Development of a multiplex droplet digital PCR method for detection and monitoring of Mycobacterium tuberculosis and drug-resistant tuberculosis.

BACKGROUND: The prevalence of multidrug-resistant tuberculosis (MDR-TB) among Korean tuberculosis patients is about 4.1%, which is higher than the OECD average of 2.6%. Inadequate drug use and poor patient compliance increase MDR-TB prevalence through selective pressure. Therefore, prompt detection of drug resistance in tuberculosis patients at the time of diagnosis and quantitative monitoring of these resistant strains during treatment are crucial. METHODS: A multiplex droplet digital PCR (ddPCR) assay was developed and assessed using DNA material of nine Mycobacterium tuberculosis strains with known mutation status that were purchased from the Korean National Tuberculosis Association. We collected a total of 18 MDR-TB residual samples referred for PCR analysis. Total DNA was extracted from the samples and subjected to the quadruplex ddPCR assay. Their results were compared to those of known resistance phenotypes. RESULTS: The analytical sensitivity and specificity of the multiplex ddPCR assay for detecting INH, RIF, EMB, FQ, and SM resistance-causing mutations ranged from 71.43 to 100% and 94.12-100%, respectively. Follow-up sample results showed that the quadruplex ddPCR assay was sensitive enough to detect IS6110 and other mutations even after onset of treatment. CONCLUSIONS: We developed a sensitive and accurate multiplex ddPCR assay that can detect the presence of tuberculosis quantitatively and resistance-conveying mutations concurrently. This tool could aid clinicians in the diagnosis and treatment monitoring of tuberculosis.

Prenatal to peripubertal exposure to Di(2-ethylhexyl) phthalate induced endometrial atrophy and fibrosis in female mice.

Di(2-ethylhexy) phthalate (DEHP) is a widely used plasticizer that is ubiquitously found in the environment. Using a mouse model, we investigated the impact of early life DEHP exposure ranging from the prenatal to peripubertal developmental period of the female reproductive system. Pregnant female mice were allocated to three groups as follows: control, 100 mg/kg/day, and 500 mg/kg/day DEHP treatment. DEHP exposure was introduced through feeding during pregnancy (3 weeks) and lactation (3 weeks). After weaning, the offspring were also exposed to DEHP through feeding for another 2 weeks. Observations were conducted on female offspring at 10 and 24 weeks. The number of live offspring per dam was significantly lower in the high-DEHP-exposed group (500 mg/kg/day) compared to the control group (7.67 ± 1.24 vs. 14.17 ± 0.31; p < 0.05) despite no difference in pregnancy rates across the groups. Low-DEHP exposure (100 mg/kg/day) resulted to a decreased body weight (36.07 ± 3.78 vs. 50.11 ± 2.11 g; p < 0.05) and decreased left uterine length (10.60 ± 1.34 vs. 14.77 ± 0.82 mm; p < 0.05) in 24-week- old female mice. As early as 10 weeks, endometrial atrophy and fibrosis were observed, and endometrial cystic hyperplasia was noted in female mice at 24 weeks. Our study is the first to demonstrate that female mice exposed to DEHP in the early life developed endometrial fibrosis in the female offspring. Further studies on the consequences of these observations in fecundity and other reproductive functions are warranted.

Microwave-Mediated, Catalyst-Free Synthesis of 1,2,4-Triazolo[1,5-a]pyridines from Enaminonitriles.

A catalyst-free, additive-free, and eco-friendly method for synthesizing 1,2,4-triazolo[1,5-a]pyridines under microwave conditions has been established. This tandem reaction involves the use of enaminonitriles and benzohydrazides, a transamidation mechanism followed by nucleophilic addition with nitrile, and subsequent condensation to yield the target compound in a short reaction time. The methodology demonstrates a broad substrate scope and good functional group tolerance, resulting in the formation of products in good-to-excellent yields. Furthermore, the scale-up reaction and late-stage functionalization of triazolo pyridine further demonstrate its synthetic utility. A plausible reaction pathway, based on our findings, has been proposed.

STAT3 Decoy Oligodeoxynucleotides Suppress Liver Inflammation and Fibrosis in Liver Cancer Cells and a DDC-Induced Liver Injury Mouse Model.

Liver damage caused by various factors results in fibrosis and inflammation, leading to cirrhosis and cancer. Fibrosis results in the accumulation of extracellular matrix components. The role of STAT proteins in mediating liver inflammation and fibrosis has been well documented; however, approved therapies targeting STAT3 inhibition against liver disease are lacking. This study investigated the anti-fibrotic and anti-inflammatory effects of STAT3 decoy oligodeoxynucleotides (ODN) in hepatocytes and liver fibrosis mouse models. STAT3 decoy ODN were delivered into cells using liposomes and hydrodynamic tail vein injection into 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed mice in which liver injury was induced. STAT3 target gene expression changes were verified using qPCR and Western blotting. Liver tissue fibrosis and bile duct proliferation were assessed in animal experiments using staining techniques, and macrophage and inflammatory cytokine distribution was verified using immunohistochemistry. STAT3 decoy ODN reduced fibrosis and inflammatory factors in liver cancer cell lines and DDC-induced liver injury mouse model. These results suggest that STAT3 decoy ODN may effectively treat liver fibrosis and must be clinically investigated.

Nursing diagnoses as factors associated with delirium among intensive care unit patients with sepsis: A retrospective correlational study.

AIMS: To examine whether nursing diagnoses were associated with delirium in patients with sepsis. BACKGROUND: Nursing diagnosis is a nurse's clinical judgement about clients' current or potential health conditions. Delirium is regarded as an important nurse-sensitive outcome. Nonetheless, nursing diagnoses associated with delirium have not yet been identified. DESIGN: Retrospective correlational study. METHODS: This study was carried out from December 2021 to January 2023. We analysed electronic health records of patients with sepsis admitted to the intensive care units (ICUs) of a tertiary hospital in Seoul, South Korea. Delirium was defined based on the Intensive Care Delirium Screening Checklist score. Nursing diagnoses established within 24 h of admission to the ICU were included and were based on the North American Nursing Diagnosis Association diagnostic classification. The data were analysed using logistic regression. Demographics, comorbidities, procedures and physiological measures were adjusted. Regression model was evaluated via receiver operating characteristic curve, Nagelkerke R2 , accuracy and F1 score. RESULTS: The prevalence of delirium in patients with sepsis was 51.8%. Ineffective breathing patterns, decreased cardiac output and impaired skin integrity were significant nursing diagnoses related to delirium. Age ≥ 65 years, Acute Physiology and Chronic Health Evaluation II score, mechanical ventilation, continuous renal replacement therapy, physical restraint and comatose state were also associated with delirium in patients with sepsis. The area under the receiver operating characteristic curve was 0.806. CONCLUSION: Ineffective breathing patterns, decreased cardiac output and impaired skin integrity could manifest as prodromal symptoms of delirium among patients with sepsis. IMPACT: The prodromal symptoms of delirium revealed through nursing diagnoses can be efficiently used to identify high-risk groups for delirium. The use of nursing diagnosis system should be recommended in clinical practice caring for sepsis patients. REPORTING METHODS: STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.

Improving Depression Severity Prediction from Passive Sensing: Symptom-Profiling Approach.

Depression is a significant mental health issue that profoundly impacts people's lives. Diagnosing depression often involves interviews with mental health professionals and surveys, which can become cumbersome when administered continuously. Digital phenotyping offers an innovative approach for detecting and monitoring depression without requiring active user involvement. This study contributes to the detection of depression severity and depressive symptoms using mobile devices. Our proposed approach aims to distinguish between different patterns of depression and improve prediction accuracy. We conducted an experiment involving 381 participants over a period of at least three months, during which we collected comprehensive passive sensor data and Patient Health Questionnaire (PHQ-9) self-reports. To enhance the accuracy of predicting depression severity levels (classified as none/mild, moderate, or severe), we introduce a novel approach called symptom profiling. The symptom profile vector represents nine depressive symptoms and indicates both the probability of each symptom being present and its significance for an individual. We evaluated the effectiveness of the symptom-profiling method by comparing the F1 score achieved using sensor data features as inputs to machine learning models with the F1 score obtained using the symptom profile vectors as inputs. Our findings demonstrate that symptom profiling improves the F1 score by up to 0.09, with an average improvement of 0.05, resulting in a depression severity prediction with an F1 score as high as 0.86.

Older adult psychopathology: international comparisons of self-reports, collateral reports, and cross-informant agreement.

OBJECTIVES: To conduct international comparisons of self-reports, collateral reports, and cross-informant agreement regarding older adult psychopathology. PARTICIPANTS: We compared self-ratings of problems (e.g. I cry a lot) and personal strengths (e.g. I like to help others) for 10,686 adults aged 60-102 years from 19 societies and collateral ratings for 7,065 of these adults from 12 societies. MEASUREMENTS: Data were obtained via the Older Adult Self-Report (OASR) and the Older Adult Behavior Checklist (OABCL; Achenbach et al., ). RESULTS: Cronbach's alphas were .76 (OASR) and .80 (OABCL) averaged across societies. Across societies, 27 of the 30 problem items with the highest mean ratings and 28 of the 30 items with the lowest mean ratings were the same on the OASR and the OABCL. Q correlations between the means of the 0-1-2 ratings for the 113 problem items averaged across all pairs of societies yielded means of .77 (OASR) and .78 (OABCL). For the OASR and OABCL, respectively, analyses of variance (ANOVAs) yielded effect sizes (ESs) for society of 15% and 18% for Total Problems and 42% and 31% for Personal Strengths, respectively. For 5,584 cross-informant dyads in 12 societies, cross-informant correlations averaged across societies were .68 for Total Problems and .58 for Personal Strengths. Mixed-model ANOVAs yielded large effects for society on both Total Problems (ES = 17%) and Personal Strengths (ES = 36%). CONCLUSIONS: The OASR and OABCL are efficient, low-cost, easily administered mental health assessments that can be used internationally to screen for many problems and strengths.

Machine Learning-Aided Chronic Kidney Disease Diagnosis Based on Ultrasound Imaging Integrated with Computer-Extracted Measurable Features.

Although ultrasound plays an important role in the diagnosis of chronic kidney disease (CKD), image interpretation requires extensive training. High operator variability and limited image quality control of ultrasound images have made the application of computer-aided diagnosis (CAD) challenging. This study assessed the effect of integrating computer-extracted measurable features with the convolutional neural network (CNN) on the ultrasound image CAD accuracy of CKD. Ultrasound images from patients who visited Severance Hospital and Gangnam Severance Hospital in South Korea between 2011 and 2018 were used. A Mask regional CNN model was used for organ segmentation and measurable feature extraction. Data on kidney length and kidney-to-liver echogenicity ratio were extracted. The ResNet18 model classified kidney ultrasound images into CKD and non-CKD. Experiments were conducted with and without the input of the measurable feature data. The performance of each model was evaluated using the area under the receiver operating characteristic curve (AUROC). A total of 909 patients (mean age, 51.4 ± 19.3 years; 414 [49.5%] men and 495 [54.5%] women) were included in the study. The average AUROC from the model trained using ultrasound images achieved a level of 0.81. Image training with the integration of automatically extracted kidney length and echogenicity features revealed an improved average AUROC of 0.88. This value further increased to 0.91 when the clinical information of underlying diabetes was also included in the model trained with CNN and measurable features. The automated step-wise machine learning-aided model segmented, measured, and classified the kidney ultrasound images with high performance. The integration of computer-extracted measurable features into the machine learning model may improve CKD classification.

Anti-Fibrotic Effect of Synthetic Noncoding Decoy ODNs for TFEB in an Animal Model of Chronic Kidney Disease.

Despite emerging evidence suggesting that autophagy occurs during renal interstitial fibrosis, the role of autophagy activation in fibrosis and the mechanism by which autophagy influences fibrosis remain controversial. Transcription factor EB (TFEB) is a master regulator of autophagy-related gene transcription, lysosomal biogenesis, and autophagosome formation. In this study, we examined the preventive effects of TFEB suppression on renal fibrosis. We injected synthesized TFEB decoy oligonucleotides (ODNs) into the tail veins of unilateral ureteral obstruction (UUO) mice to explore the regulation of autophagy in UUO-induced renal fibrosis. The expression of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and collagen was decreased by TFEB decoy ODN. Additionally, TEFB ODN administration inhibited the expression of microtubule-associated protein light chain 3 (LC3), Beclin1, and hypoxia-inducible factor-1α (HIF-1α). We confirmed that TFEB decoy ODN inhibited fibrosis and autophagy in a UUO mouse model. The TFEB decoy ODNs also showed anti-inflammatory effects. Collectively, these results suggest that TFEB may be involved in the regulation of autophagy and fibrosis and that regulating TFEB activity may be a promising therapeutic strategy against kidney diseases.

Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model.

The global burden of chronic kidney disease is increasing, and the majority of these diseases are progressive. Special site-targeted drugs are emerging as alternatives to traditional drugs. Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapies for several diseases. We designed ring-type non-coding RNAs (ncRNAs), also called mTOR ODNs to suppress mammalian target rapamycin (mTOR) translation. mTOR signaling is associated with excessive cell proliferation and fibrogenesis. In this study, we examined the effects of mTOR suppression on chronic renal injury. To explore the regulation of fibrosis and inflammation in unilateral ureteral obstruction (UUO)-induced injury, we injected synthesized ODNs via the tail vein of mice. The expression of inflammatory-related markers (interleukin-1ß, tumor necrosis factor-α), and that of fibrosis (α-smooth muscle actin, fibronectin), was decreased by synthetic ODNs. Additionally, ODN administration inhibited the expression of autophagy-related markers, microtubule-associated protein light chain 3, Beclin1, and autophagy-related gene 5-12. We confirmed that ring-type ODNs inhibited fibrosis, inflammation, and autophagy in a UUO mouse model. These results suggest that mTOR may be involved in the regulation of autophagy and fibrosis and that regulating mTOR signaling may be a therapeutic strategy against chronic renal injury.

Anti-Fibrotic Effect of Synthetic Noncoding Oligodeoxynucleotide for Inhibiting mTOR and STAT3 via the Regulation of Autophagy in an Animal Model of Renal Injury.

Renal fibrosis is a common process of various kidney diseases. Autophagy is an important cell biology process to maintain cellular homeostasis. In addition, autophagy is involved in the pathogenesis of various renal disease, including acute kidney injury, glomerular diseases, and renal fibrosis. However, the functional role of autophagy in renal fibrosis remains poorly unclear. The mammalian target of rapamycin (mTOR) plays a negative regulatory role in autophagy. Signal transducer and activator of transcription 3 (STAT3) is an important intracellular signaling that may regulate a variety of inflammatory responses. In addition, STAT3 regulates autophagy in various cell types. Thus, we synthesized the mTOR/STAT3 oligodeoxynucleotide (ODN) to regulate the autophagy. The aim of this study was to investigate the beneficial effect of mTOR/STAT3 ODN via the regulation of autophagy appearance on unilateral ureteral obstruction (UUO)-induced renal fibrosis. This study showed that UUO induced inflammation, tubular atrophy, and tubular interstitial fibrosis. However, mTOR/STAT3 ODN suppressed UUO-induced renal fibrosis and inflammation. The autophagy markers have no statistically significant relation, whereas mTOR/STAT3 ODN suppressed the apoptosis in tubular cells. These results suggest the possibility of mTOR/STAT3 ODN for preventing renal fibrosis. However, the role of mTOR/STAT3 ODN on autophagy regulation needs to be further investigated.

In Vitro Evaluation of Two Novel Antimalarial Derivatives of SKM13: SKM13-MeO and SKM13-F.

Antimalarial drugs play an important role in the control and treatment of malaria, a deadly disease caused by the protozoan parasite Plasmodium spp. The development of novel antimalarial agents effective against drug-resistant malarial parasites is urgently needed. The novel derivatives, SKM13-MeO and SKM13-F, were designed based on an SKM13 template by replacing the phenyl group with electron-donating (-OMe) or electron-withdrawing groups (-F), respectively, to reverse the electron density. A colorimetric assay was used to quantify cytotoxicity, and in vitro inhibition assays were performed on 3 different blood stages (ring, trophozoite, and schizonts) of P. falciparum 3D7 and the ring/mixed stage of D6 strain after synchronization. The in vitro cytotoxicity analysis showed that 2 new SKM13 derivatives reduced the cytotoxicity of the SKM13 template. SKM13 maintained the IC50 at the ring and trophozoite stages but not at the schizont stage. The IC50 values for both the trophozoite stage of P. falciparum 3D7 and ring/mixed stages of D6 demonstrated that 2 SKM13 derivatives had decreased antimalarial efficacy, particularly for the SKM13-F derivative. SKM13 may be comparably effective in ring and trophozoite, and electron-donating groups (-OMe) may be better maintain the antimalarial activity than electron-withdrawing groups (-F) in SKM13 modification.

Trajectory of genetic alterations associated with colistin resistance in Acinetobacter baumannii during an in-hospital outbreak of infection.

BACKGROUND: As carbapenem-resistant Acinetobacter baumannii is dominant in clinical settings, the old polymyxin antibiotic colistin has been revived as a therapeutic option. The development of colistin resistance during treatment is becoming a growing concern. OBJECTIVES: To access low- to mid-level colistin-resistant A. baumannii blood isolates recovered from an outbreak in a tertiary care hospital from a national antimicrobial surveillance study. METHODS: The entire bacterial genome was sequenced through long-read sequencing methodology. Quantitative RT-PCR was carried out to determine the level of gene expression. Relative growth rates were determined to estimate fitness costs of each isolate caused by the genetic alterations. RESULTS: The A. baumannii isolates belonged to global clone 2 harbouring two intrinsic phosphoethanolamine transferases. Cumulative alterations continuing the colistin resistance were observed. PmrC overproduction caused by the PmrBA226T alteration was identified in A. baumannii isolates with low-level colistin resistance and an additional PmrCR109H substitution led to mid-level colistin resistance. Truncation of the PmrC enzyme by insertion of ISAba59 was compensated by ISAba10-mediated overproduction of EptA and, in the last isolate, the complete PmrAB two-component regulatory system was eliminated to restore the biological cost of the bacterial host. CONCLUSIONS: During the in-hospital outbreak, a trajectory of genetic modification in colistin-resistant A. baumannii isolates was observed for survival in the harsh conditions imposed by life-threatening drugs with the clear purpose of maintaining drug resistance above a certain level with a reasonable fitness cost.

In Vitro Prebiotic and Anti-Colon Cancer Activities of Agar-Derived Sugars from Red Seaweeds.

Numerous health benefits of diets containing red seaweeds or agar-derived sugar mixtures produced by enzymatic or acid hydrolysis of agar have been reported. However, among various agar-derived sugars, the key components that confer health-beneficial effects, such as prebiotic and anti-colon cancer activities, remain unclear. Here, we prepared various agar-derived sugars by multiple enzymatic reactions using an endo-type and an exo-type of ß-agarase and a neoagarobiose hydrolase and tested their in vitro prebiotic and anti-colon cancer activities. Among various agar-derived sugars, agarotriose exhibited prebiotic activity that was verified based on the fermentability of agarotriose by probiotic bifidobacteria. Furthermore, we demonstrated the anti-colon cancer activity of 3,6-anhydro-l-galactose, which significantly inhibited the proliferation of human colon cancer cells and induced their apoptosis. Our results provide crucial information regarding the key compounds derived from red seaweeds that confer beneficial health effects, including prebiotic and anti-colon cancer activities, to the host.

How to approach the rupture of tubo-ovarian abscess during pregnancy: A case report and literature review.

We present the case of a 26-year-old multiparous woman who experienced rupture of a tubo-ovarian abscess during the second trimester of pregnancy. She presented with epigastric and right lower quadrant pain at 12 + 0 weeks' gestation. There were no other specific findings on the magnetic resonance imaging images. We recommended hospitalization to observe the changes in pain, but she refused confinement. About 3 weeks later, she revisited our emergency room at 15 + 4 weeks' gestation. She complained of worsening abdominal pain with fever. She underwent right salpingo-oophorectomy and appendectomy due to uncontrollable, severe abdominal pain without any obstetric abnormal condition. There was a rupture site in the right adnexa, which was covered with pus. The rupture of tubo-ovarian abscess during pregnancy is very rare. Therefore, obstetricians should carefully monitor the adnexal masses observed during pregnancy, which should be treated with caution, whether or not the patient is symptomatic.

Clinical outcomes of a nurse-led post-discharge education program for heart-transplant recipients: A retrospective cohort study.

BACKGROUND: Advances in immunosuppressive therapeutics and medical technology have improved survival rates after heart transplantation. Although there is a rigorous schedule of outpatient visits and testing to detect early signs of rejection and other complications in the first year after transplantation, repeated unplanned readmissions of heart transplant recipients remains a challenge. OBJECTIVE: This study aimed to compare the effects of specialized nurse-led discharge education, including continuous post-transplant education and counselling, on heart transplant recipients' clinical outcomes, with the effects of existing discharge education. METHODS: Participants were 136 heart transplantation recipients at a university-affiliated hospital in South Korea from November 1, 1994, to November 30, 2018. Participants' electronic medical records were retrospectively analyzed. Participants were grouped according to usual care (n = 25), nurse-led program (n = 66), and nurse-led program with post-discharge education (n = 45). We assessed the number of outpatient visits with clinical problems and days to first unplanned rehospitalization within one year after transplantation. RESULTS: The nurse-led program with post-discharge education was associated with significantly reduced outpatient visits with clinical problems, compared to usual care and the existing nurse-led program. We also found a significantly longer time until first unplanned rehospitalization in the nurse-led program with post-discharge education group, compared to the usual care group. CONCLUSION: This study identified the heart transplantation-specialized nurse-led discharge and subsequent post-discharge education as an effective strategy for positive clinical outcomes within one year after heart transplantation.

Impact of vanA-Positive Enterococcus faecium Exhibiting Diverse Susceptibility Phenotypes to Glycopeptides on 30-Day Mortality of Patients with a Bloodstream Infection.

This study was performed to evaluate the impacts of vanA positivity of Enterococcus faecium exhibiting diverse susceptibility phenotypes to glycopeptides on clinical outcomes in patients with a bloodstream infection (BSI) through a prospective, multicenter, observational study. A total of 509 patients with E. faecium BSI from eight sentinel hospitals in South Korea during a 2-year period were enrolled in this study. Risk factors of the hosts and causative E. faecium isolates were assessed to determine associations with the 30-day mortality of E. faecium BSI patients via multivariable logistic regression analyses. The vanA gene was detected in 35.2% (179/509) of E. faecium isolates; 131 E. faecium isolates exhibited typical VanA phenotypes (group vanA-VanA), while the remaining 48 E. faecium isolates exhibited atypical phenotypes (group vanA-atypical), which included VanD (n = 43) and vancomycin-variable phenotypes (n = 5). A multivariable logistic regression indicated that vanA positivity of causative pathogens was independently associated with the increased 30-day mortality rate in the patients with E. faecium BSI; however, there was no significant difference in survival rates between the patients of the vanA-VanA and vanA-atypical groups (log rank test, P = 0.904). A high 30-day mortality rate was observed in patients with vanA-positive E. faecium BSIs, and vanA positivity of causative E. faecium isolates was an independent risk factor for early mortality irrespective of the susceptibility phenotypes to glycopeptides; thus, intensified antimicrobial stewardship is needed to improve the clinical outcomes of patients with vanA-positive E. faecium BSI.

The generalizability of Older Adult Self-Report (OASR) syndromes of psychopathology across 20 societies.

OBJECTIVES: As the world population ages, psychiatrists will increasingly need instruments for measuring constructs of psychopathology that are generalizable to diverse elders. The study tested whether syndromes of co-occurring problems derived from self-ratings of psychopathology by US elders would fit self-ratings by elders in 19 other societies. METHODS/DESIGN: The Older Adult Self-Report (OASR) was completed by 12 826 adults who were 60 to 102 years old in 19 societies from North and South America, Asia, and Eastern, Northern, Southern, and Western Europe, plus the United States. Individual and multigroup confirmatory factor analyses (CFAs) tested the fit of the seven-syndrome OASR model, consisting of the Anxious/Depressed, Worries, Somatic Complaints, Functional Impairment, Memory/Cognition Problems, Thought Problems, and Irritable/Disinhibited syndromes. RESULTS: In individual CFAs, the primary model fit index showed good fit for all societies, while the secondary model fit indices showed acceptable to good fit. The items loaded strongly on their respective factors, with a median item loading of .63 across 20 societies, and 98.7% of the loadings were statistically significant. In multigroup CFAs, 98% of items demonstrated approximate or full metric invariance. Fifteen percent of items demonstrated approximate or full scalar invariance, and another 59% demonstrated scalar invariance across more than half of societies. CONCLUSIONS: The findings supported the generalizability of OASR syndromes across societies. The seven syndromes offer empirically based clinical constructs that are relevant for elders of different backgrounds. They can be used to assess diverse elders and as a taxonomic framework to facilitate communication, services, research, and training in geriatric psychiatry.

LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma.

Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.

Toxic Shock Syndrome Toxin 1-Producing Methicillin-Resistant Staphylococcus aureus of Clonal Complex 5, the New York/Japan Epidemic Clone, Causing a High Early-Mortality Rate in Patients with Bloodstream Infections.

This study was performed to evaluate the clinical impacts of putative risk factors in patients with Staphylococcus aureus bloodstream infections (BSIs) through a prospective, multicenter, observational study. All 567 patients with S. aureus BSIs that occurred during a 1-year period in six general hospitals were included in this study. Host- and pathogen-related variables were investigated to determine risk factors for the early mortality of patients with S. aureus BSIs. The all-cause mortality rate was 15.0% (85/567) during the 4-week follow-up period from the initial blood culture, and 76.5% (65/85) of the mortality cases occurred within the first 2 weeks. One-quarter (26.8%, 152/567) of the S. aureus blood isolates carried the tst-1 gene, and most (86.2%, 131/152) of them were identified to be clonal complex 5 agr type 2 methicillin-resistant S. aureus (MRSA) strains harboring staphylococcal cassette chromosome mec type II, belonging to the New York/Japan epidemic clone. A multivariable logistic regression showed that the tst-1 positivity of the causative S. aureus isolates was associated with an increased 2-week mortality rate both in patients with S. aureus BSIs (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 0.90 to 2.88) and in patients with MRSA BSIs (aOR, 2.61; 95% CI, 1.19 to 6.03). Two host-related factors, an increased Pitt bacteremia score and advanced age, as well as a pathogen-related factor, carriage of tst-1 by causative MRSA isolates, were risk factors for 2-week mortality in patients with BSIs. Careful management of patients with BSIs caused by the New York/Japan epidemic clone is needed to improve clinical outcomes.