This nationwide study aimed to provide risk estimates for a panel of infections subsequent to pyogenic liver abscesses (PLA) in Taiwan. In this study, we selected 12 050 patients diagnosed with PLA ...as our study cohort and 60 250 non-PLA patients as our comparison cohort. We individually tracked each subject for a 1-year period beginning with their index date to identify those who were subsequently diagnosed with any of the following infections: pneumonia, endophthalmitis, septic pulmonary embolism, pulmonary abscess, pleural empyema, meningitis, abscess of prostate, renal and perinephric abscess, epidural spinal abscess, osteomyelitis, necrotizing fasciitis, splenic abscess, psoas abscess and infectious endocarditis. We found that during the 1-year follow-up period, the subjects with PLA had a consistently higher incidence of all types of infections than comparison subjects. In particular, compared with subjects without PLA, the adjusted hazard ratios (HR) of pulmonary abscess, pleural empyema, renal and perinephric abscess, epidural spinal abscess and splenic abscess were 26.71, 18.56, 43.21, 51.32 and 126.51, respectively. We further analysed the HR of extra-hepatic Klebsiella pneumoniae infections among patients with PLA caused by K. pneumoniae. We found that the HR was higher for 12 of the 15 analysed extra-hepatic infections after restricting the analysis to only infections with K. pneumoniae aetiologies.
MicroRNAs (miRNAs) are thought to control tumor metastasis through direct interactions with target genes. Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer ...progression. However, the issue of whether miRNAs participate in T3/TR-mediated tumor migration is yet to be established. In the current study, we demonstrated that T3/TR negatively regulates mature miR-17 transcript expression, both in vitro and in vivo. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays localized the regions responding to TR-mediated repression to positions -2234/-2000 of the miR-17 promoter sequence. Overexpression of miR-17 markedly inhibited cell migration and invasion in vitro and in vivo, mediated via suppression of matrix metalloproteinases (MMP)-3. Moreover, p-AKT expression was increased in miR-17-knockdown cells that led to enhanced cell invasion, which was blocked by LY294002. Notably, low miR-17 expression was evident in highly metastatic cells. The cell migration ability was increased by T3, but partially reduced upon miR-17 overexpression. Notably, TRα1 was frequently upregulated in hepatocellular carcinoma (HCC) samples and associated with low overall survival (P=0.023). miR-17 expression was significantly negatively associated with TRα1 (P=0.033) and MMP3 (P=0.043) in HCC specimens. Data from our study suggest that T3/TR, miR-17, p-AKT and MMP3 activities are interlinked in the regulation of cancer cell metastasis.
Summary
Background and Aims: The use of herbs and dietary supplements (HDS) alone or concomitantly with medications can potentially increase the risk of adverse events experienced by the patients. ...This review aims to evaluate the documented HDS‐drug interactions and contraindications.
Methods: A structured literature review was conducted on PubMed, EMBASE, Cochrane Library, tertiary literature and Internet.
Results: While 85 primary literatures, six books and two web sites were reviewed for a total of 1,491 unique pairs of HDS‐drug interactions, 213 HDS entities and 509 medications were involved. HDS products containing St. John’s Wort, magnesium, calcium, iron, ginkgo had the greatest number of documented interactions with medications. Warfarin, insulin, aspirin, digoxin, and ticlopidine had the greatest number of reported interactions with HDS. Medications affecting the central nervous system or cardiovascular system had more documented interactions with HDS. Of the 882 HDS‐drug interactions being described its mechanism and severity, 42.3% were due to altered pharmacokinetics and 240 were described as major interactions. Of the 152 identified HDS contraindications, the most frequent involved gastrointestinal (16.4%), neurological (14.5%), and renal/genitourinary diseases (12.5%). Flaxseed, echinacea, and yohimbe had the largest number of documented contraindications.
Conclusions: Although HDS‐drug interactions and contraindications primarily concerned a relatively small subset of commonly used medications and HDS entities, this review provides the summary to identify patients, HDS products, and medications that are more susceptible to HDS‐drug interactions and contraindications. The findings would facilitate the health‐care professionals to communicate these documented interactions and contraindications to their patients and/or caregivers thereby preventing serious adverse events and improving desired therapeutic outcomes.
Linked Comment: Ernst. Int J Clin Pract 2012; 66: 1019‐20.
Periprosthetic joint infection (PJI) is a significant post-arthroplasty complication for diabetic patients, with uncontrolled diabetes identified as a PJI risk factor. Taiwan's Diabetes Shared Care ...Program (DSCP) was established for holistic diabetes care.
To evaluate the DSCP's impact on PJI incidence and patients' medical costs.
Data were analysed from Taiwan's National Health Insurance Research Database from 2010 to 2020, focusing on type 2 diabetes mellitus (DM) patients who had undergone arthroplasty. The study group involved DSCP participants, while a comparison group comprised non-participants with matched propensity scores for age, sex, and comorbidities. The primary outcome was the PJI incidence difference between the groups; the secondary outcome was the medical expense difference.
The study group consisted of 11,908 type 2 DM patients who had arthroplasty and joined the DSCP; PJI occurred in 128 patients. Among non-participants, 184 patients had PJI. The PJI incidence difference between the groups was statistically significant (1.07% vs 1.55%). The study group's medical costs were notably lower, regardless of PJI incidence. Multivariate regression showed higher PJI risk in patients in comparison group, aged >70 years, male, or who had obesity, anaemia.
The study indicates that DSCP involvement reduces PJI risks and decreases annual medical costs for diabetic patients after arthroplasty. Consequently, the DSCP is a recommendable option for such patients who are preparing for total joint arthroplasty.
Objectives
This study aims to assess the effectiveness of a multidomain intervention program on the change in functional status of hospitalized older adults.
Design
This single-arm, prospective, ...non-randomized interventional study investigates the efficacy of a multidomain interventional program including cognitive stimulation activity, simple exercises, frailty education, and nutrition counseling.
Setting and Participants
At a tertiary hospital in southern Taiwan, 352 eligible patients were sequentially enrolled. Included patients were aged ≥65 years (mean age, 79.6 ± 9.0 years; 62% male), scored 3–7 on the Clinical Frailty Scale (CFS), and were hospitalized in the geriatric acute ward.
Intervention
Those receiving standard care (physical rehabilitation and nutrition counseling) during January–July 2019 composed the historical control group. Those receiving the multidomain intervention during August–December 2019 composed the intervention group.
Measurements
The primary outcome was the change in activities of daily life (ADL) and frailty status, as assessed by Katz Index and Clinical Frailty Scale, with using the generalized estimating equation model. The length of hospital stay, medical costs, and re-admission rates were secondary outcomes.
Results
Participants undergoing intervention (n = 101; 27.9%) showed greater improvements in the ADL and CFS during hospitalization (ADL adjusted estimate, 0.61; 95% CI, 0.11–1.11; p = 0.02; CFS adjusted estimate, −1.11; 95% CI, −1.42–−0.80; p < 0.01), shorter length of hospital stay (adjusted estimate, -5.00; 95% CI, −7.99–−2.47; p < 0.01), lower medical costs (adjusted estimate, 0.58; 95% CI, 0.49–0.69; p < 0.01), and lower 30- and 90-day readmission rates (30-day adjusted OR aOR, 0.12; 95% CI, 0.27–0.50; p < 0.01; 60-day aOR, 0.04; 95% CI, 0.01–0.33; p < 0.01) than did controls.
Conclusions
Participation in the multidomain intervention program during hospitalization improved the functional status and decreased the hospital stay length, medical costs, and readmission rates of frail older people.
We report on the detection of seven bursts from the periodically active, repeating fast radio burst (FRB) source FRB 180916.J0158+65 in the 300-400 MHz frequency range with the Green Bank Telescope ...(GBT). Emission in multiple bursts is visible down to the bottom of the GBT band, suggesting that the cutoff frequency (if it exists) for FRB emission is lower than 300 MHz. Observations were conducted during predicted periods of activity of the source, and had simultaneous coverage with the Low Frequency Array (LOFAR) and the FRB backend on the Canadian Hydrogen Intensity Mapping Experiment (CHIME) telescope. We find that one of the GBT-detected bursts has potentially associated emission in the CHIME band (400-800 MHz) but we detect no bursts in the LOFAR band (110-190 MHz), placing a limit of on the spectral index of broadband emission from the source. We also find that emission from the source is severely band-limited with burst bandwidths as low as ∼40 MHz. In addition, we place the strictest constraint on observable scattering of the source, <1.7 ms at 350 MHz, suggesting that the circumburst environment does not have strong scattering properties. Additionally, knowing that the circumburst environment is optically thin to free-free absorption at 300 MHz, we find evidence against the association of a hyper-compact H ii region or a young supernova remnant (age <50 yr) with the source.
Objectives
To investigate the clinical efficacy of integrated multidomain intervention among community-living older adults with multimorbidity and physio-cognitive decline syndrome (PCDS).
Design, ...Setting and Participants
This is the secondary analysis from a randomized controlled trial that data of 340 participants with Montreal Cognitive Assessment (MoCA) scores≥18 were excerpted for analysis.
Intervention
Sixteen 2-hour sessions per year were provided for participants, including physical exercise, cognitive training, dietician education and individualized integrated care for multimorbidity.
Measurements
Handgrip strength, 6-m walking speed, MoCA (total score and sub-domains), Cardiovascular Health Study (CHS) frailty score, quality of life, and serum biochemistry biomarkers.
Results
Overall, 96/340 (28.2%) of all participants have PCDS, and the integrated multidomain intervention significantly improved global cognitive performance (overall difference 1.1, 95% CI 0.4–1.8, p=0.003), and domains of concentration (overall difference 0.3, 95%CI 0.1–0.5, p=0.011), language (overall difference 0.2, 95%CI 0.1–0.3, p=0.006), abstract thinking (overall difference 0.1, 95%CI 0.0–0.3, p=0.027), and orientation(overall difference 0.2, 95%CI 0.0–0.4, p=0.013) across all timepoints among those with PCDS. Besides, interventions also significantly reduced frailty score among those with cognitive impairment no dementia (overall difference −0.3, 95%CI −0.5 − −0.1, p=0.011) and mobility impairment no disability (overall difference −0.3, 95%CI −0.4 − −0.1, p=0.004). and improved quality of life at domain of physical role limitation among those with PCDS (overall difference 5.3, 95%CI 0.3–10.4, p=0.038).
Conclusions
The integrated multidomain lifestyle intervention plus multimorbidity management significantly improved cognitive function, and enhanced quality of life among older adults with multimorbidity and PCDS in the communities.
Sirtuin deacetylases and FOXO (Forkhead box, class O) transcription factors have important roles in many biological pathways, including cancer development. SIRT1 and SIRT2 deacetylate FOXO factors to ...regulate FOXO function. Because acetylation and ubiquitination both modify the ɛ-amino group of lysine residues, we investigated whether FOXO3 deacetylation by SIRT1 or SIRT2 facilitates FOXO3 ubiquitination and subsequent proteasomal degradation. We found that SIRT1 and SIRT2 promote FOXO3 poly-ubiquitination and degradation. Proteasome-inhibitor treatment prevented sirtuin-induced FOXO3 degradation, indicating that this process is proteasome dependent. In addition, we demonstrated that E3 ubiquitin ligase subunit Skp2 binds preferentially to deacetylated FOXO3. Overexpression of Skp2 caused poly-ubiquitination of FOXO3 and degradation, whereas knockdown of Skp2 increased the amount of FOXO3 protein. We also present evidence that SCF-Skp2 ubiquitinates FOXO3 directly in vitro. Furthermore, mutating four known acetylated lysine residues (K242, K259, K290 and K569) of FOXO3 into arginines to mimic deacetylated FOXO3 resulted in enhanced Skp2 binding but with inhibition of FOXO3 ubiquitination; this suggests that some or all of these four lysine residues are likely the sites for ubiquitination. In the livers of mice deficient in SIRT1, we detected increased expression of FOXO3, indicating SIRT1 regulates FOXO3 protein levels in vivo. Furthermore, we found that the elevation of SIRT1 and Skp2 expression in malignant PC3 and DU145 prostate cells is responsible for the downregulation of FOXO3 protein levels in these cells. Taken together, our data support the notion that deacetylation of FOXO3 by SIRT1 or SIRT2 facilitates Skp2-mediated FOXO3 poly-ubiquitination and proteasomal degradation.
MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid ...leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.
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