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Institute
Producing reliable estimates for childhood mortality rates is essential to monitor progress towards the United Nations Sustainable Development Goals (UN SDGs) and correctly evaluate policies designed to reduce childhood mortality rates. Different model-based approaches have been proposed to assess levels and trends in childhood mortality indicators. In this paper, we propose a design-based complement that accumulates birth histories across different household surveys to increase the precision of childhood mortality rates estimates. We accumulate birth histories across different cross-sectional Demographic Health Surveys/Multiple Cluster Indicator Surveys collected in Senegal and Malawi and estimate pooled childhood mortality rates based on calendar years. We show that accumulating birth histories smoothens fluctuations in time series for national and sub-national mortality rates, establishes more stable and reliable time trends, and results in estimated standard errors of the cumulated rates that are about 50–60% lower than their counterparts from separate surveys.
FTY720 is a novel immunosuppressive drug that inhibits the egress of lymphocytes from secondary lymphoid tissues and thymus. In its phosphorylated form FTY720 is a potent S1P receptor agonist. Recently it was also shown that FTY720 can reduce prostaglandin synthesis through the direct inhibition of the cytosolic phospholipase A2 (cPLA2). Since prostaglandins are important mediators of nociception, we studied the effects of FTY720 in different models of nociception. We found that intraperitoneal administration of FTY720 reduced dose-dependently the nociceptive behaviour of rats in the formalin assay. Although the antinociceptive doses of FTY720 were too low to alter the lymphocyte count, prostanoid concentrations in the plasma were dramatically reduced. Surprisingly, intrathecally administered FTY720 reduced the nociceptive behaviour in the formalin assay without altering spinal prostaglandin synthesis, indicating that additional antinociceptive mechanisms beside the inhibition of prostaglandin synthesis are involved. Accordingly, FTY720 reduced also the nociceptive behaviour in the spared nerve injury model for neuropathic pain which does not depend on prostaglandin synthesis. In this model the antinociceptive effect of FTY720 was similar to gabapentin, a commonly used drug to treat neuropathic pain. Taken together we show for the first time that FTY720 possesses antinociceptive properties and that FTY720 reduces nociceptive behaviour during neuropathic pain.
Consequences of altered eicosanoid patterns for nociceptive processing in mPGES-1-deficient mice
(2007)
Cyclooxygenase-2 (COX-2)-dependent prostaglandin (PG) E2 synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE2 synthase-1 (mPGES-1) isomerizes COX-2-derived PGH2 to PGE2. Here, we evaluated the effect of mPGES-1-deficiency on the noci-ceptive behavior in various models of nociception that depend on PGE2 synthesis. Surprisingly, in the COX-2-dependent zymosan-evoked hyperalgesia model, the nociceptive behavior was not reduced in mPGES-1-deficient mice despite a marked decrease of the spinal PGE2 synthesis. Similarly, the nociceptive behavior was unaltered in mPGES-1-deficient mice in the formalin test. Importantly, spinal cords and primary spinal cord cells derived from mPGES-1-deficient mice showed a redirection of the PGE2 synthesis to PGD2, PGF2α and 6-keto-PGF1α (stable metabolite of PGI2). Since the latter prostaglandins serve also as mediators of noci-ception they may compensate the loss of PGE2 synthesis in mPGES-1-deficient mice.
In the context of workplace health promotion, physical activity programs have been shown to reduce musculoskeletal diseases and stress, and to improve the quality of life. The aim of this study was to examine the effects of using the “five-Business” stretch training device for office workers on their quality of life. A total of 313 office workers (173m/137f) participated voluntarily in this intervention–control study with an average age of 43.37 ± 11.24 (SD) years, 175.37 ± 9.35 cm in height and 75.76 ± 15.23 kg in weight, with an average BMI of 24.5 ± 3.81 kg/m2. The participants completed the stretch training twice a week for approximately 10 minutes for a duration of 12 weeks. The SF-36 questionnaire was used to evaluate the effectiveness of the intervention at baseline and after 12 weeks. Significantly improved outcomes in mental sum score (p = 0.008), physical functioning (p < 0.001), bodily pain (p = 0.01), vitality (p = 0.025), role limitations due to physical problems (p = 0.018) and mental health (p = 0.012) were shown after the stretching training. The results suggest that a 12-week stretching program for office desk workers is suitable to improve significantly their health-related quality of life.
Hintergrund: Dehntrainings sind eine Maßnahme der betrieblichen Gesundheitsförderung (BGF) für Büroangestellte zur Prävention von muskuloskeletalen Erkrankungen (MSE). Sie können zu Beweglichkeitszuwächsen führen und auf psychischer Ebene entspannen. Ziel der Studie war es, ein standardisiertes und individualisiertes Dehntraining am Gerät, das „five-Business“, auf MSE, Lebensqualität und Beweglichkeit zu untersuchen. Dies ist eine Zusammenfassung der international publizierten Ergebnisse.
Methodik: In diese Untersuchung wurden 252 Proband(innen) eingeschlossen, 156 in die Interventionsgruppe (IG), 96 in die Kontrollgruppe (KG). Die IG absolvierte für 12 Wochen 22–24 Trainingseinheiten am „five-Business“, möglichst zweimal wöchentlich. Die Datenerhebung erfolgte mittels sportmotorischer bzw. Range-of-motion(ROM)-Tests, dem Nordic Questionnaire (NQ) und dem SF-36-Fragebogen in Form einer Prä-Post-Untersuchung.
Ergebnisse: Nach der Intervention gaben im NQ signifikant weniger Proband(innen) der IG Beschwerden im oberen Rücken (p < 0,001) im Vergleich zur KG an; keine signifikanten Unterschiede wurden bei Beschwerden im Nacken, Schultern, Hüfte und dem unteren Rücken gefunden. Der mit dem SF-36 erhobene allgemeine Gesundheitszustand und die gesundheitsbezogene Lebensqualität haben sich (nach subjektiven Angaben) signifikant verbessert (Summenscore IG: p = 0,005). In den ROM-Tests waren die Prä-Post-Differenzen bei IG-Proband(innen) in der Sagittalebene (Finger-Boden-Abstand und Retroflexion; p < 0,001) und im modifizierten Schultertest nach Janda auf der linken Seite (p = 0,003) signifikant größer.
Diskussion: Trotz des in Zeitdauer und Häufigkeit relativ geringen Trainingsaufwandes wurden sowohl auf körperlicher als auch auf psychischer Ebene relevante Verbesserungen erzielt, so dass das „five-Business“-Dehntraining als BGF-Maßnahme empfohlen werden kann.
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
Correction to: Infection (2020) 48:723–733 https://doi.org/10.1007/s15010-020-01469-6. The original version of this article unfortunately contained a mistake. In this article the authors Dirk Schürmann at affiliation Charité, University Medicine, Berlin, Olaf Degen at affiliation University Clinic Hamburg Eppendorf, Hamburg and Heinz-August Horst at affiliation University Hospital Schleswig–Holstein, Kiel, Germany were missing from the author list. The original article has been corrected.
Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated regarding its therapeutic properties in several several conditions such as epilepsy, migraine and major depressive disorder and was shown to access similar neural pathways as invasive vagus nerve stimulation. While the vagus nerve's role in gut motility is physiologically established, the effect of taVNS has scarcely been investigated in humans and yielded conflicting results. Real-time gastric magnetic resonance imaging (rtMRI) is an established reproducible method to investigate gastric motility non-invasively. Objective: To investigate the influence of taVNS on gastric motility of healthy participants using rtMRI. Methods: We conducted a randomized, double-blind study using high-frequency (HF) stimulation at 25Hz or low-frequency (LF) taVNS at 1Hz after ingestions of a standardized meal in 57 healthy participants. The gastric motility index (GMI) was determined by measuring the amplitude and velocity of the peristaltic waves using rtMRI. Results: After HF taVNS, GMI was significantly higher than after LF stimulation (p = 0.005), which was mainly attributable to a higher amplitude of the peristaltic waves (p = 0.003). Conclusion: We provide evidence that 4-h of taVNS influences gastric motility in healthy human participants for the first time using rtMRI. HF stimulation is associated with higher amplitudes of peristaltic waves in the gastric antrum compared to LF stimulation. Further studies are needed to investigate the effect of different frequencies of taVNS and its therapeutic properties in conditions with impaired gastric motility.
The NVX-CoV2373-vaccine has recently been licensed, although data on vaccine-induced humoral and cellular immunity towards the parental strain and variants of concern (VOCs) in comparison to dual-dose mRNA-regimens are limited. In this observational study including 66 participants, we show that NVX-CoV2373-induced IgG-levels were lower than after vaccination with BNT162b2 or mRNA-1273 (n=22 each, p=0.006). Regardless of the vaccine and despite different IgG-levels, neutralizing activity towards VOCs was highest for Delta, followed by BA.2 and BA.1. Interestingly, spike-specific CD8 T-cell levels after NVX-CoV2373-vaccination were significantly lower and were detectable in 3/22 (14%) individuals only. In contrast, spike-specific CD4 T-cells were induced in 18/22 (82%) individuals. However, CD4 T-cell levels were lower (p<0.001), had lower CTLA-4 expression (p<0.0001) and comprised less multifunctional cells co-expressing IFNγ, TNFαα and IL-2 (p=0.0007) as compared to mRNA-vaccinated individuals. Unlike neutralizing antibodies, NVX-CoV2373-induced CD4 T cells cross-reacted to all tested VOCs from Alpha to Omicron, which may hold promise to protect from severe disease.
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.