Impact of background music listening on anxiety in cancer patients undergoing initial radiation therapy: a randomized clinical trial.

BACKGROUND: Patients undergoing radiation therapy (RT) often experience anxiety, which may jeopardize the treatment success. The efficacy of music interventions in reducing anxiety remains contentious. This randomized trial aimed to evaluate the impact of music listening on anxiety symptoms in patients undergoing initial RT. METHODS: First-time RT patients were randomly allocated to experimental and control groups. The Brief Symptom Rating Scale (BSRS-5), Distress Thermometer (DT), and Beck Anxiety Inventory (BAI-C) were administered pre- and post-RT. Changes in physiological anxiety symptoms were monitored over 10 consecutive days starting from the first day of RT. The experimental group received music during RT; the control group did not. The generalized linear mixed model was used to estimate the pre-post difference in the BSRS-5, DT, and BAI-C scores between the music intervention and control group. RESULTS: This study included 50 patients each in the experimental and control groups. BSRS-5 and DT scores were significantly reduced in the experimental group post-RT (p = 0.0114 and p = 0.0023, respectively). When music listening was discontinued, these scores rebounded. While the posttest BAI-C score was significantly lower in the experimental group (p < 0.0001), the pre-post difference between the two groups was not significant (p = 0.0619). On cessation of music listening, the BAI-C score also rebounded. CONCLUSIONS: For cancer patients undergoing initial RT, music listening intervention significantly reduced anxiety symptoms measured using the BSRS-5, DT, and BAI-C scores after two weeks. Our results demonstrate the effectiveness of music listening intervention in reducing anxiety symptoms, thereby potentially improving the quality of life of cancer patients undergoing RT.

The relationship between oral frailty and oral dysbiosis among hospitalized patients aged older than 50 years.

OBJECTIVE: This study aimed to clarify the relationship between oral frailty and oral dysbiosis among hospitalized patients aged ≥ 50 years. METHODS: A prospective observational study was conducted. Number of teeth, masticatory ability, articulatory oral motor skill, tongue pressure, swallowing pressure, and choking were used to assess oral frailty. Saliva samples were collected from the oral cavity for bacterial culture. RESULTS: A total 103 in patients enrolled and 53.4% suffered from oral frailty. Oral frailty was found to have a 3.07-fold correlation with the presence of Enterobacterales in the oral cavity (p = 0.037), especially in poor articulatory oral motor skill, which showed at greater risk of Enterobacterales isolated from the oral cavity by 5.58-fold (p = 0.01). CONCLUSION: Half of hospitalized patients was found to have oral frailty that was related to more Enterobacterales in the oral cavity. This evidence suggests that the enhancement of articulatory oral motor skills may serve as a potential strategy for mitigating the presence of Enterobacterales within the oral cavity.

Suture Contamination During Arthroscopic Rotator Cuff Repair Is Associated With Significantly Higher Retear Rates in Magnetic Resonance Imaging: A Matched-Pair Analysis.

PURPOSE: To evaluate the correlation between suture contamination and rotator cuff tendon retear after arthroscopic rotator cuff repair. METHODS: Patients undergoing primary arthroscopic rotator cuff repair from April 1, 2020, to September 30, 2022, were enrolled. Those younger than 18 years, with a history of shoulder surgeries or shoulder infection episodes, or who declined participation were excluded. A 5-cm section of the first-cut suture, originating from the anchor eyelet ends, in each rotator cuff repair surgery was subjected to bacteria culture and polymerase chain reaction analysis. Patients with positive culture findings were matched 1:1 to those with negative culture reports based on age, sex, tear size as well as involved tendons, preoperative fatty infiltration grade (Goutallier grade), and preoperative muscle atrophy grade (Warner score). Postoperative rotator cuff tendon retear assessments were conducted at the 6-month mark using the Sugaya classification via magnetic resonance imaging. The Wilcoxon signed-rank test was used for matched-pair comparisons between the groups. RESULTS: A total of 141 patients (60 men and 81 women) with a mean age of 61.0 ± 8 years were finally enrolled. Twenty-six patients (18 men and 8 women) had a positive culture, while 115 patients (42 men and 73 women) had a negative culture. After the propensity score matching process, 24 culture-negative patients (16 men and 8 women) were selected as the culture-negative group. Age, fatty infiltration grade, and muscle atrophy grade were not significantly different between matched groups. The retear grade in the culture-positive group was significantly higher than that in the culture-negative group (P = .020) under the matched-pair comparison. Cutibacterium acnes was the most prevalent bacterial species responsible for suture contamination. CONCLUSIONS: The matched-pair analysis revealed that the presence of bacterial contamination on sutures was associated with a higher risk of retear on magnetic resonance imaging following arthroscopic rotator cuff repair. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

A longitudinal epidemiology study of fluoroquinolone-nonsusceptible Klebsiella pneumoniae reveals an increasing prevalence of qnrB and qnrS in Taiwan.

BACKGROUND: Our objective was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in fluoroquinolone-nonsusceptible Klebsiella pneumoniae (FQNSKP) in Taiwan, 1999-2022. METHODS: A total of 938 FQNSKP isolates were identified from 1966 isolates. The presence of PMQR and virulence genes, antimicrobial susceptibility, capsular types, and PMQR-plasmid transferability were determined. RESULTS: An increasing number of PMQR-containing FQNSKP isolates were observed over the study period. Our results showed that 69.0% (647 isolates) of FQNSKP isolates contained at least one PMQR gene, and 40.6%, 37.0%, and 33.9% of FQNSKP carried aac(6')-Ib-cr, qnrB, and qnrS, respectively. None of FQNSKP carried qepA and qnrC. The most common combination of PMQR genes was aac(6')-Ib-cr and qnrB (12.3%). The presence of PMQR genes is strongly related to resistance to aminoglycoside, cephalosporin, tetracycline, and sulfamethoxazole/trimethoprim in FQNSKP. The capsular serotype K64 is the most common serotype we tested in both the non-PMQR and PMQR FQNSKP isolates, while K20 showed a higher prevalence in PMQR isolates. The magA and peg-344 genes showed a significantly higher prevalence rate in non-PMQR isolates than in PMQR isolates. Eleven isolates that carried the PMQR and carbapenemase genes were identified; however, three successful transconjugants showed that the PMQR and carbapenemase genes were not located on the same plasmid. CONCLUSIONS: Our results indicated an increasing prevalence of PMQR genes, especially qnrB and qnrS, in FQNSKP in Taiwan. Moreover, the distribution of PMQR genes was associated with capsular serotypes and antimicrobial resistance gene and virulence gene distribution in FQNSKP.

Tongue pressure during swallowing is an independent risk factor for aspiration pneumonia in middle-aged and older hospitalized patients: An observational study.

AIM: To evaluate oral frailty features present in hospitalized older patients with aspiration pneumonia. METHODS: We enrolled hospitalized patients aged ≥50 years and classified them into three groups: the community-acquired, aspiration, and non-community-acquired pneumonia groups. Oral frailty was defined as meeting three or more criteria from the following: choking, and decreased occlusal force, masticatory function, tongue-lip motor function, tongue pressure, and tongue pressure during swallowing. RESULTS: Of 168 patients enrolled, the incidence of aspiration pneumonia was 23.9% (17/71) in patients admitted with pneumonia as the primary diagnosis. The occlusal force and masticatory function were significantly poorer and tongue pressure and tongue pressure during swallowing were significantly lower in the aspiration pneumonia group than in the other two groups. A higher number of chronic comorbidities, poor oral health, and lower tongue pressure during swallowing were significantly associated with aspiration pneumonia. A tongue pressure during swallowing of <10.32 kPa might be a cutoff point for predicting the risk of aspiration pneumonia. CONCLUSIONS: Hospitalized patients aged ≥50 years with multiple comorbidities, poor oral hygiene, and oral frailty during swallowing are at a higher risk of developing aspiration pneumonia, especially when their tongue pressure during swallowing is <10.32 kPa. Aspiration pneumonia is a preventable disease. Healthcare professionals should incorporate tongue pressure measurements or other screening tools into routine clinical practice to facilitate the early detection of this condition and intervention. Geriatr Gerontol Int 2024; 24: 351-357.

A 24-year longitudinal study of Klebsiella pneumoniae isolated from patients with bacteraemia and urinary tract infections reveals the association between capsular serotypes, antibiotic resistance, and virulence gene distribution.

Longitudinal studies on the variations of phenotypic and genotypic characteristics of K. pneumoniae across two decades are rare. We aimed to determine the antimicrobial susceptibility and virulence factors for K. pneumoniae isolated from patients with bacteraemia or urinary tract infection (UTI) from 1999 to 2022. A total of 699 and 1,267 K. pneumoniae isolates were isolated from bacteraemia and UTI patients, respectively, and their susceptibility to twenty antibiotics was determined; PCR was used to identify capsular serotypes and virulence-associated genes. K64 and K1 serotypes were most frequently observed in UTI and bacteraemia, respectively, with an increasing frequency of K20, K47, and K64 observed in recent years. entB and wabG predominated across all isolates and serotypes; the least frequent virulence gene was htrA. Most isolates were susceptible to carbapenems, amikacin, tigecycline, and colistin, with the exception of K20, K47, and K64 where resistance was widespread. The highest average number of virulence genes was observed in K1, followed by K2, K20, and K5 isolates, which suggest their contribution to the high virulence of K1. In conclusion, we found that the distribution of antimicrobial susceptibility, virulence gene profiles, and capsular types of K. pneumoniae over two decades were associated with their clinical source.

Effectiveness of multimedia courses in improving self-care among patients with breast cancer undergoing radiotherapy.

BACKGROUND: Ninety percent of patients receiving radiation therapy experience side effects. Busy schedules and intensive health education programs may lead to incomplete education content delivery and inaccurate patient self-care implementation. This study investigated whether multimedia health education improves the accuracy of patient self-care implementation compared with paper-based education. METHODS: From March 11, 2020 to February 28, 2021, 110 patients were randomly divided into experimental and control groups, each comprising 55 participants. Paper-based materials were used along with multimedia materials. Radiology self-care awareness questionnaires were administered to both groups before the first treatment and on day 10. The differences in radiology self-care awareness between the two groups was analyzed with inferential statistics, independent t tests, categorical data, and Pearson's chi-squared test. Differences between the two groups were considered significant at a p value of < 0.05. RESULTS: The treatment accuracy rate improved from 10.9 to 79.1% in the control group and from 24.8 to 98.5% in the experimental group, indicating an improvement in both groups. The difference was significant. These results indicate that the intervention could improve the effectiveness of self-care. CONCLUSIONS: Participants who used pretreatment multimedia health education exhibited a higher rate of having a correct understanding of treatment self-care than did the control group. These findings can inform the development of a patient-centered cancer treatment knowledge base for improved quality of care.

Re-examination of the risk of autoimmune diseases after dengue virus infection: A population-based cohort study.

Previous studies suggested that dengue was associated with an increased risk of several autoimmune diseases. However, this association still needs to be explored due to the limitations of these studies. A population-based cohort study was conducted using national health databases in Taiwan and included 63,814 newly diagnosed, laboratory-confirmed dengue patients between 2002 and 2015 and 1:4 controls (n = 255,256) matched by age, sex, area of residence and symptom onset time. Multivariate Cox proportional hazard regression models were used to investigate the risk of autoimmune diseases after dengue infection. Dengue patients had a slightly higher risk of overall autoimmune diseases than non-dengue controls (aHR 1.16; P = 0.0002). Stratified analyses by specific autoimmune diseases showed that only autoimmune encephalomyelitis remained statistically significant after Bonferroni correction for multiple testing (aHR 2.72; P < 0.0001). Sixteen (0.025%) dengue patients and no (0%) controls developed autoimmune encephalomyelitis in the first month of follow-up (HR >9999, P < 0.0001), but the risk between groups was not significantly different thereafter. Contrary to previous studies, our findings showed that dengue was associated with an increased short-term risk of a rare complication, autoimmune encephalomyelitis, but not associated with other autoimmune diseases.

Short-term effects of Chlorhexidine mouthwash and Listerine on oral microbiome in hospitalized patients.

Introduction: Chlorhexidine (CHX) and essential oil containing mouthwashes like Listerine® can improve oral hygiene via suppressing oral microbes. In hospitalized patients, CHX mouthwash reduces the incidence of ventilator-associated pneumonia. However, CHX use was also associated with increased mortality, which might be related to nitrate-reducing bacteria. Currently, no study determines oral bacteria targeted by essential oils mouthwash in hospitalized patients using a metagenomic approach. Methods: We recruited 87 hospitalized patients from a previous randomized control study, and assigned them to three mouthwash groups: CHX, Listerine, and normal saline (control). Before and after gargling the mouthwash twice a day for 5-7 days, oral bacteria were examined using a 16S rDNA approach. Results: Alpha diversities at the genus level decreased significantly only for the CHX and Listerine groups. Only for the two groups, oral microbiota before and after gargling were significantly different, but not clearly distinct. Paired analysis eliminated the substantial individual differences and revealed eight bacterial genera (including Prevotella, Fusobacterium, and Selenomonas) with a decreased relative abundance, while Rothia increased after gargling the CHX mouthwash. After gargling Listerine, seven genera (including Parvimonas, Eubacterium, and Selenomonas) showed a decreased relative abundance, and the magnitudes were smaller compared to the CHX group. Fewer bacteria targeted by Listerine were reported to be nitrate-reducing compared to the CHX mouthwash. Discussion: In conclusion, short-term gargling of the CHX mouthwash and Listerine altered oral microbiota in our hospitalized patients. The bacterial genera targeted by the CHX mouthwash and Listerine were largely different and the magnitudes of changes were smaller using Listerine. Functional alterations of gargling CHX and Listerine were also different. These findings can be considered for managing oral hygiene of hospitalized patients.

Characteristics of rectal chlamydia among men who have sex with men in southern Taiwan, 2020-2022: An emerging threat of rectal lymphogranuloma venereum L2b.

BACKGROUND: The prevalence of rectal chlamydia among men who have sex with men (MSM) without human deficiency virus infection (non-HIV) remains uncertain in Taiwan, and rectal lymphogranuloma venereum (LGV) among MSM has never been reported in the Far East. MATERIAL AND METHODS: From January 2020 to April 2022, MSM coming for anonymous voluntary counseling and testing, for pre-exposure prophylaxis, and for antiretroviral therapy were enrolled. All participants submitted his fecal samples and completed a QR-code questionnaire. Medical records of those who took regular medical visits for HIV were recorded. Multiplex polymerase chain reaction (PCR) was performed for all fecal samples, and ompA gene sequencing was therefore performed for each Chlamydia-positive fecal sample. RESULTS: Among 341 MSM during 2020-2022 in southern Taiwan, 21 (6.2%) had rectal chlamydia infection. Risk factors of rectal chlamydia included co-infection with rectal gonorrhea (adjusted odds ratio [AOR] 6.78, 95% confidence interval [CI] 1.44-31.91, P = 0.015) and multiple sexual partners (AOR 1.373, 95% CI 1.002-1.882, P = 0.048). Further ompA gene sequencing from 19 Chlamydia-positive fecal samples revealed that the prevalent genotypes or genovariants were Da (26.3%) and L2b (26.3%), followed by B (21.1%), J (14.3%), and G (9.5%). All cases of rectal LGV genovariant L2b presented as acute proctitis with diarrhea, anal pain, or discharge and were treated successfully with prolonged treatment of doxycycline. CONCLUSIONS: Rectal gonorrhea and multiple sexual partners are risk factors for rectal chlamydia. Clinicians in Taiwan should be aware of the emerging threat of rectal LGV among MSM with acute proctitis.

Extended skin cleaning on the shoulder with chlorhexidine reduces the cutaneous bacterial load but fails to decrease suture contamination in patients undergoing arthroscopy rotator cuff repair.

BACKGROUND: It remains unclear whether preoperative skin cleaning of the chin, neck, and chest with chlorhexidine soap can reduce suture contamination by Cutibacterium acnes in patients undergoing arthroscopic rotator cuff repair. METHODS: This study included patients who underwent primary arthroscopic rotator cuff repair. Exclusion criteria included age <18 years, previous shoulder surgery, history of shoulder infection, and allergy to chlorhexidine. Patients were randomized into 3 groups. Patients in the control group cleaned their skin with soap and water, as usual. Patients in the shoulder group cleaned their shoulders with chlorhexidine soap 3 days before surgery, whereas patients in the extended shoulder group additionally cleaned their chest, back, neck, and face with chlorhexidine soap. On the day of surgery, skin swab samples were obtained from the shoulder after surgical draping. After rotator cuff repair, sutures were cut from the anchor ends. Both traditional culture methods and polymerase chain reaction (PCR) were used. RESULTS: Ninety patients were enrolled (32 in the control group, 29 in the shoulder group, and 29 in the extended shoulder group) in the present study. The culture-positive rate from the posterior shoulder skin samples in the extended shoulder group (17.2%) was significantly lower than that in the control (40.6%) and shoulder (48.3%) groups (P = .036), whereas the culture-positive rates were not different among the 3 groups in other skin samples as well as the suture samples. The detection rates of C acnes in suture samples were 12.5%, 13.8%, and 17.2% in the control, shoulder, and extended shoulder groups, respectively (P = .603). CONCLUSION: Extensive skin cleaning of the shoulder region with chlorhexidine helps reduce the shoulder cutaneous bacterial load, but the detection of C acnes suture contamination in patients undergoing arthroscopic rotator cuff repair remained untouched regardless of the use of chlorhexidine soap in skin cleaning on the preoperative days.

Effect of 0.12% Chlorhexidine Oral Rinse on Preventing Hospital-Acquired Pneumonia in Nonventilator Inpatients.

BACKGROUND: Nonventilator hospital-associated pneumonia (NV-HAP) is a nosocomial infection with a multifactorial etiology that is particularly prevalent in individuals with poor oral health. PURPOSE: This study was designed to determine the effect of a 0.12% chlorhexidine gluconate oral rinse intervention on oral health and on reducing NV-HAP in inpatients. METHODS: A randomized, double-blind, and triple-arm clinical trial was conducted on a sample of 103 patients aged ≥ 50 years. Using the blocking sample method, patients were randomly assigned into three groups. These included Group A, using an oral rinse solution of 0.12% chlorhexidine; Group B, using Listerine; and Group C, using a standard saline oral rinse. In addition to routine hospital-associated pneumonia preventative nursing care, the participants used the oral rinse solutions twice a day with a period of at least 9 hours between each use. Oral health, the degree of bacterial exposure, and the clinical pneumonia index scale were evaluated in each of the groups at baseline (first day), on Intervention Days 3 and 7, and at discharge. The clearance rate was calculated by dividing the number of bacteria cleared by the total frequency of oral bacteria in the collected culture × 100%. RESULTS: Each arm of the study was composed of 34-35 participants, with an average hospitalization duration of 7.5 days. There was no incidence of NV-HAP or any changes in clinical pulmonary infection score among the three groups. Group A achieved a more significant improvement in oral health assessment tool scores between baseline and discharge than either Group B or C ( p = .03), particularly in the tongue, gums, and tissues; saliva; and oral cleanliness subscales. In addition, Group A reported higher clearance rates for Staphylococcus (100.00% vs. 66.67% vs. 66.67%, respectively), Escherichia coli (100.00% vs. 60.00% vs. 66.67%, respectively), and Pseudomonas aeruginosa (75.00% vs. 46.30% vs. 25.00%, respectively) than Groups B and C. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Although the results do not provide evidence supporting the use of a 0.12% chlorhexidine oral rinse as better in terms of preventing NV-HAP in middle-aged and elderly inpatients, nursing supervision was found to have an overall positive effect on oral health. The use of oral rinse with 0.12% chlorhexidine for nonventilated patients with poor oral health may be recommended.

The first case of Francisella novicida infection in Taiwan: bacteraemic pneumonia in a haemodialysis adult.

Tularaemia is a zoonotic disease caused by Francisella tularensis (F. tularensis). Human infection is rare and can be life-threatening. F. tularensis subsp. novicida used to be a subspecies of F. tularensis, is now considered a different species, F. novicida. Though less virulent, F. novicida can cause morbidity and mortality among debilitated or immunocompromised patients. We reported that an adult with end-stage renal disease undergoing haemodialysis and a history of melioidotic aortic aneurysm developed F. novicida bacteraemic pneumonia, which was uneventfully treated by antimicrobial therapy. The microbiological confirmation of F. novicida infection relies on 16S rRNA sequencing. It is the first case of F. novicida infection in Taiwan.

Severe Lung Infection and Septicemia Caused by Paludibacterium purpuratum-A Case Report and Evaluation of Bacterial Traits.

Paludibacterium species are gram stain-negative rods that are facultatively anaerobic; they have been isolated from wetland soil. Clinical infection caused by this genus is rarely reported. We report the case of an 84-year-old woman with chronic renal disease and hypertension who acquired P. purpuratum lung infection and septicemia in Southern Taiwan.

Role of the Inflammatory Response of RAW 264.7 Cells in the Metastasis of Novel Cancer Stem-Like Cells.

Background and objectives: Tumor progression and the immune response are intricately linked. Additionally, the presence of macrophages in the microenvironment is essential for carcinogenesis, but regulation of the polarization of M1- and M2-like macrophages and their role in metastasis remain unclear. Based on previous studies, both reactive oxygen species (ROS) and the endoplasmic reticulum (ER) are emerging as key players in macrophage polarization. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, there is limited knowledge regarding how they affect the macrophage-dependent innate host defense. Materials and methods: We detected the levels of ROS, the ability of chemotaxis, the expressions of markers of M1-/M2-like macrophages in RAW264.7 in presence of T2- and T2C-conditioned medium. Results: The results of this study indicated that ROS levels were decreased in RAW 264.7 cells when cultured with T2C-conditioned medium, while there was an improvement in chemotaxis abilities. We also found that the M2-like macrophages were characterized by an elongated shape in RAW 264.7 cells cultured in T2C-conditioned medium, which had increased CD206 expression but decreased expression of CD86 and inducible nitric oxide synthase. Suppression of ER stress shifted polarized M1-like macrophages toward an M2-like phenotype in RAW 264.7 cells cultured in T2C-conditioned medium. Conclusions: Taken together, we conclude that the polarization of macrophages is associated with the alteration of cell shape, ROS accumulation, and ER stress.

Pluripotent stem cell-derived NK cells with high-affinity noncleavable CD16a mediate improved antitumor activity.

Antibody-dependent cellular cytotoxicity (ADCC) is a key effector mechanism of natural killer (NK) cells that is mediated by therapeutic monoclonal antibodies (mAbs). This process is facilitated by the Fc receptor CD16a on human NK cells. CD16a appears to be the only activating receptor on NK cells that is cleaved by the metalloprotease a disintegrin and metalloproteinase-17 upon stimulation. We previously demonstrated that a point mutation of CD16a prevents this activation-induced surface cleavage. This noncleavable CD16a variant is now further modified to include the high-affinity noncleavable variant of CD16a (hnCD16) and was engineered into human induced pluripotent stem cells (iPSCs) to create a renewable source for human induced pluripotent stem cell-derived NK (hnCD16-iNK) cells. Compared with unmodified iNK cells and peripheral blood-derived NK (PB-NK) cells, hnCD16-iNK cells proved to be highly resistant to activation-induced cleavage of CD16a. We found that hnCD16-iNK cells were functionally mature and exhibited enhanced ADCC against multiple tumor targets. In vivo xenograft studies using a human B-cell lymphoma demonstrated that treatment with hnCD16-iNK cells and anti-CD20 mAb led to significantly improved regression of B-cell lymphoma compared with treatment utilizing anti-CD20 mAb with PB-NK cells or unmodified iNK cells. hnCD16-iNK cells, combined with anti-HER2 mAb, also mediated improved survival in an ovarian cancer xenograft model. Together, these findings show that hnCD16-iNK cells combined with mAbs are highly effective against hematologic malignancies and solid tumors that are typically resistant to NK cell-mediated killing, demonstrating the feasibility of producing a standardized off-the-shelf engineered NK cell therapy with improved ADCC properties to treat malignancies that are otherwise refractory.

Bloodstream infections in hospitalized adults with dengue fever: Clinical characteristics and recommended empirical therapy.

BACKGROUND: Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed. METHODS: Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected. RESULTS: Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week. CONCLUSIONS: BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended.

Argonaute-miRNA Complexes Silence Target mRNAs in the Nucleus of Mammalian Stem Cells.

In mammals, gene silencing by the RNA-induced silencing complex (RISC) is a well-understood cytoplasmic posttranscriptional gene regulatory mechanism. Here, we show that embryonic stem cells (ESCs) contain high levels of nuclear AGO proteins and that in ESCs nuclear AGO protein activity allows for the onset of differentiation. In the nucleus, AGO proteins interact with core RISC components, including the TNRC6 proteins and the CCR4-NOT deadenylase complex. In contrast to cytoplasmic miRNA-mediated gene silencing that mainly operates on cis-acting elements in mRNA 3' untranslated (UTR) sequences, in the nucleus AGO binding in the coding sequence and potentially introns also contributed to post-transcriptional gene silencing. Thus, nuclear localization of AGO proteins in specific cell types leads to a previously unappreciated expansion of the miRNA-regulated transcriptome.

A Muscle-Specific Enhancer RNA Mediates Cohesin Recruitment and Regulates Transcription In trans.

The enhancer regions of the myogenic master regulator MyoD give rise to at least two enhancer RNAs. Core enhancer eRNA (CEeRNA) regulates transcription of the adjacent MyoD gene, whereas DRReRNA affects expression of Myogenin in trans. We found that DRReRNA is recruited at the Myogenin locus, where it colocalizes with Myogenin nascent transcripts. DRReRNA associates with the cohesin complex, and this association correlates with its transactivating properties. Despite being expressed in undifferentiated cells, cohesin is not loaded on Myogenin until the cells start expressing DRReRNA, which is then required for cohesin chromatin recruitment and maintenance. Functionally, depletion of either cohesin or DRReRNA reduces chromatin accessibility, prevents Myogenin activation, and hinders muscle cell differentiation. Thus, DRReRNA ensures spatially appropriate cohesin loading in trans to regulate gene expression.

The Elongation Factor Spt6 Maintains ESC Pluripotency by Controlling Super-Enhancers and Counteracting Polycomb Proteins.

Spt6 coordinates nucleosome dis- and re-assembly, transcriptional elongation, and mRNA processing. Here, we report that depleting Spt6 in embryonic stem cells (ESCs) reduced expression of pluripotency factors, increased expression of cell-lineage-affiliated developmental regulators, and induced cell morphological and biochemical changes indicative of ESC differentiation. Selective downregulation of pluripotency factors upon Spt6 depletion may be mechanistically explained by its enrichment at ESC super-enhancers, where Spt6 controls histone H3K27 acetylation and methylation and super-enhancer RNA transcription. In ESCs, Spt6 interacted with the PRC2 core subunit Suz12 and prevented H3K27me3 accumulation at ESC super-enhancers and associated promoters. Biochemical as well as functional experiments revealed that Spt6 could compete for binding of the PRC2 methyltransferase Ezh2 to Suz12 and reduce PRC2 chromatin engagement. Thus, in addition to serving as a histone chaperone and transcription elongation factor, Spt6 counteracts repression by opposing H3K27me3 deposition at critical genomic regulatory regions.