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‘Chameleonic' Serological Findings Leading to Life-Threatening Hemolytic Transfusion Reactions
(2015)
Background: The phenomena of co-incidence of transfusion-induced allo- and autoantibodies, blockage and/or loss of red blood cell (RBC) antigens are conspicuous and may result in confusion and misdiagnosis. Case Report: A 67-year-old female was transferred to the intensive care unit due to hemolysis which developed 2 days following transfusion of three Rh(D)-negative RBC units in the presence of strongly reactive autoantibodies. Standard serological testing and genotyping were performed. Upon arrival, the patient was typed as Ccddee. Her hemolysis was decompensated, and an immediate blood transfusion was required. In addition, direct and indirect antiglobulin tests (DAT and IAT) as well as the eluate were strongly positive. Emergency transfusion of Rh(D)-negative RBCs resulted in increased hemolysis and renal failure. An exhaustive testing revealed anti-D, anti-c, CCddee phenotype and CCD.ee genotype. Three units of cryopreserved CCddee RBCs were transfused, and the patient's condition immediately improved. The discrepancy between Rh-D phenotyping and genotyping was likely caused by masking of the D-epitopes by the autoantibodies. In fact, further enquiry revealed that the patient had been phenotyped as Rh(D)-positive 6 months ago and had been transfused at that time following hip surgery. Conclusion: The phenomena of transfusion-induced autoantibodies, masked alloantibodies, antigen blockage and/or loss are rare but important features which should be considered in patients presenting with autoimmune hemolytic anemia and/or hemolytic transfusion reactions.
Context: 3,5-Diiodo-<smlcap>L</smlcap>-thyronine (3,5-T<sub>2</sub>) is a thyroid hormone metabolite which exhibited versatile effects in rodent models, including the prevention of insulin resistance or hepatic steatosis typically forced by a high-fat diet. With respect to euthyroid humans, we recently observed a putative link between serum 3,5-T<sub>2</sub> and glucose but not lipid metabolism. Objective: The aim of the present study was to widely screen the urine metabolome for associations with serum 3,5-T<sub>2</sub> concentrations in healthy individuals. Study Design and Methods: Urine metabolites of 715 euthyroid participants of the population-based Study of Health in Pomerania (SHIP-TREND) were analyzed by <sup>1</sup>H-NMR spectroscopy. Multinomial logistic and multivariate linear regression models were used to detect associations between urine metabolites and serum 3,5-T<sub>2</sub> concentrations. Results: Serum 3,5-T<sub>2</sub> concentrations were positively associated with urinary levels of trigonelline, pyroglutamate, acetone and hippurate. In detail, the odds for intermediate or suppressed serum 3,5-T<sub>2</sub> concentrations doubled owing to a 1-standard deviation (SD) decrease in urine trigonelline levels, or increased by 29-50% in relation to a 1-SD decrease in urine pyroglutamate, acetone and hippurate levels. Conclusion: Our findings in humans confirmed the metabolic effects of circulating 3,5-T<sub>2</sub> on glucose and lipid metabolism, oxidative stress and enhanced drug metabolism as postulated before based on interventional pharmacological studies in rodents. Of note, 3,5-T<sub>2</sub> exhibited a unique urinary metabolic profile distinct from previously published results for the classical thyroid hormones.
Synopsis
C+60 has been proposed to be responsible for two of the diffuse interstellar bands (DIBs), the absorption features observed in the visible-to-near-infrared spectra of the interstellar medium. However, a confirmation requires laboratory gas-phase spectra, which are so far not available. We plan to develop a novel spectroscopy technique that will allow us to obtain the first gas-phase spectra of C+60, and that will be applicable to other complex organic molecules such as polycyclic aromatic hydrocarbons. The current status of the experimental setup, the ideas behind the measurement scheme and the preparatory work toward its implementation will be presented.
Although the Pleistocene deposits exposed in the steep coastal cliffs of Mecklenburg-Vorpommern have been studied for more than a century, the depositional conditions of many lithostratigraphic units remain unclear. There is, in particular, a question whether the individual tills (locally more than 9 successive till units) are mainly subglacial deposits or resedimented (mass flows) in origin (at least in part). The Pleistocene deposits preserve information concerning the former glacial depositional processes. Detailed micromorphological analysis of these deposits can provide key information regarding these processes and thereby aid in the reconstruction of former glacial environments. The island of Rügen is located on the southwestern Baltic Sea coast and was situated in the marginal zone of the Scandinavian Ice Sheet during the last glacial period (Weichselian). Therefore, the region is considered as an ideal area for reconstructing the complex fluctuations in the position of the margin of this ice sheet as it expanded across the Baltic Sea and into northern Germany. Successive glacial advances and retreats of the ice sheet can be reconstructed by specific glacial sedimentation processes and flow-direction criteria derived from a variety of glacial deposits. The investigation area is located near Sassnitz on Rügen, where an imbricated and folded Weichselian succession disconformably overlies Maastrichtian chalk bedrock. The individual till units were sampled for micromorphological analyses to identify the former depositional conditions. Detailed description of the sedimentology and variation in facies, the description of macroscale deformation structures provides the context for the detailed micromorphology study. The three dimensional analysis of the microfabrics is based on the microstructural mapping methodology which enables the identification and interpretation of polyphase deformation within subglacial sediments.
Invasion of the bacterial pathogen Listeria monocytogenes into human host cells requires specialized surface molecules for attachment and induction of phagocytosis. However, efficient invasion is also dependent on factors with house-keeping functions, such as SecA2-dependent secretion of autolysins for post-divisional segregation of daughter cells. Mutations in this pathway prevent degradation of peptidoglycan cross-walls, so that long cell chains are formed that cannot be phagocytosed. The extreme chaining of such mutants manifests as rough colony phenotype. One rough clone was isolated from a transposon library with a transposon insertion in the uncharacterized lmo0720 gene (lftS) together with a spontaneous point mutation in the secA2 gene. We separated both mutations and demonstrated that this point mutation in the intramolecular regulator 2 domain of SecA2 was sufficient to inactivate the protein. In contrast, lftS deletion did not cause a ΔsecA2-like phenotype. lftS is located in an operon with lftR (lmo0719), encoding a PadR-like transcriptional regulator, and lftR deletion affected growth, invasion and day-light dependent coordination of swarming. Inactivation of lftS partially suppressed these phenotypes, suggesting a functional relationship between LftR and LftS. However, the invasion defect of the ΔlftR mutant was only marginally suppressed by lftS removal. LftR regulates expression of the lmo0979–0980 (lieAB) operon, encoding a putative multidrug resistance transporter and lieAB transcription was strongly upregulated in the absence of LftR. Deletion of lieAB in the ΔlftR background restores wild type-like invasion levels. Hence, we conclude that tight transcriptional repression of the lieAB operon is essential for efficient listerial host cell invasion.
The influence of regulatory proteins on the physiology and virulence of Streptococcus pneumoniae
(2015)
In conclusion, this work identifies the regulator ArgR2 as activator of the S. pneumoniae TIGR4 arginine deiminase system and arginine-ornithine transporter ArcD, which is needed for uptake of the essential amino acid arginine. Although ArgR2 activates ArcD expression and uptake of arginine is required to maintain pneumococcal fitness, the deficiency of ArgR2 increases TIGR4 virulence under in vivo conditions, suggesting that other factors regulated by ArgR2 counterbalance the reduced uptake of arginine by ArcD. Thus this works illustrates that the physiological homeostasis of pneumococci is complex and that ArgR2 plays a key role in maintaining bacterial fitness. Moreover, Rex was identified as a regulator of housekeeping genes including genes encoding glycolytic enzymes. In vitro studies and gene expression analyses suggested that the regulator Rex does not have an influence on the physiology of S. pneumoniae. However, a co-infection experiment demonstrated that Rex is involved in maintaining pneumococcal fitness and robustness under in vivo conditions.
The present work examines the decision-making process of clinicians and managers in terms of pricing. This dissertation attempts to make often unconscious processes in both the clinical and economic areas more transparent. Due to this increase in transparency and an illustration of the overall decision-making process, a prioritization of the decision-drivers is enabled. Similarily, overall decision-making on stakeholder level is improved. The findings of this work are based on a dual sample: The paper primarily combines qualitative expert discussions in the clinical field with a quantitative manager survey. Therefore, the advancement of knowledge is specifically furthered in terms of pricing decision-making, as well as specific economic and thematic aspects. These form the basis for clinical/managerial decision-making. Since such specific understanding enables better acting and reacting during the negotiation processs, clients of medical device companies (eg clinics) could additionally benefit from improved understanding. Although the focus of this work rests on the clinical area, this paper also examines how companies of the medical technology industry could offer more economic medical products by means of using the instrument of pricing. Based on an interdisciplinary approach and a collection of primary data, this work also discusses a solution approach for corporate/entrepreneurial inefficiencies discovered in this paper. A final conceptual model illustrates different value allocations from both stakeholder groups (clinicians vs. managers). With regard to the research focus, the conceptual model is understood as a holistic solution for recognizing and correcting business gaps in the areas of knowledge transfer, innovation, knowledge of markets and standardization of processes.
The Black Sea experienced fundamental environmental changes during the last glacial-interglacial transitions. During the last 670,000 years, the Black Sea was at least twelve times connected to Mediterranean Sea, received saltwater via the Bosporus strait, and evolved to a brackish anoxic water body. A lowered global sea level during glacials caused isolation of the basin from the open ocean, and the Black Sea became limnic and well-oxygenated. The last glacial-interglacial history of the Black Sea is relatively well understood and demonstrates the high sensitivity of this basin to global climate and environmental changes. Previous studies particularly focussed on the evolution during the last glacial with meltwater pulses, warming during the glacial-interglacial transition, and the development from a ventilated lake to the present euxinic/brackish water body. Apart from the interglacial warming, the Black Sea sediments clearly recorded short-term abrupt temperature changes associated with cooling during Heinrich events and the Younger Dryas as well the Bølling-Allerød warming, which occurred over the northern hemisphere. However, our knowledge about the Black Sea history before 40,000 BP is comparatively poor even though crucial for understanding hemisphere-wide atmospheric teleconnection patterns and climate mechanisms during older glacials and interglacials. A multiproxy approach has been applied on three gravity cores and surface sediment from the southeastern Black Sea comprising ostracod geochemistry (Mg/Ca, Sr/Ca, U/Ca, 87Sr/86Sr), major and trace elements (Al, Ca, Fe, K, Ti, Mo, Re, Sr, W, Zr) and organic biomarkers (n-alkanes, alkenones, UK’37-palaeotemperatures, glycerol dialkyl glycerol tetraethers, TEX86-palaeotemperatures, BIT-index). The cores cover the last 134,000 a and provide new findings concerning the last and penultimate glacial-interglacial transitions (12,000- 0 a BP; 134,000-120,000 a BP) as well as the abrupt climate changes during the last glacial period (64,000-20,000 a BP). The major topics of this work are i) the penultimate glacial-interglacial transition (Saalian-Eemian), ii) the environmental conditions in the Black Sea “Lake” during abrupt climate oscillations of the last glacial period, iii) and the comparison of the redox evolution during Eemian and Holocene sapropel formation. Two meltwater pulses caused a pronounced freshening of the Black Sea “Lake” during the ending penultimate glacial, which originated from the melting Fennoscandian Ice Sheet. Due to unusually high radiogenic Sr-isotope signatures of benthic ostracods, a potential Himalayan source communicated via the Caspian Sea is also likely. During the glacial-interglacial transition the temperatures in the Black Sea increased from 9°C to 17°C and the associated global sea-level rise allowed the reconnection between the Mediterranean and Black Seas around 128,000 a BP. Eemian sapropel formation started shortly after the intrusion of saltwater and the water body became gradually euxinic. In comparison with the Holocene sapropel, the Eemian proxy records imply warmer and stronger euxinic conditions and distinctly higher enrichments of redox-sensitive trace elements like e.g. Mo, Re, and W. Because the seawater forms the ultimate source for several trace metals, these enrichments were most likely favoured by the higher salinity due to a ca. 10 m higher sea level and enhanced Mediterranean Sea - Black Sea water exchange. Based on biomarker analyses, lake surface temperatures could be calculated for the first time for the period between 64,000 and 20,000 a BP, which includes the Marine Isotope Stage (MIS) 3. Abrupt stadial/interstadial temperature changes with amplitudes of up to 4°C in the Black Sea “Lake” clearly resemble the Greenland Dansgaard-Oeschger pattern. However, an exceptional cooling during the so-called Heinrich events is not evident from our cores. This finding agrees with modelling results proposing a deeper penetration of regular Dansgaard-Oeschger cycles into the Eurasian continent when compared with the Heinrich events. During the warm and more humid interstadials, the Black Sea “Lake” became fresher and more productive and the water level probably increased. During the colder and more arid stadials the freshwater supply was decreased and productivity was low. Aridity and stronger westerly winds favoured the input of aeolian transported detritus. The long-term pattern from 64,000 to 20,000 a BP demonstrates a strong influence of orbital-driven changes in the Eurasian ice volume and associated atmospheric circulation patterns over the Black Sea region. The present multi-proxy study demonstrates that the sediments from the SE Black Sea clearly record not only orbital- but also millennial-scale climate and environmental changes and thus represent an important continental archive for climate change bridging the North Atlantic-Eurasian corridor.
Although End Stage Renal Disease (ESRD) is a disease of increasing epidemiological relevance very little is known about the cost of providing the respective dialysis services in Tanzania. This study analyses the cost of outpatient dialysis at Muhimbili National Hospital (MNH) in Tanzania in the year 2014 in order to address the question weather or not dialysis treatment should be a priority intervention in a poor resource country like Tanzania. Cost analyses were performed based on the provider’s perspective including only direct costs of dialysis treatment. Cost of drugs and consumables were obtained from the price list of Medical Stores Department in Tanzania. Overhead were collected from the respective departments and allocated to the final cost centres through step down approach. The results indicates that MNH performs on average 442 hemodialyses per month (34 patients, with three sessions per week) with a personnel placement of 20 nurses, four nephrologists, eight registrars, one nutritionist, two biomedical engineers, four health attendants and nine dialysis machines. The respective average unit cost per haemodialysis is 175.91 US$. Consequently, an average patient requiring three dialyses per week (i.e. 156 dialyses per year) will cause annual costs of 27,441.95 US$. The annual cost of dialysis is enormous for a least developed country like Tanzania where resources and technology are rather limited. Infectious diseases (such as malaria and tuberculosis) are the major health problems. Therefore, from the economic point of view, it seems rational to allocate health care budgets towards diseases that are curable, have higher cost- effectiveness and cater for the majority of the population. However, before a final decision on allocation of budget towards dialysis is made, all efforts that could improve technical efficiency and reduce the costs of materials in Tanzania must be invested. For instance, reducing the nursing time per dialysis.