p = 0.03), (2) increase of D/D0 glucose ratio (p = 0.03), and (3) decrease of potassium levels (p = 0.008) in both DM and non-DM patients, as well as (4) maintenance and increase of peritoneal Kt/V in DM and non-DM patients, respectively (p = 0.03). FIR therapy is a non-invasive intervention that can decrease dialysate GDPs in PD patients by improving peritoneal transport rate and solute removal clearance, while also maintaining dialysis adequacy.

Annealing-Dependent Breakdown Voltage and Capacitance of Gallium Oxide-Based Gallium Nitride MOSOM Varactors.

Our laboratory has previously revealed the use of metal-semiconductor-metal (MSM) varactors against malicious pulses, as well as completed the related verification and measurements of such a circuit. To improve the reliability of this protection module further, in this study, we deposited a gallium oxide (Ga2O3) thin film in between the Schottky contact electrode to manufacture a metal-oxide-semiconductor-oxide-metal (MOSOM) varactor. However, the thin-film quality and heterojunction interfaces will affect these fabricated varactors in various ways, such as the asymmetry threshold voltage to the variable capacitance characteristics. This study aims to address the issues associated with the inserted oxide thin film, as well as to determine how improvements could be obtained by using an oxygen furnace annealing process. As a result, the breakdown voltage of the MOSOM varactor was further promoted and a more robust anti-surge module was thus realized.

Immunopathogenic Mechanisms and Novel Immune-Modulated Therapies in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease of unknown etiology. It is characterized by the presence of rheumatoid factor and anticitrullinated peptide antibodies. The orchestra of the inflammatory process among various immune cells, cytokines, chemokines, proteases, matrix metalloproteinases (MMPs), and reactive oxidative stress play critical immunopathologic roles in the inflammatory cascade of the joint environment, leading to clinical impairment and RA. With the growing understanding of the immunopathogenic mechanisms, increasingly novel marked and potential biologic agents have merged for the treatment of RA in recent years. In this review, we focus on the current understanding of pathogenic mechanisms, highlight novel biologic disease-modifying antirheumatic drugs (DMRADs), targeted synthetic DMRADs, and immune-modulating agents, and identify the applicable immune-mediated therapeutic strategies of the near future. In conclusion, new therapeutic approaches are emerging through a better understanding of the immunopathophysiology of RA, which is improving disease outcomes better than ever.

Targeting Ubiquitin Proteasome Pathway with Traditional Chinese Medicine for Treatment of Spinocerebellar Ataxia Type 3.

Nine autosomal dominant spinocerebellar ataxias (SCAs) are caused by an abnormal expansion of CAG trinucleotide repeats that encodes a polyglutamine (polyQ) tract within different genes. Accumulation of aggregated mutant proteins is a common feature of polyQ diseases, leading to progressive neuronal dysfunction and degeneration. SCA type 3 (SCA3), the most common form of SCA worldwide, is characterized by a CAG triplet expansion in chromosome 14q32.1 ATXN3 gene. As accumulation of the mutated polyQ protein is a possible initial event in the pathogenic cascade, clearance of aggregated protein by ubiquitin proteasome system (UPS) has been proposed to inhibit downstream detrimental events and suppress neuronal cell death. In this study, Chinese herbal medicine (CHM) extracts were studied for their proteasome-activating, polyQ aggregation-inhibitory and neuroprotective effects in GFPu and ATXN3/Q 75 -GFP 293/SH-SY5Y cells. Among the 14 tested extracts, 8 displayed increased proteasome activity, which was confirmed by 20S proteasome activity assay and analysis of ubiquitinated and fused GFP proteins in GFPu cells. All the eight extracts displayed good aggregation-inhibitory potential when tested in ATXN3/Q 75 -GFP 293 cells. Among them, neuroprotective effects of five selected extracts were shown by analyses of polyQ aggregation, neurite outgrowth, caspase 3 and proteasome activities, and ATXN3-GFP, ubiquitin, BCL2 and BAX protein levels in neuronal differentiated ATXN3/Q 75 -GFP SH-SY5Y cells. Finally, enhanced proteasome function, anti-oxidative activity and neuroprotection of catalpol, puerarin and daidzein (active constituents of Rehmannia glutinosa and Pueraria lobata) were demonstrated in GFPu and/or ATXN3/Q 75 -GFP 293/SH-SY5Y cells. This study may have therapeutic implication in polyQ-mediated disorders.

An investigation of vancomycin minimum inhibitory concentration creep among methicillin-resistant Staphylococcus aureus strains isolated from pediatric patients and healthy children in Northern Taiwan.

BACKGROUND AND PURPOSE: The phenomenon of vancomycin minimum inhibitory concentration (MIC) creep is an increasingly serious problem in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. In this study, we investigated the vancomycin and daptomycin MIC values of MRSA strains isolated from pediatric patients and MRSA colonized healthy children. Then, we assessed whether there was evidence of clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5 µg/mL. METHODS: We collected clinical MRSA isolates from pediatric patients and from healthy children colonized with MRSA during 2008-2012 at a tertiary medical center in northern Taiwan and obtained vancomycin and daptomycin MIC values using the Etest method. Pulse-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome (SCCmec) typing were used to assess clonal dissemination for strains with an MIC to vancomycin of ≥ 1.5 µg/mL. RESULTS: A total 195 MRSA strains were included in this study; 87 were isolated patients with a clinical MRSA infection, and the other 108 strains from nasally colonized healthy children. Vancomycin MIC≥1.5 µg/mL was seen in more clinical isolates (60/87, 69%) than colonized isolates (32/108, 29.6%), p < 0.001. The PFGE typing of both strains revealed multiple pulsotypes. CONCLUSION: Vancomycin MIC creeps existed in both clinical MRSA isolates and colonized MRSA strains. Great diversity of PFGE typing was in both strains collected. There was no association between the clinical and colonized MRSA isolates with vancomycin MIC creep.

Kawasaki disease shock syndrome: case report.

Kawasaki disease (KD) is a systemic vasculitis which presents with stable vital signs. Shock rarely occurs in such cases, but it may occur in the acute phase of KD. This report describes a 7-year-old boy with KD shock syndrome (KDSS) who presented with persistent fever, injected conjunctiva, a polymorphic skin rash, echocardiography indicating coronary artery dilatation, and shock. The patient's haemodynamic status markedly improved with immunoglobulin therapy. Early recognition of KDSS can be challenging; however, delay in diagnosis can increase the risk of coronary artery abnormalities and death.

Craniofacial reconstruction of primary osteogenic sarcoma of the skull.

BACKGROUND: Osteosarcoma of the skull is an extremely rare tumour. Because it has few symptoms initially, it usually presents after signs and symptoms of local invasion are present. Obtaining negative surgical margins is one of few modifiable survival factors. Resection of these invasive tumours is often limited by the ability to perform a reconstruction that is adequate in form and function. Despite this critical limitation, there are no articles describing reconstructive techniques used after resection of osteosarcoma of the skull. The purpose of this article is, therefore, to describe the reconstructive methods that can be used in the treatment of osteosarcoma of the skull. METHODS: A retrospective chart, photographic and radiological study was conducted of cases performed between 1986 and 2007. Tumour characteristics and reconstructive methods were compiled. RESULTS: Six patients were operated for osteosarcoma of the skull. The mean age at surgery was 27 years. Resection margins were positive in three cases. Bony reconstructive methods were split calvarial bone, iliac bone grafts and bone cement. Dural repair was made with a variety of materials. Complex deficits were repaired with rotation and free flaps. CONCLUSION: This article presents reconstructive methods used for reconstruction of skull defects left after resection of osteosarcoma of the skull. A variety of methods are available to repair complex deficits. Obtaining negative surgical margins is critical for survival. The ability to completely resect an invasive tumour is often limited by advances in reconstructive methods. Thus, progress in craniofacial reconstruction techniques warrant further investigations.