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Background: Extended-spectrum β-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

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

IntroductionFollowing acute enterovirus (EV) infection, outcomes vary based on factors like the immune response, viral cell entry receptor expression levels, tissue tropism, and genetic factors of both the host and virus. While most individuals exhibit mild, self-limited symptoms, others may suffer severe complications or prolonged infections that can lead to autoimmune disorders.MethodsTo elucidate host responses to EV infection, we performed whole exome sequencing on blood samples from both infected and uninfected individuals. Our initial focus was on genes encoding EV entry receptors—PSGL-1, SCARB2, and ANAXA2 for EV-A71, and CD155 for poliovirus—and on host genes ACBD3 and PI4KΒ, crucial for EV replication.ResultsAlthough no specific genetic variants directly associated with EV infection were identified, we discovered 118 variants across 116 genes enriched in East Asian populations through multi-layered variant filtering. These variants were further analyzed for their potential impacts on organs, biological processes, and molecular pathways. Phenome-wide association studies were conducted to refine our understanding of their contributions to EV infection susceptibility.DiscussionOur findings aim to develop a predictive panel based on these 118 variants, which could help susceptible individuals during EV outbreaks, guiding targeted clinical interventions and preventative strategies.

Leiomyomas, also known as fibroids, are benign tumors originating from smooth muscle and can arise in soft tissue, most commonly in the uterus or bladder. Those that arise in the extremities usually form subcutaneous masses. Leiomyoma of the foot has rarely been reported, and leiomyoma of the ankle is even rarer. A 52-year-old male presented with a tender nodule on the lateral aspect of his right ankle. The tumor was surgically excised and was shown to be a leiomyoma.

Background: Dedifferentiated fat cells (DFATs) are highly homogeneous and multipotent compared with adipose-derived stromal cells (SCs). Infrapatellar fat pad (IFP)–SCs have advanced chondrogenic potency; however, whether IFP-DFATs could serve as better cell material remains unclear. Here, we aimed to examine the influence of age and body mass index (BMI) on the features of IFPs and IFP-derived cells (IFP–SCs and IFP-DFATs) with exploration of the clinical utilization of IFP-DFATs. Methods: We collected IFPs with isolation of paired IFP-SCs and IFP-DFATs from individuals aged 65 years and older with distinct body weights who underwent total knee replacement for osteoarthritis (OA). Flow cytometry was used to characterize the cellular immunophenotypes. Adipogenesis and chondrogenesis were performed in vitro. Real-time qPCR, western blotting, and Oil Red O or Alcian blue staining were performed to evaluate inflammation, adipogenesis, and chondrogenesis. RNA sequencing and Seahorse analyses were conducted to explore the underlying mechanisms. Results: We found that IFPs from old or normal-weight individuals with knee OA were pro-inflammatory, and that interleukin-6 (IL-6) signaling was associated with multiple immune-related molecules, whereas IFP-derived cells could escape the inflammatory properties. Aging plays an important role in diminishing the chondrogenic and adipogenic abilities of IFP-SCs; however, this effect was avoided in IFP-DFATs. Generally, IFP-DFATs presented a steady state of chondrogenesis (less influenced by age) and consistently enhanced adipogenesis compared to paired IFP-SCs in different age or BMI groups. RNA sequencing and Seahorse analysis suggested that the downregulation of eukaryotic initiation factor 2 (EIF2) signaling and enhanced mitochondrial function may contribute to the improved cellular biology of IFP-DFATs. Conclusions: Our data indicate that IFP-DFATs are superior cell material compared to IFP-SCs for cartilage differentiation and adipogenesis, particularly in advanced aging patients with knee OA. The translational potential of this article: These results provide a novel concept and supportive evidence for the use of IFP-DFATs for cell therapy or tissue engineering in patients with knee OA. Using Ingenuity Pathway Analysis (IPA) of RNA-seq data and Seahorse analysis of mitochondrial metabolic parameters, we highlighted that some molecules, signaling pathways, and mitochondrial functions are likely to be jointly coordinated to determine the enhanced biological function in IFP-DFATs.

Objectives Various treatment options are available for degenerative joint disease (DJD). During clinical visits, patients and clinicians collaboratively make decisions regarding the optimal treatment for DJD; this is the essence of shared decision-making (SDM). Here, we collated and assessed the SDM-related experiences and perspectives of outpatients with DJD in Taiwan.Design In-depth interviews and thematic analysis.Setting Primary care clinics of a regional teaching hospital in Taiwan, October 2021–May 2022.Participants 21 outpatients with at least three visits for DJD and who were aware of SDM.Results Four main themes emerged in this study: first, equipping themselves with knowledge: outpatients obtained disease-related and treatment-related knowledge in various ways—seeking relevant information online, discussing with family and friends, learning from their own experiences or learning from professionals. Second, shared or not shared: physicians had different patterns for communicating with patients, particularly when demonstrating authority, performing mutual discussion, respecting patient preferences or responding perfunctorily. Third, seldom saying no to physician-prescribed treatment plans during clinical visits: most patients respected physicians’ professionalism; however, some patients rejected physicians’ recommendations indirectly, whereas some responded depending on their disease prognosis. Fourth, whose call?—participants decided to accept or reject a treatment plan independently or by discussing it with their families or by obeying their physicians’ recommendations.Conclusions In general, patients with DJD sought reliable medical information from various sources before visiting doctors; however, when having a conversation with patients, physicians dominated the discussion on treatment options. The patient–physician interaction dynamics during the SDM process determined the final medical decision, which was in accordance with either patients’ original autonomy or physicians’ recommendations. To alleviate medical paternalism and physician dominance, patients should be empowered to engage in medical decision-making and share their opinions or concerns with their physicians. Family members should also be included in SDM.

There is the minimal restriction to users’ speech in cyberspace. The Internet provides a space where people can freely present their speech, which puts a Utopian sense of freedom of speech into practice. However, the appearance of hate speech is a significant side effect of online freedom of speech. Some users use hate speech to attack others, making the attacked targets uncomfortable. The proliferation of hate speech poses severe challenges to cyber society. Users may hope that social media platforms and online communities promote anti-hate speech. However, hate speech detection is still a developing technology that requires system developers to create a method to detect unacceptable hate speech while maintaining the online freedom of speech environment. No excellence detection approach has yet been proposed, although some literature has focused on it. The current study proposes an approach to build a political hate speech lexicon and train artificial intelligence classifiers to detect hate speech. Our academic and practical contributions include the collection of a Chinese hate speech dataset, creating a Chinese hate speech lexicon, and developing both a deep learning-based and a lexicon-based approach to detect Chinese hate speech. Although we focus on Chinese hate speech detection, our proposed hate speech detection system and hate speech lexicon development approach can also be used for other languages.

Morganella morganii is a rare cause of neonatal infections, and early-onset neonatal sepsis caused by M. morganii is serious and even fatal. We describe an extremely low birth weight female infant with early-onset M. morganii sepsis to highlight the importance of awareness of this potentially fatal organism.

Abstract Background Leiomyosarcoma (LMS), the most common soft tissue sarcoma, exhibits heterogeneous and complex genetic karyotypes with severe chromosomal instability and rearrangement and poor prognosis. Methods Clinical variables associated with NKX6-1 were obtained from The Cancer Genome Atlas (TCGA). NKX6-1 mRNA expression was examined in 49 human uterine tissues. The in vitro effects of NXK6-1 in LMS cells were determined by reverse transcriptase PCR, western blotting, colony formation, spheroid formation, and cell viability assays. In vivo tumor growth was evaluated in nude mice. Results Using The Cancer Genome Atlas (TCGA) and human uterine tissue datasets, we observed that NKX6-1 expression was associated with poor prognosis and malignant potential in LMS. NKX6-1 enhanced in vitro tumor cell aggressiveness via upregulation of cell proliferation and anchorage-independent growth and promoted in vivo tumor growth. Moreover, overexpression and knockdown of NKX6-1 were associated with upregulation and downregulation, respectively, of stem cell transcription factors, including KLF8, MYC, and CD49F, and affected sphere formation, chemoresistance, NOTCH signaling and Sonic hedgehog (SHH) pathways in human sarcoma cells. Importantly, treatment with an SHH inhibitor (RU-SKI 43) but not a NOTCH inhibitor (DAPT) reduced cell survival in NKX6-1-expressing cancer cells, indicating that an SHH inhibitor could be useful in treating LMS. Finally, using the TCGA dataset, we demonstrated that LMS patients with high expression of NKX6-1 and HHAT, an SHH pathway acyltransferase, had poorer survival outcomes compared to those without. Conclusions Our findings indicate that NKX6-1 and HHAT play critical roles in the pathogenesis of LMS and could be promising diagnostic and therapeutic targets for LMS patients.

Purpose: The purpose of this study was to evaluate the radiographic and clinical outcomes of hook plate fixation with and without coracoclavicular (CC) ligament augmentation with suture anchors for acute acromioclavicular (AC) joint dislocation. Methods: The study included 67 patients (48 males and 19 females; average age: 45.5 years) with acute AC joint dislocation (Rockwood types III and V) treated with hook plate fixation. The patients were divided into two groups: those treated with hook plate fixation with or without CC ligament augmentation with suture anchors. We used the CC distance and ratio as radiographic outcomes. We evaluated the American Shoulder and Elbow Surgeons (ASES) score and the Constant Shoulder Score as functional outcomes. The following were considered major complications: symptomatic acromial osteolysis, peri-implant fracture, acromial cut-out, and hook plate disengagement. Results: Among the Rockwood type III patients, there was no significant difference between the two subgroups in terms of the functional outcome after adjusting for sex and age. However, among the type V patients, treatment with CC ligament augmentation with suture anchors revealed a superior outcome in terms of the ASES score (P = 0.01). There was no difference in the risk of developing major complications between the two subgroups among type III and type V patients. The risk of residual subluxation of the AC joint was significantly lower in the CC augmentation subgroup among the type III patients (P = 0.04), and a similar result was obtained among the type V patients with borderline significance (P = 0.06). Conclusions: Hook plate fixation with CC suture anchor augmentation provided radiographic benefits in both type III and type V patients and yielded better functional outcomes in type V patients after implant removal but had no significant influence on the complication rate. Additional CC suture anchor augmentation may prevent residual subluxation and yield better functional outcomes.

Scrub typhus is caused by the intracellular pathogen Orientia tsutsugamushi, which is transmitted to humans by infected chigger mites. The disease causes a febrile illness accompanied by regional or generalized lymphadenopathy, hepatomegaly, splenomegaly, as well as nonspecific manifestations. Scrub typhus is an important cause of febrile disease in South and East Asia and in the Western Pacific, and can cause severe complications including meningoencephalitis and pneumonitis. Herein, we report a case of scrub typhus accompanied by meningitis, which was definitively diagnosed by serology assay, in a 4-year-old girl who presented with prolonged fever, skin rash, cough, general weakness, and poor appetite. Scrub typhus should be considered in the differential diagnosis when evaluating patients who present with nonspecific febrile illness or meningitis in areas that are endemic for O. tsutsugamushi.

Cystic fibrosis (CF) is a genetic disease affects CFTR channel synthesis. While 90 percent of the CF patients now benefit from small molecule target therapies, this treatment has yet to extend to those bearing nonsense mutations. Studies of these rare mutations using cell lines with native pathological signatures of the disease may lead to breakthroughs in therapeutic development. Here, we report the generation of CF patient-derived induced pluripotent stem cells (iPSCs) carrying a nonsense mutation at position 308 (S308X). The pluripotency and genomic profile of the iPSC line was validated as a resource that can enable future research for CF.

Introduction: Fluoroquinolone exposure is reportedly associated with a higher risk of tendon disorders, tendonitis, or tendon rupture. However, studies in East Asian populations have not confirmed these risks in patients with comorbidities or concomitant medication use. This cohort study was designed to investigate the associations among fluoroquinolone exposure, comorbidities, medication use, and tendon disorders in Taiwan.Materials and Methods: This population-based, nationwide, observational, cohort study used data from the National Health Insurance Research database in Taiwan, a nationwide claims database that covers more than 99% of the Taiwanese population. The study period was from January 2000 to December 2015, and the median follow-up time was 11.05 ± 10.91 years. Patients who were exposed to fluoroquinolones for more than three consecutive days were enrolled, and patients without fluoroquinolone exposure who were matched by age, sex, and index year were enrolled as controls. The associations of comorbidities and concomitant medication use with tendon disorder occurrence were analyzed using Cox regression models.Results: The incidence of tendon disorders were 6.61 and 3.34 per 105 person-years in patients with and without fluoroquinolone exposure, respectively (adjusted hazard ratio, 1.423; 95% confidence interval [1.02,1.87]; p = 0.021). Sensitivity analyses yielded similar results. Patients under 18 and over 60 years with fluoroquinolone exposure; those with chronic kidney disease, diabetes, rheumatologic disease, cardiac disease, lipid disorder, or obesity; and those who concomitantly used statins, aromatase inhibitors, or glucocorticoids, had a significantly higher risk of tendon disorders.Conclusion: The long-term risk of tendon disorders was higher in patients with fluoroquinolone exposure than in those without fluoroquinolone exposure. Clinicians should assess the benefits and risks of fluoroquinolone use in patients at high risk of tendon disorders who require fluoroquinolone administration.

Abstract Although human leucocyte antigen (HLA)‐B27 is strongly associated with ankylosing spondylitis (AS), the association of unfolded protein response (UPR) induced by HLA‐B27 misfolding in AS remains controversial. Since dendritic cells (DCs) are crucial in induction of AS in HLA‐B27‐transgenic rats, and plasmacytoid DCs (pDCs) belong to one type of DCs, we here aim to study the relevance of pDCs and UPR in AS. Peripheral pDCs were isolated from 27 HLA‐B27(+) AS patients and 37 controls. The bone marrow (BM) and synovium of inflamed hips from AS patients and controls were obtained. We found a significantly higher frequency of pDCs in the peripheral blood, BM, or inflamed synovium of hips, which is associated with the enhanced expression of pDC trafficking molecules, CCR6 and CCL20 in the synovium of AS patients. Functional analysis further revealed that several inflammatory cytokines, including TNFα, IL‐6, and IL‐23, secreted by pDCs were significantly increased in AS patients as compared with those in controls. Remarkably, protein kinase RNA‐like endoplasmic reticulum kinase (PERK) pathway in UPR was up‐regulated in pDCs of AS patients. Notably, PERK inhibitor treatment significantly inhibited the enhanced cytokine production by pDCs of AS patients. Further, the extent of PERK activation was significantly associated with the increased disease severity of AS patients. Our data uncover the aberrant distribution and function of pDCs in AS patients. The up‐regulated PERK pathway in UPR of pDCs not only contributes to enhanced cytokine production of pDCs, but also is associated with increased disease activity of AS patients.

Few cystic fibrosis (CF) cases in Taiwan have been published. We report a case of 2.5-month-old male infant presented recurrent infection, failure to thrive, and nutritional deficiency dermatitis initially. Sweat chloride test confirmed the diagnosis at 4 months old. We highlight that CF should always be the differential diagnosis of patient with failure to thrive and recurrent pulmonary infections.

Background Osteoarthritis (OA) is an important health issue in elderly people. Many studies have suggested that genetic factors are important risk factors for OA, of which tumor necrosis factor-α (TNF-α) is one of the most examined genes. Moreover, several studies have investigated the relationship between TNF-α G-308A polymorphisms and OA risk, but consistent results have not been obtained. Objective This study examines the association between TNF-α G-308A polymorphisms and knee OA. Moreover, meta-analysis and trial sequential analysis (TSA) was used to determine whether this is a susceptibility gene for knee OA. Methods Between 2015 and 2019, 591 knee OA cases and 536 healthy controls were recruited. The Kellgren–Lawrence grading system was used to identify the knee OA cases. A meta-analysis was conducted including related studies published until 2020 from PubMed, Embase, and previous meta-analysis to improve the evidence level of the current study. The results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) to evaluate the effect of this polymorphism on knee OA risk. The TSA was used to estimate the sample sizes required in this issue. Results A nonsignificant association was found between the AA genotype and knee OA [adjusted OR, 0.84; 95% CI, 0.62–1.15) in the recessive model] in the present case–control study, and analysis of other genetic models showed a similar trend. After adding the critical case–control samples for Asians, the TNF-α G-308A, AA genotype exhibited 2.57 times more risk of developing arthritis when compared with the GG + GA genotype (95% CI, 1.56–4.23), and the cumulative samples for TSA (n = 2182) were sufficient to obtain a definite conclusion. Conclusions The results of this meta-analysis revealed that the TNF-α G-308A, AA genotype is a susceptible genotype for OA in the Asian population. This study integrated all current evidence to arrive at this conclusion, suggesting that future studies on Asians are not required.

The existence of red, inflammatory, and chronic itchy condition in the skin is commonly speculated as the presence of Atopic Dermatitis (AD) in patients. The use of silk clothing as a non-pharmacological approach in the management of AD has been noticed as an effective alternative therapy; however, the evidence based on its usage is poorly served. Hence, we aim to evaluate the effectiveness of using pure silk clothing in the therapy of AD patients. The clinical trial was performed by recruiting 30 patients with AD for up to 8 weeks of observation. They were instructed to wear pure silk clothing for the whole day without any additional medication and were investigated using the AD-related questionnaires. The findings revealed a significant decrease of AD occurrence along with a great improvement of patient’s quality of life at each time point. Our investigation demonstrated that this treatment promotes good skin appearance, comfort, and remarkable improvement in the quality of life. This promising preliminary outcome warrants a further study; hence, it can be a potential non-pharmacological treatment choice for controlling the severity of AD.

Abstract Background Differences between staged bilateral total knee replacement (TKR) and simultaneous bilateral TKR have been investigated, but few studies have investigated differences in the functional improvements resulting from these methods. Therefore, this study investigates the different functional improvements between staged bilateral total knee TKR and simultaneous bilateral TKR. Methods Among 144 potential bilateral TKR patients who were included in this study, 93 (64.6%) patients selected unilateral TKR and 51 (35.4%) selected bilateral TKR. Functional improvements were assessed using the Western Ontario and McMaster University osteoarthritis index (WOMAC) and the Medical Outcomes Trust Short Form-36 (SF-36), and patients were interviewed pre-operatively and after 6 months. A generalized equation was used to test for differences in functional improvements. Results After TKR, pain, stiffness, function and total WOMAC scores were significantly reduced in both groups, with mean changes from − 26.6 to − 41.4 and from − 27.5 to − 42.2.The mean health change of SF-36 scores, physical component and mental component scores changed to 45.2 ± 18.2, 74.0 ± 15.4 and 77.0 ± 9.6, respectively, in Group 1 and 47.1 ± 17.1, 74.0 ± 15.2 and 75.5 ± 12.1, respectively, in Group 2. Unilateral and simultaneous bilateral TKR produce similar functional improvements, although current work status may be a novel impact factor. Conclusion No differences in functional improvements were identified between patients who selected unilateral versus bilateral TKR, indicating no recommendation for one procedure over the other.

Background: Painful procedures are unavoidable in the medical care of preterm babies. The unpleasant experience during the neonatal period may contribute to hyperalgesia and poor neurodevelopment outcome later. Seeking effective interventions to reduce pain are strongly indicated for these very small premature babies. The aim of this study is to investigate if instilling breast milk (BM) or dextrose water into oral cavity can reduce the procedural pain of heel stick for preterm babies. Methods: This is a prospective study; 20 premature neonates are enrolled. Each study case received heel stick 4 times. BM, 10% dextrose water (D10W), distilled water (placebo) and nothing (control group) were given one after the other in random order to the same patient before heel stick. Premature infant pain profile (PIPP) was used to assess the pain scores. The whole process consisted of 4 sections: a baseline period for 1 min, intervention period for 1 min, heel stick period for 20 s, and recovery period for 5 min. The primary outcome is to compare the PIPP scores in the 4 groups. Results: Totally 20 babies completed this study. Median gestational age was 32 weeks 2 days (26 weeks 4 days–35 weeks 6 days) and median birth body weight was 1596 g (766–2435 g). The median PIPP scores and interquartile range at each time period were listed in the context. There are significant differences between BM/control group at all time periods, between BM/placebo group at 30–60 s, 1–2 min, and 2–3 min, and between D10W/control group at 0–30 s, 30–60 s, 3–4 min, and 4–5 min. There are no significant differences between BM/D10W, D10W/placebo, and placebo/control groups at any time periods. Conclusion: Giving something with taste such as BM or D10W is safe and effective in reducing the procedural pain of heel stick in preterm neonates; BM is the priority.

Background: Vancomycin is widely prescribed to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). According to the Infectious Disease Society of America 2011 MRSA guidelines for adults, trough concentrations of 15–20 μg/ml were recommended with vancomycin 15–20 mg/kg/dose every 8–12 h not to exceed 2 g per dose in patients with normal renal function. As the data for dosage and monitoring of vancomycin in children are still controversial, physicians often follow the guidelines established for adults. To evaluate serum vancomycin trough concentrations in pediatric patients with currently recommended dosing regimen, we evaluated clinical data. Methods: This retrospective observational study collected pediatric patients aged

Bacterial enteritis has been reported to be a risk factor for childhood intussusception. However, no case report concerning children with concurrent Campylobactor bacteremia and intussusception were found in the literature.Herein, we report a 5-year-old male preschool child who presented symptoms of infectious diarrhea, and ileocecal type intussuscepton and Campylobactor jejuni bacteremia were found after a series of investigations. Keywords: Bacterial enteritis, Intussusception, Campylobacter jejuni, Bacteremia

Spontaneous regression of an osteochondroma of the distal femur is unusual. This report highlights the spontaneous regression of a sessile osteochondroma of the distal femur in a 9-year-old boy which resolved over a 4-year period. The mechanism underlying regression of the tumor is discussed with a review of previous reports. Since this type of osteochondroma can spontaneously resolve, conservative treatment is always the first choice to avoid unnecessary surgery.

Recent evidence has suggested that synovial inflammation and macrophage polarization were involved in the pathogenesis of osteoarthritis (OA). Additionally, high-molecular-weight hyaluronic acid (HMW-HA) was often used clinically to treat OA. GRP78, an endoplasmic reticulum (ER) stress chaperone, was suggested to contribute to the hyperplasia of synovial cells in OA. However, it was still unclear whether HMW-HA affected macrophage polarization through GRP78. Therefore, we aimed to identify the effect of HMW-HA in primary synovial cells and macrophage polarization and to investigate the role of GRP78 signaling. We used IL-1β to treat primary synoviocytes to mimic OA, and then treated them with HMW-HA. We also collected conditioned medium (CM) to culture THP-1 macrophages and examine the changes in the phenotype. IL-1β increased the expression of GRP78, NF-κB (p65 phosphorylation), IL-6, and PGE2 in primary synoviocytes, accompanied by an increased macrophage M1/M2 polarization. GRP78 knockdown significantly reversed the expression of IL-1β-induced GRP78-related downstream molecules and macrophage polarization. HMW-HA with GRP78 knockdown had additive effects in an IL-1β culture. Finally, the synovial fluid from OA patients revealed significantly decreased IL-6 and PGE2 levels after the HMW-HA treatment. Our study elucidated a new form of signal transduction for HMW-HA-mediated protection against synovial inflammation and macrophage polarization and highlighted the involvement of the GRP78-NF-κB signaling pathway.

The inflammatory cytokine interleukin-26 (IL-26) is highly expressed in the serum and synovial fluid of patients with inflammatory arthritis. The effect of IL-26 on human articular chondrocytes (HACs) remains unclear. Obesity is associated with disability of patients with rheumatoid arthritis and disease activity in those with ankylosing spondylitis. The saturated free fatty acid palmitate with IL-1β can synergistically induce catabolic effects in HACs. The aim of this study was to evaluate the effects of IL-26 and palmitate in HACs. In this study, palmitate markedly synergizes the IL-26-induced proinflammatory effects and matrix protease, including COX-2, IL-6, and MMP-1, in HACs via the toll-like receptor 4 (TLR4)-ERK1/2-c-Jun signal transduction pathway. The synergistic catabolic effects of palmitate and IL-26 were attenuated by inhibitors of TLR4 (TAK242), ERK1/2 (U0126), or c-Jun (SP600125) in HACs and cartilage matrix. In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate. IL-26 and palmitate synergistically induced expression of inflammatory and catabolic mediators, resulting in articular cartilage matrix breakdown. The present study also revealed a possible mechanism and therapeutic targets against articular cartilage degradation by increased saturated fatty acids in patients with inflammatory arthritis.

Background and Objectives: Gouty arthritis is an acute inflammatory response caused by the precipitation of monosodium urate (MSU) crystals in joints. The triggering of MSU leads to increased production of inflammatory cytokines, such as interleukin-1β, which in turn lead to the formation of macromolecular complexes, referred to as inflammasomes. Thorough characterization of the NLRP3 inflammasome can be used as an indicator of an immune response against harmful stimuli. Cardamonin is a chalcone, mainly found in the seeds of Alpinia katsumadai, and exhibits anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines in vitro. However, the mechanism by which cardamonin treatment alleviates gouty arthritis has yet to be fully elucidated. Materials and Methods: In vitro or in vivo models were used to study whether cardamonimn inhibited NLRP3 inflammasome activation or suppressed gouty inflammation. Results: In the current study, we determined that most NLRP3 was released passively after MSU stimulation, and this release of NLRP3 promoted caspase-1 activation and IL-1β secretion. Cardamonin was shown to decrease both the activity of caspase-1 and secretion of IL-1β in J774A.1 macrophage cells subjected to MSU stimulation. Cardamonin was also shown to attenuate the production of COX-2 in MSU-stimulated J774A.1 macrophage cells. Finally, cardamonin reduced the thickness of the synovial lining and the infiltration of gouty arthritis in a rat model. Conclusions: Overall, cardamonin significantly attenuated IL-1β secretion, caspase-1 activity, and COX-2 production stimulated by MSU. These findings provide new insights into the molecular mechanisms underlying the effects of cardamonin treatment for gouty arthritis.

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

Background: Poor glycemic control in patients with diabetes mellitus can increase associated complications and mortality. We use the telehomecare system in patients with diabetes and investigate the associated impact in clinical practice. Materials and Methods: The purpose of the study is to examine the effectiveness of the telehomecare system on diabetic self-care. The telehomecare system incorporated into the daily care program in the experimental group. A cloud health-care platform designed for information storage and exchange be constructed and monitored by case managers. Comprehensive care instructions and in-time consultation in case of abnormalities were provided. The patients in the control group adopted conventional care program. Self-care questionnaires were completed by both groups before and after the study. All participants measured before the experiment and at 4 months after. Results: The participants were 117 patients (including 56 at the experimental and 61 at the control group), which recruited from a community hospital in New Taipei city, Taiwan. In two-way mixed design ANCOVA, in self-care behaviors, there are significant differences between two groups. The outcome of experimental group is superior to the control group both in posttest. However, there is no significant difference between two groups in subscales of foot care and athletics care. Moreover, there is no delayed effect in self-care behaviors of drug adjustment and blood sugar surveillance. Conclusions: This observational study revealed early intervention model to the health education strategy, the telehomecare might strengthen self-care behaviors of the participants. To the future study, we can put emphasis on the diabetes mellitus patient's foot care and exercise behaviors. The telehomecare model could also become the important health-care policy for the government in the future.

In this case report, we describe a rare clinical situation of acute arterial thoracic outlet syndrome (TOS) after osteosynthesis, using an intramedullary Knowles pin, to treat nonunion of a midshaft clavicular fracture. Existing evidence was reviewed to appraise the relationship between TOS and nonunion of clavicular fractures, including the timing of the development of this complication, as well as to identify the relationship between surgical technique and choice of implant and the occurrence of TOS. Perioperative measures used to prevent TOS were identified.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the deterioration of articular cartilage. The progression of OA leads to an increase in inflammatory mediators in the joints, thereby promoting the destruction of the cartilage matrix. Recent studies have reported on the anti-inflammatory and antioxidant properties of cardamonin, which also appears to interact with cellular targets, such as nuclear erythroid 2-related factor 2 (Nrf2), extracellular signal-regulated kinase (ERK), and mammalian target of rapamycin (mTOR) during the progression of tumors. To date, few studies have investigated the effects of cardamonin on chondrocyte inflammation. In the current study, we determined that treating interleukin-1 beta (IL-1β-stimulated chondrocyte cells) with cardamonin significantly reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) and significantly inhibited the expression of pro-inflammatory proteins, including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). Cardamonin was also shown to: (1) inhibit the activation and production of matrix metalloproteinases (MMPs), (2) suppress the nuclear factor-κB (NF-κB) signaling pathway, (3) suppress the expression of toll-like receptor proteins, (4) activate the Nrf2 signaling pathway, and (5) increase the levels of antioxidant proteins heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). The increase in antioxidant proteins led to corresponding antioxidant effects (which were abolished by Nrf2 siRNA). Our findings identify cardamonin as a candidate Nrf2 activator for the treatment and prevention of OA related to inflammation and oxidative stress.

Profunda femoris artery (PFA) injury is a rare complication following fracture of the femoral neck. Here, we present a case of a patient with an injured branch of the PFA following internal fixation with cannulated hip screws for a femoral neck fracture. Computed tomography angiography revealed active bleeding from the ascending and descending branches of lateral femoral circumflex artery. We suspected that the cause of the vessel laceration was the sharp tip of the guidewire used during surgery or the closed reduction performed during surgery. The patient was successfully treated with coil embolization. With early recognition and prompt radiological intervention, this rare complication following fracture fixation surgery can be treated without the need for additional surgery.

We report the case of 32-year-old male who had a painful knee due to tophus formation in the interosseous area of the bipartite patella. There was neither a history of previous trauma to his patella nor a family history of gouty arthritis. Intraoperatively, we found chalky white-yellow material deposited at the bipartite space and it was curetted. The second part of the patella was fixed by a screw for functional preservation. In addition, hyperuricemia was also noted and controlled by uricosuric agents postoperatively. Gout should be included in the differential diagnosis of painful bipartite patella, and we suggest surgical intervention in combination with antihyperuricemic therapy for tophaceous deposits of the bipartite patella.

Recently, stem cell-based bone tissue engineering (BTE) has been recognized as a preferable and clinically significant strategy for bone repair. In this study, a pure 3D silk fibroin (SF) scaffold was fabricated as a BTE material using a lyophilization method. We aimed to investigate the efficacy of the SF scaffold with and without seeded human adipose-derived mesenchymal stem cells (hASCs) in facilitating bone regeneration. The effectiveness of the SF-hASCs scaffold was evaluated based on physical characterization, biocompatibility, osteogenic differentiation in vitro, and bone regeneration in critical rat calvarial defects in vivo. The SF scaffold demonstrated superior biocompatibility and significantly promoted osteogenic differentiation of hASCs in vitro. At six and twelve weeks postimplantation, micro-CT showed no statistical difference in new bone formation amongst all groups. However, histological staining results revealed that the SF-hASCs scaffold exhibited a better bone extracellular matrix deposition in the defect regions compared to other groups. Immunohistochemical staining confirmed this result; expression of osteoblast-related genes (BMP-2, COL1a1, and OCN) with the SF-hASCs scaffold treatment was remarkably positive, indicating their ability to achieve effective bone remodeling. Thus, these findings demonstrate that SF can serve as a potential carrier for stem cells, to be used as an osteoconductive bioscaffold for BTE applications.

We compared our clinical experience with currently available reference oxygen saturation level (SpO2) values from the American Academy of Pediatrics/American Heart Association (AAP/AHA) neonatal resuscitation program guidelines. Methods: We enrolled 145 healthy full-term neonates; infants showing respiratory distress and those with serious congenital anomalies were excluded. SpO2 values at every 1 minute until 10 minutes after birth were measured and recorded. Infants were classified into the cesarean section (CS) and normal spontaneous delivery (NSD) groups for evaluating differences. The 10th percentiles of SpO2 at each minute were used as the lower limits of normal oxygen saturation, and these were compared with the lowest target values recommended in the AAP/AHA guidelines. Results: Overall, 130 vigorous full-term neonates (median gestational age: 38 5/7 weeks; body weight at birth: 2405–3960 g) were analyzed. The median SpO2 were 67% and 89% at the 1st and 4th minute, respectively. On average, SpO2 values reached >90% at the 5th minute. No statistical differences were noted in the SpO2 values between the CS and NSD groups after 5 minutes; however, a trend of higher SpO2 was observed in the NSD group. We noted a gradually increasing trend for SpO2 values over time, similar to that noted in the AAP/AHA guidelines. However, SpO2 values at the 10th percentiles of each minute within the first 5 minutes in our study were equal to or significantly lower than those in the AAP/AHA guidelines; moreover, at the 10th minute, SpO2 values at the 10th percentiles were significantly higher than those in the guidelines. Conclusion: The delivery modes did not affect the SpO2 values of full-term healthy neonates. Discrepancies in SpO2 changes in full-term neonates not requiring resuscitation between this study and the AAP/AHA guidelines were significant. SpO2 ranges for each time point within the first 10 minutes after birth should therefore be reevaluated locally.

Background: Skin tape and silicone gel are two common over-the-counter preparations used to enhance the cosmesis of keloids and hypertrophic scars of posttrauma wounds. This animal study was performed to determine the clinical efficacy of skin tape versus silicone gel in subjects with scars. Materials and Methods: Three New Zealand rabbits that received total 12 incision wounds which two incision wounds on one ear side and subsequent primary suturing were studied. Stitches were removed after 1 week. Silicone gel was applied right upper side of the rabbit′s ear directly on surgical incision wounds, and skin tapes were also applied left upper side of the rabbit′s ear directly on another surgical incision wounds after 1 week of surgery. The lower incisions in both ears were covered with sterilized gauze and served as controls. We compared two experimental groups at binaural with using Vancouver Scar Scale, Manchester Scar Scale, and The Stony Brook Scar Evaluation Scale. These are widely used in clinical practice and research to document change in scar appearance. Results: We describe a rabbit model for incisional wounds and scarring outcome measures. The results of scar measuring devices demonstrated that skin tape reduced scar formation as well as silicone gel. Conclusions: The results of cosmetic demonstrated that skin tape reduced scar formation as well as silicone gel. However, the economical and effective materials were the important subject that suffices for clinical requirement. The application of these scar prevention devices to reduce scar formation after surgical incision is worthy of future investigation. Moreover, skin tape may represent a low-cost alternative and low scar formation for closure of surgical incisions.

This report describes two children who presented with status epilepticus. Both patients had hyponatremia, hypochloremia, low serum osmolality, and low urine osmolality caused by voluntary drinking of excessive quantities of water or diluted formula. Seizures were controlled by the administration of benzodiazepines, antiepileptic drugs, and hypertonic saline. Educating parents regarding hazards of excessive ingestion of fluid could reduce the incidence of this preventable and life-threatening condition.

Genistein is an isoflavone extracted from soybean (Glycine max). This compound has anti-inflammatory, anti-oxidative, and anti-cancer effects; however, the mechanism underlying the effects of genistein on IL-1β-stimulated human osteoarthritis (OA) chondrocytes remains unknown. Our objectives in this study were to explore the anti-inflammatory effects of genistein on IL-1β-stimulated human OA chondrocytes and to investigate the potential mechanisms which underlie them. Our results from an in-vitro model of osteoarthritis indicate that genistein inhibits the IL-1β-induced expression of the catabolic factors nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX-2), and matrix metalloproteinases (MMPs). Genistein was shown to stimulate Ho-1 expression, which has been associated with Nrf-2 pathway activation in human chondrocytes. In a rat model, genistein was also shown to attenuate the progression of traumatic osteoarthritis. Taken together, these results demonstrate the effectiveness of genistein in mediating the inflammation associated with joint disorders. Our results also indicate that genistein could potentially serve as an alternative therapeutic treatment for OA.

We report on a 17-year-old man who underwent prophylactic fixation of the incomplete subtrochanteric femur fracture produced by a low-velocity gunshot. The subtrochanteric region is a high-stress site. Therefore, to avoid progression to complete fracture and displacement requiring secondary surgical stabilization, we used a proximal femoral nail for prophylactic fixation of the incomplete subtrochanteric femur fracture. The patient was able to walk and bear weight on the injured side immediately after surgery. At the 1-year follow-up, the patient was pain-free with a full range of motion of his right hip and had a bony union.

The bacillus Calmette–Guérin (BCG) reaction is not included in the classical clinical criteria for Kawasaki disease (KD). However, a reaction at the BCG inoculation site has been mentioned among the “other clinical findings” that are present in about 30–50% of KD patients. The objective of this study was to investigate the clinical characteristics of KD patients with reactions at the BCG inoculation site. Methods: A retrospective study of all patients diagnosed with KD between September 2000 and August 2010 was performed. The clinical presentations, laboratory results, treatment outcomes, and coronary artery abnormalities in the BCG-reactive [BCG(+)] and BCG-nonreactive [BCG(–)] groups were analyzed and compared. Results: In total, 145 patients with KD diagnosed at our institution were included; 46 (31.7%) had a reaction at the BCG inoculation site. The BCG(+) group was younger than the BCG(–) group. Laboratory results showed higher white blood cell counts, platelet counts, and serum potassium levels, and lower low-density lipoprotein levels in the BCG(+) group. The BCG(+) group had a shorter fever duration before intravenous immunoglobulin treatment and a shorter total fever duration than the BCG(–) group. Multivariable logistic regression analysis showed that the age at diagnosis was the only factor significantly associated with a reaction at the BCG inoculation site in KD patients. Conclusions: In countries with a national BCG vaccination program, a reaction at the BCG inoculation site could be a useful and early diagnostic sign of KD among younger patients, especially those younger than 6 months.

BACKGROUND:Studies of angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and the risks of knee osteoarthritis (OA) have yielded conflicting results. OBJECTIVE:To determine the association between ACE I/D and knee OA, we conducted a combined case-control study and meta-analysis. METHODS:For the case-control study, 447 knee OA cases and 423 healthy controls were recruited between March 2010 and July 2011. Knee OA cases were defined using the Kellgren-Lawrence grading system, and the ACE I/D genotype was determined using a standard polymerase chain reaction. The association between ACE I/D and knee OA was detected using allele, genotype, dominant, and recessive models. For the meta-analysis, PubMed and Embase databases were systematically searched for prospective observational studies published up until August 2015. Studies of ACE I/D and knee OA with sufficient data were selected. Pooled results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for the D versus I allele with regard to knee OA risk. RESULTS:We found no significant association between the D allele and knee OA [OR: 1.09 (95% CI: 0.76-1.89)] in the present case-control study, and the results of other genetic models were also nonsignificant. Five current studies were included, and there were a total of six study populations after including our case-control study (1165 cases and 1029 controls). In the meta-analysis, the allele model also yielded nonsignificant results [OR: 1.37 (95% CI: 0.95-1.99)] and a high heterogeneity (I2: 87.2%). CONCLUSIONS:The association between ACE I/D and knee OA tended to yield negative results. High heterogeneity suggests a complex, multifactorial mechanism, and an epistasis analysis of ACE I/D and knee OA should therefore be conducted.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen that causes serious infectious diseases and was endemic in hospitals by the late 1960s. Beginning with its first report in the late 1990s, the rapid emergence of community-associated MRSA (CA-MRSA) worldwide responsible for a wide spectrum of diseases ranging from minor skin infections to fatal necrotizing pneumonia has been found in previously healthy individuals without established risk factors for MRSA acquisition. Recently, various virulence determinants unique to CA-MRSA have been uncovered, which explain how the pathogen spreads easily and causes severe CA-MRSA infections among humans. However, the role of Panton-Valentine leukocidin (PVL) in the pathogenesis of CA-MRSA infection is currently a matter of much debate because of conflicting data from epidemiologic studies of CA-MRSA infections and various murine disease models. Identifying specialized pathogenic traits of CA-MRSA and the concerted regulation of these factors remains a challenge that will foster development of vaccines and therapies designed to control CA-MRSA infections. This review focuses on the current status of molecular epidemiology associated with CA-MRSA in Taiwan and progresses toward understanding the enhanced virulence properties of CA-MRSA, with an emphasis on the role of Panton-Valentine leukocidin.

Dandy–Walker syndrome (DWS) is a congenital brain malformation involving the cerebellum and fourth ventricle. We report a 6-month-old girl with DWS presenting an initially normal ventricular system and mild cyst-like lesion over the posterior fossa as assessed by postnatal brain sonography. However, symptoms and signs of increased intracranial cerebral pressure in terms of frequent vomiting and tense anterior fontanel developed, and these were associated with mild hypotonia and poor neck support, and upward-gaze palsy at the age of 6 months. Magnetic resonance imaging revealed a huge cystic lesion of the fourth ventricle, which filled the posterior fossa and ventricular dilatation. The tentorium was progressively displaced upward by the cyst. A nearly complete agenesis of the cerebellar vermis was also confirmed. After a successful endoscopic third ventriculostomy, a series of brain magnetic resonance imaging scans, taken during a follow-up survey, showed normal lateral and third ventricles. Consequently, symptoms of intracranial cerebral pressure resolved, and a developmental milestone was achieved. In conclusion, DWS can be confirmed postpartum, and endoscopic third ventriculostomy was found to be a preferential operative procedure for DWS with hydrocephalus. It may be effective for patients younger than 1 year.

Inhaled β2-adrenergic receptor (β2-AR) agonists are the mainstay of treatment of acute asthma. Polymorphisms of the β2-AR, especially codons 16, 27, and 164, may affect the functions of the receptor. This study was conducted to investigate whether different polymorphisms of the β2-AR are related to the treatment responses of an inhaled β2-AR agonist in children with nocturnal and nonnocturnal asthma in Taiwan. Methods: The nocturnal asthma group consisted of 27 children (mean age of 10.3±2.4 years), and the nonnocturnal asthma group consisted of 24 patients (mean age of 9.9±3.0 years). Allele-specific polymerase chain reaction was performed to determine 16, 27, and 164 loci alleles of β2-AR genetic polymorphisms, and peak expiratory flow (PEF) was measured before and 1 hour after inhalation of 0.2 mg/kg/dose of terbutaline to determine the treatment response in these patients. Results: The polymorphisms of β2-AR 27 but not 16 or 164 were significantly associated with the response to terbutaline nebulizer (p

In the early stage of Lyme disease, atypical lesions of erythema migrans rash can develop and extend over the neck region, mimicking cervical cellulitis with deep neck infection. Here, we report a 9-year-old Taiwanese boy with a recent history of exposure to deer during his visit to Nanto County in central Taiwan. Cervical cellulitis with lymphadenitis was initially diagnosed. Erythema migrans developed in the following days and Lyme disease was finally diagnosed by a Western immunoblot test. Alertness to this unique clinical feature is required for prompt differential diagnosis of Lyme disease with a presentation of erythema migrans mimicking cervical cellulitis.

Highly virulent community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) with Panton-Valentine leukocidin (PVL) is common worldwide. Using antimicrobial drug susceptibility testing, staphylococcal cassette chromosome mec typing, exotoxin profiling, and pulsed-field gel electrophoresis typing, we provide evidence that supports the relationship between nasal strains of PVL-positive MRSA and community-acquired disease.