Candida albicans (C. albicans) CDC4 (CaCDC4), encoding the F‑box protein for the substrate specificity of the Skp1‑cullin‑F‑box E3 ubiquitin ligase complex, suppresses the yeast‑to‑filament ...transition in C. albicans. In our previous study, Thr1 was identified as a CaCdc4‑associated protein using affinity purification. THR1 encodes a homoserine kinase, which is involved in the threonine biosynthesis pathway. The present study generated a strain with repressible CaCDC4 expression and continuous THR1 expression. Colony and cell morphology analyses, as well as immunoblotting, revealed that the Thr1 protein was detectable under conditions in which the expression of CaCDC4 was repressed and that the filaments resulting from the repressed expression of CaCDC4 were suppressed by the constitutive expression of THR1 in C. albicans. Additionally, by using the CaSAT1‑flipper method, the present study produced null mutants of THR1, GCN4, and CaCDC4. The phenotypic consequences were evaluated by growth curves, spotting assays, microscopic analysis, reverse transcription‑polymerase chain reaction and XTT‑based biofilm formation ability. The results revealed that fewer cells lacking THR1 entered the stationary phase but had no apparent morphological alteration. It was observed that the expression of THR1 was upregulated concurrently with GCN4 during nutrient depletion and that cells lacking GCN4 rescued the lethality of cells in the absence of THR1 in conditions accumulating homoserine in the threonine biosynthesis pathway. Of note, it was found that cells with either CaCDC4 or THR1 loss were sensitive to oxidative stress and osmotic stress, with those with THR1 loss being more sensitive. In addition, it was observed that cells with loss of either CaCDC4 or THR1 exhibited the ability to increase biofilm formation, with those lacking CaCDC4 exhibiting a greater extent of enhancement. It was concluded that CaCDC4 is important in the coordination of morphogenesis, nutrient sensing, and the stress response through THR1 in C. albicans.
This study investigated the effects of electric current and external stress on electromigration of intermetallic compounds (IMC) between solder and copper substrate. Different samples were tested ...under three different sets of conditions: (1) thermal aging only, (2) thermal aging with electric current ,where resistivity changes were measured using four-point probe measurements, (3) thermal aging with electric current and external stress provided using a four-point bending apparatus. The micro-structural changes in the samples were observed. The results were closely examined; particularly the coupling effect of electric current and external stress to elucidate the electromigration mechanism, as well as the formation of IMC in the samples. For thermal-aging-only samples, the IMC growth mechanism was controlled by grain boundary diffusion. Meanwhile, for thermal aging and applied electric current samples, the IMC growth mechanism was dominated by volume diffusion and interface reaction. Lastly, the IMC growth mechanism in the electric current and external stress group was dominated by grain boundary diffusion with grain growth. The results reveal that the external stress/strain and electric current play a significant role in the electromigration of copper-tin IMC. The samples exposed to tensile stress have reduced electromigration, while those subjected under compressive stress have enhanced electromigration.
Given that evidence supporting chronic hepatitis C (CHC) infection developed chance for hepatocellular carcinoma (HCC) following antiviral agents therapy is controversial. We conducted a ...meta-analysis to examine the risk.We evaluated 20 retrospective and prospective cohort studies published up to 31 December 2017 which investigated the association between sustained virological response (SVR) and incidence of HCC patients treated with monotherapy interferon (IFN) or IFN plus ribavirin (RBV) therapy. The primary outcome of the study was the cumulative incidence of HCC. Odds ratio (OR) was used to evaluate the index of effect size for the association between SVR and treatment with IFN alone or IFN/RBV in CHC patients.SVR patients demonstrated a lower incidence of HCC compared to non-SVR patients. Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN plus RBV (pooled OR = 7.405, 95% CI = 4.689 to 11.694, P < .001). Non-SVR patients had greater odds of HCC incidence compared to SVR patients in the treatment of IFN monotherapy (pooled OR = 4.135, 95% CI = 3.009 to 5.682, P < .001). Lack of SVR to IFN therapy was significantly associated with greater risk of HCC incidence (pooled OR = 5.035, 95% CI = 3.915 to 6.474, P < .001).SVR could be as a predictor of HCC in CHC patients treated with IFN or IFN plus RBV, and have important implications during HCC screening, whereby patients who fail to achieve SVR need to be screened more rigorously.
BACKGROUND:The efficacy and safety of switching from tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir ...alafenamide (E/C/F/TAF) has not been widely investigated in HIV/HBV-coinfected Asian population.
METHODS:Between February and October 2018, HIV/HBV-coinfected patients who had achieved HIV viral suppression with TDF-containing regimens were switched to E/C/F/TAF. Assessments of plasma HBV and HIV viral load, HBV serology, renal function, lipid profiles, and bone mineral density (BMD) were performed at weeks 24 and 48 after switch.
RESULTS:A total of 274 HIV/HBV-coinfected participants were enrolled, with 12.8% testing HBeAg-positive and 94.2% having plasma HBV DNA <20 IU/mL at baseline. At weeks 24 and 48, 92.7% and 89.8% achieved plasma HBV DNA <20 IU/mL; 4.7% and 5.1% had HBV DNA ≥20 IU/mL; and 2.6% and 5.1% had no data, respectively. At weeks 24 and 48, 95.6% and 94.2% of participants maintained HIV RNA <50 copies/mL, respectively. Compared with baseline, the median urine β2-microglobulin-to-creatinine ratio at week 48 decreased significantly from 241 to 134 μg/g (p<0.001). The mean BMD of the spine and hip improved at week 48 (+1.77% and +1.33%, respectively). Significantly higher lipid profiles were observed after switch to E/C/F/TAF. Thirteen (4.7%) patients withdrew from the study before week 48, with 7 (2.6%) due to adverse effects.
CONCLUSIONS:Switch to E/C/F/TAF maintained HBV and HIV viral suppression and resulted in improvement of proteinuria and BMD of the spine and hip, but increased lipid levels in HIV/HBV-coinfected patients at week 48.
During an AHA outbreak, we found that HIV-infected patients had a lower severity, but delayed resolution, of AHA than HIV-uninfected patients. Better viral suppression by cART alleviated the impact ...of HIV infection on the disease course of AHA in HIV-infected patients.
Abstract
Background
This multicenter retrospective cohort study aimed to compare the clinical presentations and evolution of acute hepatitis A (AHA) between human immunodeficiency virus (HIV)-infected patients and HIV-uninfected counterparts during the AHA outbreak.
Methods
Clinical and laboratory data were collected from the medical records of the patients with AHA at the 14 hospitals around Taiwan between May 2015 and May 2017.
Results
A total of 297 adult patients with AHA were included during the study period. Their mean age was 31.4 years (range, 19.0-76.1 years); 93.4% were men and 58.6% were men who have sex with men. Of 265 patients with known HIV serostatus, 166 (62.6%) were HIV infected. Compared with HIV-uninfected patients, HIV-infected patients had a lower peak alanine aminotransferase (ALT) level (median, 1312 vs 2014 IU/L, P = .003), less coagulopathy (6.0% vs 16.2%, P = .007), and less hepatomegaly or splenomegaly on imaging studies, but a higher rate of delayed resolution of hepatitis (38.8% vs 21.3%, P = .009). HIV-infected patients with plasma RNA load <1000 copies/mL while receiving combination antiretroviral therapy (cART) had a higher peak ALT level (median, 1420 vs 978 IU/L, P = .006) and less delay in resolution of hepatitis (30.6% vs 48.8%, P = .047) than patients without cART or with plasma RNA load ≥1000 copies/mL.
Conclusions
During an AHA outbreak, HIV-infected patients had a lower severity, but delayed resolution, of AHA than HIV-uninfected patients. Better viral suppression by cART alleviated the impact of HIV infection on the disease course of AHA in HIV-infected patients.
How do we decide to de-isolate COVID-19 patients? Liao, Chia-Hung; Hung, Shih-Chang; Lee, Yuan-Ti ...
Journal of microbiology, immunology and infection,
06/2020, Letnik:
53, Številka:
3
Journal Article
Background
Lymphopenia and the resultant high neutrophil-to-lymphocyte ratio (NLR) are hallmark signs of severe COVID-19, and effective treatment remains unavailable. We retrospectively reviewed the ...outcomes of COVID-19 in a cohort of 26 patients admitted to Chung Shan Medical University Hospital (Taichung City, Taiwan). Twenty-five of the 26 patients recovered, including 9 patients with mild/moderate illness and 16 patients with severe/critical illness recovered. One patient died after refusing treatment.
Case presentation
We report the cases of four patients with high NLRs and marked lymphopenia, despite receiving standard care. A novel injectable botanical drug, PG2, containing
Astragalus
polysaccharides, was administered to them as an immune modulator. The decrease in the NLR in these four patients was faster than that of other patients in the cohort (0.80 vs. 0.34 per day).
Conclusion
All patients recovered from severe COVID-19 showed decreased NLR and normalized lymphocyte counts before discharge. Administration of PG2 may be of benefit to patients with moderate to severe COVID-19 and lymphopenia.
The information of antimicrobial susceptibility, toxin gene, and ribotype distribution of toxigenic
isolates in Taiwan remain limited.
The study was conducted from January 2015 to December 2016 in 5 ...hospitals in Taiwan. Adults aged ≥20 years with a hospital stay for >5 days were included, and those with colectomy or intestinal infection due to other enteropathogens were excluded. Multiplex PCR was used to detect
, and
deletions, and antimicrobial susceptibility for metronidazole, vancomycin, doxycycline, and tigecycline was investigated. Ribotypes of those isolates with
deletion and
were determined.
Of 1112
isolates collected from adults at 5 hospitals, 842 were toxigenic, including 749 (89.0%) tcdA+/tcdB+ isolates and 93 (11.0%)
. Of the toxigenic isolates, 76 (9.0%) had a
deletion and were
, indicative of hypervirulence, and RT078 lineage, including RT126, RT127, and RT078, predominated (n=53, 76.3%). Similar to the susceptibility data in Asia countries, metronidazole or vancomycin resistance was rare, noted in 1.2% or 2.1%, respectively. Reduced doxycycline susceptibility (minimum inhibitory concentration MIC of ≥8 mg/L) was more common among RT078 lineage than non-RT078 lineage (75.9%, 44/58 vs 6.0%, 47/784;
<0.001). Also reduced tigecycline susceptibility (MIC ≥0.125 mg/L) was more common among RT078 lineage (20.7%, 12/58 vs 6.5%, 51/784;
<0.001).
In Taiwan, toxigenic
isolates remain susceptible to metronidazole and vancomycin. RT078 lineage predominated among toxigenic isolates with
, and
deletion, and more often had reduced doxycycline and tigecycline susceptibility than the isolates other than RT078 lineage.
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