Search

Background: Klebsiella pneumoniae is a Gram-negative bacterium that can cause infections, especially in individuals with diabetes. Recently, more hypervirulent strains have emerged, posing a threat even to healthy individuals. Understanding how K. pneumoniae regulates its virulence factors is crucial. Acetyl-phosphate (AcP) is essential for bacterial metabolism and can affect virulence factor expression. However, the role of the Pta-AckA pathway, which regulates AcP levels, in K. pneumoniae pathogenesis remains unclear. Methods: Deletion mutants lacking the pta and ackA, involved in AcP production and hydrolysis, were generated in K. pneumoniae CG43S3. Their effects on AcP levels, the patterns of global acetylated protein, capsular polysaccharide (CPS) amount, serum resistance, type 3 fimbriae expression, biofilm formation, and virulence in G. mellonella larva were assessed. Results: Deletion of ackA in K. pneumoniae CG43S3 led to AcP accumulation, while pta deletion abolished AcP synthesis when grown in TB7+1 % glucose. This pathway influenced global protein acetylation, with pta deletion decreasing acetylation and ackA deletion increasing it. Additionally, pta deletion decreased the CPS amount, serum resistance, and type 3 fimbriae expression, while ackA deletion increased these factors. Furthermore, deleting pta and ackA attenuated the infected larva's virulence and death rate. Conclusion: Our findings highlight the critical role of the Pta-AckA pathway in K. pneumoniae pathogenesis. This pathway regulates AcP levels, global protein acetylation, CPS production, serum resistance, and type 3 fimbriae expression, ultimately impacting virulence. The information provides insights into potential therapeutic targets for combating K. pneumoniae infection.

Arrhythmia, a frequently encountered and life-threatening cardiac disorder, can manifest as a transient or isolated event. Traditional automatic arrhythmia detection methods have predominantly relied on QRS-wave signal detection. Contemporary research has focused on the utilization of wearable devices for continuous monitoring of heart rates and rhythms through single-lead electrocardiogram (ECG), which holds the potential to promptly detect arrhythmias. However, in this study, we employed a convolutional neural network (CNN) to classify distinct arrhythmias without QRS wave detection step. The ECG data utilized in this study were sourced from the publicly accessible PhysioNet databases. Taking into account the impact of the duration of ECG signal on accuracy, this study trained one-dimensional CNN models with 5-s and 10-s segments, respectively, and compared their results. In the results, the CNN model exhibited the capability to differentiate between Normal Sinus Rhythm (NSR) and various arrhythmias, including Atrial Fibrillation (AFIB), Atrial Flutter (AFL), Wolff-Parkinson-White syndrome (WPW), Ventricular Fibrillation (VF), Ventricular Tachycardia (VT), Ventricular Flutter (VFL), Mobitz II AV Block (MII), and Sinus Bradycardia (SB). Both 10-s and 5-s ECG segments exhibited comparable results, with an average classification accuracy of 97.31%. It reveals the feasibility of utilizing even shorter 5-s recordings for detecting arrhythmias in everyday scenarios. Detecting arrhythmias with a single lead aligns well with the practicality of wearable devices for daily use, and shorter detection times also align with their clinical utility in emergency situations.

Background: Klebsiella pneumoniae is a gram-negative opportunistic pathogen that causes diseases mostly in immunocompromised individuals. Recently, hypervirulent K. pneumoniae strains also cause severe disease in healthy individuals. Capsular polysaccharide (CPS) is the major virulence determinant in hypervirulent K. pneumoniae and protects the cell against the bactericidal activity of the immune system. Gallic acid (GA), a natural phenolic compound, is known to exhibit wide spectrum antibacterial activity; however, its effect on hypervirulent K. pneumoniae remains largely unresolved. We aimed to identify the effects of GA on CPS biosynthesis in hypervirulent K. pneumoniae. Methods: Antibacterial activity of GA was evaluated by counting colonies. CPS amount was determined by glucuronic acid content. The transcriptions of cps gene cluster were measured by quantitative real time PCR (qRT-PCR) and the β-galactosidase activity. The effect of GA on the resistance of K. pneumoniae to streptonigrin (SNG), an iron-activated antibiotic, was evaluated. The effect of GA on the resistance of K. pneumoniae to serum killing and phagocytosis by macrophages was observed. Results: GA inhibited the growth and CPS biosynthesis in K. pneumoniae. GA may affect the iron availability in K. pneumoniae, thus possibly repressing the cps transcription. In addition, GA reduced the resistance of K. pneumoniae to serum killing and enhanced its susceptibility to phagocytosis. Conclusion: GA possesses bactericidal activity and inhibits the CPS biosynthesis in hypervirulent K. pneumoniae, thereby facilitating pathogen clearance by the host immune system. Therefore, GA may represent a promising strategy for the prevention or treatment of patients with hypervirulent K. pneumoniae infections.

IntroductionRib fractures are a prevalent injury among trauma patients, and accurate and timely diagnosis is crucial to mitigate associated risks. Unfortunately, missed rib fractures are common, leading to heightened morbidity and mortality rates. While more sensitive imaging modalities exist, their practicality is limited due to cost and radiation exposure. Point of care ultrasound offers an alternative but has drawbacks in terms of procedural time and operator expertise. Therefore, this study aims to explore the potential of deep convolutional neural networks (DCNNs) in identifying rib fractures on chest radiographs.MethodsWe assembled a comprehensive retrospective dataset of chest radiographs with formal image reports documenting rib fractures from a single medical center over the last five years. The DCNN models were trained using 2000 region-of-interest (ROI) slices for each category, which included fractured ribs, non-fractured ribs, and background regions. To optimize training of the deep learning models (DLMs), the images were segmented into pixel dimensions of 128 × 128.ResultsThe trained DCNN models demonstrated remarkable validation accuracies. Specifically, AlexNet achieved 92.6%, GoogLeNet achieved 92.2%, EfficientNetb3 achieved 92.3%, DenseNet201 achieved 92.4%, and MobileNetV2 achieved 91.2%.DiscussionBy integrating DCNN models capable of rib fracture recognition into clinical decision support systems, the incidence of missed rib fracture diagnoses can be significantly reduced, resulting in tangible decreases in morbidity and mortality rates among trauma patients. This innovative approach holds the potential to revolutionize the diagnosis and treatment of chest trauma, ultimately leading to improved clinical outcomes for individuals affected by these injuries. The utilization of DCNNs in rib fracture detection on chest radiographs addresses the limitations of other imaging modalities, offering a promising and practical solution to improve patient care and management.

Background/purpose: Interfacility transfer (IFT) in Asian communities is seldom discussed. We aimed to describe the characteristics of IFT in Taiwan and to explore the adequacy of care during transfer. Methods: A retrospective, cross-sectional, descriptive study was conducted using standardized, paper-based interfacility ambulance transfer records between 1 January 2018 and 31 January 2018 from Tainan City, Taiwan. The mode of patient care needed was classified as advanced life support (ALS) or basic life support (BLS) cares based on clinical conditions. ALS providers were defined as physicians and EMT-Paramedics, while BLS providers were defined as nurse practitioners, nurses, EMT-1s and EMT-2s. Results: Of the 377 (227 [60.2%] were >65 years old; 219 [58.1%] were male) IFTs enrolled in the final analysis, 210 (55.7%) patients met the ALS transfer criteria, with poor consciousness (n = 158), tachypnea (n = 17), tachycardia (n = 5), bradycardia (n = 7), hypertension (n = 12), hypotension (n = 13), hypoxia (n = 4), endotracheal intubation (n = 18), a tracheostomy (n = 25), a precipitous labor (n = 1), and after resuscitation for out-of-hospital cardiac arrest (n = 10) or in-hospital cardiac arrest (n = 3). None of the patients who required ALS care had adequate ambulance staffing. Of the 167 BLS IFTs, 9 (5.4%) patients deteriorated and required ALS care during transportation, which included worsened consciousness (n = 2), tachycardia (n = 1), hypertension (n = 2), hypotension (n = 1), and hypoxia (n = 3). The rates of deterioration during BLS-transferals from the emergency departments, general wards, nursing facilities, and unknown areas were 4.8%, 4.7%, 7.7%, and 7.1%, respectively (p = 0.93). Conclusion: The patient care during IFT in Taiwan is inadequate currently and should warrant attention.

This study investigates age-specific prostate-specific antigen (PSA) distributions in Taiwanese men and recommends reference ranges for this population after comparison with other studies. From January 1999 to December 2016, a total of 213,986 Taiwanese men aged above 19 years old without history of prostate cancer, urinary tract infection, or prostate infection were recruited from the Taiwan MJ cohort, an ongoing prospective cohort of health examinations conducted by the MJ Health Screening Center in Taiwan. Participants were divided into seven age groups. Simple descriptive statistical analyses were carried out and quartiles and 95th percentiles were calculated for each group as reference ranges for serum PSA in screening for prostate cancer in Taiwanese men. Serum PSA concentration correlated with age (r = 0.274, p

Abstract Purpose Some predictive systems using machine learning models have been developed to predict sepsis; however, they were mostly built with a low percent of missing values, which does not correspond with the actual clinical situation. In this study, we developed a machine learning model with a high rate of missing and erroneous data to enable prediction under missing, noisy, and erroneous inputs, as in the actual clinical situation. Materials and methods The proposed artificial neural network model was implemented using the MATLAB ANN toolbox, based on stochastic gradient descent. The dataset was collected over the past decade with approval from the appropriate institutional review boards, and the sepsis status was identified and labeled using Sepsis-3 clinical criteria. The imputation method was built by last observation carried forward and mean value, aimed to simulate clinical situation. Results The mean area under the receiver operating characteristic (ROC) curve (AUC) of classifying sepsis and nonsepsis patients was 0.82 and 0.786 at 0 h and 40 h prior to onset, respectively. The highest model performance was found for one-hourly data, demonstrating that our ANN model can perform adequately with limited hourly data provided. Conclusions Our model has the moderate ability to predict sepsis up to 40 h in advance under simulated clinical situation with real-world data.

(1) Background: Salivary gland tumors are rare in the head and neck. To determine the need and extent of surgical intervention, fine needle aspiration (FNA) is a widely accepted tool to approach salivary gland lesions. However, the FNA cytology varies between entities, while the lack of uniform terminology makes diagnosis more challenging. Since establishing the Milan system for reporting salivary gland cytopathology (MSRSGC) has become an increasingly accepted reporting standard, further examination and detailed recommendations were needed. (2) Methods: Between April 2013 and October 2021, 375 cases with FNA and salivary gland resection were retrospectively collected. All FNA specimens were reclassified according to the criteria of MSRSGC. After surgical excision, the FNA data were compared with the histological diagnosis to estimate the risk of malignancy (ROM), the risk of neoplasm (RON), and the diagnostic accuracy for each diagnostic category. (3) Results: Our cohort’s distribution of ROM and RON was similar to the MSRSGC’s recommendation. Carcinoma ex pleomorphic adenoma (CXPA) has the highest rate (66.7%) of misdiagnosed as a nonneoplastic lesion or benign salivary gland tumor. Pleomorphic adenoma (PA) and Warthin’s tumor were the most common benign salivary gland tumors, while the cytology diagnosis of Warthin’s tumor seems more challenging than PAs. (4) Conclusions: Despite the convenience and effectiveness of MSRSGC, we suggest close follow-up, re-biopsy, or surgical removal for salivary lesions even in Milan IVA-Benign for possibly missing FNA of malignancy, mixed lesions, or prevention of malignant transformation.

Bone metastasis is the primary cause of death among patients with advanced prostate cancer (PCa). PCa tends to spread to bones and acquire the bone‐like phenotype, causing osteoblastic bone metastasis. Unfortunately, there is no effective treatment for this condition. However, melatonin, which regulates our circadian rhythm, has been found to have anti‐tumor properties. It has yet to be established whether it is effective in treating osteoblastic PCa metastasis. Our findings show that melatonin inhibits the production of endothelin‐1 (ET‐1) in osteoblastic PCa cells, suppressing osteoblast differentiation. Clinical results indicate that bone metastatic PCa patients have higher levels of ET‐1 compared to nonmetastatic PCa patients. Furthermore, melatonin‐induced miR‐let‐7f‐5p inhibits ET‐1‐promoted osteoblast differentiation in osteoblastic PCa. Melatonin also suppresses the property of osteomimicry in osteoblastic PCa cells. Importantly, in the intratibia injection PCa metastasis model, melatonin decreased osteoblastic PCa tumor growth, inhibiting ET‐1 production and osteoblast differentiation in vivo. Taken together, melatonin inhibits osteoblastic PCa‐regulated osteoblastogenesis by reducing ET‐1 production through upregulation of miR‐let‐7f‐5p, while suppressing the property of osteomimicry in osteoblastic PCa. Melatonin therapy could be a promising approach to treating bone metastasis in osteoblastic PCa. [ABSTRACT FROM AUTHOR]

Melatonin, a naturally biosynthesized molecule secreted by the pineal gland, exhibits antitumor activities against several different types of cancer. The mechanisms of action of melatonin against tumor progression involve cellular apoptosis, antimetastatic activity, antioxidant and mutagenic effects, antiangiogenic activity, and the restoration of cancer immune surveillance. Melatonin has anticancer activity when administered alone or in combination with standard chemotherapeutic agents, with measurable improvements seen in the clinical endpoints of tumor regression and patient survival. However, scant clinical evidence supports the use of melatonin in bladder cancer treatment. Our study has found that melatonin treatment suppresses the bladder cancer cell migratory ability by inhibiting the epithelial-mesenchymal transition (EMT) process, which appears to be linked to melatonin-induced decreases in bladder cancer cell autophagy. Finally, an evaluation of in vivo melatonin-induced antitumor effects in an orthotopic animal model of bladder cancer indicated that melatonin treatment slightly prolonged the survival of tumor-bearing mice. Our study offers novel insights into the use of melatonin in bladder cancer treatment.

Prostate cancer commonly affects the urinary tract of men and metastatic prostate cancer has a very low survival rate. Apelin belongs to the family of adipokines and is associated with cancer development and metastasis. However, the effects of apelin in prostate cancer metastasis is undetermined. Analysis of the database revealed a positive correlation between apelin level with the progression and metastasis of prostate cancer patients. Apelin treatment facilitates cell migration and invasion through inhibiting tissue inhibitor of metalloproteinase 2 (TIMP2) expression. The increasing miR-106a-5p synthesis via c-Src/PI3K/Akt signaling pathway is controlled in apelin-regulated TIMP2 production and cell motility. Importantly, apelin blockade inhibits prostate cancer metastasis in the orthotopic mouse model. Thus, apelin is a promising therapeutic target for curing metastatic prostate cancer.

Vented brake rotors used in an automobile behave similarly to centrifugal fans, drawing cool air from the inboard side, passing it through the disc vents, and exhausting it from the periphery. A vented brake rotor with a better heat dispersing ability is often superior to a solid rotor, in both thermal performance and brake efficiency. In this research, a fully parameterized model for a ventilated brake rotor is created using the ANSYS Parametric Design Language, to uniquely define the rotor’s geometry. With this parameterized model, two structural optimization cases are studied in this paper. The first one investigated is a modal frequency separation problem: The frequency differences in a tangential mode sandwiched between two nodal diameter modes of the brake rotor model are maximized. An automatic identification scheme for extracting correct mode orders is implemented in the program to track the correct modes during optimization. The second case is a thermal deformation problem: The distortion on the frictional surfaces of the rotor loaded with heat flux generated during the braking process is minimized. The optimization results show that a brake rotor design with a thinner outboard disc and a thicker inboard disc provides a great choice for rotor coning reduction.

Abstract Background We evaluated the impact of temperature and Wolbachia infection on vector competence of the local Aedes aegypti and Ae. albopictus populations of southern Taiwan in the laboratory. Results After oral infection with dengue serotype 1 virus (DENV-1), female mosquitoes were incubated at temperatures of 10, 16, 22, 28 and 34 °C. Subsequently, salivary gland, head, and thorax-abdomen samples were analyzed for their virus titer at 0, 5, 10, 15, 20, 25 and 30 days post-infection (dpi) by real-time RT-PCR. The results showed that Ae. aegypti survived significantly longer and that dengue viral genome levels in the thorax-abdomen (103.25 ± 0.53–104.09 ± 0.71 PFU equivalents/ml) and salivary gland samples (102.67 ± 0.33–103.89 ± 0.58 PFU equivalents/ml) were significantly higher at high temperature (28–34 °C). The survival of Ae. albopictus was significantly better at 16 or 28 °C, but the virus titers from thorax-abdomen (100.70–102.39 ± 1.31 PFU equivalents/ml) and salivary gland samples (100.12 ± 0.05–101.51 ± 0.31 PFU equivalents/ml) were significantly higher at 22–28 °C. Within viable temperature ranges, the viruses were detectable after 10 dpi in salivary glands and head tissues in Ae. aegypti and after 5–10 dpi in Ae. albopictus. Vector competence was measured in Ae. albopictus with and without Wolbachia at 28 °C. Wolbachia-infected mosquitoes survived significantly better and carried lower virus titers than Wolbachia-free mosquitoes. Wolbachia coinfections (92.8–97.2%) with wAlbA and wAlbB strains were commonly found in a wild population of Ae. albopictus. Conclusions In southern Taiwan, Ae. aegypti is the main vector of dengue and Ae. albopictus has a non-significant role in the transmission of dengue virus due to the high prevalence of Wolbachia infection in the local mosquito population of southern Taiwan.

Abstract A series of novel polyimidothioethers (PITEs) and the respective polymer hybrids of titania or zirconia with fantastic thermal stability and optical properties have been successfully prepared. These colorless PITEs with high transparency were synthesized by Michael polyaddition from commercially available dithiol and bismaleimides monomers. The PITE with sulfide and hydroxyl groups (S-OH) and the corresponding hybrid films declare ultra-lowest birefringence value of 0.002 and tunable refractive index (1.65–1.81 for S-OH/titania and 1.65–1.80 for S-OH/zirconia), implying large potential to the optical applications in the future. Moreover, the S-OH/zirconia hybrid films exhibit higher Abbe’s number and optical transparency than those of S-OH/titania system because larger energy band gap of ZrO2. Furthermore, by adding titania and zirconia as electron acceptor into S-OH system, the charge transfer complex can be facilitated and stabilized caused by the lower LUMO energy level of hybrid materials. Consequently, the devices of memory prepared from these polymer films of hybrid showed interesting and adjustable memory behavior from DRAM, SRAM, to WORM at various titania or zirconia contents with a large ON/OFF ratio (108), denoting that the memory devices derived from these highly transparent novel S-OH/TiO2 and S-OH/ZrO2 hybrid films are attractive for the electrical applications.

Fumarate nitrate reduction regulator (FNR) is a direct oxygen-responsive transcriptional regulator containing an iron-sulfur (Fe–S) cluster. During anaerobic growth, the [4Fe–4S] cluster in FNR (holo-FNR) binds specifically to DNA, whereas exposure to oxygen results in the loss of its DNA-binding activity via oxidation of the [4Fe–4S] cluster. In this study, we aimed to investigate the role of FNR in regulation of capsular polysaccharide (CPS) biosynthesis, serum resistance, and anti-phagocytosis of K. pneumoniae. We found that the CPS amount in K. pneumoniae increased in anaerobic conditions, compared to that in aerobic conditions. An fnr deletion mutant and a site-directed mutant (fnr3CA), with the three cysteines (C20, C23, and C29) replaced with alanines to mimic an FNR lacking the [4Fe-4S] cluster, showed marked increase in CPS amount under anaerobic conditions. A promoter-reporter assay and qRT-PCR confirmed that the transcription of the cps genes was repressed by holo-FNR. In addition, we found that holo-FNR could repress the transcription of rmpA and rmpA2, encoding cps transcriptional activators. Deletion of rmpA or rmpA2 in the Δfnr strain reduced CPS biosynthesis, suggesting that RmpA and RmpA2 participated in the holo-FNR–mediated repression of cps transcription, thereby regulating the CPS amount, serum resistance, and anti-phagocytosis. Taken together, our results provided evidence that RmpA and RmpA2 participated in the holo-FNR–mediated repression of CPS biosynthesis, and resistance to the host defense in response to oxygen availability.

Abstract Background Thrombospondin-2 (TSP-2) is a secreted matricellular glycoprotein that is found to mediate cell-to-extracellular matrix attachment and participates in many physiological and pathological processes. The expression profile of TSP-2 on tumors is controversial, and it up-regulates in some cancers, whereas it down-regulates in others, suggesting that the functional role of TSP-2 on tumors is still uncertain. Methods The expression of TSP-2 on prostate cancer progression was determined in the tissue array by the immunohistochemistry. The molecular mechanism of TSP-2 on prostate cancer (PCa) metastasis was investigated through pharmaceutical inhibitors, siRNAs, and miRNAs analyses. The role of TSP-2 on PCa metastasis in vivo was verified through xenograft in vivo imaging system. Results Based on the gene expression omnibus database and immunohistochemistry, we found that TSP-2 increased with the progression of PCa, especially in metastatic PCa and is correlated with the matrix metalloproteinase-2 (MMP-2) expression. Additionally, through binding to CD36 and integrin ανβ3, TSP-2 increased cell migration and MMP-2 expression. With inhibition of p38, ERK, and JNK, the TSP-2-induced cell migration and MMP-2 expression were abolished, indicating that the TSP-2’s effect on PCa is MAPK dependent. Moreover, the microRNA-376c (miR-376c) was significantly decreased by the TSP-2 treatment. Furthermore, the TSP-2-induced MMP-2 expression and the subsequent cell motility were suppressed upon miR-376c mimic stimulation. On the other hand, the animal studies revealed that the bone metastasis was abolished when TSP-2 was stably knocked down in PCa cells. Conclusions Taken together, our results indicate that TSP-2 enhances the migration of PCa cells by increasing MMP-2 expression through down-regulation of miR-376c expression. Therefore, TSP-2 may represent a promising new target for treating PCa.

OmpR/EnvZ is a two-component system that senses osmotic signals and controls downstream gene expression in many species of Enterobacteriaceae. However, the role of OmpR/EnvZ in Klebsiella pneumoniae remains unknown. In this study, we found that production of MrkA, the major subunit of type 3 fimbriae, was decreased under hypertonic conditions. A deletion mutant of ompR and a site-directed mutant with a single amino acid substitution of aspartate 55 to alanine (D55A), which mimics the unphosphorylated form of OmpR, markedly reduced MrkA production under hypertonic conditions. These results indicate that K. pneumoniae type 3 fimbriae expression is activated by the phosphorylated form of OmpR (OmpR∼P). Although no typical OmpR∼P binding site was found in the PmrkA sequence, mrkA mRNA levels and PmrkA activity were decreased in the ΔompR and ompRD55A strains compared with the wild type (WT) strain, indicating that OmpR∼P mediates type 3 fimbriae expression at the transcriptional level. Previous reports have demonstrated that a cyclic-di-GMP (c-di-GMP) related gene cluster, mrkHIJ, regulates the expression of type 3 fimbriae. We found that both the ompR and ompRD55A mutants exhibited decreased mrkHIJ mRNA levels, intracellular c-di-GMP concentration, and bacterial biofilm amount, but increased total intracellular phosphodiesterase activity in response to hypertonic conditions. These results indicate that OmpR∼P regulates type 3 fimbriae expression to influence K. pneumoniae biofilm formation via MrkHIJ and modulation of intracellular c-di-GMP levels. Taken together, we herein provide evidence that OmpR∼P acts as a critical factor in the regulation of the c-di-GMP signaling pathway, type 3 fimbriae expression, and biofilm amount in K. pneumoniae in response to osmotic stresses.

In Klebsiella pneumoniae, we have previously shown that IscR, an Fe–S cluster-containing transcriptional factor, plays a dual role in controlling capsular polysaccharide biosynthesis and iron-acquisition systems by switching between its holo and apo forms. In this study, the effect of IscR on type 3 fimbriae expression and biofilm formation was investigated. We found that production of the major subunit of type 3 fimbriae, MrkA, was increased in the ΔiscR and iscR3CA strains, a strain expressing a mutant IscR that mimics apo-IscR, at both the translational and transcriptional levels. Based on the fact that type 3 fimbriae expression is the major factor affecting biofilm formation, increased biofilm formation was also found in ΔiscR or iscR3CA, suggesting that holo-IscR represses biofilm formation. However, the repression of type 3 fimbriae expression by IscR is indirect. To further understand the regulatory mechanism of IscR, the effect of IscR on the expression of mrkHIJ, which encodes cyclic di-GMP (c-di-GMP)-related regulatory proteins that control type 3 fimbriae expression, was studied. We found that holo-IscR could directly repress mrkHI transcription, indicating that MrkHI is required for IscR regulation of type 3 fimbriae expression. Finally, deletion of iscR attenuated K. pneumoniae virulence in a peritonitis model of mouse infection, while the absence of the [2Fe–2S] cluster of IscR had no effect on K. pneumoniae virulence during infection. Taken together, our results demonstrate the underlying mechanism of the [2Fe–2S] cluster of IscR in controlling type 3 fimbriae expression and its effect on K. pneumoniae pathogenesis.

The effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with diabetes mellitus (DM) remain unknown. We investigated the effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with DM.We conducted a cohort study by using the diabetes dataset of the Taiwan National Health Insurance Research Database from 1 January, 2002 to 31 December, 2013. We included 10,938 patients received one type of oxybutynin, solifenacin, or tolterodine, while 564,733 had not. We included a comparable number of patients not receiving oxybutynin, solifenacin, or tolterodine as controls through systematic random sampling matching by age, gender, and the year of the index date with 1 to 1 ratio. The dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors.The dementia event rates were 3.9% in the oxybutynin group, 4.3% in the solifenacin group, 2.2% in the tolterodine group and 1.2% in the control group (P