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Medlin Lawson opublikował 5 miesięcy, 1 tydzień temu
These new findings will enhance our understandings of parasite immunogenicity and immune evasion mechanisms of E. necatrix and facilitate the discovery phase of highly effective vaccine candidates.
The Chang Gung Research Database (CGRD) is the largest multi-institutional electronic medical records database in Taiwan and has been widely used to establish evidence studies. However, the accuracy of CGRD has rarely been validated. This study aims to validate the discharge status, especially with a focus on mortality, of admission data under CGRD.
We constructed an observational study using CGRD linked with TDR to validate the discharge status. The CGRD and TDR data were obtained from the Chang Gung Memorial Hospital system and the Health and Welfare Data Science Center, respectively. The accuracy, positive predictive value (PPV), and underestimated mortality rate (UEM) were employed as indicators for validation. Year, sex, age, and the primary cause for admission (PCA) were analyzed.
A total of 1,972,044 admission records under CGRD were analyzed. The overall accuracy for mortality coding on discharge status was higher than 97% within one week after discharge. The accuracy increased by year and was more than 98% after 2010. A similar result was observed in UEM; the UEM within one week was lower than 10% after 2010. These indicators varied by age group and PCA-elderly patients had relatively lower accuracy and higher UEM (approximately 11%). The presence of UEM within one week was better but varied by disease.
Considering the data accuracy and UEM discharge status, prioritizing the use of inpatient data after 2010 under CGRD for mortality outcome follow-up studies is recommended.
Considering the data accuracy and UEM discharge status, prioritizing the use of inpatient data after 2010 under CGRD for mortality outcome follow-up studies is recommended.
We investigated the relationship between inducible nitric oxide synthase (iNOS) and arginase pathways, cytokines, macrophages, oxidative damage and lung granulomatous inflammation in S. mansoni-infected and doxycycline-treated mice.
Swiss mice were randomized in four groups (i) uninfected, (ii) infected with S. mansoni, (iii) infected+200mg/kg praziquantel (Pzt), (iv) and (v) infected+5 and 50mg/kg doxycycline. Pzt (reference drug) was administered in a single dose and doxycycline for 60 days.
S. mansoni-infection determined extensive lung inflammation, marked recruitment of M2 macrophages, cytokines (IL-4, IL-5, IFN-γ, TNF-α) upregulation, intense eosinophil peroxidase (EPO) levels, arginase expression and activity, reduced iNOS expression and nitric oxide (NO) production. The higher dose of doxycycline aggravated lung granulomatous inflammation, downregulating IL-4 levels and M2 macrophages recruitment, and upregulating iNOS expression, EPO, NO, IFN-γ, TNF-α, M1 macrophages, protein carbonyl and malonseveral intracellular pathogens, effective schistosomicidal responses are dependent of the Th2 phenotype. Thus, doxycycline contributes to the worsening of lung granulomatous inflammation by potentiating eosinophils influx and downregulating Th2 effectors, reinforcing lipid and protein oxidative damage in chronic S. mansoni infection.
Stressed animals may perform depression-like behavior insomuch as stress-provoking blood-brain barrier (BBB) disruption, central immune activation, and autophagic flux changes. This study was undertaken to assess whether adult mice having (executive) vs. lacking (yoke) of behavioral control in otherwise equivalent stress magnitude condition, may display differences in their BBB integrity, ventral hippocampal (VH) interleukin-6 (IL-6) and autophagic flux level and VH-related depression-like behavior. To further understand the causative relation of enhanced autophagic flux and stress-primed depression-like behavior, we assessed the effects of bilateral intra-VH 3-methyladenine (3-MA), an autophagic flux inhibitor, infusion in stressed mice.
Adult mice used had comparable genetic background and housing condition. Executive/yoke pairs of mice received a 10-day (1h/day) footshock stressor regimen. Throughout the regimen, the ongoing footshock was terminated immediately contingent on the executive mouse’, whilesceptible to exhibit depression-like behavior.
The aim of this study was to analyze whether subgroups of immunosuppressive (IS) medications conferred different outcomes in COVID-19.
The study involved a multicenter retrospective cohort of consecutive immunosuppressed patients (ISPs) hospitalized with COVID-19 from March to July, 2020. The primary outcome was in-hospital mortality. A propensity score-matched (PSM) model comparing ISP and non-ISP was planned, as well as specific PSM models comparing individual IS medications associated with mortality.
Out of 16647 patients, 868 (5.2%) were on chronic IS therapy prior to admission and were considered ISPs. In the PSM model, ISPs had greater in-hospital mortality (OR 1.25, 95% CI 0.99-1.62), which was related to a worse outcome associated with chronic corticoids (OR 1.89, 95% CI 1.43-2.49). Other IS drugs had no repercussions with regard to mortality risk (including calcineurin inhibitors (CNI); OR 1.19, 95% CI 0.65-2.20). In the pre-planned specific PSM model involving patients on chronic IS treatment before admission, corticosteroids were associated with an increased risk of mortality (OR 2.34, 95% CI 1.43-3.82).
Chronic IS therapies comprise a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid therapy is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes.
Chronic IS therapies comprise a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid therapy is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes.
The coronavirus disease 2019 (COVID-19) first reported in Wuhan, China in December 2019 is a global pandemic that is threatening the health and wellbeing of people worldwide. To date there have been more than 274 million reported cases and 5.3 million deaths. The Omicron variant first documented in the City of Tshwane, Gauteng Province, South Africa on 9 November 2021 led to exponential increases in cases and a sharp rise in hospital admissions. The clinical profile of patients admitted at a large hospital in Tshwane is compared with previous waves.
466 hospital COVID-19 admissions since 14 November 2021 were compared to 3962 admissions since 4 May 2020, prior to the Omicron outbreak. Ninety-eight patient records at peak bed occupancy during the outbreak were reviewed for primary indication for admission, clinical severity, oxygen supplementation level, vaccination and prior COVID-19 infection. Provincial and city-wide daily cases and reported deaths, hospital admissions and excess deaths data were sourceses and deaths compared to previous waves, corroborating the clinical findings of decreased severity of disease seen in patients admitted to the Steve Biko Academic Hospital.
There was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.
There was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.
The aim of this study was to inform public health policy decisions through the assessment of IgG antibody seroprevalence in the population and the risk factors for SARS-CoV-2 infection.
The seroprevalence of IgG antibodies among different subpopulations at the end of the first and second waves of the pandemic was estimated. Various risk factors associated with seropositivity, including sociodemography, IgG antibodies against endemic human coronavirus, and vaccination status, were also assessed.
For all 2433 consenting participants, the overall estimated seroprevalences at the end of first and second waves were 28.5% (95% CI 22.3-33.7%) and 71.5% (95% CI 62.8-80.5%), respectively. The accrual of IgG positivity was heterogeneous, with the highest seroprevalences found in urban slum populations (75.1%). Vaccine uptake varied among the subpopulations, with low rates (< 10%) among rural and urban slum residents. The majority of seropositive individuals (75%) were asymptomatic. Residence in urban slums (OR 2.02, 95% CI 1.57-2.6; p < 0.001), middle socioeconomic status (OR 1.77, 95% CI 1.17-2.67; p=0.007), presence of diabetes (OR 1.721, 95% CI 1.148-2.581; p=0.009), and hypertension (OR 1.75, 95% CI 1.16-2.64; p=0.008) were associated with seropositivity in multivariable analyses.
Although considerable population immunity has been reached, with more than two-thirds seropositive, improved vaccination strategies among unreached subpopulations and high-risk individuals are suggested for better preparedness in future.
Although considerable population immunity has been reached, with more than two-thirds seropositive, improved vaccination strategies among unreached subpopulations and high-risk individuals are suggested for better preparedness in future.
Dietary signals are known to modulate stemness and tumorigenicity of intestinal progenitors; however, the impact of a high-fat diet (HFD) on the intestinal stem cell (ISC) niche and its association with colorectal cancer remains unclear. Thus, we aimed to investigate how a HFD affects the ISC niche and its regulatory factors.
Mice were fed a purified diet (PD) or HFD for 2 months. The expression levels of ISC-related markers, ISC-supportive signals, and Wnt2b were assessed with real-time quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence staining. RNA sequencing and metabolic function were analyzed in mesenchymal stromal cells (MSCs) from PD- and HFD-fed mice. Fecal microbiota were analyzed by 16s rRNA sequencing. Bile salt hydrolase activity and bile acid (BA) levels were measured.
We found that expression of CD44 and Wnt signal-related genes was higher in the colonic crypts of HFD-fed mice than in those fed a PD. Within the ISC niche, MSCs were expanded and secreted predominant levels of Wnt2b in the colon of HFD-fed mice. Of note, increased energy metabolism and cancer-associated fibroblast (CAF)-like properties were found in the colonic MSCs of HFD-fed mice. Moreover, colonic MSCs from HFD-fed mice promoted the growth of tumorigenic properties and accelerated the expression of cancer stem cell (CSC)-related markers in colon organoids. In particular, production of primary and secondary BAs was increased through the expansion of bile salt hydrolase-encoding bacteria in HFD-fed mice. Most importantly, BAs-FXR interaction stimulated Wnt2b production in colonic CAF-like MSCs.
HFD-induced colonic CAF-like MSCs play an indispensable role in balancing the properties of CSCs through activation of the BAs-FXR axis.
HFD-induced colonic CAF-like MSCs play an indispensable role in balancing the properties of CSCs through activation of the BAs-FXR axis.
This study evaluated the effects of final agitation methods of irrigants to remove methylene blue and sodium hypochlorite residues after PDT-assisted endodontic treatment on the bond strength of fiber posts cemented with etch-and-rinse adhesive and conventional resin cement.
Ninety bovine teeth were endodontically treated. In sequence, post space preparation followed by methylene blue-mediated PDT and sodium hypochlorite (NaOCl) irrigation were performed. Six final irrigations protocols for dye and NaOCl removal were performed prior to cementation with etch-and-rinse adhesive (Adper Scocthbond Multipurpose) and conventional dual resin cement (RelyX ARC) Conventional endodontic irrigation (CEI), passive ultrasonic irrigation (PUI), mechanical agitation with XP Endo Finisher (XPF), XP Clean (XPC) or Easy Clean (ECL) and distilled water (NCO – control). After fiber post cementation, push-out bond strength test was performed at different thirds of the post space. Failure mode was also analyzed. ANOVA and Tukey’s post-hoc test was used for data analysis (α=5%).