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- ItemEffects of new beta-type Ti-40Nb implant materials, brain-derived neurotrophic factor, acetylcholine and nicotine on human mesenchymal stem cells of osteoporotic and non osteoporotic donors(San Francisco, CA : Public Library of Science (PLoS), 2018) Kauschke, V.; Gebert, A.; Calin, M.; Eckert, J.; Scheich, S.; Heiss, C.; Lips, K.S.Introduction Treatment of osteoporotic fractures is still challenging and an urgent need exists for new materials, better adapted to osteoporotic bone by adjusted Young’s modulus, appropriate surface modification and pharmaceuticals. Materials and methods Titanium-40-niobium alloys, mechanically ground or additionally etched and titanium-6-alu-minium-4-vanadium were analyzed in combination with brain-derived neurotrophic factor, acetylcholine and nicotine to determine their effects on human mesenchymal stem cells in vitro over 21 days using lactate dehydrogenase and alkaline phosphatase assays, live cell imaging and immunofluorescence microscopy. Results Cell number of human mesenchymal stem cells of osteoporotic donors was increased after 14 d in presence of ground titanium-40-niobium or titanium-6-aluminium-4-vanadium, together with brain-derived neurotrophic factor. Cell number of human mesenchymal stem cells of non osteoporotic donors increased after 21 d in presence of titanium-6-aluminium-4-vanadium without pharmaceuticals. No significant increase was measured for ground or etched titanium-40-niobium after 21 d. Osteoblast differentiation of osteoporotic donors was significantly higher than in non osteoporotic donors after 21 d in presence of etched, ground titanium-40-niobium or titanium-6-aluminium-4-vanadium accompanied by all pharmaceuticals tested. In presence of all alloys tested brain-derived neurotrophic factor, acetylcholine and nicotine increased differentiation of cells of osteoporotic donors and accelerated it in non osteoporotic donors. Conclusion We conclude that ground titanium-40-niobium and brain-derived neurotrophic factor might be most suitable for subsequent in vivo testing.
- ItemEffect on healthcare utilization and costs of spinal manual therapy for acute low back pain in routine care: A propensity score matched cohort study(San Francisco, California, US : PLOS, 2017) Walker, Jochen; Mertens, Ulf Kai; Schmidt, Carsten Oliver; Chenot, Jean-FrançoisSpinal manual therapy (SMT) is a popular treatment option for low back pain (LBP). The aim of our analysis was to evaluate the effects of manual therapy delivered by general practitioners and ambulatory orthopedic surgeons in routine care on follow up consultations, sick leave, health service utilization and costs for acute LBP compared to matched patients not receiving manual therapy. This is a propensity score matched cohort study based on health claims data. We identified a total of 113.652 adult patients with acute LBP and no coded red flags of whom 21.021 (18%) received SMT by physicians. In the final analysis 17.965 patients in each group could be matched. Balance on patients' coded characteristics, comorbidity and prior health service utilization was achieved. The provision of SMT for acute LBP had no relevant impact on follow up visits and days of sick leave for LBP in the index billing period and the following year. SMT was associated with a higher proportion of imaging studies for LBP (30.6% vs. 23%, SMD: 0.164 [95% CI 0.143-0.185]). SMT did not lead to meaningful savings by replacing other health services for LBP. SMT for acute non-specific LBP in routine care was not clinically meaningful effective to reduce sick leave and reconsultation rates compared to no SMT and did not lead to meaningful savings by replacing other health services from the perspective of health insurance. This does not imply that SMT is ineffective but might reflect a problem with selection of suitable patients and the quality and quantity of SMT in routine care. National Manual Medicine societies should state clearly that imaging is not routinely needed prior to SMT in patients with low suspicion of presence of red flags and monitor the quality of provided services.
- ItemLiver Dysfunction and Phosphatidylinositol-3-Kinase Signalling in Early Sepsis: Experimental Studies in Rodent Models of Peritonitis(San Francisco, CA : Public Library of Science, 2012) Recknagel, P.; Gonnert, F.A.; Westermann, M.; Lambeck, S.; Lupp, A.; Rudiger, A.; Dyson, A.; Carré, J.E.; Kortgen, A.; Krafft, C.; Popp, J.; Sponholz, C.; Fuhrmann, V.; Hilger, I.; Claus, R.A.; Riedemann, N.C.; Wetzker, R.; Singer, M.; Trauner, M.; Bauer, M.Background: Hepatic dysfunction and jaundice are traditionally viewed as late features of sepsis and portend poor outcomes. We hypothesized that changes in liver function occur early in the onset of sepsis, yet pass undetected by standard laboratory tests. Methods and Findings: In a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on subsequent disease severity, as early as 6 h after peritoneal contamination. Phosphatidylinositol-3-kinase (PI3K) signalling was simultaneously induced at this time point. At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic anion transport machinery at the canalicular pole. Inhibitors of PI3K partially prevented cytokine-induced loss of villi in cultured HepG2 cells. Notably, mice lacking the PI3Kγ gene were protected against cholestasis and impaired bile acid conjugation. This was partially confirmed by an increase in plasma bile acids (e.g., chenodeoxycholic acid [CDCA] and taurodeoxycholic acid [TDCA]) observed in 48 patients on the day severe sepsis was diagnosed; unlike bilirubin (area under the receiver-operating curve: 0.59), these bile acids predicted 28-d mortality with high sensitivity and specificity (area under the receiver-operating curve: CDCA: 0.77; TDCA: 0.72; CDCA+TDCA: 0.87). Conclusions: Liver dysfunction is an early and commonplace event in the rat model of sepsis studied here; PI3K signalling seems to play a crucial role. All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes significantly precede conventional markers and are reflected by early alterations in plasma bile acids. These observations carry important implications for the diagnosis of liver dysfunction and pharmacotherapy in the critically ill. Further clinical work is necessary to extend these concepts into clinical practice. Please see later in the article for the Editors' Summary.
- ItemGuidance of mesenchymal stem cells on fibronectin structured hydrogel films(San Francisco, California, US : PLOS, 2014) Kasten, Annika; Naser, Tamara; Brüllhoff, Kristina; Fiedler, Jörg; Müller, Petra; Möller, Martin; Rychly, Joachim; Groll, Jürgen; Brenner, Rolf E.; Engler, Adam J.Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.
- ItemThe role of risk communication in public health interventions. An analysis of risk communication for a community quarantine in Germany to curb the SARS-CoV-2 pandemic(San Francisco, California, US : PLOS, 2021) Scholz, Juliane; Wetzker, Wibke; Licht, Annika; Heintzmann, Rainer; Scherag, André; Weis, Sebastian; Pletz, Mathias; Betsch, Cornelia; Bauer, Michael; Dickmann, Petra; Frey, RosemaryBackground: Separating ill or possibly infectious people from their healthy community is one of the core principles of non-pharmaceutical interventions. However, there is scarce evidence on how to successfully implement quarantine orders. We investigated a community quarantine for an entire village in Germany (Neustadt am Rennsteig, March 2020) with the aim of better understanding the successful implementation of quarantine measures. Methods: This cross-sectional survey was conducted in Neustadt am Rennsteig six weeks after the end of a 14-day mandatory community quarantine. The sample size consisted of 562 adults (64% of the community), and the response rate was 295 adults, or 52% (33% of the community). Findings: National television was reported as the most important channel of information. Contact with local authorities was very limited, and partners or spouses played a more important role in sharing information. Generally, the self-reported information level was judged to be good (211/289 [73.0%]). The majority of participants (212/289 [73.4%]) approved of the quarantine, and the reported compliance was 217/289 (75.1%). A self-reported higher level of concern as well as a higher level of information correlated positively with both a greater acceptance of quarantine and self-reported compliant behaviour. Interpretation: The community quarantine presented a rare opportunity to investigate a public health intervention for an entire community. In order to improve the implementation of public health interventions, public health risk communication activities should be intensified to increase both the information level (potentially leading to better compliance with community quarantine) and the communication level (to facilitate rapport and trust between public health authorities and their communities). © 2021 Scholz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- ItemGlobal, regional, and national burden of mortality associated with non-optimal ambient temperatures from 2000 to 2019: a three-stage modelling study(Amsterdam : Elsevier, 2021) Zhao, Qi; Guo, Yuming; Ye, Tingting; Gasparrini, Antonio; Tong, Shilu; Overcenco, Ala; Urban, Aleš; Schneider, Alexandra; Entezari, Alireza; Vicedo-Cabrera, Ana Maria; Zanobetti, Antonella; Analitis, Antonis; Zeka, Ariana; Tobias, Aurelio; Nunes, Baltazar; Alahmad, Barrak; Armstrong, Ben; Forsberg, Bertil; Pan, Shih-Chun; Íñiguez, Carmen; Ameling, Caroline; De la Cruz Valencia, César; Åström, Christofer; Houthuijs, Danny; Dung, Do Van; Royé, Dominic; Indermitte, Ene; Lavigne, Eric; Mayvaneh, Fatemeh; Acquaotta, Fiorella; de'Donato, Francesca; Di Ruscio, Francesco; Sera, Francesco; Carrasco-Escobar, Gabriel; Kan, Haidong; Orru, Hans; Kim, Ho; Holobaca, Iulian-Horia; Kyselý, Jan; Madureira, Joana; Schwartz, Joel; Jaakkola, Jouni J. K.; Katsouyanni, Klea; Hurtado Diaz, Magali; Ragettli, Martina S.; Hashizume, Masahiro; Pascal, Mathilde; de Sousa Zanotti Stagliorio Coélho, Micheline; Valdés Ortega, Nicolás; Ryti, Niilo; Scovronick, Noah; Michelozzi, Paola; Matus Correa, Patricia; Goodman, Patrick; Nascimento Saldiva, Paulo Hilario; Abrutzky, Rosana; Osorio, Samuel; Rao, Shilpa; Fratianni, Simona; Dang, Tran Ngoc; Colistro, Valentina; Huber, Veronika; Lee, Whanhee; Seposo, Xerxes; Honda, Yasushi; Guo, Yue Leon; Bell, Michelle L.; Li, ShanshanBackground: Exposure to cold or hot temperatures is associated with premature deaths. We aimed to evaluate the global, regional, and national mortality burden associated with non-optimal ambient temperatures. Methods: In this modelling study, we collected time-series data on mortality and ambient temperatures from 750 locations in 43 countries and five meta-predictors at a grid size of 0·5° × 0·5° across the globe. A three-stage analysis strategy was used. First, the temperature–mortality association was fitted for each location by use of a time-series regression. Second, a multivariate meta-regression model was built between location-specific estimates and meta-predictors. Finally, the grid-specific temperature–mortality association between 2000 and 2019 was predicted by use of the fitted meta-regression and the grid-specific meta-predictors. Excess deaths due to non-optimal temperatures, the ratio between annual excess deaths and all deaths of a year (the excess death ratio), and the death rate per 100 000 residents were then calculated for each grid across the world. Grids were divided according to regional groupings of the UN Statistics Division. Findings: Globally, 5 083 173 deaths (95% empirical CI [eCI] 4 087 967–5 965 520) were associated with non-optimal temperatures per year, accounting for 9·43% (95% eCI 7·58–11·07) of all deaths (8·52% [6·19–10·47] were cold-related and 0·91% [0·56–1·36] were heat-related). There were 74 temperature-related excess deaths per 100 000 residents (95% eCI 60–87). The mortality burden varied geographically. Of all excess deaths, 2 617 322 (51·49%) occurred in Asia. Eastern Europe had the highest heat-related excess death rate and Sub-Saharan Africa had the highest cold-related excess death rate. From 2000–03 to 2016–19, the global cold-related excess death ratio changed by −0·51 percentage points (95% eCI −0·61 to −0·42) and the global heat-related excess death ratio increased by 0·21 percentage points (0·13–0·31), leading to a net reduction in the overall ratio. The largest decline in overall excess death ratio occurred in South-eastern Asia, whereas excess death ratio fluctuated in Southern Asia and Europe. Interpretation: Non-optimal temperatures are associated with a substantial mortality burden, which varies spatiotemporally. Our findings will benefit international, national, and local communities in developing preparedness and prevention strategies to reduce weather-related impacts immediately and under climate change scenarios. Funding: Australian Research Council and the Australian National Health and Medical Research Council. © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
- ItemInsulin adsorption to catheter materials used for intensive insulin therapy in critically ill patients: Polyethylene versus polyurethane - possible cause of variation in glucose control?(Sharjah : Bentham Science Publishers B.V., 2014) Ley, S.C.; Ammann, J.; Herder, C.; Dickhaus, T.; Hartmann, M.; Kindgen-Milles, D.Introduction: Restoring and maintaining normoglycemia by intensified insulin therapy in critically ill patients is a matter of ongoing debate since the risk of hypoglycemia may outweigh positive effects on morbidity and mortality. In this context, adsorption of insulin to different catheter materials may contribute to instability of glucose control. We studied the adsorption of insulin to different tubing materials in vitro and the effects on glycemic control in vivo. Materials and Methods: In vitro experiments: A syringe pump was filled with 50 IU insulin diluted to 50 ml saline. A flow of 2 ml/h was perfused through polyethylene (PET) or polyurethane (PUR) tubing. Insulin concentrations were measured at the end of the tube for 24 hours using Bradford's protein assay. In vivo study: In a randomized double-blinded cross-over design, 10 intensive care patients received insulin via PET and PUR tubes for 24 hours each, targeting blood glucose levels of 80-150 mg/dl. We measured blood glucose levels, the insulin dose required to maintain target levels, and serum insulin and C-peptide levels. Results: In vitro experiments: After the start of the insulin infusion, only 20% (median, IQR 20-27) (PET) and 22% (IQR 16-27) (PUR) of the prepared insulin concentration were measured at the end of the 2 meter tubing. Using PET, after one hour infusion the concentration increased to 34% (IQR 29-36) and did not increase significantly during the next 24 hours (39% (IQR 39-40)). Using PUR, higher concentrations were detected than for PET at every measurement from 1 hour (82% (IQR 70-86)) to 24 hours (79% (IQR 64-87)). In vivo study: Glycemic control was effective and not different between groups. Significantly higher volumes of insulin solution had to be infused with PET compared to PUR (median PET 70.0 (IQR 56-82) ml vs. PUR 42 (IQR 31-63) ml; p=0.0015). Serum insulin concentrations did not decrease significantly one hour after changing to PET or PUR tubing. Conclusion: Polyurethane tubing systems allow application of insulin with significantly lower adsorption rates than polyethylene tubing systems. As a consequence, less insulin solution has to be infused to patients for effective blood glucose control. Tubing material of the insulin infusion may be crucial for safe and effective glycemic control in critically ill patients.
- ItemImpact of unseasonable flooding on women's food security and mental health in rural Sylhet, Bangladesh: a longitudinal observational study(Amsterdam : Elsevier, 2022) Gepp, Sophie; Waid, Jillian L; Brombierstäudl, Dagmar; Kader, Abdul; Müller-Hauser, Anna A; Wendt, Amanda S; Dame, Juliane; Gabrysch, SabineBackground Climate change will lead to more frequent and intensive flooding. In April, 2017, unseasonably early flooding led to the inundation of low-lying cropland before the rice harvest in northeastern Bangladesh. We describe coping strategies and quantify short-term and medium-term effects of flooding events on food security and depressive symptoms of women. Methods This observational study is part of the cluster-randomised Food and Agricultural Approaches to Reducing Malnutrition trial (FAARM; NCT02505711). Women self-reported flooding exposure on behalf of their households when surveyed (approximately 6 months after the event). Remote sensing analysis was used to detect the extent of the flooding. We collected data on household food security at baseline, depressive symptoms 4–5 months before the flooding, and coping strategies immediately after the event. We followed up on these outcome measurements for depressive symptoms and food security for up to 2·5 years after the flooding event. We used multilevel regression adjusting for intervention allocation and pre-flooding measures to quantify the flood's effect on household food security and women's mental health. Findings The FAARM trial included 2700 young women in 96 settlements in rural Sylhet, Bangladesh. 1335 (56%) of 2405 women reported that their household being greatly affected, with many losing a large part of their rice harvest. Borrowing money with interest was the most common coping strategy, with households paying back on average 1·5 times the borrowed amount. Greatly affected households had higher odds of food insecurity, with a decreasing effect with increasing time after the flood (odds ratio: 2·4 [p<0·0001] 0·5 years after; 1·6 [p<0·0001] 2·0 years after]; and 1·3 [p=0·012] 2·5 years after). Women in such households also had 1·45 times higher odds of depression (p=0·0001) 2·5 years after the flooding event. Interpretation The 2017 flooding event negatively affected food security and the mental health of women in rural Sylhet, Bangladesh, and few affected women received formal government support. To reduce the impact of future floods, livelihood adaptations and expansion of financial protection programmes are essential measures to pursue. Funding German Federal Ministry for Education and Research (Berlin, Germany) and UK Department for International Development (London, UK).
- ItemFiber-based SORS-SERDS system and chemometrics for the diagnostics and therapy monitoring of psoriasis inflammatory disease in vivo(Washington, DC : Optica, 2021-1-28) Schleusener, Johannes; Guo, Shuxia; Darvin, Maxim E.; Thiede, Gisela; Chernavskaia, Olga; Knorr, Florian; Lademann, Jürgen; Popp, Jürgen; Bocklitz, Thomas W.Psoriasis is considered a widespread dermatological disease that can strongly affect the quality of life. Currently, the treatment is continued until the skin surface appears clinically healed. However, lesions appearing normal may contain modifications in deeper layers. To terminate the treatment too early can highly increase the risk of relapses. Therefore, techniques are needed for a better knowledge of the treatment process, especially to detect the lesion modifications in deeper layers. In this study, we developed a fiber-based SORS-SERDS system in combination with machine learning algorithms to non-invasively determine the treatment efficiency of psoriasis. The system was designed to acquire Raman spectra from three different depths into the skin, which provide rich information about the skin modifications in deeper layers. This way, it is expected to prevent the occurrence of relapses in case of a too short treatment. The method was verified with a study of 24 patients upon their two visits: the data is acquired at the beginning of a standard treatment (visit 1) and four months afterwards (visit 2). A mean sensitivity of ≥85% was achieved to distinguish psoriasis from normal skin at visit 1. At visit 2, where the patients were healed according to the clinical appearance, the mean sensitivity was ≈65%.
- ItemAlterations in Event Related Potentials (ERP) associated with tinnitus distress and attention(Dordrecht [u.a.] : Springer Science + Business Media B.V, 2008) Delb, W.; Strauss, D.J.; Low, Y.F.; Seidler, H.; Rheinschmitt, A.; Wobrock, T.; D'Amelio, R.Tinnitus related distress corresponds to different degrees of attention paid to the tinnitus. Shifting attention to a signal other than the tinnitus is therefore particularly difficult for patients with high tinnitus related distress. As attention effects on Event Related Potentials (ERP) have been shown this should be reflected in ERP measurements (N100, phase locking). In order to prove this hypothesis single sweep ERP recordings were obtained in 41 tinnitus patients as well as 10 control subjects during a period of time when attention was shifted to a tone (attended) and during a second phase (unattended) when they did not focus attention to the tone. Whereas tinnitus patients with low distress showed a significant reduction in both N100 amplitude and phase locking when comparing the attended and unattended measurement condition a group of patients with high tinnitus related distress did not show such ERP alterations. Using single sweep ERP measurements the results of our study show, that attention in high tinnitus related distress patients is captured by their tinnitus significantly more than in low distress patients. Furthermore our results provide the basis for future neurofeedback based tinnitus therapies aiming at maximizing the ability to shift attention away from the tinnitus. © 2008 The Author(s).