Highly ordered chromophoric linkers positioned within the metal-organic frameworks (MOFs) have the potential to mimic natural light-harvesting complexes. Herein we report topological control over the ...photophysical properties of MOFs via modular interchromophoric electronic coupling to manifest different steady-state singlet emission spectra and their corresponding fluorescence lifetimes.
Abstract
Background
The relative safety of bacterial risk control strategies for platelets that include culture with or without rapid testing has been compared using simulation analysis. A wide range ...of bacterial lag and doubling times were included. However, published data on growth rates are available and these data have not been synthesized. We conducted a systematic review and meta‐analysis to estimate growth rates and used these estimates to refine a comparative safety analysis of bacterial risk control strategies in the
FDA
guidance
Study Design and Methods
Data were extracted from published studies on bacterial growth rates in platelet components during storage. These data were used to estimate the practical range of growth rates. This refined the inputs for a simulation model comparing the safety of the testing strategies.
Results
In total, 108 growth curves for 11 different aerobic organisms were obtained. Doubling times ranged from 0.8 to 12 h, but the lower 90% range was approximately 1–5 h. The revised comparative safety simulation using the narrower 1–5‐h range showed similar rankings to the prior simulation, with 48‐h large‐volume delayed sampling with 7‐day expiration (48C‐7) demonstrating the lowest‐ranking relative performance at the 10
3
and 10
5
colony forming unit (CFU)/mL exposure thresholds.
Discussion
This was a two‐step study. First, meta‐analysis of published data on aerobic bacterial growth rates in stored platelets showed the vast majority of doubling times were 1–5 h. Next, an updated comparative safety simulation yielded similar results to a prior study, with 48C‐7 showing the least favorable relative safety performance.
Background
The purpose of this scoping review was to identify available sources of evidence on the epidemiology of transfusion‐related acute lung injury (TRALI) and whether meta‐analysis on the ...incidence of TRALI is feasible. TRALI is a serious complication and the second leading cause of death related to blood transfusion. Estimates of the incidence of TRALI would provide a useful benchmark for research to reduce TRALI.
Study Design and Methods
We searched the Medline, EMBASE, and PubMed databases for publications related to the incidence of TRALI and hemovigilance. We included all studies irrespective of language or country. Both full‐text articles and conference s were included. Participants of the studies must all have received a blood transfusion. Reviews and case studies were excluded.
Results
We identified 427 articles or s to include for review. More than half were s, and the majority were published after 2010. Reported TRALI definitions varied, but only 27.2% of studies reported any definition for TRALI. TRALI rates were reported using different denominators, such as per blood unit (54.1%), patient (34.4%), and transfusion episode (14.8%). Study populations and contexts were mostly general (75.6% and 80.3%, respectively). There was also variation in study design with most being observational (90.6%) and only 13.1% of all studies used modern donor restriction policies.
Discussion
There was substantial variation in reporting in studies on TRALI incidence. Meta‐analysis of TRALI rates may be feasible in specific circumstances where reporting is clear. Future studies should clearly report key items, such as a TRALI definition.
A diverse suite of effector immune responses provide protection against various pathogens. However, the array of effector responses must be immunologically regulated to limit pathogen- and ...immune-associated damage. CD4(+)Foxp3(+) regulatory T cells (Treg) calibrate immune responses; however, how Treg cells adapt to control different effector responses is unclear. To investigate the molecular mechanism of Treg diversity we used whole genome expression profiling and next generation small RNA sequencing of Treg cells isolated from type-1 or type-2 inflamed tissue following Leishmania major or Schistosoma mansoni infection, respectively. In-silico analyses identified two miRNA "regulatory hubs" miR-10a and miR-182 as critical miRNAs in Th1- or Th2-associated Treg cells, respectively. Functionally and mechanistically, in-vitro and in-vivo systems identified that an IL-12/IFNγ axis regulated miR-10a and its putative transcription factor, Creb. Importantly, reduced miR-10a in Th1-associated Treg cells was critical for Treg function and controlled a suite of genes preventing IFNγ production. In contrast, IL-4 regulated miR-182 and cMaf in Th2-associed Treg cells, which mitigated IL-2 secretion, in part through repression of IL2-promoting genes. Together, this study indicates that CD4(+)Foxp3(+) cells can be shaped by local environmental factors, which orchestrate distinct miRNA pathways preserving Treg stability and suppressor function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is limited information on the natural history of building occupants' health in relation to attempts to remediate moisture damage. We examined changes in respiratory and non-respiratory symptoms ...in 1,175 office building occupants over seven years with multiple remediation attempts. During each of four surveys, we categorized participants using a severity score: 0 = asymptomatic; 1 = mild, symptomatic in the last 12 months, but not frequently in the last 4 weeks; 2 = severe, symptomatic at least once weekly in the last 4 weeks. Building-related symptoms were defined as improving away from the building. We used random intercept models adjusted for demographics, smoking, building tenure, and microbial exposures to estimate temporal changes in the odds of building-related symptoms or severity scores independent of the effect of microbial exposures. Trend analyses of combined mild/severe symptoms showed no changes in the odds of respiratory symptoms but significant improvement in non-respiratory symptoms over time. Separate analyses showed increases in the odds of severe respiratory symptoms (odds ratio/year = 1.15‒1.16, p-values<0.05) and severity scores (0.02/year, p-values<0.05) for wheezing and shortness of breath on exertion, due to worsening of participants in the mild symptom group. For non-respiratory symptoms, we found no changes in the odds of severe symptoms but improvement in severity scores (-0.04‒-0.01/year, p-values<0.05) and the odds for mild fever and chills, excessive fatigue, headache, and throat symptoms (0.65-0.79/year, p-values<0.05). Our study suggests that after the onset of respiratory and severe non-respiratory symptoms associated with dampness/mold, remediation efforts might not be effective in improving occupants' health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Transfusion‐related acute lung injury (TRALI) is a leading cause of transfusion‐related mortality. A concern with passive surveillance to detect transfusion reactions is underreporting. ...Our aim was to obtain evidence‐based estimates of TRALI incidence using meta‐analysis of active surveillance studies and to compare these estimates with passive surveillance.
Study Design and Methods
We performed a systematic review and meta‐analysis of studies reporting TRALI rates. A search of Medline and Embase by a research librarian identified studies published between January 1, 1991 and January 20, 2023. Prospective and retrospective observational studies reporting TRALI by blood component (red blood cells RBCs, platelets, or plasma) were identified and all inpatient and outpatient settings were eligible. Adult and pediatric, as well as general and specific clinical populations, were included. Platelets and plasma must have used at least one modern TRALI donor risk mitigation strategy. A random effects model estimated TRALI incidence by blood component for active and passive surveillance studies and heterogeneity was examined using meta‐regression.
Results
Eighty studies were included with approximately 176‐million blood components transfused. RBCs had the highest number of studies (n = 66) included, followed by platelets (n = 35) and plasma (n = 34). Pooled TRALI estimates for active surveillance studies were 0.17/10,000 (95% confidence intervals CI: 0.03–0.43; I2 = 79%) for RBCs, 0.31/10,000 (95% CI: 0.22–0.42; I2 = <1%) for platelets, and 3.19/10,000 (95% CI: 0.09–10.66; I2 = 86%) for plasma. Studies using passive surveillance ranged from 0.02 to 0.10/10,000 among the various blood components.
Discussion
In summary, these estimates may improve a quantitative understanding of TRALI risk, which is important for clinical decision‐making weighing the risks and benefits of transfusion.
BACKGROUND
Platelets have the highest bacterial contamination risk of all blood components, and septic transfusion reactions remain a problem. A good estimate of contamination rates could provide ...information about residual risk and inform optimal testing strategies. We performed a systematic review and meta‐analysis of platelet contamination rates by primary culture.
STUDY DESIGN AND METHODS
A literature search in December 2019 identified articles on platelet contamination rates using primary culture. We used meta‐analysis to estimate the overall rate of contamination and meta‐regression to identify heterogeneity. We studied the following sources of heterogeneity: collection method, sample volume, positivity criteria, and study date. Contamination rate estimates were obtained for apheresis (AP), platelet rich plasma (PRP), and buffy coat (BC) collection methods.
RESULTS
The search identified 6102 studies, and 22 were included for meta‐analysis. Among these 22 studies, there were 21 AP cohorts (4,072,022 components), 4 PRP cohorts (138,869 components), and 15 BC cohorts (1,474,679 components). The overall mean contamination rate per 1000 components was 0.51 (95% CI: 0.38‐0.67) including AP (0.23, 95% CI: 0.18‐0.28), PRP, (0.38, 95% CI: 0.15‐0.70), and BC (1.12, 95% CI: 0.51‐1.96). There was considerable variability within each collection method. Sample volume, positivity criteria, and publication year were significant sources of heterogeneity.
CONCLUSION
The bacterial contamination rate of platelets by primary culture is 1 in 1961. AP and PRP components showed a lower contamination rate than BC components. There is clinically significant between‐study variability for each method. Larger sample volumes increased sensitivity, and bacterial contamination rates have decreased over time.
Increasing evidence suggests that asthma is a heterogeneous disorder regulated by distinct molecular mechanisms. In a cross-sectional study of asthmatics of varying severity (n = 51), endobronchial ...tissue gene expression analysis revealed three major patient clusters: TH2-high, TH17-high, and TH2/17-low. TH2-high and TH17-high patterns were mutually exclusive in individual patient samples, and their gene signatures were inversely correlated and differentially regulated by interleukin-13 (IL-13) and IL-17A. To understand this dichotomous pattern of T helper 2 (TH2) and TH17 signatures, we investigated the potential of type 2 cytokine suppression in promoting TH17 responses in a preclinical model of allergen-induced asthma. Neutralization of IL-4 and/or IL-13 resulted in increased TH17 cells and neutrophilic inflammation in the lung. However, neutralization of IL-13 and IL-17 protected mice from eosinophilia, mucus hyperplasia, and airway hyperreactivity and abolished the neutrophilic inflammation, suggesting that combination therapies targeting both pathways may maximize therapeutic efficacy across a patient population comprising both TH2 and TH17 endotypes.
Background
Primary culture alone was a bacterial risk control strategy intended to facilitate interdiction of contaminated platelets (PLTs). A September 2019 FDA guidance includes secondary testing ...options to enhance safety. Our objective was to use meta‐analysis to determine residual contamination risk after primary culture using secondary culture and rapid testing.
Study Design and Methods
A December 2019 literature search identified articles on PLT bacterial detection rates using primary culture and a secondary testing method. We used meta‐analysis to estimate secondary testing detection rates after a negative primary culture. We evaluated collection method, sample volume, sample time, and study date as potential sources of heterogeneity.
Results
The search identified 6102 articles; 16 were included for meta‐analysis. Of these, 12 used culture and five used rapid testing as a secondary testing method. Meta‐analysis was based on a total of 103 968 components tested by secondary culture and 114 697 by rapid testing. The residual detection rate using secondary culture (DRSC) was 0.93 (95% CI, 0.24‐0.6) per 1000 components, while residual detection rate using rapid testing (DRRT) was 0.09 (95% CI, 0.01‐0.25) per 1000 components. Primary culture detection rate was the only statistically significant source of heterogeneity.
Conclusion
We evaluated bacterial detection rates after primary culture using rapid testing and secondary culture. These results provide a lower and upper bound on real‐world residual clinical risk because these methods are designed to detect high‐level exposures or any level of exposure, respectively. Rapid testing may miss some harmful exposures and secondary culture may identify some clinically insignificant exposures.
Objectives: To determine the accuracy of Fungitell, a beta-D-glucan (BDG) test, for the diagnosis of invasive fungal infection (IFI) among cancer patients. Methods: For this meta-analysis, MEDLINE ...and EMBASE were searched for references related to BDG testing. Study quality was evaluated using QUADAS-2. Statistical analysis was performed using Stata 14. Results: We screened 12,426 references and identified 189 studies for full-text review. Nineteen studies were included in the final meta-analysis. There was moderate heterogeneity between studies. Nine studies had a high risk of bias, which significantly elevated the overall specificity estimate. Restricting to only low-bias studies, the sensitivity and specificity were 80% and 63%, respectively. Conclusions: The overall sensitivity and specificity of Fungitell as a diagnostic test for IFI is moderate, and there is substantial heterogeneity between studies. Limiting studies to only low-bias risk reduced heterogeneity but also lowered the overall specificity estimate. Key Words: Sensitivity; Specificity; Cancer; beta-D-glucan; Fungal infection; Immunocompromised; Diagnostic accuracy; Meta-analysis
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