The Origins of Proslavery Christianity: White and Black Evangelicals in Colonial and Antebellum Virginia

Christianity and the Defense of Slavery The Origins of Proslavery Christianity begins by posing a compelling question: why did the majority of Southern Christians fail to hear the moral call of their religion to reject slavery? But this is not solely a book about white Southern e...

Micronutrient status in morbidly obese patients undergoing bariatric surgery - assessment and intervention

Although the benefits of bariatric surgery have been frequently proven, less is known about the micronutrient status of morbidly obese patients undergoing bariatric surgery. A deficiency in vitamin D pre- and postoperatively impairs bone, lipid, and glucose metabolism and increases the risk of osteomalacia and cardiometabolic diseases in these patients. However, there is a lack of reliable data on preoperative nutritional status and on the efficacy of adequate postoperative dietary measures with regard to vitamin D. Previous supplemental trials did not achieve the recommended serum 25-hydroxycholecalciferol (25-OHD) level of at least 50 nmol/L which is necessary to prevent a vitamin D deficiency. The aim of this thesis was to investigate whether obese patients are at risk of deficiency of several micronutrients which may postoperatively be related to nutrition-related diseases and may worsen malnourishment. Within a cross-sectional study (CHAPTER ONE), the plasma/serum status of retinol, ascorbic acid, tocopherol, β-carotene, and 25-hydroxycholecalciferol were determined in 43 obese patients (body mass index: 52.6 ± 10.5 kg/m2) before undergoing sleeve gastrectomy (SG), between April and June 2012. Moreover, markers to specify bone metabolism, like parathyroid hormone, alkaline phosphatase, calcium, phosphate, magnesium, and albumin were assessed. Dietary intake was estimated by 3 day food records. One-third of the patients had ascorbic acid levels below the cutoff value ( 2.8 µmol/mmol). 84% of the patients had 25-OHD levels below 50 nmol/L. The intake of pro-/vitamins were often below the corresponding reference values, but neither correlations between status and intake, nor associations between low serum/plasma levels and inadequate intakes were observed. In a double-blind, placebo-controlled, randomized trial (CHAPTER TWO), 94 morbidly obese patients (body mass index: 51.8 ± 11.5 kg/m2) underwent SG between June and October 2013. The verum group received an oily suspension (Vigantol oil®, diluted with Miglyol 812®) orally for 12 weeks after surgery providing 80 µg vitamin D3 per day; the placebo group received an identical looking oil of middle chain triglycerides (Miglyol 812®) instead. Before the operation, then both 4 and 12 weeks after SG, 25-OHD, parathyroid hormone, alkaline phoshatase, calcium, magnesium, phosphate, glucose, triglycerides, total cholesterol, HDL and LDL cholesterol, creatinine, albumin, C-reactive protein, and TNF-α were analyzed in serum and HbA1ct was determined in EDTA-whole blood. Dietary intake of energy, macronutrients, and vitamin D were monitored using a 3 day food record. After 12 weeks, 25-OHD levels increased in 92% of the patients of the verum group to levels > 50 nmol/L and in 68% to levels > 75 nmol/L compared to only 54% and 22% of the patients in the placebo group, respectively. Vitamin D-related parameters of mineral metabolism and of cardiometabolic risk were not modulated by intervention. Adverse effects from the intake of the supplement containing vitamin D were not reported. The highest individual 25-OHD level observed after 12 weeks was 191 nmol/L, which was below the maximum safe level of 250 nmol/L. In conclusion, many morbidly obese patients already suffer from subclinical deficiencies in multiple micronutrients, particularly concerning vitamin D, ascorbic acid, and β-carotene before undergoing SG. Measuring the preoperative micronutrient status will help when supplementing patients before surgery and in optimizing dietary strategies afterwards. High-dose vitamin D3 supplementation by an oily preparation is an effective and safe measure to prevent vitamin D deficiency in obese patients after SG, but higher doses will be necessary to achieve 25-OHD levels > 75 nmol/L in all patients.Obwohl die Wirksamkeit der Adipositaschirurgie erwiesen ist, ist wenig über den Mikronährstoffstatus morbid adipöser Patienten, die sich einem bariatrischen Eingriff unterziehen, bekannt. Ein prä- und postoperativ inadäquater Vitamin D-Status beeinträchtigt den Mineral-, Fett- und Glukosestoffwechsel und erhöht das Risiko für Osteomalazie und das kardiometabolische Risiko bei diesen Patienten. Verlässliche Daten zum präoperativen Mikronährstoffstatus und zur Wirksamkeit einer adäquaten postoperativen diätetischen Maßnahme zur Prävention eines Vitamin D Mangels liegen bisher nicht vor. In früheren Interventionsstudien konnte ein 25-Hydoxycholecalciferol (25-OHD)-Spiegel von mindestens 50 nmol/L im Serum, der zur Prävention eines Vitamin D Mangels notwendig ist, nicht erreicht werden. Das Ziel dieser Dissertation war es zu untersuchen, ob adipöse Patienten ein hohes Risiko für verschiedene Mikronährstoffmängel haben, die nach operativem Eingriff Mangelernährung verstärken und ernährungsbedingte Erkrankungen begünstigen können. In einer Querschnittsstudie (Kapitel 1) wurden bei 43 adipösen Patienten (Body-Mass-Index: 52,6 ± 10,5 kg/m2) vor Durchführung einer Schlauchmagen-Operation zwischen April und Juni 2012 die Konzentrationen der Vitamine A, C, E, sowie von β-Carotin und 25 Hydroxycholecalciferol im Serum/Plasma bestimmt. Weiterhin wurden verschiedene Parameter zur Beurteilung des Knochenstoffwechsels, wie Parathormon, alkalische Phosphatase, Kalzium, Phosphat, Magnesium, und Albumin im Serum analysiert. Der Lebensmittelverzehr wurde über 3-Tages-Ernährungsprotokolle erfasst. Die Konzentration von Vitamin C im Plasma war bei einem Drittel der Patienten unterhalb des Referenzwerts ( 2,8 µmol/mmol). 84% der Patienten hatten eine 25-OHD-Konzentration unter 50 nmol/L. Die Pro-/Vitaminzufuhr lag häufig unter den jeweiligen Referenzwerten, wobei weder Korrelationen zwischen Zufuhr und Serum-/Plasmaspiegeln, noch Assoziationen zwischen geringen Spiegeln in Serum/Plasma und unzureichender Zufuhr beobachtet werden konnten. In einer doppelblinden, placebo-kontrollierten, randomisierten Studie (Kapitel 2) wurden 94 morbid adipöse Patienten (Body-Mass-Index: 51,8 ± 11,5 kg/m2) eingeschlossen, bei denen zwischen Juni und Oktober 2013 eine Schlauchmagen-Operation durchgeführt wurde. Patienten in der Verumgruppe erhielten über einen Zeitraum von 12 Wochen nach der Operation oral ein öliges Supplement (Vigantol Öl®, verdünnt mit Miglyol 812®), das 80 µg Vitamin D3 pro Tag enthielt. Patienten in der Plazebogruppe wurde stattdessen ein Öl mit mittelkettigen Triglyzeriden (Miglyol 812®) verabreicht. Präoperativ sowie 4 und 12 Wochen nach der Operation wurden die Serum Konzentrationen von 25-OHD, Parathormon, alkalischer Phosphatase, Kalzium, Magnesium, Phosphat, Glukose, Triglyzeriden, Gesamt-cholesterol, HDL- und LDL- Cholesterol, Kreatinin, Albumin, C-reaktivem Protein und TNF-α analysiert sowie das HbA1c im Vollblut bestimmt. Die Zufuhr von Energie, Makronährstoffen und Vitamin D wurde über 3-Tages-Ernährungsprotokolle erfasst. Nach 12 Wochen stieg die 25-OHD Konzentration bei 92% der Teilnehmer der Verumgruppe auf > 50 nmol/L und bei 68% auf > 75 nmol/L an; in der Plazebogruppe wurden diese Werte nur von 54% bzw. 22% der Teilnehmer erreicht. Vitamin D-assoziierte Parameter des Mineralstoffwechsels sowie kardiometabolische Parameter wurden durch die Intervention nicht beeinflusst. Nach Einnahme des Vitamin D-haltigen Supplements wurden keine unerwünschten Effekte festgestellt. Die höchste individuelle 25-OHD Konzentration nach 12 Wochen war 191 nmol/L und lag unterhalb der sicheren Höchstkonzentration von 250 nmol/L. Daraus lässt sich schlussfolgern, dass viele morbid-adipöse Patienten vor Schlauchmagen-Operation einen Mangel an verschiedenen Mikronährstoffen aufweisen, speziell an Vitamin D, Vitamin C und β-Carotin. Die präoperative Bestimmung des Mikronährstoffstatus kann daher hilfreich sein, um Patienten rechtzeitig vor Operation zu supplementieren und die Ernährungstherapie postoperativ anzupassen. Die Supplementierung einer hohen Dosis an Vitamin D über ein öliges Präparat ist eine wirksame und sichere Maßnahme, um einem Vitamin D Mangel bei adipösen Patienten bei Schlauchmagen-Operation vorzubeugen. Jedoch sind noch höhere Dosierungen notwendig, um 25-OHD-Spiegel von > 75 nmol/L bei allen Patienten zu erreichen

Architecture and ssDNA interaction of the Timeless-Tipin-RPA complex

The Timeless-Tipin (Tim-Tipin) complex, also referred to as the fork protection complex, is involved in coordination of DNA replication. Tim-Tipin is suggested to be recruited to replication forks via Replication Protein A (RPA) but details of the interaction are unknown. Here, using cryo-EM and biochemical methods, we characterized complex formation of Tim-Tipin, RPA and single-stranded DNA (ssDNA). Tim-Tipin and RPA form a 258 kDa complex with a 1:1:1 stoichiometry. The cryo-EM 3D reconstruction revealed a globular architecture of the Tim-Tipin-RPA complex with a ring-like and a U-shaped domain covered by a RPA lid. Interestingly, RPA in the complex adopts a horse shoe-like shape resembling its conformation in the presence of long ssDNA (>30 nucleotides). Furthermore, the recruitment of the TimTipin- RPA complex to ssDNA is modulated by the RPA conformation and requires RPA to be in the more compact 30 nt ssDNA binding mode. The dynamic formation and disruption of the Tim-Tipin-RPA-ssDNA complex implicates the RPA-based recruitment of Tim-Tipin to the replication fork

Management of elderly patients with acute promyelocytic leukemia: progress and problems

Despite substantial progress in the management and outcome of acute promyelocytic leukemia (APL) during the last decades, older age remains a prominent negative prognostic factor. The improvement of long-term stabilization and cure of older APL patients is therefore a particular challenge. Data of unselected population-based studies suggest a high rate of exclusion from clinical trials in older age. The comparison of registry and study data indicates that study patients represent a positive selection. Older APL patients seem as sensitive to therapy as younger patients. With conventional therapy, based on all-trans retinoic acid (ATRA) and chemotherapy, over 50 % of older APL patients can probably be cured. Special problems of advanced age are the high rate of early death before or during induction therapy and the high frequency of death in remission with negative influence on the outcome. Both may be related in part to a higher vulnerability against the common treatment with ATRA and chemotherapy. Alternative less toxic approaches including arsenic trioxide (ATO) with or without ATRA and combinations with gemtuzumab ozogamicin or with reduced chemotherapy can induce long-lasting remission in all stages of APL. Considering the high curative potential and the excellent tolerance of ATO in newly diagnosed and relapsed APL, older patients are probably a particular target group for a chemotherapy-free approach with ATO

The evolutionary history of Cochlearia L. : Cytogenetics, phylogenomics and metabolomics of a cold relic in a warming world

The cold-adapted genus Cochlearia L. (scurvy grass), a young polyploid complex within the Brassicaceae family (Cruciferae), displays a range of highly interesting cytogenetic and ecotypic characteristics and might serve as an excellent model system to study general evolutionary mechanisms such as polyploidization, hybridization, or cold and edaphic adaptation. The presented study provides, for the first time, comprehensive cytogenetic and highly-resolving phylogenomic analyses, and first metabolomic insights into the Cochlearia cold response. Thus, the findings presented herein might constitute a good starting point for further in-depth analyses of said evolutionary aspects e.g. based on population-genomic datasets. In chapter 1, the cytogenetic evolution within the genus Cochlearia is analyzed via both conventional chromosome counts and flow cytometry measurements. Based on a comprehensive literature review on published chromosome counts, the geographical distribution of cytogenetic variability is described, suggesting an early evolutionary separation of the two diploid karyotypes (2n=12 and 2n=14). The high frequency of aberrant chromosome numbers in polyploid taxa is interpreted as a result of frequent interploidal hybridization, given the near absence of interspecific fertility barriers, and thus reflecting the dynamics of polyploid evolution within the genus Cochlearia. Moreover, a correlation between genome size and chromosome number, as well as genome downsizing in polyploid taxa are revealed. Chapter 2 provides comprehensive phylogenomic analyses based on Illumina high-throughput sequencing data. Chloroplast and mitochondrial phylogenies are largely in congruence and indicate a glacial survival of the whole genus in arctic refuge areas as well as repeated adaptation to alpine habitats in Central Europe. Divergence time estimates, based on complete chloroplast genomes, imply a diversification of the whole genus over the course of several Pleistocene glaciations within the last ~700,000 years. Results from nuclear data analyses support both the clear evolutionary separation of the two diploid karyotypes as described in chapter 1, as well as the basal phylogenetic position of arctic taxa as shown in organellar phylogenies, and they reveal new insights into the evolutionary origins of the different polyploid taxa. In chapter 3, the metabolomic analysis of the Cochlearia cold response via metabolite profiling using gas chromatography-mass spectrometry (GC-MS) is described. Based on temperature-related bioclimatic variables (WorldClim), four bioclimatic ecotypes are defined and utilized as group priors for statistical analyses. All studied plants/ecotypes show strong metabolomic adjustments in reaction to 20 days of cold treatment under 5°C, especially with regard to increased levels of soluble carbohydrates and amino acids. Statistical analyses do not show a strong discrimination of the four bioclimatic ecotypes based on the analyzed metabolites, yet slight intrageneric variation among the bioclimatic clusters is described, implying similarities in the cold response between arctic and alpine taxa

The impact of implementing a person-centred pain management intervention on resistance to change and organizational culture

Background: Resistance to change and organizational culture are essential factors to consider in change management in health care settings. Implementation of structural change remains a challenge. There is a lack of studies providing information on the impact of implementation processes on the organization. The aim of this study was to describe the impact of implementing a systematic change process concerning postoperative person-centred pain management on resistance to change and organizational culture in an orthopaedic spine surgery unit. Methods: The study was set in an orthopaedic spine surgery unit at a university hospital. Person-centred bundles of care for postoperative pain management of spine surgery patients were developed in co-creation by a multi-professional expert group and implemented throughout the care pathway. The intervention was underpinned by theories on organizational culture and inspired by principles of person-centred care. Quantitative data were collected using the Resistance to Change Scale and the Organizational Culture Assessment Instrument and analysed using descriptive statistics. Results: The findings showed a low resistance to change decreasing during the study. The organizational culture shifted from a result-oriented to a formalized and structured culture after the implementation. The culture preferred by the staff was team-oriented and participation-focused throughout the study. The discrepancy between the current and preferred cultures remained extensive over time. Conclusion: It is challenging to describe the influence of the development and implementation of a postoperative pain management program on organizational culture as well as in terms of resistance to change, in a complex health care setting. In the current study the unit was under organizational strain during the implementation. Albeit, the important discrepancy between the current and preferred organizational culture could imply that structural changes aren’t enough when implementing person-centred pain management structures and needs to be combined with relational aspects of change

Layering of stomach contents in drowning cases in post-mortem computed tomography compared to forensic autopsy.

BACKGROUND In forensic autopsy, the analysis of stomach contents is important when investigating drowning cases. Three-layering of stomach contents may be interpreted as a diagnostic hint to drowning due to swallowing of larger amounts of water or other drowning media. The authors experienced frequent discrepancies of numbers of stomach content layering in drowning cases between post-mortem computed tomography (PMCT) and autopsy in forensic casework. Therefore, the goal of this study was to compare layering of stomach contents in drowning cases between PMCT and forensic autopsy. METHODS Drowning cases (n = 55; 40 male, 15 female, mean age 45.3 years; mean amount of stomach content 223 ml) that received PMCT prior to forensic autopsy were retrospectively analyzed by a forensic pathologist and a radiologist. Number of layers of stomach content in PMCT were compared to number of layers at forensic autopsy. RESULTS In 28 of the 55 evaluated drowning cases, a discrepancy between layering of stomach contents at autopsy compared to PMCT was observed: 1 layer at autopsy (n = 28): 50% discrepancy to PMCT, 2 layers (n = 20): 45% discrepancy, and 3 layers (n = 7): 71.4% discrepancy. Sensitivity of correctly determining layering (as observed at forensic autopsy) in PMCT was 52% (positive predictive value 44.8%). Specificity was 46.6% (negative predictive value 53.8%). In a control group (n = 35) of non-drowning cases, three-layering of stomach contents was not observed. CONCLUSION Discrepancies of observed numbers of stomach content layers between PMCT and forensic autopsy are a frequent finding possibly due to stomach content sampling technique at autopsy and movement of the corpse prior to PMCT and autopsy. Three-layering in PMCT, if indeed present, may be interpreted as a hint to drowning

Baseline MELD score predicts hepatic decompensation during antiviral therapy in patients with chronic hepatitis C and advanced cirrhosis

Background and Aims: In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined. Methods: In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks). Results: Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001). Conclusions: Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis