Molecular Characterization of High and Low Virulent Escherichia coli Clinical Strains Isolated from Patients with Urinary Tract Infections with or without Bacteremia in Southern Taiwan.

Objective: The most common extraintestinal pathogen and infection site is uropathogenic Escherichia coli (UPEC), which causes urinary tract infections (UTIs). UPEC is also a common pathogen in bloodstream infections; in severe cases, it can lead to death. Although host and bacterial virulence factors have been demonstrated to be associated with UTI pathogenesis, the role of the related contributing factors in UTI and urinary source bacteremia is not yet fully understood. This study aimed to compare and analyze the factors contributing to urinary bacteremia in patients with UTI. Methods: A total of 171 E. coli strains collected from patients with UTI and urinary source bacteremia at Chiayi Christian Hospital were used. Phylogenetic groups and virulence factors were determined using PCR. Drug resistance patterns were determined using the disk diffusion assay. Results: Previous studies have demonstrated that fimbriae and papGII may be associated with first-step infections and severe UTIs, respectively. As expected, highly virulent E. coli strains (belonging to the phylogenetic B2 and D groups) were dominant in the bacteremic UTI (90%) and UTI (86.27%) groups. However, our results showed that the UTI group had a significantly higher prevalence of sfa/focDE (belonging to the S and FIC fimbriae) than the bacteremic UTI group (29.4% vs 12.5%; p=0.008). In the bacteremic group, we found that sfa/focDE was only detected in highly virulent strains. The bacteremic UTI group had a significantly higher prevalence of papGII (belonging to P fimbriae) than the UTI group (55.8% vs 37.3%; p=0.026). In addition, the P fimbriae gene cluster, including papC, papEF, and papGII, was predominant in highly virulent strains. Notably, our results show that multidrug-resistant (MDR) strains were significantly less virulent than non MDR strains. Conclusion: Taken together, our results provide insights into the contributing factors in patients with UTI and urinary bacteremia.

Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

Comparable clinical outcomes with same-day versus rapid initiation of antiretroviral therapy in Taiwan.

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

Single-worm long-read sequencing reveals genome diversity in free-living nematodes.

Obtaining sufficient genetic material from a limited biological source is currently the primary operational bottleneck in studies investigating biodiversity and genome evolution. In this study, we employed multiple displacement amplification (MDA) and Smartseq2 to amplify nanograms of genomic DNA and mRNA, respectively, from individual Caenorhabditis elegans. Although reduced genome coverage was observed in repetitive regions, we produced assemblies covering 98% of the reference genome using long-read sequences generated with Oxford Nanopore Technologies (ONT). Annotation with the sequenced transcriptome coupled with the available assembly revealed that gene predictions were more accurate, complete and contained far fewer false positives than de novo transcriptome assembly approaches. We sampled and sequenced the genomes and transcriptomes of 13 nematodes from early-branching species in Chromadoria, Dorylaimia and Enoplia. The basal Chromadoria and Enoplia species had larger genome sizes, ranging from 136.6 to 738.8 Mb, compared with those in the other clades. Nine mitogenomes were fully assembled, and displayed a complete lack of synteny to other species. Phylogenomic analyses based on the new annotations revealed strong support for Enoplia as sister to the rest of Nematoda. Our result demonstrates the robustness of MDA in combination with ONT, paving the way for the study of genome diversity in the phylum Nematoda and beyond.

Direct Visualization of the Self-Alignment Process for Nanostructured Block Copolymer Thin Films by Transmission Electron Microscopy.

Herein, this work aims to directly visualize the morphological evolution of the controlled self-assembly of star-block polystyrene-block-polydimethylsiloxane (PS-b-PDMS) thin films via in situ transmission electron microscopy (TEM) observations. With an environmental chip, possessing a built-in metal wire-based microheater fabricated by the microelectromechanical system (MEMS) technique, in situ TEM observations can be conducted under low-dose conditions to investigate the development of film-spanning perpendicular cylinders in the block copolymer (BCP) thin films via a self-alignment process. Owing to the free-standing condition, a symmetric condition of the BCP thin films can be formed for thermal annealing under vacuum with neutral air surface, whereas an asymmetric condition can be formed by an air plasma treatment on one side of the thin film that creates an end-capped neutral layer. A systematic comparison of the time-resolved self-alignment process in the symmetric and asymmetric conditions can be carried out, giving comprehensive insights for the self-alignment process via the nucleation and growth mechanism.

The Aphelenchoides genomes reveal substantial horizontal gene transfers in the last common ancestor of free-living and major plant-parasitic nematodes.

Aphelenchoides besseyi is a plant-parasitic nematode (PPN) in the family Aphelenchoididae capable of infecting more than 200 plant species. A. besseyi is also a species complex with strains exhibiting varying pathogenicity to plants. We present the genome and annotations of six Aphelenchoides species, four of which belonged to the A. besseyi species complex. Most Aphelenchoides genomes have a size of 44.7-47.4 Mb and are among the smallest in clade IV, with the exception of A. fujianensis, which has a size of 143.8 Mb and is one of the largest. Phylogenomic analysis successfully delimited the species complex into A. oryzae and A. pseudobesseyi and revealed a reduction of transposon elements in the last common ancestor of Aphelenchoides. Synteny analyses between reference genomes indicated that three chromosomes in A. besseyi were derived from fission and fusion events. A systematic identification of horizontal gene transfer (HGT) genes across 27 representative nematodes allowed us to identify two major episodes of acquisition corresponding to the last common ancestor of clade IV or major PPNs, respectively. These genes were mostly lost and differentially retained between clades or strains. Most HGT events were acquired from bacteria, followed by fungi, and also from plants; plant HGT was especially prevalent in Bursaphelenchus mucronatus. Our results comprehensively improve the understanding of HGT in nematodes.

Characteristics and local risk factors of community-acquired and health-care-associated Staphylococcus aureus pneumonia.

This study aims at identifying characteristics, risk factors and mortality of community-acquired (CAP) and health-care-associated pneumonia (HCAP) by Staphylococcus aureus (S. aureus). We retrieved adults with S. aureus CAP or HCAP diagnosed by blood or pleural effusion culture in 2.6 years, and compared with those of Streptococcus pneumoniae (S. pneumoniae) CAP or HCAP diagnosed by blood or respiratory culture, or urine antigen. We found 18 patients with CAP and 9 HCAP due to S. aureus (female 33%, 66.6 ± 12.4 years-old), and 48 patients with CAP and 15 HCAP due to S pneumoniae (female 41%, 69.5 ± 17.5 years). Diabetes mellitus (52% vs. 24%, p = 0.019), hemodialysis (11% vs. 0%, p = 0.046), skin lesions (44% vs. 0%, p < 0.001), cavitary nodules (37% vs. 1.6%, p < 0.001) and pleural effusions (48% vs. 18%, p = 0.007) were more common in staphylococcal than pneumococcal group. Three patients with staphylococcal pneumonia had acute myocardial infarction. Pneumonia severity index (139 ± 52 vs. 109 ± 43, p = 0.005) and 30-day mortality (41% vs. 9.5%, p = 0.001) were higher in staphylococcal group. Multivariate analysis showed underlying disease (especially cancer and cirrhosis), risk class 4/5, altered mentality, shock and bilateral pneumonia were risk factors for 30-day mortality.

Vacuum-Driven Orientation of Nanostructured Diblock Copolymer Thin Films.

This work aims to demonstrate a facile method for the controlled orientation of nanostructures of block copolymer (BCP) thin films. A simple diblock copolymer system, polystyrene-block-polydimethylsiloxane (PS-b-PDMS), is chosen to demonstrate vacuum-driven orientation for solving the notorious low-surface-energy problem of silicon-based BCP nanopatterning. By taking advantage of the pressure dependence of the surface tension of polymeric materials, a neutral air surface for the PS-b-PDMS thin film can be formed under a high vacuum degree (∼10-4 Pa), allowing the formation of the film-spanning perpendicular cylinders and lamellae upon thermal annealing. In contrast to perpendicular lamellae, a long-range lateral order for forming perpendicular cylinders can be efficiently achieved through the self-alignment mechanism for induced ordering from the top and bottom of the free-standing thin film.

Ureteral stone with hydronephrosis and urolithiasis alone are risk factors for acute kidney injury in patients with urinary tract infection.

To identify whether urolithiasis with or without hydronephrosis has an impact on acute kidney injury (AKI) in patients with urinary tract infection (UTI). This study aimed to identify whether urolithiasis with or without hydronephrosis has an impact on AKI in patients with UTI. This retrospective study enrolled hospitalized UTI patients who underwent imaging in an acute care setting from January 2006 to April 2019. Of the 1113 participants enrolled, 191 (17.2%) had urolithiasis and 76 (6.8%) had ureteral stone complicated with hydronephrosis. Multivariate logistic regression analysis showed that in UTI patients with urolithiasis, the presence of ureteral stone with concomitant hydronephrosis was an independent risk factor for AKI (odds ratio [OR] 2.299, 95% confidence interval [CI] 1.112-4.755, P = 0.025). In addition, urolithiasis was associated with an increased risk for AKI (OR 2.451, 95% CI 1.369-4.389, P = 0.003) in UTI patients without hydronephrosis. The presence of ureteral stone with hydronephrosis increases the risk for AKI of UTI patients with urolithiasis, and urolithiasis remains a risk factor of AKI in UTI patients without hydronephrosis.

Glycan Masking of Epitopes in the NTD and RBD of the Spike Protein Elicits Broadly Neutralizing Antibodies Against SARS-CoV-2 Variants.

Glycan-masking the vaccine antigen by mutating the undesired antigenic sites with an additional N-linked glycosylation motif can refocus B-cell responses to desired epitopes, without affecting the antigen's overall-folded structure. This study examined the impact of glycan-masking mutants of the N-terminal domain (NTD) and receptor-binding domain (RBD) of SARS-CoV-2, and found that the antigenic design of the S protein increases the neutralizing antibody titers against the Wuhan-Hu-1 ancestral strain and the recently emerged SARS-CoV-2 variants Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). Our results demonstrated that the use of glycan-masking Ad-S-R158N/Y160T in the NTD elicited a 2.8-fold, 6.5-fold, and 4.6-fold increase in the IC-50 NT titer against the Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2) variants, respectively. Glycan-masking of Ad-S-D428N in the RBD resulted in a 3.0-fold and 2.0-fold increase in the IC-50 neutralization titer against the Alpha (B.1.1.7) and Beta (B.1.351) variants, respectively. The use of glycan-masking in Ad-S-R158N/Y160T and Ad-S-D428N antigen design may help develop universal COVID-19 vaccines against current and future emerging SARS-CoV-2 variants.

Impact of Nutritional Assessment on the Clinical Outcomes of Patients with Non-albicans Candidemia: A Multicenter Study.

Several studies have demonstrated that malnutrition is a negative prognostic factor for clinical outcomes. However, there is limited evidence for the effect of malnutrition on clinical outcomes in patients with candidemia. We investigated the relationship between malnutrition and all-cause 28-day mortality among patients with non-albicans candidemia. Between July 2011 and June 2014, all adult patients with non-albicans candidemia, including C. tropicalis, C. glabrata, C. parapsilosis and so on, were enrolled. The Malnutrition Universal Screening Tool (MUST) scores were used to determine the patients' nutritional status before the onset of candidemia. A total of 378 patients were enrolled; 43.4% developed septic shock and 57.1% had a high risk of malnutrition (MUST ≥ 2). The all-cause 28-day mortality rate was 40.7%. The Cox proportional hazards model revealed that C. tropicalis (HR, 2.01; 95% CI, 1.24-3.26; p = 0.005), Charlson comorbidity index (HR, 1.10; 95% CI, 1.03-1.18; p = 0.007), Foley catheter use (HR, 1.68; 95% CI, 1.21-1.35; p = 0.002), concomitant bacterial infections (HR, 1.55; 95% CI, 1.11-2.17; p = 0.010), low platelet count (HR, 3.81; 95% CI, 2.45-5.91; p < 0.001), not receiving antifungals initially (HR, 4.73; 95% CI, 3.07-7.29; p < 0.001), and MUST ≥ 2 (HR, 1.54; 95% CI, 1.09-2.17; p = 0.014) were independently associated with all-cause 28-day mortality. A simple screening tool for nutritional assessment should be used for patients with non-albicans candidemia to detect early clinical deterioration, and a tailored nutritional care plan should be established for malnourished individuals, to improve their clinical outcomes.

COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay.

Coatomer complexes function in the sorting and trafficking of proteins between subcellular organelles. Pathogenic variants in coatomer subunits or associated factors have been reported in multi-systemic disorders, i.e., coatopathies, that can affect the skeletal and central nervous systems. We have identified loss-of-function variants in COPB2, a component of the coatomer complex I (COPI), in individuals presenting with osteoporosis, fractures, and developmental delay of variable severity. Electron microscopy of COPB2-deficient subjects' fibroblasts showed dilated endoplasmic reticulum (ER) with granular material, prominent rough ER, and vacuoles, consistent with an intracellular trafficking defect. We studied the effect of COPB2 deficiency on collagen trafficking because of the critical role of collagen secretion in bone biology. COPB2 siRNA-treated fibroblasts showed delayed collagen secretion with retention of type I collagen in the ER and Golgi and altered distribution of Golgi markers. copb2-null zebrafish embryos showed retention of type II collagen, disorganization of the ER and Golgi, and early larval lethality. Copb2+/- mice exhibited low bone mass, and consistent with the findings in human cells and zebrafish, studies in Copb2+/- mouse fibroblasts suggest ER stress and a Golgi defect. Interestingly, ascorbic acid treatment partially rescued the zebrafish developmental phenotype and the cellular phenotype in Copb2+/- mouse fibroblasts. This work identifies a form of coatopathy due to COPB2 haploinsufficiency, explores a potential therapeutic approach for this disorder, and highlights the role of the COPI complex as a regulator of skeletal homeostasis.

Hepatitis B virus seroprevalence among HIV-infected patients receiving combination antiretroviral therapy three decades after universal neonatal hepatitis B immunization program in Taiwan.

BACKGROUND/PURPOSE: This multicenter study aimed to evaluate the seroprevalence of hepatitis B virus (HBV) and the use of combination antiretroviral therapy (cART) among patients receiving HIV care in Taiwan. METHODS: We retrospectively reviewed the medical records of HIV-infected adult patients who initiated cART at 11 designated hospitals in Taiwan between 2012 and 2016. The clinical information collected included serological profiles on HBV, hepatitis C virus (HCV), and syphilis, plasma HIV RNA load, nadir CD4 cell count, and antiretrovirals with activity against both HBV and HIV (tenofovir disoproxil fumarate [TDF], lamivudine [LAM], and emtricitabine [FTC]). RESULTS: We analyzed 1800 HIV-infected patients; 1742 (96.8%) were male and 794 (44.1%) were born after July, 1986, when nationwide universal neonatal HBV vaccination was implemented. HBsAg positive results were 11.6% (209/1800), which decreased significantly from 18.1% (182/1006) in those born before July 1986 to 3.4% (27/794) in those born after. In multivariable analysis, HBsAg positivity was significantly associated with age (adjusted odds ratio [aOR] 1.06, 95% confidence interval [CI] 1.05-1.08), CD4≧200 cells/µL (aOR 0.73, 95% CI 0.53-0.99), and HCV seropositivity (aOR 1.62, 95% CI 1.06-2.50). Of 209 HBV/HIV-coinfected patients, 31.1% started cART containing only LAM with anti-HBV activity, while 68.9% started cART containing TDF plus LAM or coformulated TDF/FTC. CONCLUSIONS: The overall prevalence of HBV/HIV coinfection remained high among HIV-infected patients in Taiwan. Despite recommendations of the HIV treatment guidelines for the management of HBV infection, a substantial proportion of HIV/HBV-coinfected patients received cART containing only LAM for HBV infection.

Glycated Hemoglobin < 6.5% Is Associated With Uroseptic Shock in Diabetic Patients With Urinary Tract Infection.

This study aimed to compare the clinical characteristics and treatment outcomes of diabetic and non-diabetic individuals with urinary tract infection (UTI) and determine whether glycated hemoglobin (HbA1c) levels <6. 5% leads to uroseptic shock in diabetic individuals. We retrospectively collected and analyzed the clinical data of 1,363 individuals with UTIs in Taiwan from January 2006 to January 2018. Of the 345 diabetic individuals, 61 (17.7%) developed uroseptic shock. Diabetic patients who developed uroseptic shock tended to be older and males and, had a history of congestive heart failure, urolithiasis, higher serum creatinine level during hospitalization, lower serum HbA1c level, bacteremia, and acute kidney injury. Backward stepwise multivariate logistic regression analysis showed that male gender [odds ratio (OR), 1.861; 95% confidence interval (CI), 1.009-3.433; P = 0.047], congestive heart failure (OR, 4.036; 95% CI, 1.542-10.565; P = 0.004), bacteremia (OR, 2.875; 95% CI, 1.539-5.370; P = 0.001), and HbA1c level <6.5% (OR, 2.923; 95% CI, 1.580-5.406; P = 0.001) were associated with an increased risk of developing uroseptic shock among diabetic patients during hospitalization due to UTI. HbA1c level <6.5% is independently associated with uroseptic shock in diabetic patients with UTI.

Prevalence of fosfomycin resistance and gene mutations in clinical isolates of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Fosfomycin exhibits excellent in vitro activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Increasing fosfomycin resistance among clinical MRSA isolates was reported previously, but little is known about the relative abundance of Fosfomycin resistance genes in MRSA isolates circulating in Taiwan. METHODS: All MRSA isolates, collected in 2002 and 2012 by the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program, were used in this study. Susceptibility to various antimicrobial agents, including fosfomycin, was determined by broth microdilution. Genetic determinants of fosfomycin resistance, including fosB carriage and murA, glpT and uhpT mutations, were investigated using PCR and sequencing of amplicons. Staphylococcal protein A (spa) typing was also performed to determine the genetic relatedness of MRSA isolates. RESULTS: A total of 969 MRSA strains, 495 in the year 2002 and 474 in the year 2012, were analyzed. The overall in vitro susceptibility was 8.2% to erythromycin, 18.0% to clindamycin, 29.0% to tetracycline, 44.6% to ciprofloxacin, 57.5% to trimethoprim/sulfamethoxazole, 86.9% to rifampicin, 92.9% to fosfomycin and 100% to linezolid and vancomycin. A significant increase in the fosfomycin resistance rate was observed from 3.4% in 2002 to 11.0% in 2012. Of 68 fosfomycin-resistant MRSA isolates, several genetic backgrounds probably contributing to fosfomycin resistance were identified. Twelve isolates harbored the fosB gene, and various mutations in murA, uhpT, and glpT genes were noted in 11, 59, and 66 isolates, respectively. The most prevalent gene mutations were found in the combination of uhpT and glpT genes (58 isolates). The vast majority of the fosfomycin-resistant MRSA isolates belonged to spa type t002. CONCLUSIONS: An increased fosfomycin resistance rate of MRSA isolates was observed in our present study, mostly due to mutations in the glpT and uhpT genes. Clonal spread probably contributed to the increased fosfomycin resistance.

Risk factors for uroseptic shock in hospitalized patients aged over 80 years with urinary tract infection.

BACKGROUND: The purpose of this study was to compare clinical characteristics and outcomes in individuals of different age groups with urinary tract infection (UTI), and to identify the relationships among advanced age and uroseptic shock. METHODS: This retrospective study compared clinical characteristics and outcomes in patients in different age groups with UTI and identified relationships between advanced age and uroseptic shock among hospitalized patients with UTI in an acute hospital care setting from January 2006 to October 2018. Patients were divided into young (age below 65 years), old (65-80 years), and very old (above 80 years) groups. RESULTS: Of 1,043 participants, 269 (25.8%) were very old and 200 (19.2%) developed uroseptic shock. Very old age [odds ratio (OR) 1.99, 95% confidence interval (CI): 1.25-3.19, P=0.004], male (OR 1.54, 95% CI: 1.07-2.24, P=0.022), presented flank pain (OR 1.54, 95% CI: 1.05-2.24, P=0.025), congestive heart failure (CHF) (OR 2.54, 95% CI: 1.27-5.06, P=0.008), acute kidney injury (AKI) (OR 4.19, 95% CI: 2.78-6.30, P<0.001), bacteremia (OR 1.78, 95% CI: 1.25-2.53, P=0.001), and multiple drug-resistant (MDR) bacteria (OR 1.43, 95% CI: 1.02-2.00, P=0.039) were associated with an increased risk of uroseptic shock in patients with UTI. In very old patients with UTI, bacteremia (OR 2.54, 95% CI: 1.38-4.69, P=0.003) and AKI (OR 4.37, 95% CI: 2.15-8.90, P<0.001) were independently associated with uroseptic shock. CONCLUSIONS: Very old patients with UTI had a higher risk of developing uroseptic shock than younger patients. Bacteremia was an independent risk factor for uroseptic shock in very old patients with UTI.

A mouse model of chemotherapy-related cognitive impairments integrating the risk factors of aging and APOE4 genotype.

Some cancer survivors experience marked cognitive impairment, referred to as cancer-related cognitive impairment (CRCI). CRCI has been linked to the genetic factor APOE4, the strongest genetic risk factor for Alzheimer's disease (AD). We used APOE knock-in mice to test whether the relationship between APOE4 and CRCI can be demonstrated in a mouse model, to identify associations of chemotherapy with behavioural and structural correlates of cognition, and to test whether chemotherapy affects markers of AD. Twelve-month old C57BL/6 J female APOE3 (n = 30) and APOE4 (n = 31) knock-in mice were randomized to treatment with either doxorubicin (10 mg/kg) or saline. Behavioural assays at 2-21 weeks-post exposure included open field maze, elevated zero maze, pre-pulse inhibition, Barnes maze, and fear conditioning. Ex-vivo magnetic resonance imaging was used to determine regional volume differences at 31-35 weeks-post exposure, and tissue sections were analyzed for markers of AD pathogenesis. Minimal toxicities were observed in the aged mice after doxorubicin exposure. In the Barnes maze assay, APOE3 mice did not exhibit impairment in spatial learning after doxorubicin treatment, but APOE4 mice demonstrated significant impairments in both the initial identification of the escape hole and the latency to full escape at 6 weeks post-exposure. Both APOE3 and APOE4 mice treated with doxorubicin showed impairment of spatial memory. Grey matter volume in the frontal cortex decreased in APOE4 mice treated with doxorubicin vs. APOE3 mice. This study demonstrates cognitive impairments in aged APOE4 knock-in mice after doxorubicin treatment and establishes this system as a novel and powerful model of CRCI.

Urolithiasis Is a Risk Factor for Uroseptic Shock and Acute Kidney Injury in Patients With Urinary Tract Infection.

Urinary tract infection (UTI) is a common complication in patients with urolithiasis. This study aimed to compare clinical manifestations and treatment outcomes among UTI patients with or without urolithiasis. It also focused on identifying relationships among urolithiasis, uroseptic shock, and acute kidney injury (AKI). This retrospective study enrolled hospitalized UTI patients who underwent imaging in an acute care setting from January 2006 to March 2015. Of 662 participants enrolled, 113 (17.1%) had urolithiasis, 107 (16.2%) developed uroseptic shock, and 184 (27.8%) developed AKI. A multivariate logistic regression analysis showed that in UTI patients, urolithiasis is associated with an increased risk of uroseptic shock (OR 1.80, 95% CI: 1.08-3.02, P = 0.025), AKI (OR 1.95, 95% CI: 1.22-3.12, P = 0.005), and bacteremia (OR 1.68, 95% CI: 1.08-2.64, P = 0.022). Urolithiasis is common in UTI patients and is associated with an increased risk of uroseptic shock and AKI.

Non-traumatic perforation of the jejunum in a human immunodeficiency virus-infected patient receiving combination antiretroviral therapy: A case report.

RATIONALE: Non-traumatic bowel perforation caused by cytomegalovirus (CMV) and Mycobacterium avium complex (MAC) infections has become rare among patients with acquired immunodeficiency syndrome (AIDS) in the era of combination antiretroviral therapy (cART); however, CMV-associated and MAC-related immune reconstitution inflammatory syndrome (IRIS) has subsequently emerged owing to the wide use of integrase inhibitor-based regimens. Here we report a case of spontaneous perforation of the jejunum in a patient with human immunodeficiency virus (HIV) infection with good compliance to cART. PATIENT CONCERNS: A 32-year-old HIV-infected man developed CMV disease and DMAC infection, as unmasking IRIS, 3 days after the initiation of cART. After appropriate treatment for opportunistic infections, intermittent fever with enlarged lymph nodes in the abdomen occurred as paradoxical IRIS. The patient was administered prednisolone with subsequent tapering according to his clinical condition. DIAGNOSES: Unexpected perforation of hollow organ during the titration of steroid dose with clinical presentations of severe abdominal pain was diagnosed by chest radiography. INTERVENTIONS: He underwent surgical repair with peritoneal toileting smoothly. OUTCOMES: He was discharged well with a clean surgical wound on post-operative day 10. LESSONS: Bowel perforation may be a life-threatening manifestation of IRIS in the era of cART. Steroids should be avoided, if possible, to decrease the risk of bowel perforation, especially in IRIS occurred after opportunistic diseases involving the gastrointestinal tract.