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Differential effects of purified low molecular weight Poly(I:C) in the maternal immune activation model depend on the laboratory environment.
The Poly (I:C) (polyriboinosinic-polyribocytidilic acid) paradigm of maternal immune activation (MIA) is most widely used as experimental model for the evaluation of the effects of gestational infection on the brain and behavior of the progeny. We have previously reported significant batch-to-batch variability in the effects of Poly (I:C), purchased from the same supplier (Sigma-Aldrich), on maternal and fetal immune responses and found these differences to be dependent on the relative amount of synthetic double-stranded RNA fragments in the high versus low molecular weight (LMW) range contained in the compound. We here resorted to Poly (I:C) purified for LMW dsRNA fragments to establish a MIA paradigm with increased reproducibility and enhanced standardization in an effort to refine the MIA paradigm and characterize its effect on offspring behavior. We found that the parallel application of LMW Poly (I:C) in two different MIA-experienced laboratories (Vienna and Zurich) yielded differential outcomes in terms of maternal immune responses and behavioral phenotypes in the offspring generation. In both experimental sites, administration of LMW Poly (I:C) induced a significant sickness response and cytokine induction in the pregnant dam and fetal brains, while the expected deficit in sociability as one main behavioral outcome parameter in the MIA progeny, was only present in the Zurich, but not the Vienna cohort. We conclude that although using Poly (I:C) purified for a defined molecular weight range reduces batch-to-batch variability, it does not make the MIA model more reliable and robust. The differential response in behavioral phenotypes of the MIA offspring between the two laboratories illustrates the highly complex interaction between prenatal and postnatal milieus - including the laboratory environment - that determine offspring phenotypic outcomes after MIA. Consequently, establishing a new MIA protocol or implementing the MIA model firstly under new or changed environmental conditions must include the assessment of offspring behavior to ensure solid and reproducible experimental outcomes
Low-pressure versus standard-pressure pneumoperitoneum in minimally invasive colorectal surgery: a systematic review, meta-analysis, and meta-regression analysis.
BACKGROUND
We aimed to assess the efficacy and safety of low-pressure pneumoperitoneum (LPP) in minimally invasive colorectal surgery.
METHODS
A PRISMA-compliant systematic review/meta-analysis was conducted, searching PubMed, Scopus, Google Scholar, and clinicaltrials.gov for randomized-controlled trials assessing outcomes of LPP vs standard-pressure pneumoperitoneum (SPP) in colorectal surgery. Efficacy outcomes [pain score in post-anesthesia care unit (PACU), pain score postoperative day 1 (POD1), operative time, and hospital stay] and safety outcomes (blood loss and postoperative complications) were analyzed. Risk of bias2 tool assessed bias risk. The certainty of evidence was graded using GRADE.
RESULTS
Four studies included 537 patients (male 59.8%). LPP was undertaken in 280 (52.1%) patients and associated with lower pain scores in PACU [weighted mean difference: -1.06, 95% confidence interval (CI): -1.65 to -0.47, P = 0.004, I 2 = 0%] and POD1 (weighted mean difference: -0.49, 95% CI: -0.91 to -0.07, P = 0.024, I 2 = 0%). Meta-regression showed that age [standard error (SE): 0.036, P < 0.001], male sex (SE: 0.006, P < 0.001), and operative time (SE: 0.002, P = 0.027) were significantly associated with increased complications with LPP. In addition, 5.9%-14.5% of surgeons using LLP requested pressure increases to equal the SPP group. The grade of evidence was high for pain score in PACU and on POD1 postoperative complications and major complications, and blood loss, moderate for operative time, low for intraoperative complications, and very low for length of stay.
CONCLUSIONS
LPP was associated with lower pain scores in PACU and on POD1 with similar operative times, length of stay, and safety profile compared with SPP in colorectal surgery. Although LPP was not associated with increased complications, older patients, males, patients undergoing laparoscopic surgery, and those with longer operative times may be at risk of increased complications
Long-term sequelae after viral meningitis and meningoencephalitis are frequent, even in mildly affected patients, a prospective observational study
Introduction: An increasing number of studies demonstrate that viral meningitis and meningoencephalitis, even those with a mild course of meningitis, can result in residual sequelae.
Methods: We aimed to investigate the long-term outcome in both viral meningitis and meningoencephalitis/encephalitis patients and impact of long-term sequelae on patients’ social and professional daily lives in a prospective observational study with a follow-up period of 20 months.
Results: A total of 50 patients (12% encephalitis, 58% meningoencephalitis and 30% meningitis) and 21 control persons participated in the study. The most common cause was the tick-borne encephalitis (TBE) virus. The most important persistent signs and symptoms after 2 years were subjective cognitive impairment (36%), fatigue and/or excessive daytime sleepiness (31%), disturbed nighttime sleep (31%) and headaches (13%), as well as feeling more rapidly exhausted after cognitive effort (53%). Independent of disease severity in the acute phase, almost one third of patients still reported mildly impaired social and/or professional life due to the long-term sequelae, with scores in the health status assessment still significantly lower compared to healthy controls.
Discussion: Regardless of the severity of the acute illness and despite constant improvement within 2 years, 67% of patients still had persistent signs and symptoms, but these were only relevant to everyday social or professional life in about 30% of these patients
What a socio-legal approach to the accountability gap in migration control can tell us about contemporary governance?
Impact of gender in patients with device-related thrombosis after left atrial appendage closure - A sub-analysis from the multicenter EUROC-DRT-registry.
BACKGROUND
Device-related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted.
METHODS AND RESULTS
This sub-analysis from the EUROC-DRT-registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0 ± 6.7 vs. 74.9 ± 9.1 years, p = .06) with lower rates of comorbidities. While DRT was detected significantly later in women (173 ± 267 vs. 127 ± 192 days, p = .01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p = .40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p = .24). Women were followed-up for a similar time as men (779 ± 520 vs. 908 ± 687 days, p = .51). Kaplan-Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%-Confidence interval [95%-CI]: .68-4.37, p = .25) and no differences in stroke (HR: .83, 95%-CI: .30-2.32, p = .72) within 2 years after LAAC.
CONCLUSION
Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective
The relationship between urban greenery, mixed land use and life satisfaction: An examination using remote sensing data and deep learning
Most Europeans reside in urban areas. Due to anthropogenic air and noise pollution, as well as crowdedness, urban residents experience lower levels of well-being and life satisfaction. The literature indicates that greening urban spaces can help to mitigate these negative effects on life satisfaction. This study employs a deep learning approach in conjunction with high-resolution satellite imagery and land use data to obtain the distribution of different green space types in the residents’ neighborhood and examine their effect on life satisfaction. Furthermore, the study sheds light on the indeterminate relationship between mixed urban land use and life satisfaction. In both cases, the study considers heterogeneous age group effects. The empirical results reveal that in Switzerland, (1) solely older residents’ life satisfaction is positively affected by a greener neighborhood; (2) trees and grass located in gardens and parks are the primary drivers of this effect; and (3) the positive association between land use mixture and life satisfaction decreases with age, with no association found for older individuals. These findings provide practical implications for future city planning in Switzerland and other European countries and highlight the importance of considering the neighborhood’s age distribution in this process to maximize the positive impact of urban greenery and mixed land use on residents’ life satisfaction
Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b.
Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5 μm to 12 μm with the JWST's Mid-Infrared Instrument. The spectra reveal a large day-night temperature contrast (with average brightness temperatures of 1,524 ± 35 K and 863 ± 23 K, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase-curve shape and emission spectra strongly suggest the presence of nightside clouds that become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2σ upper limit of 1-6 ppm, depending on model assumptions). Our results provide strong evidence that the atmosphere of WASP-43b is shaped by disequilibrium processes and provide new insights into the properties of the planet's nightside clouds. However, the remaining discrepancies between our observations and our predictive atmospheric models emphasize the importance of further exploring the effects of clouds and disequilibrium chemistry in numerical models
A systematic review and meta-analysis on early-childhood-caries global data.
OBJECTIVES
The present study systematically reviewed and provided a meta-analysis on early childhood caries (ECC) global prevalence and its association with socioeconomic indicators, both geographical and regarding unemployment rate, national income as well as income inequalities.
METHODS
Only cross-sectional or cohort studies covering ECC prevalence and experience in children younger than 71 months, reporting sample size, diagnostic criteria and conducted in urban and rural communities were considered. No language restriction was selected. Studies published from 2011 to 2022 available in PubMed, Web of Science, Embase and Open Grey literature were retrieved by ad hoc prepared search strings. The meta-analyses were conducted for both overall ECC prevalence and experience stratified by country of publication as well as measures of socioeconomic indicators using a random effects model using STATA 18®.
RESULTS
One hundred publications reporting ECC data from 49 countries (published from 2011 to 2022) were included and summarized by meta-analysis. The lowest prevalence was reported in Japan (20.6%) and Greece (19.3%). The global estimated random-effect pooled prevalence of ECC was 49% (95%CI: 0.44-0.55). The random-effect pooled caries prevalence (ECC) was 34% (95%CI: 02.20-0.48) (Central/South America), 36% (95%CI: 0.25-0.47) (Europe), 42% (95%CI: 0.32-0.53) (Africa), 52% (95%CI: 0.45-0.60) (Asia-Oceania), 57% (95%CI: 0.36-0.77) (North America) and 72% (95%CI: 0.58-0.85) (Middle East). When stratified by gross national income (GNI) the ECC prevalence ranged from 30% (39,999) to 57% in countries with the lowest GNI (<$5000). Stratification by inequality index (Gini index) resulted in an ECC prevalence range of 39% (low inequality) to 62% (no inequality), while for life expectancy the ECC prevalence ranged from 28% in countries with the highest life expectancy (< 80 years) to 62% in countries with 71-75 years life expectancy.
DISCUSSION
Within the limitations of this study (lack of certainty about the results as many countries are not represented and lack of uniformity in prevalence and experience data represented), results from 49 different countries reported a wide range of ECC prevalence. These reports indicated persisting high worldwide distribution of the disease. Both ECC prevalence and experience were associated with geographical areas and GNI.
REGISTRATION
PROSPERO: CRD-42,022,290,418