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High-quality ocean colour observations are increasingly accessible to support various monitoring and research activities for water quality measurements. In this paper, we present a newly developed regional total suspended solids (TSSs) empirical model using MODIS Aqua's Rrs(530) and Rrs(666) reflectance bands to investigate the spatial and temporal variation in TSS dynamics along the southwest coast of Sarawak, Borneo, with the application of the Open Data Cube (ODC) platform. The performance of this TSS retrieval model was evaluated using error metrics (bias = 1.0, MAE = 1.47, and RMSE = 0.22, in milligrams per litre) with a log10 transformation prior to calculation as well as using a k-fold cross-validation technique. The temporally averaged map of the TSS distribution, using daily MODIS Aqua satellite datasets from 2003 until 2019, revealed that large TSS plumes were detected – particularly in the Lupar and Rajang coastal areas – on a yearly basis. The average TSS concentration in these coastal waters was in the range of 15–20 mg L−1. Moreover, the spatial map of the TSS coefficient of variation (CV) indicated strong TSS variability (approximately 90 %) in the Samunsam–Sematan coastal areas, which could potentially impact nearby coral reef habitats in this region. Study of the temporal TSS variation provides further evidence that monsoonal patterns drive the TSS release in these tropical water systems, with distinct and widespread TSS plume variations observed between the northeast and southwest monsoon periods. A map of relative TSS distribution anomalies revealed strong spatial TSS variations in the Samunsam–Sematan coastal areas, while 2010 recorded a major increase (approximately 100 %) and widespread TSS distribution with respect to the long-term mean. Furthermore, study of the contribution of river discharge to the TSS distribution showed a weak correlation across time at both the Lupar and Rajang river mouth points. The variability in the TSS distribution across coastal river points was studied by investigating the variation in the TSS pixels at three transect points, stretching from the river mouth into territorial and open-water zones, for eight main rivers. The results showed a progressively decreasing pattern of nearly 50 % in relation to the distance from shore, with exceptions in the northeast regions of the study area. Essentially, our findings demonstrate that the TSS levels on the southwest coast of Sarawak are within local water quality standards, promoting various marine and socio-economic activities. This study presents the first observation of TSS distributions in Sarawak coastal systems with the application of remote sensing technologies and aims at enhancing coastal sediment management strategies for the sustainable use of coastal waters and their resources.

Abstract Background In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program ‘Palliative care in Pandemics’ (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). Methods Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. Discussion For a future “pandemic preparedness” national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

The steady increase of chief executives' compensation in both public and private universities has long been at the centre of public debate and has received a lot of criticism in the UK. As higher education is considered as an industry, a pay for performance relationship is expected. This paper differs by demonstrating that UK Vice Chancellors consider incentives other than remuneration in their career progression. By constructing a comprehensive dataset of UK Vice Chancellors covering academic years 2012/2013 to 2016/2017, we demonstrate that UK university chief executives, especially if young, are willing to accept lower salaries when they interpret their role as a springboard for visible high-profile positions in the public arena.

In situ investigations of the rhizosphere require high-resolution imaging techniques, which allow a look into the optically opaque soil compartment. We present the novel combination of magnetic resonance imaging (MRI) and neutron computed tomography (NCT) to achieve synergistic information such as water mobility in terms of three-dimensional (3D) relaxation time maps and total water content maps. Besides a stationary MRI scanner for relaxation time mapping, we used a transportable MRI system on site in the NCT facility to capture rhizosphere properties before desiccation and after subsequent rewetting. First, we addressed two questions using water-filled test capillaries between 0.1 and 5 mm: which root diameters can still be detected by both methods, and to what extent are defined interfaces blurred by these imaging techniques? Going to real root system architecture, we demonstrated the sensitivity of the transportable MRI device by co-registration with NCT and additional validation using X-ray computed tomography. Under saturated conditions, we observed for the rhizosphere in situ a zone with shorter T1 relaxation time across a distance of about 1 mm that was not caused by reduced water content, as proven by successive NCT measurements. We conclude that the effective pore size in the pore network had changed, induced by a gel phase. After rewetting, NCT images showed a dry zone persisting while the MRI intensity inside the root increased considerably, indicating water uptake from the surrounding bulk soil through the still hydrophobic rhizosphere. Overall, combining NCT and MRI allows a more detailed analysis of the rhizosphere’s functioning.

Background. Stress reduction and relaxation exercises are therapeutically suggested to patients with Parkinson’s disease (PD) and tremor, but data regarding efficacy or preferential methods are missing. Objective. To investigate the effect of a standardized stress management training (SMT) according to Kaluza on coping with tremor-boosting psychosocial stress factors. Methods. 8-week SMT was applied to 82 PD patients with tremor and 30 controls. Changes in stress-associated factors were measured applying four scales: Kaluza’s “warning signs for stress” and “stress-amplifying thoughts” and Beck Depression Inventory (BDI) and quality of life (PDQ-8). Short-term outcome (8 weeks) was evaluated in both groups, and long-term outcome (3–6 months) was evaluated only in PD patients. Results. At baseline, PDQ-8 was worse in PD patients compared to controls. PD patients improved significantly regarding short- and long-term outcome scores of “warning signs for stress,” “stress-amplifying thoughts,” and BDI scores, independently of disease severity or duration. Younger and male PD patients showed the best benefit. Controls improved comparably to PD patients but significantly only with respect to “stress-amplifying thoughts.” Retrospectively, 88% (29/33) of PD patients were rated SMT as helpful 12–18 months later. Self-practicing SMT exercises correlated significantly with subjectively better coping with tremor-related daily impairment and subjective short-term and long-term tremor reduction. Conclusion. SMT should be a part of therapy of PD patients with tremor.

Con el objeto de estimar la frecuencia de aislamientos de Candida dubliniensis en materiales clínicos en el Hospital de Infecciosas F. J. Muñiz, se identificaron 388 levaduras entre setiembre de 2005 y agosto de 2007. Doscientos doce aislamientos presentaban color verde en CHROMagar® y producían tubos germinativos y clamidoconidias en agarleche. Para diferenciar cuales de ellos correspondían a Candida albicans o a C. dubliniensis, se utilizaron distintos métodos fenotípicos y se evaluó la utilidad de cada técnica a fin de proponer un algoritmo de identificación simple, económico y confiable. Se estudió el color en 2 medios con sustratos cromogénicos, la producción de clamidoconidias en medios de Staib, agar tomate-zanahoria y agar-tabaco; en este último medio también se evaluaron las características macromorfológicas de las colonias; se evaluó la presencia de actividad lipolítica (medio-opacidad), capacidad de desarrollo a 45 °C y asimilación de D-xilosa. El 6,1% (13/212 aislamientos) correspondió a C. dubliniensis (3,3% del total de levaduras). No se pudo diferenciar entre ambas especies por el color en los medios cromogénicos usados. Las pruebas que resultaron más sensibles y específicas fueron crecimiento a 45 °C, asimilación de D-xilosa, color y desarrollo en agar-tabaco. C. albicans produjo clamidoconidias en los 3 medios diferenciales, entre 11,6% y 15,1% de los casos. La presencia de lipasas se evidenció en el 95,6% de C. albicans pero 2 de las 13 cepas de C. dubliniensis también presentaron halo de opacidad. Consideramos que se deben usar, al menos, 3 métodos diferentes para discriminar entre estas levaduras ya que ninguna prueba es absolutamente sensible o específica.In order to estimate the frequence of Candida dubliniensis in clinical samples in F. J. Muñiz Infectious Diseases Hospital, a total of 388 yeasts from September 2005 to August 2007. There were 212 isolates which presented a green color on CHROMagar® Candida medium and produced germ tubes and chlamidoconidiae in milk-agar; so as to distinguish whether they corresponded to Candida albicans or C. dubliniensis, different phenotypical methods were utilized. It was also evaluated the usefulness of each one in order to suggest a simple, economic and reliable identification algorithm. Each isolate was subcultured in two chromogenic media and then, the following determinations were done: chlamidospores production in Staib-agar, tomato-carrot-agar and tobacco-agar, colonies macromorphology was also studied in the last medium; opacity-test in Tween 80-CaCl2 agar (lipase activity), growing capacity at 45 °C, and D-xylose assimilation. Thirteen strains (6.1%) corresponded to C. dubliniensis. The difference in color between both species on chromogenic media was not so stressed as it is pointed out in some works. The more specific and sensitive tests were the ability to grow at 45 °C, D-xylose assimilation, color and macroscopic appearance in tobacco-agar. Between 11.6% and 15.1% of C. albicans strains produced chlamidoconidiae in the 3 differential media tested. The opacity halo (lipase) was evident in 95.6% of C. albicans isolates but 2 out of 13 C. dubliniensis also presented precipitation halo. We consider that at least 3 different phenotypical methods should be used to distinguish properly these two species since none of the tests is absolutely sensitive or specific.

Abstract  Aggregated soils are structured systems susceptible to non-uniform flow. The hydraulic properties depend on the aggregate fabric and the way the aggregates are assembled. We examined the hydraulic behavior of an aggregate packing. We focused on conditions when water mostly flows through the aggregates, leaving the inter-aggregate pore space air-filled. The aggregates were packed in 3 mm thick slabs forming a quasi two-dimensional bedding. The larger aggregates were wetted with water and embedded in smaller aggregates equilibrated at a lower water content. The water exchange between wet and drier aggregates was monitored by neutron radiography. The three-dimensional arrangement of the aggregates was reconstructed by neutron tomography. The water flow turned out to be controlled by the contacts between aggregates, bottle-necks that slow down the flow. The bottle-neck effect is due to the narrow flow cross section of the contacts. The water exchange was simulated by considering the contact area between aggregates as the key parameter. In order to match the observed water flow, the contact area must be reduced by one to two orders of magnitude relative to that obtained from image analysis. The narrowness of the contacts is due to air-filled voids within the contacts. [ABSTRACT FROM AUTHOR]

The understanding and modelling of the process of water imbibition is important for various applications of physics (e.g. building or soil physics). To measure the spatial distribution of the water content at arbitrary times is not trivial. Neutron radiography provides an appropriate tool for such investigations with excellent time and spatial resolution. Because of the high sensitivity to hydrogen, even small amounts of water in a porous structure can be detected in samples with dimensions up to 40?cm. Three different porous stones found in Indiana, USA, have been investigated (Mansfield sandstone, Salem limestone and Hindustan whetstone). The imbibition of deionized water and a NaCl solution in up- and downwards directions has been tracked during several hours and radiographed at regular intervals. A correction method to reduce the disturbing effects due to neutron scattering is applied. This allows a quantitative evaluation of the water content in addition to the visualization of the water distribution. The results agree well with theoretical models describing water infiltration and reproduce the water content with a pixel resolution of 272?µm in time steps of 1?min. The comparison with the radiographed structure of the dry stone explains variations in the conduction or retention of the water, respectively. The experimental and correction procedures described here can be applied to other porous media and their uptake and loss of fluids. [ABSTRACT FROM AUTHOR]

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This paper extends the empirical results on online retailing by studying prices for nearly homogenous services – holiday packages – matched across conventional and Internet channels. Controlling for vertical product differentiation, there is no evidence for lower prices and price dispersion advertised in the online medium in general, as hypothesized by search theory. It therefore remains an open issue whether Internet trade can be associated with a more competitive market structure than the conventional market. [ABSTRACT FROM AUTHOR]

Abstract Objective As exclusively endoscopic endonasal resection of benign orbital tumors has become more widespread, high‐quality outcomes data are lacking regarding the decision of when and how to reconstruct the medial orbital wall following resection. The goal of this study was to systematically review pertinent literature to assess clinical outcomes relative to orbital reconstruction practices. Methods Data Sources: PubMed, EMBASE, Web of Science. A systematic review of studies reporting exclusively endoscopic endonasal resections of benign orbital tumors was conducted. Articles not reporting orbital reconstruction details were excluded. Patient and tumor characteristics, operative details, and outcomes were recorded. Variables were compared using χ2, Fisher's exact, and independent t tests. Results Of 60 patients included from 24 studies, 34 (56.7%) underwent orbital reconstruction following resection. The most common types of reconstruction were pedicled flaps (n = 15, 44.1%) and free mucosal grafts (n = 11, 32.4%). Rigid reconstruction was uncommon (n = 3, 8.8%). Performance of orbital reconstruction was associated with preoperative vision compromise (p

Endothelial dysfunction underlies many of the major complications following hematopoietic cell transplantation (HCT), including transplant-associated thrombotic microangiopathy (TA-TMA), veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), and engraftment syndrome (ES). Emerging evidence similarly implicates endothelitis and microangiopathy in severe COVID-19-related multi-system organ dysfunction. Given the overlap in these two illness states, we hypothesize that prior COVID-19 infection may increase risk for HCT-related endotheliopathies. This retrospective, multicenter study included patients aged 0-25 years who underwent autologous or allogeneic HCT for any indication between January 1, 2020 and September 21, 2021, with close attention to those infected with COVID-19 in either the six months prior to transplant or twelve months following transplant. Incidences of TA-TMA, VOD/SOS, and ES were compared among patients with COVID-19 infection pre-HCT and post-HCT, as well as with historical controls who were never infected with SARS-CoV-2. Those who underwent HCT following COVID-19 infection displayed significantly increased rates of TA-TMA compared to those who were never infected. Additionally, our data suggests a similar trend for increased VOD/SOS and ES rates, although this did not reach statistical significance. Therefore, a history of COVID-19 infection prior to undergoing HCT may be a nonmodifiable risk factor for endothelial-related complications following HCT. Further studies are warranted to better clarify this relationship among larger cohorts and in the era of the Omicron SARS-CoV-2 variants.

PURPOSEIn describing our ten-year experience with treating chronic myeloid leukemia (CML) as part of the Glivec Patient Assistance Program (GIPAP) in rural Rwanda, we evaluate (1) patient characteristics and treatment outcomes, (2) resource-adapted management strategies, and (3) the impact of diagnostic capacity development.METHODSWe retrospectively reviewed all patients with BCR-ABL–positive CML enrolled in this GIPAP program between 2009 and 2018. Clinical data were analyzed using descriptive statistics, Kaplan-Meier methods, proportional hazards regression, and the Kruskal-Wallis test.RESULTSOne hundred twenty-four patients were included. The median age at diagnosis was 34 (range 8-81) years. On imatinib, 91% achieved complete hematologic response (CHR) after a median of 49 days. Seven (6%) and 12 (11%) patients had primary and secondary imatinib resistance, respectively. The 3-year overall survival was 80% (95% CI, 72 to 87) for the cohort, with superior survival in imatinib responders compared with those with primary and secondary resistance. The median time from imatinib initiation to CHR was 59 versus 38 days (P = .040) before and after in-country diagnostic testing, whereas the median time to diagnosis (P = .056) and imatinib initiation (P = .170) was not significantly different.CONCLUSIONCoupling molecular diagnostics with affordable access to imatinib within a comprehensive cancer care delivery program is a successful long-term strategy to treat CML in resource-constrained settings. Our patients are younger and have higher rates of imatinib resistance compared with historic cohorts in high-income countries. High imatinib resistance rates highlight the need for access to molecular monitoring, resistance testing, and second-generation tyrosine kinase inhibitors, as well as systems to support drug adherence. Hematologic response is an accurate resource-adapted predictor of survival in this setting. Local diagnostic capacity development has allowed for continuous, timely CML care delivery in Rwanda.

BACKGROUND Gut decontamination (GD) can decrease the incidence and severity of acute graft-versus-host disease (aGVHD) in murine models of allogeneic hematopoietic cell transplantation (HCT). In this pilot study, we examined the impact of GD on gut microbiome composition and the incidence of aGVHD in HCT patients.METHODS We randomized 20 patients undergoing allogeneic HCT to receive (GD) or not receive (no-GD) oral vancomycin-polymyxin B from day –5 through neutrophil engraftment. We evaluated shotgun metagenomic sequencing of serial stool samples to compare the composition and diversity of the gut microbiome between study arms. We assessed clinical outcomes in the 2 arms and performed strain-specific analyses of pathogens that caused bloodstream infections (BSI).RESULTS The 2 arms did not differ in the predefined primary outcome of Shannon diversity of the gut microbiome at 2 weeks post-HCT (genus, P = 0.8; species, P = 0.44) or aGVHD incidence (P = 0.58). Immune reconstitution of T cell and B cell subsets was similar between groups. Five patients in the no-GD arm had 8 BSI episodes versus 1 episode in the GD arm (P = 0.09). The BSI-causing pathogens were traceable to the gut in 7 of 8 BSI episodes in the no-GD arm, including Staphylococcus species.CONCLUSION While GD did not differentially affect Shannon diversity or clinical outcomes, our findings suggest that GD may protect against gut-derived BSI in HCT patients by decreasing the prevalence or abundance of gut pathogens.TRIAL REGISTRATION ClinicalTrials.gov NCT02641236.FUNDING NIH, Damon Runyon Cancer Research Foundation, V Foundation, Sloan Foundation, Emerson Collective, and Stanford Maternal & Child Health Research Institute.

Summary: Hematopoietic stem cell transplant (HSCT) can prevent progression of several genetic disorders. Although a subset of these disorders are identified on newborn screening panels, others are not identified until irreversible symptoms develop. Genetic testing is an efficient methodology to ascertain pre-symptomatic children, but the penetrance of risk-associated variants in the general population is not well understood. We developed a list of 127 genes associated with disorders treatable with HSCT. We identified likely pathogenic or pathogenic (LP/P) and loss-of-function (LoF) variants in these genes in the Genome Aggregation Database (gnomAD), a dataset containing exome and genome sequencing data from 141,456 healthy adults. Within gnomAD, we identified 59 individuals with a LP/P or LoF variant in 15 genes. Genes were associated with bone marrow failure syndromes, bleeding disorders, primary immunodeficiencies, osteopetrosis, metabolic disorders, and epidermolysis bullosa. In conclusion, few ostensibly healthy adults had genotypes associated with pediatric disorders treatable with HSCTs. Given that most of these disorders do not have biomarkers that could be cheaply and universally assessed on a standard newborn screen, our data suggest that genetic testing may be a complementary approach to traditional newborn screening methodology that has the potential to improve mortality and is not expected to lead to a high burden of false-positive results.

Removal of foreign bodies from the infratemporal fossa is surgically challenging and fraught with risks. This report describes our experience with a minimally invasive transoral technique, utilizing endoscopic and image guidance technology, for retrieval of infratemporal fossa foreign bodies in 6 patients. The technique was successfully applied in all cases with identification and retrieval of the foreign bodies, which included 4 hypodermic needles broken off during dental injections, a cottonoid surgical sponge lost during a facial fracture repair, and a maxillary molar displaced during attempted extraction. Complications were limited to transient postoperative lingual and inferior alveolar nerve sensory deficits in 1 patient.

Abstract Introduction Human papillomavirus (HPV) related multiphenotypic sinonasal carcinoma (HMSC) is a newly described entity. The prognosis of this neoplasm is not well understood, but cases often demonstrate high-grade features and paradoxically indolent behavior. Case Report We present the case of a 65-year-old man referred with unilateral nasal congestion and epistaxis. Nasal endoscopy and imaging revealed an expansile mass filling the left nasal cavity. The patient underwent endoscopic-assisted medial maxillectomy, with complete resection and negative margins. Pathology revealed a basaloid tumor consisting of solid nests with multiple foci of cribriform architecture, with positivity for high-risk HPV, thus supporting the diagnosis of HMSC. Postoperatively, the patient received 66.6-Gy adjuvant three-dimensional proton therapy. Twenty-three months after surgical resection, he developed enlarging pulmonary nodules with biopsy features consistent with the primary sinonasal tumor. He was treated with three cycles of chemotherapy and eight cycles of immunotherapy, progressing on both therapies. He remains on palliative chemotherapy. Conclusion Here, we present a case of HMSC with early and progressive distant metastasis. We aim to add to an understanding of the behavior of this entity. Although this neoplasm may typically be indolent, further classification of high-risk features is necessary to identify rare aggressive cases.

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The reliable quantification of gene copy number variations is a precondition for future investigations regarding their functional relevance. To date, there is no generally accepted gold standard method for copy number quantification, and methods in current use have given inconsistent results in selected cohorts. In this study, we compare two methods for copy number quantification. β-defensin gene copy numbers were determined in parallel in 80 genomic DNA samples by real-time PCR and multiplex ligation-dependent probe amplification (MLPA). The pyrosequencing-based paralog ratio test (PPRT) was used as a standard of comparison in 79 out of 80 samples. Realtime PCR and MPLA results confirmed concordant DEFB4, DEFB103A, and DEFB104A copy numbers within samples. These two methods showed identical results in 32 out of 80 samples; 29 of these 32 samples comprised four or fewer copies. The coefficient of variation of MLPA is lower compared with PCR. In addition, the consistency between MLPA and PPRT is higher than either PCR/MLPA or PCR/PPRT consistency. In summary, these results suggest that MLPA is superior to real-time PCR in β-defensin copy number quantification.

In-canopy turbulence is a required input to study pollutant cycling and chemistry within plant canopies and to link concentrations and sources. Despite the importance of grasslands worldwide, most previous work has focused on forests and crops. Here, turbulence parameters in a mature agricultural grassland canopy were measured with a combination of a small ultrasonic anemometer, hotwire anemometry and a radon (Rn) tracer technique, as part of a measurement to study ammonia (NH3) exchange with grassland. The measurements are used to derive vertical profiles of basic turbulent parameters, for quadrant-hole analysis of the two-parametric frequency distributions of u'−w' and to derive in-canopy eddy diffusivities as input for models of in-canopy tracer transport. The results are in line with previous measurements on taller canopies, but shows increased decoupling between in-canopy flow and above-canopy turbulence. The comparison of sonic anemometry and Rn measurements implies that Lagrangian time-scales must decrease sharply at the ground, with important implications for estimating the magnitude of ground-level and soil emissions from concentration measurements. Atmospheric stability above and within the canopy has little influence on the standard deviation of vertical wind component inside the canopy. Use of the turbulence parameters in an analytical Lagrangian framework, which is here validated for heat transfer, suggests that measured in-canopy profiles of NH3 are consistent with a ground-level source, presumably from senescent plant parts, which is recaptured by the overlying canopy.

The permeability of softwoods can be enhanced by selective bacterial attack of the pit membranes. In this paper, green flat-sawn Pinus radiata sapwood boards were sprinkled for various exposure times with a nutrient solution containing a mixed bacterial population. The timber samples were subsequently dried and the tangential absorption of water was measured using neutron radiography to track the movement of moisture within the wood. There was a significant increase in water absorption after only two days of bacterial exposure, and the quantity of water absorption nearly doubled after a fortnight of bacterial exposure. These measurements showed that dried timber that has had a greater extent of bacterial exposure in the green condition has more void space available to store and conduct water. Scanning electron micrographs showed that bacteria had colonised the pits near the surface of the wood after only two days bacterial exposure. There was also clear evidence of damage to the margo-fibrils and tori of the pit membranes, which was attributed to enzymatic degradation by the bacteria. This study confirms the conclusions drawn by other investigators that bacteria degrade the pits in the green sapwood, so that many of the pathways for moisture flow remain unblocked once the wood is dried

We have previously investigated the diverse levels of disruption caused by Zn(II)BLMs with different C-termini to DNA hairpins containing 5′-GC-3′ and 5′-GT-3′ binding sites. The results of this investigation indicated that both the DNA-binding site and the bleomycin C-termini have an impact on the final conformation of the aforementioned hairpins in the drug-target complexes, as suggested by the different sets of intramolecular NOEs displayed by both oligonucleotides when bound to each Zn(II)BLM. The NMR signals elicited by 1H nuclei in the oligonucleotide bases and sugar moieties were also affected differently (shifted upfield or downfield in various patterns) depending on the BLM C-termini and the binding site in the oligonucleotides. The overall conclusion derived from the precedent research is that the spatial conformation of target DNA segments in DNA-Zn(II)BLM complexes could be forged by interactions between drug and DNA that are guided by the DNA binding site and the BLM C-termini. The present study focuses on the structural alterations exhibited by Zn(II)bleomycin-A2, -B2, -A5 and Zn(II)peplomycin molecules upon binding to the previously studied hairpins. Our main goal is to determine if different spatial conformations of the drugs in their DNA-bound forms are found in drug-DNA complexes that differ in the oligonucleotide binding site and BLM C-termini. Evidence that suggest that each Zn(II)bleomycin is structurally affected depending these two factors, as indicated by different sets of intramolecular NOE connectivities between drug protons and diverse patterns of shifting of their 1H-NMR signals, is provided.

To investigate the suitability of blood granulocyte and monocyte sensitivity, as measured by the quantity of different agonists required to induce CD62L shedding, for assessment of perioperative immune changes in patients undergoing cardiac surgery with cardiopulmonary bypass.Patients scheduled for aortocoronary bypass grafting or for valve surgery were included in this prospective observational study. Blood samples were drawn before anesthesia induction, directly after surgery and 48 hours after anesthesia induction. We determined the concentration of two different inflammatory stimuli--lipoteichoic acid (LTA) and tumor necrosis factor alpha (TNF)--required to induce shedding of 50% of surface CD62L from blood granulocytes and monocytes. In parallel monocyte surface human leukocyte antigen (HLA)-DR, and plasma interleukin (IL)-8, soluble (s)CD62L, soluble (s)Toll-like receptor (TLR)-2 and ADAM17 quantification were used to illustrate perioperative immunomodulation.25 patients were enrolled. Blood granulocytes and monocytes showed decreased sensitivity to the TLR 2/6 agonist Staphylococcus aureus LTA immediately after surgery (p = 0.001 and p = 0.004 respectively). In contrast, granulocytes (p = 0.01), but not monocytes (p = 0.057) displayed a decreased postoperative sensitivity to TNF. We confirmed the presence of a systemic inflammatory response and a decreased immune sensitivity in the post-surgical period by measuring significant increases in the perioperative plasma concentration of IL-8 (p ≤ 0.001) and sTLR (p = 0.004), and decreases in monocyte HLA-DR (p

BACKGROUND: The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. METHODS: Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA) for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity), EM (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers, increased CYP2D6 activity). Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. RESULTS: Metabolism differed between CYP2D6 genotypes. Mean (95%-CI) oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18 (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p = 0.005). Oxycodone consumption up to the 12(th) hour was highest in PM (p = 0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p

BackgroundUrinary tract infections (UTI) are frequent in outpatients. Fast pathogen identification is mandatory for shortening the time of discomfort and preventing serious complications. Urine culture needs up to 48 hours until pathogen identification. Consequently, the initial antibiotic regimen is empirical.AimTo evaluate the feasibility of qualitative urine pathogen identification by a commercially available real-time PCR blood pathogen test (SeptiFast®) and to compare the results with dipslide and microbiological culture.Design of studyPilot study with prospectively collected urine samples.SettingUniversity hospital.Methods82 prospectively collected urine samples from 81 patients with suspected UTI were included. Dipslide urine culture was followed by microbiological pathogen identification in dipslide positive samples. In parallel, qualitative DNA based pathogen identification (SeptiFast®) was performed in all samples.Results61 samples were SeptiFast® positive, whereas 67 samples were dipslide culture positive. The inter-methodological concordance of positive and negative findings in the gram+, gram- and fungi sector was 371/410 (90%), 477/492 (97%) and 238/246 (97%), respectively. Sensitivity and specificity of the SeptiFast® test for the detection of an infection was 0.82 and 0.60, respectively. SeptiFast® pathogen identifications were available at least 43 hours prior to culture results.ConclusionThe SeptiFast® platform identified bacterial DNA in urine specimens considerably faster compared to conventional culture. For UTI diagnosis sensitivity and specificity is limited by its present qualitative setup which does not allow pathogen quantification. Future quantitative assays may hold promise for PCR based UTI pathogen identification as a supplementation of conventional culture methods.