End-of-life decisions in acute stroke patients: an observational cohort study

Background: Crucial issues of modern stroke care include best practice end-of-life-decision (EOLD)-making procedures and the provision of high-quality palliative care for dying stroke patients. Methods: We retrospectively analyzed records of those patients who died over a 4-year period (2011–2014) on our Stroke Unit concerning EOLD, focusing on the factors that most probably guided decisions to induce limitation of life-sustaining therapy and subsequently end-of-life-care procedures thereafter. Results: Of all patients treated at our Stroke Unit, 120 (2.71 %) died. In 101 (86.3 %), a do-not-resuscitate-order (DNRO) was made during early treatment. A decision to withdraw/withhold further life supportive therapy was made in 40 patients (34.2 %) after a mean of 5.0 days (range 0–29). Overall patient death occurred after a mean time of 7.0 days (range 1–30) and 2.6 days after therapy restrictions. Disturbance of consciousness at presentation, dysphagia on day 1 and large supratentorial stroke were possible indicators of decisions to therapeutic withdrawing/withholding. Proceedings of EOL care in these patients were heterogeneous; in most cases monitoring (95 %), medical procedures (90 %), oral medication (88 %), parenteral nutrition (98 %) and antibiotic therapy (86 %) were either not ordered or withdrawn, however IV fluids were continued in all patients. Conclusions: A high percentage of stroke patients were rated as terminally ill and died in the course of caregiving. Disturbance of consciousness at presentation, dysphagia on day 1 and large supratentorial stroke facilitated decisions to change therapeutic goals thus initiating end-of-life-care. However, there is further need to foster research on this field in order to ameliorate outcome prognostication, to understand the dynamics of EOLD-making procedures and to educate staff to provide high-quality patient-centred palliative care in stroke medicine

Is the Brain Cortex a Fractal?

The question is analysed if the human cerebral cortex is self similar in a statistical sense, a property which is usually referred to as being a fractal. The presented analysis includes all spatial scales from the brain size to the ultimate image resolution. Results obtained in two healthy volunteers show that the self similarity does take place down to the spatial scale of 2.5 mm. The obtained fractal dimensions read D=2.73±.05 and D=2.67±.05 correspondingly, which is in good agreement with previously reported results. The new calculational method is volumetric and is based on the fast Fourier Transform of segmented three dimensional high resolved magnetic resonance images. Engagement of FFT enables a simple interpretation of the results and achieves a high performance, which is necessary to analyse the entire cortex

Human palaeodiet at Zamostje 2, central Russia:Results of radiocarbon and stable isotope analyses

Only 21 human remains have been identified at Zamostje 2, despite extraordinarily good conditions for organic preservation, and the recovery of thousands of animal bones from layers dating from the Late Mesolithic to the Middle Neolithic (c.6500–4000 cal BC). Almost all the human remains are fragments of the cranium, maxilla, mandible, which are potentially reworked from earlier depositions, uphill or upstream of Zamostje 2, or isolated teeth. Disregarding naturally shed deciduous teeth, these remains have been attributed to between 5 and 14 individuals, ranging in age from 6 to 7 years to mature adult. We report AMS radiocarbon (14C) dating and dietary stable isotopes, δ13C and δ15N, for all the human bones, and δ13C and δ15N values from 63 prehistoric animal bones from Zamostje 2, including 18 fish and 7 dogs. Using the faunal isotope data, we construct isotope signatures for different food groups, which we use to interpret the human δ13C and δ15N values. Based on 14C ages and dietary stable isotopes, we propose that the human bones represent 10–12 individuals, most of whom date to the Late Mesolithic occupation at Zamostje 2; one is somewhat earlier in the Mesolithic, one (probably from the nearby site, Zamostje 1) may date to the Middle Neolithic, and two (one from Zamostje 1, one unprovenanced) date to the Late Neolithic or Eneolithic. The earliest and latest individuals may have obtained most of their dietary protein intake from fish, but Late Mesolithic individuals probably had more mixed diets. Palaeodiet reconstruction is complicated by unusual δ13C and δ15N values for local fish in the Late Mesolithic, which are reflected in δ13C and δ15N values from dogs

High throughput, small scale methods to characterise the growth of marine fungi

Various marine fungi have been shown to produce interesting, bioactive compounds, but scaling up the production of these compounds can be challenging, particularly because little is generally known about how the producing organisms grow. Here we assessed the suitability of using 100-well BioScreen plates or 96-well plates incubated in a robot hotel to cultivate eight filamentous marine fungi, six sporulating and two non-sporulating, to obtain data on growth and substrate (glucose, xylose, galactose or glycerol) utilisation in a high throughput manner. All eight fungi grew in both cultivation systems, but growth was more variable and with more noise in the data in the Cytomat plate hotel than in the BioScreen. Specific growth rates between 0.01 (no added substrate) and 0.07 h-1 were measured for strains growing in the BioScreen and between 0.01 and 0.27 h-1 for strains in the plate hotel. Three strains, Dendryphiella salina LF304, Penicillium chrysogenum KF657 and Penicillium pinophilum LF458, consistently had higher specific growth rates on glucose and xylose in the plate hotel than in the BioScreen, but otherwise results were similar in the two systems. However, because of the noise in data from the plate hotel, the data obtained from it could only be used to distinguish between substrates which did or did not support growth, whereas data from BioScreen also provided information on substrate preference. Glucose was the preferred substrate for all strains, followed by xylose and galactose. Five strains also grew on glycerol. Therefore it was important to minimise the amount of glycerol introduced with the inoculum to avoid misinterpreting the results for growth on poor substrates. We concluded that both systems could provide physiological data with filamentous fungi, provided sufficient replicates are included in the measurements

Solid Surface Structure Affects Liquid Order at the Polystyrene/SAM Interface

We present a combined x-ray and neutron reflectivity study characterizing the interface between polystyrene (PS) and silanized surfaces. Motivated by the large difference in slip velocity of PS on top of dodecyl-trichlorosilane (DTS) and octadecyl-trichlorosilane (OTS) found in previous studies, these two systems were chosen for the present investigation. The results reveal the molecular conformation of PS on silanized silicon. Differences in the molecular tilt of OTS and DTS are replicated by the adjacent phenyl rings of the PS. We discuss our findings in terms of a potential link between the microscopic interfacial structure and dynamic properties of polymeric liquids at interfaces

Flavin-Dependent Monooxygenases as a Detoxification Mechanism in Insects: New Insights from the Arctiids (Lepidoptera)

Insects experience a wide array of chemical pressures from plant allelochemicals and pesticides and have developed several effective counterstrategies to cope with such toxins. Among these, cytochrome P450 monooxygenases are crucial in plant-insect interactions. Flavin-dependent monooxygenases (FMOs) seem not to play a central role in xenobiotic detoxification in insects, in contrast to mammals. However, the previously identified senecionine N-oxygenase of the arctiid moth Tyria jacobaeae (Lepidoptera) indicates that FMOs have been recruited during the adaptation of this insect to plants that accumulate toxic pyrrolizidine alkaloids. Identification of related FMO-like sequences of various arctiids and other Lepidoptera and their combination with expressed sequence tag (EST) data and sequences emerging from the Bombyx mori genome project show that FMOs in Lepidoptera form a gene family with three members (FMO1 to FMO3). Phylogenetic analyses suggest that FMO3 is only distantly related to lepidopteran FMO1 and FMO2 that originated from a more recent gene duplication event. Within the FMO1 gene cluster, an additional gene duplication early in the arctiid lineage provided the basis for the evolution of the highly specific biochemical, physiological, and behavioral adaptations of these butterflies to pyrrolizidine-alkaloid-producing plants. The genes encoding pyrrolizidine-alkaloid-N-oxygenizing enzymes (PNOs) are transcribed in the fat body and the head of the larvae. An N-terminal signal peptide mediates the transport of the soluble proteins into the hemolymph where PNOs efficiently convert pro-toxic pyrrolizidine alkaloids into their non-toxic N-oxide derivatives. Heterologous expression of a PNO of the generalist arctiid Grammia geneura produced an N-oxygenizing enzyme that shows noticeably expanded substrate specificity compared with the related enzyme of the specialist Tyria jacobaeae. The data about the evolution of FMOs within lepidopteran insects and the functional characterization of a further member of this enzyme family shed light on this almost uncharacterized detoxification system in insects

Neural correlates of hyperalgesia in the monosodium iodoacetate model of osteoarthritis pain

Background: The mechanisms driving osteoarthritic pain remain poorly understood, but there is increasing evidence for a role of the central nervous system in the chronification of pain.We used functional magnetic resonance imaging to investigate the influence of a model of unilateral knee osteoarthritis on nociceptive processing. Results: Four to five weeks post intra-articular injection of monosodium iodoacetate (MIA, 1 mg) into the left knee, Sprague Dawley rats were anesthetized for functional magnetic resonance imaging studies to characterize the neural response to a noxious stimulus (intra-articular capsaicin injection). In a two-arm cross-over design, 5 mM/50 ml capsaicin was injected into either the left knee (n¼8, CAPS-MIA) or right control knee (n¼8, CAPS-CON), preceded by contralateral vehicle (SAL) injection. To assess neural correlates of mechanical hyperalgesia, hindpaws were stimulated with von Frey hairs (8 g: MIA; 15 g: control knee, based on behavioral withdrawal responses). The CAPS-MIA group exhibited significant activation of the periaqueductal gray, unilateral thalamus and bilateral mensencephalon, superior-colliculus, and hippocampus, with no significant activation in the other groups/conditions. Capsaicin injection increased functional connectivity in the mid-brain network and mediodorsal thalamic nucleus, hippocampus, and globus pallidus, which was significantly stronger in CAPS-MIA compared to CAPS-CON groups. Mechanical stimulation of the hyperalgesic (ipsilateral to MIA knee) and normalgesic (contralateral) hindpaws evoked qualitatively different brain activation with more widespread brainstem and anterior cingulate (ACC) activation when stimulating the hyperalgesic paw, and clearer frontal sensory activation from the normalgesic paw. Conclusions: We provide evidence for modulation of nociceptive processing in a chronic knee osteoarthritis pain model with stronger brain activation and alteration of brain networks induced by the pro-nociceptive stimulus. We also report a shift to a medial pain activation pattern following stimulation of the hyperalgesic hindpaw. Taken together, our data support altered neural pain processing as a result of peripheral and central pain sensitization in this model

Long-Term Results of Bariatric Restrictive Procedures: A Prospective Study

Laparoscopic adjustable gastric banding (LAGB) and vertical-banded gastroplasty (VBG) are surgical treatment modalities for morbid obesity. This prospective study describes the long-term results of LAGB and VBG. One hundred patients were included in the study. Fifty patients underwent LAGB and 50 patients, open VBG. Study parameters were weight loss, changes in obesity-related comorbidities, long-term complications, re-operations including conversions to other bariatric procedures and laboratory parameters including vitamin status. From 91 patients (91%), data were obtained with a mean follow-up duration of 84 months (7 years). Weight loss [percent excess weight loss (EWL)] was significantly more after VBG compared with LAGB, 66% versus 54%, respectively. All comorbidities significantly decreased in both groups. Long-term complications after VBG were mainly staple line disruption (54%) and incisional hernia (27%). After LAGB, the most frequent complications were pouch dilatation (21%) and anterior slippage (17%). Major re-operations after VBG were performed in 60% of patients. All re-operations following were conversions to Roux-en-Y gastric bypass (RYGB). In the LAGB group, 33% of patients had a refixation or replacement of the band, and 11% underwent conversion to another bariatric procedure. There were no significant differences in weight loss between patients with or without re-interventions. No vitamin deficiencies were present after 7 years, although supplement usage was inconsistent. This long-term follow-up study confirms the high occurrence of late complications after restrictive bariatric surgery. The failure rate of 65% after VBG is too high, and this procedure is not performed anymore in our institution. The re-operation rate after LAGB is decreasing as a result of new techniques and materials. Results of the re-operations are good with sustained weight loss and reduction in comorbidities. However, in order to achieve these results, a durable and complete follow-up after restrictive procedures is imperative