Τετάρτη, 6 Σεπτεμβρίου 2017

Behavioral responses to visual overstimulation in the cockroach Periplaneta americana L.

Abstract

In the visual systems of insects, different types of photoreceptors contribute to specialized visual channels that mediate distinct functions and behaviors. Large compound eyes of Periplaneta americana contain photoreceptors of two spectral classes, broadband green-sensitive photoreceptors and narrow-band UV-sensitive photoreceptors. Here, we investigated how visual stimulation by UV and green light affects locomotor, resting, and grooming behaviors in P. americana under conditions when light avoidance is not possible. We show that green but not UV light stimulates locomotor activity, inducing paradoxical positive masking. Duration of resting and grooming decreased with increasing light intensity, consistent with development of behavioral stress in response to visual overstimulation. A reaction of full immobility is described under UV light and at higher intensities of green light, with relative periods of immobility and grooming strongly negatively correlated. Low-intensity UV was more effective than low-intensity green light in suppressing grooming and inducing immobility. Our results suggest that locomotor activity in P. americana is mainly regulated by green-sensitive photoreceptors, and that dim UV light can trigger behavioral immobility, whereas both wavelengths induce stress-like reactions at high intensities. Considering the intrinsic UV sensitivity of green-sensitive photoreceptors, the contrasting behavioral responses indicate antagonistic interactions between UV and green visual channels.



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Auto-Identification of Neuronal Activity Patterns as a Physiological Mechanism of Awareness

How do humans become aware of things, for example, flashes of light, odors, or pain? There is still no convincing answer to this question, though it is key to understanding any kind of consciousness. This article postulates an autorecognition mechanism whereby patterns of input excitation generated by a stimulus in one or several areas of the cortex give rise to patterns of output excitation identical (coinciding in terms of its main features) to the pattern of input excitation. The output excitation pattern is transmitted via massively parallel positive feedback to the inputs of the same areas of the cortex. Identical excitation patterns generated by the stimulus and transmitted by back projections, are combined in the same neural structures, producing intense firing. This cyclic process accentuates the characteristics and intensifies stimulus mapping, creating the optimum conditions for its categorization by a distributed long-term memory. The sensory category is the response of the cortex to the input excitation and is mapped as a specific pattern of neuron activity. Categorization patterns are transmitted to the input and are included in the auto-identification cycle, providing for the intensive mapping of the subjective meaning of the stimulus. Mapping of sensory categories (internal data) as patterns of input neuron activity in the cortex forms the representation of categories to the subject as elements in the mapping of the external world. The result is that the external word is represented to the subject not in terms of the objective features of the physical world, but in terms of sensory categories: color, taste, odor, tactile sensations, etc., which constitutes the phenomenon of sensory awareness.



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Comparison of the Efficacy and Safety of Memantal and the Original Drug Memantine in Mild and Moderate Alzheimer’s Disease-Associated Dementia

Objective. To carry out a comparative assessment of the clinical efficacy and safety of the original drug memantine and the generic drug (memantal) in patients with mild and moderate dementia in Alzheimer's disease (AD). Materials and methods. A randomized, controlled, comparative study was performed over a period of six months in 50 patients with mild or moderate AD-associated dementia who had not previously received acetylcholinesterase inhibitors or memantine. The original memantine and memantal were prescribed at a starting dose of 5 mg/day, after which the dose was titrated in accordance with the manufacturer's recommendations. Patients' status was evaluated using the MMSE scale, the Cummings NPI questionnaire, and the IADL questionnaire, and side effects were recorded. Results and conclusions. There were no significant differences in the actions of memantal and the original memantine in relation to measures of cognitive functioning, behavioral or psychotic symptoms, or operant activity, and there were no differences in safety. Both study drugs evoked minor improvements in cognitive functions, which were more marked in patients with mild AD-associated dementia than in those with late-onset AD. These results lead to the conclusion that there are no significant differences in the efficacy and safety of the generic (memantal) and the original memantine in patients with mild and moderate AD-associated dementia.



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Spontaneous EPSP of Command Neurons in the Common Snail during Heterosynaptic Potentiation

The presynaptic mechanism of short-term plasticity of synaptic transmission was studied by analyzing the effects of rhythmic orthodromic stimulation of the intestinal nerve, inducing short-term potentiation of evoked EPSP, on spontaneous EPSP in defensive behavior command neurons in the common snail. Rhythmic stimulation had no effect on the amplitude of spontaneous EPSP but led to significant increases in the number of spontaneous EPSP. The increase in the frequency of spontaneous EPSP suggested a role for a presynaptic mechanism in the short-term potentiation of synaptic transmission. This presynaptic mechanism may include a decrease in the action potential generation threshold (AP) in presynaptic neurons, which leads to an increase in the proportion of spontaneously active neurons and, thus, supports an increase in the number of spontaneous presynaptic AP.



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Comparison of Bedside and Remote Assessments on the NIHSS Scale in Patients in the Acute Period of Stroke

Objectives – remote assessments on the NIHSS conducted by neurologists using high-quality video conferencing (VC) is recommended when bedside assessment by such a specialist is not available. This recommendation is based on a small number of studies which are not free of systematic errors associated with the subjectivity of the NIHSS. The aim of this study was to minimize these errors. Materials and methods. Six experienced neurologists took part in the study and worked in 15 pairs, along with 90 patients with stable poststroke status no more than 48 h after symptom onset. Each pair of doctors assessed six patients. Each patient was independently evaluated once at the bedside and once remotely. During remote assessment using high-quality VC, the neurologist was assisted by a nurse at the patient's bedside. The distribution of patients by pairs of doctors and sequences of bedside and remote assessments were randomized by block randomization. The comparability of the assessments was evaluated using the κ coefficient and in terms of the proportion of patients for which difference between total NIHSS scores were no more than three points. Results. Differences in NIHSS assessments of no more than three points were obtained in 85.6% (95% CI 76.6–92.1%) of patients. Thus, in practice, remote assessments were clinically significantly different from bedside assessments in one in five patients. Quadratically weighted κ values for total scale scores were 0.91 (95% CI 0.87–0.95). The least concordant subscales were: following commands (ϰ = 0.46), facial muscle paresis (ϰ = 0.43), and limb ataxia (ϰ = 0.27). Remote assessments took longer than bedside assessments: 8 [7, 9] min compared with 6 [5, 8] min (p < 0.001). Conclusions. Remote NIHSS assessments of stroke patients using high-quality VC were comparable with bedside assessments, though further evaluation is required to determine suitability for clinical practice.



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Experience in the Use of Valdoxan (agomelatine) in the Treatment of Depression in Patients with Dyscirculatory Encephalopathy

Objective – to study the efficacy and tolerance of agomelatine (Valdoxan) in mild depressive states in patients with chronic cerebral ischemia (CCI). Materials and methods. The study included 33 patients (23 women, 10 men, mean age 54.5 years). Grade I CCI was diagnosed in 12 patients (36.4%) and grade II in 21 (63.6%). All patients had single depressive episodes of mild severity. Diagnoses of affective and cognitive impairments were based on the Hamilton Rating Scale for Depression (HRDS-17), the Hospital Anxiety and Depression Scale (HADS), the Vein Nocturnal Sleep Questionnaire, the Mini Mental State Examination (MMSE), the Mini-Cog test, the Montreal Cognitive Assessment Scale, the physician's Clinical Global Impression scale for assessment of the severity and dynamics of illness (CGI-S, CGI-I), and the Patients' Global Impression of Change Scale (PGIC). Investigations were performed at prescription of agent and at 2, 4, and 8 weeks of treatment. All patients received agomelatine (Valdoxan) once daily at a dose of 25 mg. Results and conclusions. Use of agomelatine led to improvements in sleep from week 2, with reductions in anxiety symptoms at six weeks, and reductions in depressive symptomatology at eight weeks of treatment. In addition, treatment with agomelatine produced improvements in cognitive functions in the patients. No patient experienced any treatment side effects. The study results demonstrated high antidepressant activity in the treatment of mild depressive disorders in patients with CCI, with a balanced spectrum of actions in relation to symptoms of anxiety, depression, and dyssomnia, along with positive actions on cognitive functions, allowing the use of agomelatine in the treatment of patients with CCI to be recommended.



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Effects of Nonspecific Cytoprotective Treatment on Stress Resistance and Compensatory Potential in Patients with Chronic Cerebral Ischemia

Objective – to study the effects of nonspecific cytoprotective therapy on the clinical manifestations, course of illness, and measures of the stress system in patients with different grades of chronic cerebral ischemia (CCI). Materials and methods. The study included 266 patients aged 35–55 years who received basal and nonspecific cytoprotective therapy. Changes in subjective and objective symptoms of CCI were studied, along with clinical outcomes at one year of follow-up, with assessment of the state of the stress system. Treatment effects on stress resistance were evaluated in terms of changes in blood stress reactions. Results and conclusions. This open, comparative, randomized study showed that inclusion of a nonspecific cytoprotective agent (Cytoflavin) in the therapeutic complex increased the efficacy of treatment of the clinical manifestations of CCI. An increase in the proportion of favorable outcomes at one year of follow-up was associated with optimization of the activity of the stress system using nonspecific cytoprotective therapy, accompanied by increases in stress resistance.



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Structural Organization and Interaction of Intrapancreatic Ganglia with the Myenteric Nerve Plexus of the Duodenum at the Early Stages of Postnatal Ontogeny in Rats

Studies using immunohistochemical markers – synaptophysin (SP), protein gene product 9.5 (PGP 9.5), and tyrosine hydroxylase (TH) – addressed the innervation of the pancreas and the myenteric nerve plexus of the duodenum (duodenum) in neonatal rats (n = 4) and demonstrated a tight link between the nerve plexuses in these organs. Some elements of the myenteric plexus penetrate the pancreas from the walls of the duodenum. Morphological and biochemical similarity was demonstrated between microganglia in the myenteric plexus of the duodenum and pancreas. Most differentiated neurons and bundles of axons in both plexuses were part of the parasympathetic compartment of the autonomic nervous system. There were no catecholaminergic neurons in the pancreas, and bundles of sympathetic fibers entering the organ from outside were few in number and were involved mainly in innervating blood vessels. This is the first report of the use of immunohistochemical reactions for PGP 9.5, SP, and TH to detect two types of nerve fibers in ganglia in the pancreas whose varicose terminals form cholinergic and catecholaminergic synapses around nerve cell bodies.



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Melatonin in Chronic Pain Syndromes

Melatonin is a neurohormone synthesized in the pineal gland and extrapineal structures and has a number of functions, including chronobiotic, antioxidant, oncostatic, immunomodulatory, normothymic, and anxiolytic actions, the abilities to affect the cardiovascular system and the gastrointestinal tract and take part in reproductive functions, and a role in regulating substance metabolism and body weight. In addition, recent studies have demonstrated the efficacy of melatonin in relation to pain syndromes. We present here a review of studies of the use of melatonin in fibromyalgia, headaches, irritable bowel syndrome, chronic back pain, and rheumatoid arthritis. The possible mechanisms mediating the analgesic properties of melatonin are discussed. On the one hand, normalization of circadian rhythms, which are inevitably deranged by chronic pain syndromes, improves sleep and activates the intrinsic adaptive potential of melatonin; on the other, data have been obtained showing that melatonin has independent analgesic influences mediated via melatonin receptors and various neurotransmitter systems.



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Strategies for Improving the Efficacy of Treatment of Chronic Migraine

Objective – to assess the efficacy of botulinum toxin type A (Lantox) in the treatment of chronic migraine. Materials and methods. A total of 22 patients with chronic migraine were investigated before treatment and at four and 12 weeks after administration of 150 IU of Lantox into the muscles of the head and neck using the "follow the pain" method. Drug was administered into the corrugator, procerus, frontalis, temporalis, and occipitalis muscles. Clinical neurological investigations were carried out; the emotional domain was evaluated, with assessment of anxiety and depression, activities of daily living, and quality of life; patients completed a questionnaire on the subjective satisfaction with treatment. Results and conclusions. Treatment was found to have a significant effect on the frequency of headache attacks, which is important in the conversion of chronic headache into episodic headache. Compliance barriers were overcome by addressing psychological problems, especially depression. Use of a drug with virtually no side effects and rapid responses increased patients' confidence in the treatment.



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Comparative Analysis of Brain Activity in Verbal and Spatial Thought in Healthy Subjects and Patients with Speech Disorders

We report here an analysis of specific brain activity measured by fMRI during solution of spatial and verbal tasks in 15 healthy subjects and nine patients with dysarthria or mild sensorimotor aphasia. In healthy subjects, activation of Brodmann area (BA) 19 and Broca's area was more characteristic of verbal thought, while greater bilateral activation of the temporal-parietal-occipital zone, along with the left insula and visual fields 17 and 18 on the left, was specific for spatial thought. In patients with speech disorders, the distribution of areas specific to one task or another underwent significant changes, with non-activation of areas of brain activation characteristic of healthy subjects. Despite the absence of clinical signs of cognitive impairments, the mean verbal task solution time was significantly longer and the proportion of correct responses was smaller in patients than in healthy subjects.



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Recovery of Speech Functions in Patients with Poststroke Aphasia Depending on the Severity of Atherosclerotic Lesions of the Cerebral Arteries

Objective. To study the effects of stenosing lesions of the carotid arteries on recovery of aphatic impairments during the acute period of stroke. Materials and methods. The case histories of 253 patients (median age 58 [52; 63] years) with acute left-hemisphere ischemic and hemorrhagic stroke including motor or sensorimotor aphasia were analyzed. The severity of atherosclerotic lesions to the brachiocephalic arteries was evaluated by color duplex scanning, whose results were used to divide patients into three groups: group 1, without stenosis of the extracranial arteries; group 2, with carotid artery stenosis of <50% of the vessel lumen; and group 3, with >50% stenosis of the carotid arteries. Results. The presence of stenosing lesions of the extracranial arteries in patients with aphasia narrowing the vessel lumen by more than 50% (group 3) significantly (p = 0.0001) degraded prognoses for recovery of speech functions, while stenosis of less than 50% (groups 1 and 2) had no significant influence on the prognosis for speech rehabilitation. Conclusions. Severe atherosclerosis of the carotid arteries had adverse influences on the dynamics of speech recovery in patients during the acute period of stroke.



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Long-Term Contextual Memory in Mice: Persistence and Associability with Reinforcement

Many animal species are able to use context as a conditioned signal for learning. In some cases, the initial memorization of the context and its subsequent association with an unconditioned stimulus can be separated by a long period of time – a phenomenon termed the "context preexposure effect." This type of associative learning is based on a reminder and is significantly different from the classical version, though its properties have previously been studied only in rats. The present study addressed the formation of this type of conditioned link in mice. The conditioned signal was the context of a chamber, which the animals were allowed to explore for 5 min. After different time intervals, the mice were placed in the same chamber for 2 sec, during which they were given immediate electrocutaneous shocks (ECS). The mice formed a specific aversive memory for the preexplored context; formation of the memory did not occur if the animals received the same ECS in a context which was novel for them. This associative learning occurred in mice on application of the conditioned and unconditioned stimuli with intervals ranging from 30 min to 30 days. The resulting memory was long-term, persisting for at least 30 days. These results open up the potential for using mice of various transgenic strains for studying the cellular and molecular mechanisms of this type of associative learning.



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The Role of Prolonged Stress and the Functional State of the Endothelium in the Development of Autonomic Dystonia Syndrome

Objective – to study the role of prolonged stress and the functional state of the endothelium in the development of autonomic dystonia syndrome (ADS) in young patients. Materials and methods. A total of 75 male patients aged 17–28 years with ADS were investigated. Group 1 included 41 patients with no clinically significant signs of psychoemotional stress; group 2 included 34 patients with high levels of psychoemotional stress; the reference group consisted of healthy subjects (n = 21). Anxiety levels were assessed using the Spielberger–Hanin self-assessment scale and the functional state of the endothelium was evaluated using an endothelium-dependent vasodilatation (EDV) test; a standard physical exercise test (PET) using a bicycle ergometer was also performed. Results and conclusions. Correlational relationships were found between reactive and trait anxiety in all groups. These values were maximal among patients with high levels of psychoemotional stress, reflecting high levels of anxiety. Patients of group 1 showed a common reactivity of vascular walls in the EDV and PET tests, while group 2 showed the opposite reactions in these tests – both increases and decreases in the diameters of the brachial artery. This appears to result from an increase in the lability of the sympathetic branch of the autonomic nervous system on the background of stress. These data lead to the conclusion that prolonged emotional stress in young patients with ADS induces dysfunction of the endothelium of the vascular wall, exacerbating the severity of clinical signs of disease and leading to an increased risk of developing cardiovascular pathology.



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Morphofunctional Characteristics of the Microcirculatory Bed and Neurons in the Neocortex after Ischemic Postconditioning

Expression of PECAM-1/CD31 protein (a biomarker for endothelial function and neovascularization processes) was studied in microvessels in layers II, III, and V of the cerebral cortex in Mongolian gerbils (Meriones unguiculatus) in the early (day 2) and late (day 7) parts of the reperfusion period after 7-min forebrain ischemia, ischemic postconditioning (iPostC), and sham-operated animals (n = 60). In the latter, the lowest level of PECAM-1/CD31 immunoreactivity was seen in structures in layer III of the cerebral cortex. Reversible ischemic brain injury decreased the number of morphologically unaltered neurons in the neocortex with increases in the duration of the reperfusion period; cortical layers II, III, and V also showed increased levels of PECAM-1/CD31 immunoreactivity with significant increases in the late reperfusion period. iPostC consisting of three stimulatory episodes of reperfusion-ischemia (15/15 sec) led to significant increases in the number of morphologically unaltered neurons and PECAM-1/CD31 immunoreactivity in layers II and III in the early reperfusion period. In the later reperfusion period following iPostC, the number of unaltered neurons in layers II, III, and V of the cortex increased, while the level of PECAM-1/CD31 immunoreactivity decreased significantly. The results lead to the conclusion that the cytoprotective effect of iPostC in forebrain ischemia is mediated by a physiological adaptive mechanism leading to increases in PECAM-1/CD31 immunoreactivity in cortical microvessels in the early reperfusion period and a decrease in the later reperfusion period.



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Establishment of the GABAergic Neural Network in the Ventrolateral Part of the Solitary Tract Nucleus in Normal Conditions and in Prenatal Serotonin Deficiency in Rats

The dynamics of the formation of the inhibitory neural GABAergic network in the ventral and lateral subnuclei of the solitary tract nucleus (STN) in the early postnatal period were studied in Wistar rats in normal conditions and in prenatal serotonin deficiency (n = 27). GABAergic neurons were detected immunocytochemically using rabbit polyclonal antibodies to GAD-67. The STN subnuclei studied were found to display high levels of GABA expression during the first week of postnatal development, as evidenced by the significant number of GAD-67-immunopositive neurons, of which the number in the ventral subnucleus was almost 1.3 times greater than that in the lateral subnucleus. GABA expression decreased during the second and third weeks, with a simultaneous increase in the density of the network of terminals and GABAcontaining synaptic structures in the neuropil of both subnuclei. Prenatal serotonin deficiency was found to produce sharp decreases in GABA expression in the ventral and lateral subnuclei of the STN during the early postnatal period of development. By the end of the third week, a loose network of GABAergic terminals persisted in the neuropil and the density of synaptic structures increased.



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Effects of Probiotic Enterococci and Glatiramer Acetate on the Severity of Experimental Allergic Encephalomyelitis in Rats

The intestinal microbiota is currently regarded as a potential target for treatments in many pathologies underlying the genesis of inflammation, autoimmune reactions, and neurodegeneration. Multiple sclerosis (MS) is a disease whose pathogenesis combines all these processes. MS also involves impairment to the balance between the components of the intestinal microbiota, with development of dysbiosis. Various probiotics are widely used to correct dysbiotic conditions – bacteria with proven useful properties. We report here the use of a model of multiple sclerosis – experimental allergic encephalomyelitis (EAE) – to study the ability of the probiotic Enterococcus faecium strain L-3 to decrease disease severity in rats when used alone and in combination with glatiramer acetate (GA). Administration of E. faecium L-3 was found to decrease the severity of EAE in rats to essentially the same extent as GA. However, simultaneous use of probiotic enterococci with GA produced no protective action. It is suggested that these agents stimulate different components of the immune system, as their actions produce increases in different populations of immune cells circulating in the blood. The study results demonstrate the ability of E. faecium L-3 to produce significant direct and indirect (via correction of dysbacteriosis) influences on the immune system in MS, which allows these bacteria to be regarded as a potential agent for immunocorrection in autoimmune, inflammatory, and neurodegenerative disease.



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Intercellular Contact Protein β-Catenin in Neurons of the Habenula of the Rat Brain

Studies were performed on frontal brain sections (n = 5) from Wistar rats using immunocytochemical methods. This is the first report on the detection of the protein β-catenin in the nuclei of mature neurons in the medial part of the habenula. As the intranuclear localization of this protein points to its involvement in the canonical Wnt signal pathway, which is expressed during embryogenesis, it can be suggested that habenular neurons retain properties not typical of mature neurons.



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NDM-1 Hazard in the Balkan States: Evidence of the First Outbreak of NDM-1-Producing Klebsiella pneumoniae in Bulgaria

Microbial Drug Resistance , Vol. 0, No. 0.


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Tests of the sorption and olfactory 'fovea' hypotheses in the mouse.

The spatial distribution of receptors within sensory epithelia (e.g. retina and skin) is often markedly non-uniform to gain efficiency in information capture and neural processing. By contrast, odors, unlike visual and tactile stimuli, have no obvious spatial dimension. What need then could there be for either nearest-neighbor relationships or non-uniform distributions of receptor cells in the olfactory epithelium (OE)? Adrian (1942; 1950) provided the only widely debated answer to this question when he posited that the physical properties of odors, such as volatility and water solubility, determine a spatial pattern of stimulation across the OE that could aid odor discrimination. Unfortunately, despite its longevity, few critical tests of the 'sorption hypothesis' exist. Here we test the predictions of this hypothesis by mapping mouse OE responses using the electroolfactogram (EOG) and comparing these response 'maps' to computational fluid dynamics (CFD) simulations of airflow and odorant sorption patterns in the nasal cavity. CFD simulations were performed for airflow rates corresponding to quiet breathing and sniffing. Consistent with predictions of the sorption hypothesis, water soluble odorants tended to evoke larger EOG responses in the central portion of the OE than the peripheral portion. However, sorption simulation patterns along individual nasal turbinates for particular odorants did not correlate with their EOG response gradients. Indeed, the most consistent finding was a rostral-greater to caudal-lesser response gradient for all the odorants tested that is un explained by sorption patterns. The viability of the sorption and related olfactory 'fovea' hypotheses are discussed in light of these findings.



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Constitutive activity of 5-HT2c receptors is present following incomplete spinal cord injury but is not modified after chronic SSRI or baclofen treatment

Following spinal cord injury (SCI), reflexes become hyperexcitable, leading to debilitating muscle spasms and compromised motor function. Previous work has described adaptations in spinal systems that might underlie this hyperexcitability, including an increase in constitutively active 5-HT2C receptors in spinal motoneurons. That work, however, examined adaptations following complete transection SCI, whereas SCI in humans is usually anatomically and functionally incomplete. We therefore evaluated whether constitutive activity of 5-HT2C receptors contributes to reflex hyperexcitability in an incomplete compression model of SCI and to spasms in vitro and in vivo. Our results confirm that 5-HT2C receptor constitutive activity contributes to reflex excitability following incomplete SCI. We also evaluated whether constitutive activity could be altered by manipulating neural activity levels following SCI, testing the hypothesis that it reflects homeostatic processes acting to maintain spinal excitability. We decreased neural activity following SCI by administering baclofen and increased activity by administering the SSRI fluoxetine. We found that drug administration produced minimal alterations in in vivo locomotor function or reflex excitability. Similarly, we found that neither baclofen nor fluoxetine altered the contribution of constitutively active 5-HT2C receptors to reflexes following SCI, although the contribution of 5-HT2C receptors to reflex activity was altered following SSRIs. These results confirm the importance of constitutively activity in 5-HT2C receptors to spinal hyperexcitability following SCI in the clinically relevant case of incomplete SCI, but suggest that this activity is not driven by homeostatic processes that act to maintain overall levels of spinal excitability.



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The effect of prior knowledge and intelligibility on the cortical entrainment response to speech

It has been suggested that cortical entrainment plays an important role in speech perception by helping to parse the acoustic stimulus into discrete linguistic units (Giraud & Poeppel, 2012). However, the question of whether the entrainment response to speech depends on the intelligibility of the stimulus remains open. Studies addressing this question of intelligibility have, for the most part, significantly distorted the acoustic properties of the stimulus to degrade the intelligibility of the speech stimulus, making it difficult to compare across "intelligible" and "unintelligible" conditions. To avoid these acoustic confounds, we follow Millman et al. (2015) and use priming to manipulate the intelligibility of vocoded speech. We use EEG to measure the entrainment response to vocoded target sentences that are preceded by natural-speech (non-vocoded) prime sentences that are either valid (match the target) or invalid (do not match the target). For unintelligible speech, valid primes have the effect of restoring intelligibility (Remez et al., 1980). We compared the effect of priming on the entrainment response for both 3-channel (unintelligible) and 16-channel (intelligible) speech (Loizou et al., 1999). We observed a main effect of priming, suggesting that the entrainment response depends on prior knowledge, but not a main effect of vocoding (16-channel vs. 3-channel). Furthermore, we found no difference in the effect of priming on the entrainment response to 3-channel and 16-channel vocoded speech, suggesting that for vocoded speech entrainment response does not depend on intelligibility.



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Pretreatment with fish oil attenuates heart ischemia consequences in rats

Abstract

Omega-3 polyunsaturated fatty acid (ω-3 PUFA)-rich fish oil supplementation has protective effects on heart ischemic injury. Left ventricular (LV) ischemia was induced in rats by permanent ligation of the left coronary artery. Saline, fish oil or soybean oil was administered daily by gavage (3 g kg−1 b.w.) for 20 days before inducing ischemia. Outcomes were assessed 24 hours after left coronary artery ligation. Pretreatment with fish oil decreased the ω-6/ω-3 fatty acid ratio in the LV. Reduction in infarct size and in the intensity of ventricular systolic dysfunction was found in the fish oil group as compared with the saline or soybean oil groups through echocardiographic evaluation. LV glycogen levels were decreased in the fish oil group as compared with the saline before infarction. Soybean oil pretreatment led to a further increase in the LV levels of CINC 2/αβ, IL1β and TNFα induced by the heart infarction. In heart infarcted rats, fish oil pretreatment decreased creatine kinase and caspase 3 activities; prevented the decrease in the coronary blood flow; increased LV levels of ATP and lactate; increased the mRNA levels of iNOS, eNOS, HIF-1α, GLUT-1, VEGF-α and p53 in the LV as measured by RT-PCR; and did not change LV pro-inflammatory cytokine levels as compared to the control group. Fish oil protected the heart from ischemia as indicated by the decrease in the heart infarction area and systolic dysfunction associated with increased LV ATP levels and maintenance of the coronary blood flow with no change in pro-inflammatory cytokine levels.

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Epigenetic regulation of SIRT1-induced skeletal muscle mass: exercise and heart diseases

Abstract

Skeletal myopathy is commonly recognized as a major cause of exercise intolerance in cardiac diseases such as chronic heart failure; which contributes to increased morbidity and mortality.

This article is protected by copyright. All rights reserved



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The Transcriptional Response of Candida albicans to Weak Organic Acids, Carbon Source and MIG1 Inactivation Unveils a Role for HGT16 in Mediating the Fungistatic Effect of Acetic Acid

Candida albicans is a resident fungus of the human intestinal microflora. Commonly isolated at low abundance in healthy people, C. albicans outcompetes local microbiota during candidiasis episodes. Under normal conditions, members of the human gastrointestinal microbiota were shown to keep C. albicans colonization under control. By releasing weak organic acids (WOAs), bacteria are able to moderate yeast growth. This mechanism displayed a synergistic effect in vitro with the absence of glucose in medium of culture, which underline the complex interaction that C. albicans faces in its natural environment. Inactivation of the transcriptional regulator MIG1 in C. albicans results in a lack of sensitivity to this synergistic outcome. To decipher C. albicans transcriptional responses to glucose, WOAs and the role of MIG1, we performed RNA sequencing on four biological replicates exposed to combinations of these 3 parameters. We were able to characterise the i) glucose response, ii) response to acetic and butyric acid, iii) MIG1 regulation of C. albicans and iv) genes responsible for WOAs resistance. We identified a group of 6 genes linked to WOAs sensitivity in a glucose-MIG1-dependent manner and inactivated one of these genes, the putative glucose transporter HGT16, in a SC5314 wild-type background. As expected, the mutant displayed a partial complementation to WOAs resistance in absence of glucose. This result points towards a mechanism of WOAs sensitivity in C. albicans involving membrane transporters which could be exploited to control yeast colonisation in human body niches.



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Genome-Wide Analysis of DNA Methylation During Ovule Development of Female-Sterile Rice fsv1

The regulation of female fertility is an important field of rice sexual reproduction research. DNA methylation is an essential epigenetic modification that dynamically regulates gene expression during development processes. However, few reports have described the methylation profiles of female sterile rice during ovule development. In this study, ovules were continuously acquired from the beginning of megaspore mother cell meiosis until the mature female gametophyte formation period, and global DNA methylation patterns were compared in the ovules of a high-frequency female-sterile line (fsv1) and a wild-type rice line (Gui99) using whole-genome bisulfite sequencing (WGBS). Profiling of the global DNA methylation revealed hypomethylation, and 3471 significantly differentially methylated regions (DMRs) were observed in fsv1 ovules compared with Gui99. Based on functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of differentially methylated genes (DMGs), we observed more DMGs enriched in cellular component, reproduction regulation, metabolic pathway and other pathways. In particular, many ovule development genes and plant hormone-related genes showed significantly different methylation patterns in the two rice lines, and these differences may provide important clues for revealing the mechanism of female gametophyte abortion.



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Developing Item Response Theory-Based Short Forms to Measure the Social Impact of Burn Injuries

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Publication date: Available online 6 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Molly Marino, Emily C. Dore, Pengsheng Ni, Colleen M. Ryan, Jeff C. Schneider, Amy Acton, Alan M. Jette, Lewis E. Kazis
ObjectiveTo develop self-reported short forms for the LIBRE Profile.DesignParticipants were selected for inclusion in the short forms based upon the item parameters of discrimination and average difficulty. Test information function, as well as floor and ceiling effects, were evaluated for both the full item bank and the short forms.SettingParticipants were recruited were from the Phoenix Society (a support network for burn survivors), peer support networks, social media, and mailings.Participants601 burn survivors over 18 years of age in North America.InterventionsnoneMain Outcome MeasuresThe LIBRE-ProfileResultsTen-item short forms were developed to cover the six LIBRE Profile scales: Relationships with Family & Friends, Social Interactions, Social Activities, Work & Employment, Romantic Relationships, and Sexual Relationships. Ceiling effects were ≤15% for all scales; floor effects were all <1%. The marginal reliability of the short forms ranged from 0.85-0.89.ConclusionsThe LIBRE Profile-Short Forms demonstrated credible psychometric properties. The short form version provides a viable alternative to administering the LIBRE Profile when resources do not allow for computer/internet access. The full item bank, Computerized Adaptive Test, and short forms are all scored along the same metric and therefore scores are comparable regardless of mode of administration.



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Ulnar Nerve Cross-sectional Area for the Diagnosis of Cubital Tunnel Syndrome: A Meta-analysis of Ultrasonographic Measurements

Publication date: Available online 6 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Ke-Vin Chang, Wei-Ting Wu, Der-Sheng Han, Levent Özçakar
ObjectiveThis meta-analysis aimed to examine the performance of sonographic cross-sectional area (CSA) measurements, in the diagnosis of cubital tunnel syndrome (CuTS).Data sourceElectronic databases, comprising of PubMed and Embase, were searched for the pertinent literature before July 2017.Study selectionFourteen trials comparing the ulnar nerve CSA measurements between participants, with and without CuTS, were included.Data extractionStudy design, participants' demographics, diagnostic reference of CuTS and methods of CSA measurement.Data synthesisAmong different elbow levels, the between-group difference in CSA was the largest at the medial epicondyle [6.0 mm2 (95% confidence interval [CI]: 4.5-7.4)]. The pooled mean CSA from the healthy participants was 5.5 mm2 (95%CI: 4.4-6.6) at the arm level, 7.4 mm2 (95% CI: 6.7-8.1) at the cubital tunnel inlet, 6.6 mm2 at the medial epicondyle (95% CI: 5.9-7.2), 7.3 mm2 (95%CI: 5.6-9.0) at the cubital tunnel outlet, and 5.5 mm2 (95% CI: 4.7-6.3) at the forearm level. The sensitivity, specificity, and diagnostic odds ratios pooled from 5 studies, using 10 mm2 as the cut-off point, were 0.85 (95% CI: 0.78-0.90), 0.91 (95% CI: 0.86-0.94), and 53.96 (95% CI: 14.84-196.14), respectively.ConclusionThe ulnar nerve CSA measured by US imaging is useful for the diagnosis of CuTS, and is most significantly different between patients and controls at the medial epicondyle. As the ulnar nerve CSA in normal subjects, at various locations, rarely exceeds 10 mm2, this value can be considered as a cut-off point to diagnose ulnar nerve entrapment at the elbow region.



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One-day low-intensity combined arm-leg (Cruiser) ergometer exercise intervention: cardiorespiratory strain and gross mechanical efficiency in one-legged and two-legged exercise.

This study aims to research whether there is a difference in cardiorespiratory variables and gross mechanical efficiency (GE) in healthy individuals during low-intensity one-legged and two-legged exercise on the combined arm-leg (Cruiser) ergometer and whether motor learning occurs. The outcome of this study will support the use of the Cruiser ergometer in future as a testing and training instrument in the rehabilitation of patients with a lower limb amputation. Twenty-eight healthy men participated in this randomized-controlled trial. One group (n=14) used one leg and both arms during the exercise and the other group (n=14) used both legs and both arms. All participants performed a 1-day low-intensity exercise protocol. This included a standardized pretest and post-test of three bouts of 4 min exercise at 40 W and an exercise intervention of seven bouts of 2x4 min exercise at 40 W. The one-legged and two-legged group differed significantly in the heart rate and GE between the pretest and post-test. At the post-test, the one-legged group showed motor learning. GE improved significantly in both groups over the duration of the three exercise bouts of the pretest, but it did not improve during the post-test. There are differences in cardiorespiratory variables and GE between one-legged and two-legged exercise on the Cruiser ergometer. When using this ergometer in the rehabilitation of patients with a lower limb amputation, it is important to consider these differences and the occurrence of motor learning. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Comparison of polyvinyl chloride and tin stylets for postoperative sore throat and hoarseness: A randomised trial

imageNo abstract available

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The renoprotective properties of xenon and argon in kidney transplantation

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No abstract available

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Anaesthetic management of patients with myopathies

image The anaesthetic management of patients with myopathies is challenging. Considering the low incidence and heterogeneity of these disorders, most anaesthetists are unfamiliar with key symptoms, associated co-morbidities and implications for anaesthesia. The pre-anaesthetic assessment aims at the detection of potentially undiagnosed myopathic patients and, in case of known or suspected muscular disease, on the quantification of disease progression. Ancillary testing (e.g. echocardiography, ECG, lung function testing etc.) is frequently indicated, even at a young patient age. One must differentiate between myopathies associated with malignant hyperthermia (MH) and those that are not, as this has significant impact on preoperative preparation of the anaesthesia workstation and pharmacologic management. Only few myopathies are clearly associated with MH. If a regional anaesthetic technique is not possible, total intravenous anaesthesia is considered the safest approach for most patients with myopathies to avoid anaesthesia-associated rhabdomyolysis. However, the use of propofol in patients with mitochondrial myopathies may be problematic, considering the risk for propofol-infusion syndrome. Succinylcholine is contra-indicated in all patients with myopathies. Following an individual risk/benefit evaluation, the use of volatile anaesthetics in several non-MH-linked myopathies (e.g. myotonic syndromes, mitochondrial myopathies) is considered to be well tolerated. Perioperative monitoring should specifically focus on the cardiopulmonary system, the level of muscular paralysis and core temperature. Given the high risk of respiratory compromise and other postoperative complications, patients need to be closely monitored postoperatively.

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Microvascular reactivity monitored with near-infrared spectroscopy is impaired after induction of anaesthesia in cardiac surgery patients: An observational study

imageBACKGROUND: Induction of anaesthesia causes significant macrohaemodynamic changes, but little is known about its effects on the microcirculation. However, alterations in microvascular perfusion are known to be associated with impaired tissue oxygenation and organ dysfunction. Microvascular reactivity can be assessed with vascular occlusion testing, which evaluates the response of tissue oxygen saturation to transient ischaemia and reperfusion. OBJECTIVE: The aim of the current study was to evaluate the effects of an opioid-based anaesthesia induction on microvascular reactivity. We hypothesised that despite minimal blood pressure changes, microvascular function would be impaired. DESIGN: Prospective, observational study. SETTING: Single-centre, tertiary university teaching hospital, Belgium. PATIENTS: Thirty-five adult patients scheduled for elective coronary artery bypass grafting surgery. INTERVENTION: Microvascular reactivity was assessed before and 30 min after anaesthesia induction by means of vascular occlusion testing and near-infrared spectroscopy. MAIN OUTCOME MEASURES: Tissue oxygen saturations, desaturation rate, recovery time (time from release of cuff to the maximum value) and rate of recovery were determined. RESULTS: Data are expressed as median (minimum to maximum). Tissue oxygen saturation was higher after induction of anaesthesia [70 (54 to 78) vs. 73 (55 to 94)%, P = 0.015]. Oxygen consumption decreased after induction, appreciable by the higher minimum tissue oxygen saturation [45 (29 to 69) vs. 53 (28 to 81)%, P 

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Acute and chronic neuropathic pain after surgery: Still a lot to learn

No abstract available

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Effect of intravenous dextrose administration on postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy: A randomised controlled trial

imageNo abstract available

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Early postoperative neuropathic pain assessed by the DN4 score predicts an increased risk of persistent postsurgical neuropathic pain

imageBACKGROUND: Acute neuropathic pain can occur in the postoperative period but any link with persistent post-surgical neuropathic pain remains unclear. OBJECTIVES: The objectives of this study were to prospectively describe the incidence of acute post-surgical neuropathic pain in a large population using the DN4 (clinician administered) questionnaire and to confirm the hypothetical link between acute and persistent neuropathic pain at 2 months after surgery in a large population using the DN2 (self administered) questionnaire. DESIGN: A multi-centre, prospective and observational trial. SETTING: Two consecutive days in 27 hospitals in France. PATIENTS: Six hundred and eight patients undergoing 13 different types of surgery. Fifteen patients were excluded as data were incomplete, and 229 (38.6%) and 260 (43.8%) were not contactable for assessment at 1 and 2 months after surgery, respectively. MAIN OUTCOME MEASURES: Pain was evaluated at least 2 h postoperatively on the same day (D0),on the second day (D2) and at 1 and 2 months after surgery (M1 and M2). Pain was assessed using a 10-point Numeric Rating Scale. If the Numeric Rating Scale score was greater than 0, neuropathic pain was assessed using a DN4 (clinician administered) questionnaire or using a DN2 (self-administered) questionnaire. Acute and persistent postsurgical neuropathic pain (PPSNP) were defined respectively by a DN4 score at least 4/10 on day 0 and/or day 2 and a DN2 score at least 3/7 at 2 months after surgery. RESULTS: Of the 593 patients included, 41.2% were in pain before surgery and 8.2% described neuropathic pain. Early after surgery, the majority of the 593 patients (72.2% on the day of surgery and 71.3% on day 2) experienced acute pain. It was neuropathic in nature in 5.6% of patients (95% CI, 3.6 to 8.3) on the day of surgery and 12.9% (95% CI, 9.7 to 16.7) on day 2. Two months after surgery, PPSNP was present in 33.3% of the 333 patients assessed. Multivariate analysis showed that a DN4 score at least 4/10 on the day of surgery or on day 2 was a significant risk factor for PPSNP [odds ratios 4.22 (95% CI, 2.19 to 8.12)]. CONCLUSION: Our results suggest that early acute postsurgical neuropathic pain significantly increases the risk of persistent post-surgical neuropathic pain. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NTC NCT02826317.

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Women awaken faster than men after electroencephalogram-monitored propofol sedation for colonoscopy: A prospective observational study

imageBACKGROUND: Sedation for colonoscopy using intravenous propofol has become standard in many Western countries. OBJECTIVE: Gender-specific differences have been shown for general anaesthesia in dentistry, but no such data existed for gastrointestinal endoscopy. DESIGN: A prospective observational study. SETTING: An academic teaching hospital of Hannover Medical School. PATIENTS: A total of 219 patients (108 women and 111 men) scheduled for colonoscopy. INTERVENTION: Propofol sedation using electroencephalogram monitoring during a constant level of sedation depth (D0 to D2) performed by trained nurses or physicians after a body-weight-adjusted loading dose. MAIN OUTCOME MEASURES: The primary end-point was the presence of gender-specific differences in awakening time (time from end of sedation to eye-opening and complete orientation); secondary outcome parameters analysed were total dose of propofol, sedation-associated complications (bradycardia, hypotension, hypoxaemia and apnoea), patient cooperation and patient satisfaction. Multivariate analysis was performed to correct confounding factors such as age and BMI. RESULTS: Women awakened significantly faster than men, with a time to eye-opening of 7.3 ± 3.7 versus 8.4 ± 3.4 min (P = 0.005) and time until complete orientation of 9.1 ± 3.9 versus 10.4 ± 13.7 min (P = 0.008). The propofol dosage was not significantly different, with some trend towards more propofol per kg body weight in women (3.98 ± 1.81 mg versus 3.72 ± 1.75 mg, P = 0.232). CONCLUSION: The effect of gender aspects should be considered when propofol is used as sedation for gastrointestinal endoscopy. That includes adequate dosing for women as well as caution regarding potential overdosing of male patients. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02687568).

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Intraoperative magnesium sulphate decreases agitation and pain in patients undergoing functional endoscopic surgery: A randomised double-blind study

imageBACKGROUND: Postoperative agitation is harmful for the patient as it may be associated with removal of catheters, nasal packs, oxygen masks and self-injury, and pose a danger to operating theatre staff. OBJECTIVE: The current study investigated the potential role of magnesium sulphate in treatment of postoperative agitation following functional endoscopic sinus surgery. DESIGN: A randomised, double-blinded, placebo-controlled trial. SETTING: ENT operating room, Menofia University Hospitals, Egypt. PATIENTS: A total of 312 adult patients (171 men and 141 women) were enrolled in the study. Eighteen patients (10 men and eight women) were excluded; data from 294 patients were analysed. Inclusion criteria were age between 20 and 60 years, American Society of Anesthesiologists' physical status 1 or 2 scheduled for functional endoscopic sinus surgery. Exclusion criteria were hypertension, cardiac ischaemia, cerebrovascular insufficiency, neuromuscular diseases, pregnancy, prolonged treatment with calcium-channel blockers, diabetic neuropathy or a known allergy to magnesium compounds. INTERVENTIONS: Patients were allocated randomly to either the magnesium group (a magnesium infusion of 30 mg kg−1 in the first hour followed by 9 mg kg−1 h−1 until the end of the surgical procedure) or the control group (0.9% saline at the same volume and rate). Hypotensive anaesthesia was induced by nitroglycerine 5 to 20 μg kg−1 min−1. In the postanaesthetic care unit (PACU), patients were assessed for agitation and pain using the Richmond agitation-sedation scale and numerical rating scale, respectively. PRIMARY OUTCOME: The incidence and severity of agitation measured 5 min after admission to the PACU. RESULTS: Magnesium reduced postoperative agitation at time 0 (P = 0.009) and 5, 10, 15 and 30 min after PACU admission (P 

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Prophylactic atropine administration attenuates the negative haemodynamic effects of induction of anaesthesia with propofol and high-dose remifentanil: A randomised controlled trial

imageBACKGROUND: Induction of anaesthesia with propofol and remifentanil often induces unwanted bradycardia and hypotension, raising concerns regarding tissue oxygenation. The electrophysiological cardiac effects of remifentanil can be reversed by atropine. OBJECTIVE: To investigate if prophylactic administration of atropine can attenuate the negative haemodynamic effects of propofol and a high dose of remifentanil during induction of anaesthesia. DESIGN: A double-blind, randomised controlled trial. SETTING: Single-centre, University Medical Center Groningen, The Netherlands. PATIENTS: Sixty euvolaemic patients scheduled for surgery under general anaesthesia. INTERVENTIONS: Anaesthesia was induced and maintained with a target-controlled infusion of propofol with a target effect-site concentration (Ce) of 2.5 μg ml−1, remifentanil (target-controlled infusion), (Ce 8 ng ml−1) and cis-atracurium. Methylatropine (500 μg) or 0.9% saline was administered at immediately before induction of anaesthesia. MAIN OUTCOME MEASURES: The changes (Δ) in mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), rate pressure product, cerebral tissue oxygenation and peripheral tissue oxygenation between induction of anaesthesia (T0) and 10 min later (T10). RESULTS: Atropine significantly attenuated the changes in the outcome measures between T0 and T10. Median (inter-quartile range) changes were MAP, Δ = −24 (−40 to −21) vs. Δ = −37 mmHg (−41 to −31) (P = 0.02); HR, Δ = 0 ± 13 vs. −19 ± 11 bpm (P 

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Effects of anaesthesia and analgesia on long-term outcome after total knee replacement: A prospective, observational, multicentre study

imageBACKGROUND: Perioperative regional anaesthesia may protect from persistent postsurgical pain (PPSP) and improve outcome after total knee arthroplasty (TKA). OBJECTIVES: Aim of this study was to evaluate the impact of regional anaesthesia on PPSP and long-term functional outcome after TKA. DESIGN: A web-based prospective observational registry. SETTING: Five Italian Private and University Hospitals from 2012 to 2015. PATIENTS: Undergoing primary unilateral TKA, aged more than 18 years, informed consent, American Society of Anesthesiologists (ASA) physical status classes 1 to 3, no previous knee surgery. INTERVENTION(S): Personal data (age, sex, BMI and ASA class), preoperative pain assessed by numerical rating scale (NRS) score, and risk factors for PPSP were registered preoperatively. Data on anaesthetic and analgesic techniques were collected. Postoperative pain (NRS), analgesic consumption, major complications and patient satisfaction were registered up to the time of discharge. PPSP was assessed by a blinded investigator during a phone call after 1, 3 and 6 months, together with patient satisfaction, quality of life (QOL) and walking ability. MAIN OUTCOME MEASURES: Experience of PPSP according to the type of peri-operative analgesia. RESULTS: Five hundred sixty-three patients completed the follow-up. At 6 months, 21.6% of patients experienced PPSP, whereas autonomy was improved only in 56.3%; QOL was worsened or unchanged in 30.7% of patients and improved in 69.3%. Patients receiving continuous regional anaesthesia (epidural or peripheral nerve block) showed a lower NRS through the whole peri-operative period up to 1 month compared with both single shot peripheral nerve block and those who did not receive any type of regional anaesthesia. No difference was found between these latter two groups. Differences in PPSP at 3 or 6 months were not significantly affected by the type of anaesthesia or postoperative analgesia. A higher NRS score at 1 month, younger age, history of anxiety or depression, pro-inflammatory status, higher BMI and a lower ASA physical status were associated with a higher incidence of PPSP and worsened QOL at 6 months. CONCLUSION: Continuous regional anaesthesia provides analgesic benefit for up to 1 month after surgery, but did not influence PPSP at 6 months. Better pain control at 1 month was associated with reduced PPSP. Patients with higher expectations from surgery, enhanced basal inflammation and a pessimistic outlook are more prone to develop PPSP. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02147730

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Transcutaneous monitoring of partial pressure of carbon dioxide during bronchoscopic procedures performed with jet ventilation: Role of the perfusion index

imageNo abstract available

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The use of dipyrone in the ICU is associated with acute kidney injury: A retrospective cohort analysis

imageBACKGROUND: Use of dipyrone (metamizole) in perioperative and ICU pain therapy remains controversial due to a lack of solid evidence weighing dipyrone benefit against its potential life-threatening complications. Although dipyrone has known analgesic and antipyretic properties, its mechanisms of actions are incompletely understood. Although dipyrone effects on renal vasodilator prostaglandin synthesis are documented, little is known about its potential renal side effects, especially in the critical care environment. OBJECTIVE: Investigation of the perioperative nephrotoxic potential of dipyrone in patients prone to acute kidney injury (AKI). DESIGN: Retrospective cohort study. SETTING: Single centre study in a tertiary referral hospital from January 2013 until June 2013. PATIENTS: A total of 500 consecutive patients aged 18 years and older referred to the anaesthesia ICU. Patients were excluded if admitted from or discharged to other ICUs, if referred for post resuscitation care, or if repeatedly admitted to the ICU. MAIN OUTCOME MEASURES: Incidence of AKI, as defined by the Kidney Disease: Improving Global Outcomes Acute Kidney Injury Work Group criteria, and duration of vasopressor therapy. RESULTS: Use of dipyrone was associated with an increased incidence of AKI in a dose-dependent manner with a 1.6-fold increase in the incidence of AKI with each additional gram of intravenous dipyrone per day. Dipyrone dose of more than 2.5 g day−1 was the best risk predictive cut-off for AKI. Patients receiving dipyrone on the ICU presented with a prolonged duration of vasopressor therapy. CONCLUSION: Increasing dipyrone dosage is a potential independent risk factor for AKI in adult ICU patients and may prolong vasopressor therapy. Clinical evidence for a benefit of dipyrone therapy in the ICU is insufficient and needs further critical evaluation.

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Quality and Safety in Anesthesia and Perioperative Care

No abstract available

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Transcriptional factors Eaf1/2 inhibit endoderm and mesoderm formation via suppressing TGF-β signaling

Publication date: Available online 6 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Jing-Xia Liu, Qin-Han Xu, Sen Li, XueDong Yu, WenYe Liu, Gang Ouyang, Ting Zhang, Ling-Ling Chen
Eaf family genes act in multiple cellular responses such as tumor suppression and embryonic development. In our previous work, Eaf1/2 was found to modulate convergence and extension (C&E) movements and pattern the embryonic anterior-posterior axis during zebrafish embryogenesis. Here, we found that loss-of-function of eaf1/2 caused expanded mesoderm and endoderm in zebrafish embryos and led to the recovery of endoderm specification in TGF-β factor-mzoeptz257 mutants, while gain-of-function of eaf1/2 induced reduced mesoderm and endoderm. Analyses of gene expression profiles in Eaf deleted or over-expressed mammalian cells indicated that the roles of Eaf1 and Eaf2 in inhibiting TGF-β signals were conserved from fish to mammals. By taking advantages of TGF-β reporters, eaf1/2-fused engrailed proteins, and P53M214K mutant, we revealed that Eaf1 and Eaf2 might suppress TGF-β transduction by synergistically inhibiting none-P53 and P53-required TGF-β signaling. Furthermore, Eaf1/2 might co-localize and interact with TGF-β transcriptional factors in the transcriptional complex as repressors to target and suppress TGF-β signaling activity. Our study unveiled a previously unrecognized link of Eaf1/2 genes with TGF-β and P53 in vertebrates and demonstrated a conservation of TGF-β suppression activity for Eaf1/2 family genes from fish to mammals, which might shed some light on the molecular mechanistic basis of Eaf1 and Eaf2 in tumor suppression.



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Geographical variations in clinical presentation and outcomes of decompressive surgery in patients with symptomatic degenerative cervical myelopathy: analysis of a prospective, international multicenter cohort study of 757 patients

Degenerative cervical myelopathy (DCM) is a progressive degenerative spine disease and the most common cause of spinal cord impairment in adults worldwide. There is a paucity of studies reporting on regional variations in demographics, clinical presentation, disease causation and surgical effectiveness.

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Endoscopic ultrasonography in chronic asymptomatic pancreatic hyperenzymemia: why not?



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Clinical profile of cannabis-associated acute pancreatitis



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Endoscopic ultrasonography in chronic asymptomatic pancreatic hyperenzymemia: why not?



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Clinical profile of cannabis-associated acute pancreatitis



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European Society of Anaesthesiology and European Board of Anaesthesiology guidelines for procedural sedation and analgesia in adults.

: Procedural sedation and analgesia (PSA) has become a widespread practice given the increasing demand to relieve anxiety, discomfort and pain during invasive diagnostic and therapeutic procedures. The role of, and credentialing required by, anaesthesiologists and practitioners performing PSA has been debated for years in different guidelines. For this reason, the European Society of Anaesthesiology (ESA) and the European Board of Anaesthesiology have created a taskforce of experts that has been assigned to create an evidence-based guideline and, whenever the evidence was weak, a consensus amongst experts on: the evaluation of adult patients undergoing PSA, the role and competences required for the clinicians to safely perform PSA, the commonly used drugs for PSA, the adverse events that PSA can lead to, the minimum monitoring requirements and post-procedure discharge criteria. A search of the literature from 2003 to 2016 was performed by a professional librarian and the retrieved articles were analysed to allow a critical appraisal according to the Grading of Recommendations Assessment, Development and Evaluation method. The Taskforce selected 2248 articles. Where there was insufficiently clear and concordant evidence on a topic, the Rand Appropriateness Method with three rounds of Delphi voting was used to obtain the highest level of consensus among the taskforce experts. These guidelines contain recommendations on PSA in the adult population. It does not address sedation performed in the ICU or in children and it does not aim to provide a legal statement on how PSA should be performed and by whom. The National Societies of Anaesthesiology and Ministries of Health should use this evidence-based document to help decision-making on how PSA should be performed in their countries. The final draft of the document was available to ESA members via the website for 4 weeks with the facility for them to upload their comments. Comments and suggestions of individual members and national Societies were considered and the guidelines were amended accordingly. The ESA guidelines Committee and ESA board finally approved and ratified it before publication. (C) 2017 European Society of Anaesthesiology

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Recovery From Ropivacaine-Induced or Levobupivacaine-Induced Cardiac Arrest in Rats: Comparison of Lipid Emulsion Effects.

BACKGROUND: Lipid emulsion treatment appears to have application in the treatment of local anesthetic-induced cardiac arrest. To examine whether the efficacy of lipid resuscitation in the treatment of local anesthetic-induced cardiac arrest is affected by lipophilicity, the effects of lipid infusions were compared between levobupivacaine-induced (high lipophilicity) and ropivacaine-induced (lower lipophilicity) rat cardiac arrest model. METHODS: A total of 28 female Sprague-Dawley rats were anesthetized using sevoflurane, which subsequently underwent tracheostomy, followed by femoral artery and vein cannulation. Two hours after the discontinuation of sevoflurane, either levobupivacaine 0.2% (n = 14) or ropivacaine 0.2% (n = 14) was administered at a rate of 2 mg/kg/min to the awake rats. When the pulse pressure decreased to 0, the infusion of local anesthetic was discontinued, and treatment with chest compressions and ventilation with 100% oxygen were immediately initiated. The total doses of local anesthetics needed to trigger the first seizure and pulse pressure of 0 mm Hg were calculated. The 2 groups were each subdivided into a lipid emulsion group (n = 7) and a control group (n = 7). In the lipid emulsion group, 20% lipid emulsion was administered intravenously (5 mL/kg bolus plus continuous infusion of 0.5 mL/kg/min), while in the control group, the same volume of normal saline was administered. Chest compressions were discontinued when the rate-pressure product had increased by more than 20% of baseline. RESULTS: The cumulative doses of levobupivacaine and ropivacaine that produced seizures and 0 pulse pressure showed no significant difference. Mean arterial blood pressure (MAP) values were higher in the levobupivacaine group than in the ropivacaine group after resuscitation was initiated (P 20% baseline), while only 2 of 7 rats in the control group achieved spontaneous circulation at 10 minutes. In ropivacaine-induced cardiac arrest, there were no significant differences in heart rate and MAP between the lipid and control groups from the start of resuscitation to 10 minutes; spontaneous circulation returned in 6 of 7 lipid group rats, but in only 2 of 7 control group rats at 10 minutes. CONCLUSIONS: Lipid emulsion treatment was more effective for levobupivacaine-induced cardiac arrest than for ropivacaine-induced cardiac arrest. Although lipid therapy is also effective for ropivacaine-induced cardiac arrest, it takes more time than in levobupivacaine-induced cardiac arrest. This suggests that the lipophilicity of local anesthetics influences the efficacy of lipid infusion when treating cardiac arrest caused by these drugs. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. (C) 2017 International Anesthesia Research Society

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MIT-Skywalker: considerations on the Design of a Body Weight Support System

To provide body weight support during walking and balance training, one can employ two distinct embodiments: support through a harness hanging from an overhead system or support through a saddle/seat type. Thi...

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Ascension Wisconsin - EMS Carrers! - Ascension Health Care

Ascension Wisconsin offers EMS careers in both Prehospital/911 and Medical Transportation, see our current openings below. Spirit Medical Transportation 210433 – EMT – Casual – Woodruff, WI 165386 – Paramedic – FT – Rhinelander, WI 165457 – Paramedic – FT – Woodruff, WI 215560 – Paramedic – PT – Weston/Wausau, WI 215560 – ...

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Comprehensive assessment of cytochromes P450 and transporter genetics with endoxifen concentration during tamoxifen treatment.

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Objectives: Tamoxifen bioactivation to endoxifen is mediated primarily by CYP2D6; however, considerable variability remains unexplained. Our aim was to perform a comprehensive assessment of the effect of genetic variation in tamoxifen-relevant enzymes and transporters on steady-state endoxifen concentrations. Patients and methods: Comprehensive genotyping of CYP enzymes and transporters was performed using the iPLEX ADME PGx Pro Panel in 302 tamoxifen-treated breast cancer patients. Predicted activity phenotype for 19 enzymes and transporters were analyzed for univariate association with endoxifen concentration, and then adjusted for CYP2D6 and clinical covariates. Results: In univariate analysis, higher activity of CYP2C8 (regression [beta]=0.22, P=0.020) and CYP2C9 ([beta]=0.20, P=0.04), lower body weight ([beta]=-0.014, P

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Preparation and Evaluation of 177Lu-Labeled Gemcitabine: An Effort Toward Developing Radiolabeled Chemotherapeutics for Targeted Therapy Applications

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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Sex differences in the role of phospholipase A2-dependent arachidonic acid pathway in the perivascular adipose tissue function in pigs

Abstract

Previous studies have demonstrated that perivascular adipose tissue (PVAT) causes vasoconstriction. In this present study, we determined the role of cyclooxygenase-derived prostanoids in this contractile response and determined whether there were any sex differences in the regulation of vascular tone by PVAT. Contractions in isolated segments of coronary arteries were determined using isolated tissue baths and isometric tension recording. Segments were initially cleaned of PVAT, which was then re-added to the tissue bath and changes in tone measured over 1 h. Levels of PGF and thromboxane B2 (TXB2) were quantified by ELISA and PGF (FP) and thromboxane A2 (TP) receptor expression determined by Western blotting. In arteries from both male and female pigs, re-addition of PVAT caused a contraction, which was partially inhibited by the cyclooxygenase inhibitors indomethacin and flurbiprofen. The FP receptor antagonist AL8810 attenuated the PVAT-induced contraction in arteries from males, whereas the TP receptor antagonist GR32191B inhibited the PVAT-induced contraction in arteries from females. Although there was no difference in PGF levels in PVAT between females and males, PGF produced a larger contraction in arteries from males, correlating with a higher FP receptor expression. In contrast, release of TXB2 from PVAT from females was greater than from males, but there was no difference in the contraction by the TXA2 agonist U46619, or TP receptor expression in arteries from different sexes. These findings demonstrate clear sex differences in PVAT function in which PGF and TXA2 antagonists can inhibit the PVAT-induced vasoconstriction in male and female PCAs, respectively.

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Preparation and Evaluation of 177Lu-Labeled Gemcitabine: An Effort Toward Developing Radiolabeled Chemotherapeutics for Targeted Therapy Applications

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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Personality correlates of individual differences in the recruitment of cognitive mechanisms when rewards are at stake

Abstract

Individuals differ greatly in their sensitivity to rewards and punishments. In the extreme, these differences are implicated in a range of psychiatric disorders from addiction to depression. However, it is unclear how these differences influence the recruitment of attention, working memory, and long-term memory when responding to potential rewards. Here, we used a rewarded memory-guided visual search task and ERPs to examine the influence of individual differences in self-reported reward/punishment sensitivity, as measured by the Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) scales, on the recruitment of cognitive mechanisms in conditions of potential reward. Select subscales of the BAS, including the fun seeking and reward responsiveness scales, showed unique relationships with context updating to reward cues and working memory maintenance of potentially rewarded stimuli. In contrast, BIS scores showed unique relationships with deployment of attention at different points in the task. These results suggest that sensitivity to rewards (i.e., BAS) and to punishment (i.e., BIS) may play an important role in the recruitment of specific and distinct cognitive mechanisms in conditions of potential rewards.



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Chalk and cheese 2.0

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Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): Bernard Wood




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A chronological framework connecting the early Upper Palaeolithic across the Central Asian piedmont

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Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): Kathryn E. Fitzsimmons, Radu Iovita, Tobias Sprafke, Michelle Glantz, Sahra Talamo, Katharine Horton, Tyler Beeton, Saya Alipova, Galymzhan Bekseitov, Yerbolat Ospanov, Jean-Marc Deom, Renato Sala, Zhaken Taimagambetov
Central Asia has delivered significant paleoanthropological discoveries in the past few years. New genetic data indicate that at least two archaic human species met and interbred with anatomically modern humans as they arrived into northern Central Asia. However, data are limited: known archaeological sites with lithic assemblages generally lack human fossils, and consequently identifying the archaeological signatures of different human groups, and the timing of their occupation, remains elusive. Reliable chronologic data from sites in the region, crucial to our understanding of the timing and duration of interactions between different human species, are rare. Here we present chronologies for two open air Middle to Upper Palaeolithic (UP) sequences from the Tien Shan piedmont in southeast Kazakhstan, Maibulak and Valikhanova, which bridge southern and northern Central Asia. The chronologies, based on both quartz optically stimulated luminescence (OSL) and polymineral post-infrared infrared luminescence (pIR-IRSL) protocols, demonstrate that technological developments at the two sites differ substantially over the ∼47–19 ka time span. Some of the innovations typically associated with the earliest UP in the Altai or other parts of northeast Asia are also present in the Tien Shan piedmont. We caution against making assumptions about the directionality of spread of these technologies until a larger, better defined database of transitional sites in the region is available. Connections between the timing of occupation of regions, living area setting and paleoenvironmental conditions, while providing hypotheses worth exploring, remain inconclusive. We cautiously suggest a trend towards increasing occupation of open air sites across the Central Asian piedmont after ∼40 ka, corresponding to more humid climatic conditions which nevertheless included pulses of dust deposition. Human occupation persisted into the Last Glacial Maximum, despite cooler, and possibly drier, conditions. Our results thus provide additional data to substantiate arguments for occupation of Central Asia.



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The 8 things I'd tell my 21-year-old EMS self

I struggled through far too much of an overall satisfying career in EMS. Looking back, it is easy to see where I went wrong. I wasted much of my youth being young and idealistic. I still have those ideals; somehow they remained intact, but experience changed my expectations. The job has remained the same, I'm a little different. When you change the way you look at things, the things you look at ...

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How to support Medicare add-on and super-rural bonus payments

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PART TIME EMT in SAN ANTONIO TX - U.S. Safety Services

U.S. Safety Services is a San Antonio based company that is hiring event medics to work every Wednesdays from 4:30-7:30 along with our many event medic opportunity's Applicants need to be at a minimum, a Texas Certified EMT with a valid CPR/AED card, valid driver's license & social security card. Applicants must have a high school diploma or GED. Applicant will need to be flexible to ...

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Complete Sequence of pCY-CTX, a Plasmid Carrying a Phage-Like Region and an ISEcp1-Mediated Tn2 Element from Enterobacter cloacae

Microbial Drug Resistance , Vol. 0, No. 0.


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How to support Medicare add-on and super-rural bonus payments

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High but not moderate-intensity endurance training increases pain tolerance: a randomised trial

Abstract

Purpose

To examine the effect of high-intensity interval training (HIIT) compared to volume-matched moderate-intensity continuous training (CONT) on muscle pain tolerance and high-intensity exercise tolerance.

Methods

Twenty healthy adults were randomly assigned (1:1) to either 6 weeks of HIIT [6–8 × 5 min at halfway between lactate threshold and maximal oxygen uptake (50%Δ)] or volume-matched CONT (~60–80 min at 90% lactate threshold) on a cycle ergometer. A tourniquet test to examine muscle pain tolerance and two time to exhaustion (TTE) trials at 50%Δ to examine exercise tolerance were completed pre- and post-training; the post-training TTE trials were completed at the pre-training 50%Δ (same absolute-intensity) and the post-training 50%Δ (same relative-intensity).

Results

HIIT and CONT resulted in similar improvements in markers of aerobic fitness (all P ≥ 0.081). HIIT increased TTE at the same absolute- and relative-intensity as pre-training (148 and 43%, respectively) to a greater extent than CONT (38 and −4%, respectively) (both P ≤ 0.019). HIIT increased pain tolerance (41%, P < 0.001), whereas CONT had no effect (−3%, P = 0.720). Changes in pain tolerance demonstrated positive relationships with changes in TTE at the same absolute- (r = 0.44, P = 0.027) and relative-intensity (r = 0.51, P = 0.011) as pre-training.

Conclusion

The repeated exposure to a high-intensity training stimulus increases muscle pain tolerance, which is independent of the improvements in aerobic fitness induced by endurance training, and may contribute to the increase in high-intensity exercise tolerance following HIIT.



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Preoperative Pulmonary Function Tests Predict Aspiration Pneumonia After Gastric Endoscopic Submucosal Dissection

Abstract

Background

ESD allows higher rates of en-bloc and R0 resections, but has occasionally complications such as aspiration pneumonia. Factors associated with aspiration pneumonia are not completely understood.

Aims

To analyze the relationship between aspiration pneumonia and preoperative factors including pulmonary function tests.

Methods

A total of 978 patients with gastric tumors who had received pulmonary function tests were treated by ESD between June 2006 and May 2014. Pulmonary function tests were assessed using a spirometer. The patients were categorized into four groups according to the predicted vital capacity (%VC) and forced expiratory volume in 1 s as a percentage of forced vital capacity (FEV1.0%): normal; restrictive pulmonary dysfunction; obstructive; and mixed. The factors associated with aspiration pneumonia were retrospectively analyzed.

Results

Among the 268 cases with abnormal pulmonary function, 10 cases (3.7%) developed aspiration pneumonia. On the other hand, 7 cases (1.0%) with normal pulmonary function developed pneumonia. There was a significant correlation between pulmonary function and aspiration pneumonia (p = 0.010). When the pulmonary function cases were stratified into subgroups, 2.5% of cases with obstructive pulmonary dysfunction developed pneumonia, 5.5% with restrictive and 5.3% with mixed. By logistic regression analysis, pulmonary function, the presence of cerebral vascular disease, and procedure time were identified as significant independent risk factors associated with aspiration pneumonia. The odds ratios for pulmonary function, cerebral vascular disease, and procedure time were 3.6, 5.1, and 5.2, respectively.

Conclusions

Preoperative pulmonary function tests may be useful markers to evaluate the risk for aspiration pneumonia after gastric ESD.



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How to support Medicare add-on and super-rural bonus payments

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Watch this AAA Medicare PSA.

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How to support Medicare add-on and super-rural bonus payments

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Watch this AAA Medicare PSA.

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Analgesia nociception index for the assessment of pain in critically ill patients: a diagnostic accuracy study

Abstract
Background. Behavioural pain tools are used in Intensive Care Unit (ICU) patients unable to self-report their pain-intensity but need sustained efforts to educate and train the ICU team because of the subjective nature of these clinical tools. This study measured the validity and performance of an electrophysiological monitoring tool based on the spectral analysis of heart rate variability, the Analgesia Nociception Index (ANI) which varies from 0 (minimal parasympathetic tone, maximal stress-response and pain) to 100 (maximal parasympathetic tone, minimal stress-response and pain).Methods. Mean-ANI (ANIm) and Instant-ANI (ANIi) were continuously recorded then compared with the Behavioral Pain Scale (BPS) before, during and after routine care procedures in critically-ill non-comatose patients.Results. 969 assessments were performed in 110 patients. ANIi was the most discriminative pain tool. It was significantly correlated with BPS (r=–0.30; 95%CI –0.37 to –0.25; P<0.001). For an ANIi threshold of 42.5, the sensitivity, specificity, positive and negative predictive values were respectively 61.4%, 77.4%, 37.0%, and 90.4%. Compared with the BPS, ANIi had no significantly different ability to change during turning and tracheal-suctioning but changed significantly more during dressing change. ANIi increased independently with age, obesity and severity of illness, and controlled mechanical-ventilation, vasopressors use and analgesia. ANIi decreased independently when vigilance status and respiratory rate increased. ANIm demonstrated poor psychometric properties to detect pain.Conclusions. Despite low sensitivity/specificity, ANIi≥43 had a Negative-Predictive-Value of 90%. Hence ANIi may be of highest benefit for excluding significant pain. A randomized controlled trial should compare sedation-analgesia protocols based on ANIi to presently recommended behavioural-pain-tools.

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Benefit and harm of pregabalin in acute pain treatment: a systematic review with meta-analyses and trial sequential analyses

Abstract
Pregabalin has demonstrated anti-hyperalgesic properties and was introduced into acute pain treatment in 2001. Our aim was to evaluate the beneficial and harmful effects of pregabalin in postoperative pain management. We included randomized clinical trials investigating perioperative pregabalin treatment in adult surgical patients. The review followed Cochrane methodology, including Grading of Recommendations Assessment, Development, and Evaluation (GRADE), and used trial sequential analyses (TSAs). The primary outcomes were 24 h morphine i.v. consumption and the incidence of serious adverse events (SAEs) defined by International Conference of Harmonisation Good Clinical Practice guidelines. Conclusions were based primarily on trials with low risk of bias. Ninety-seven randomized clinical trials with 7201 patients were included. The 24 h morphine i.v. consumption was reported in 11 trials with overall low risk of bias, finding a reduction of 5.8 mg (3.2, 8.5; TSA adjusted confidence interval: 3.2, 8.5). Incidence of SAEs was reported in 21 trials, with 55 SAEs reported in 12 of these trials, and 22 SAEs reported in 10 trials with overall low risk of bias. In trials with overall low risk of bias, Peto's odds ratio was 2.9 (1.2, 6.8; TSA adjusted confidence interval: 0.1, 97.1). Based on trials with low risk of bias, pregabalin may have a minimal opioid-sparing effect, but the risk of SAEs seems increased. However, the GRADE-rated evaluations showed only moderate to very low quality of evidence. Consequently, a routine use of pregabalin for postoperative pain treatment cannot be recommended.

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Association between intraoperative non-depolarising neuromuscular blocking agent dose and 30-day readmission after abdominal surgery

Abstract
Background. We hypothesised that intraoperative non-depolarising neuromuscular blocking agent (NMBA) dose is associated with 30-day hospital readmission.Methods. Data from 13,122 adult patients who underwent abdominal surgery under general anaesthesia at a tertiary care hospital were analysed by multivariable regression, to examine the effects of intraoperatively administered NMBA dose on 30-day readmission (primary endpoint), hospital length of stay, and hospital costs.Results. Clinicians used cisatracurium (mean dose [SD] 0.19 mg kg−1 [0.12]), rocuronium (0.83 mg kg−1 [0.53]) and vecuronium (0.14 mg kg−1 [0.07]). Intraoperative administration of NMBAs was dose-dependently associated with higher risk of 30-day hospital readmission (adjusted odds ratio 1.89 [95% Confidence Interval (CI) 1.26–2.84] for 5th quintile vs 1st quintile; P for trend: P<0.001), prolonged hospital length of stay (adjusted incidence rate ratio [aIRR] 1.20 [95% CI 1.11–1.29]; P for trend: P<0.001) and increased hospital costs (aIRR 1.18 [95% CI 1.13-1.24]; P for trend: P<0.001). Admission type (same-day vs inpatient surgery) significantly modified the risk (interaction term: aOR 1.31 [95% CI 1.05–1.63], P=0.02), and the adjusted odds of readmission in patients undergoing ambulatory surgical procedures who received high-dose NMBAs vs low-dose NMBAs amounted to 2.61 [95% CI 1.11–6.17], P for trend: P<0.001. Total intraoperative neostigmine dose increased the risk of 30-day readmission (aOR 1.04 [1.0–1.08], P=0.048).Conclusions. In a retrospective analysis, high doses of NMBAs given during abdominal surgery was associated with an increased risk of 30-day readmission, particularly in patients undergoing ambulatory surgery.

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Comparison of ICD-9 Codes for Depression and Alcohol Misuse to Survey Instruments Suggests These Codes Should Be Used with Caution

Abstract

Background

Research suggests depression and alcohol misuse are highly prevalent among chronic hepatitis C (CHC) patients, which is of clinical concern.

Aims

To compare ICD-9 codes for depression and alcohol misuse to validated survey instruments.

Methods

Among CHC patients, we assessed how well electronic ICD-9 codes for depression and alcohol misuse predicted these disorders using validated instruments.

Results

Of 4874 patients surveyed, 56% were male and 52% had a history of injection drug use. Based on the PHQ-8, the prevalence of depression was 30% compared to 14% based on ICD-9 codes within 12 months of survey, 37% from ICD-9 codes any time before or within 12 months after survey, and 48% from ICD-9 codes any time before or within 24 months after survey. ICD-9 codes predicting PHQ-8 depression had a sensitivity ranging from 59 to 88% and a specificity ranging from 33 to 65%. Based on the AUDIT-C, the prevalence of alcohol misuse was 21% compared to 3–23% using ICD-9 codes. The sensitivity of ICD-9 codes to predict AUDIT-C score ranged from 9 to 35% and specificity from 80 to 98%. Overall 39% of patients reported ever binge drinking, with a sensitivity of ICD-9 to predict binge drinking ranging from 7 to 33% and a specificity from 84 to 98%. More than half of patients had either an ICD-9 code for depression, a survey score indicating depression, or both (59%); more than one-third had the same patterns for alcohol misuse (36%).

Conclusions

ICD-9 codes were limited in predicting current depression and alcohol misuse, suggesting that caution should be exercised when using ICD-9 codes to assess depression or alcohol misuse among CHC patients.



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Erratum to: Non-coding RNA: It’s Not Junk



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Regeneration of sciatic nerve crush injury by a hydroxyapatite nanoparticle-containing collagen type I hydrogel

Abstract

The current study aimed to enhance the efficacy of peripheral nerve regeneration using a hydroxyapatite nanoparticle-containing collagen type I hydrogel. A solution of type I collagen, extracted from the rat tails, was incorporated with hydroxyapatite nanoparticles (with the average diameter of ~212 nm) and crosslinked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) to prepare the hydrogel. The Schwann cell cultivation on the prepared hydrogel demonstrated a significantly higher cell proliferation than the tissue culture plate, as positive control, after 48 h (n = 3, P < 0.005) and 72 h (n = 3, P < 0.01). For in vivo evaluation, the prepared hydrogel was administrated on the sciatic nerve crush injury in Wistar rats. Four groups were studied: negative control (with injury but without interventions), positive control (without injury), collagen hydrogel and hydroxyapatite nanoparticle-containing collagen hydrogel. After 12 weeks, the administration of hydroxyapatite nanoparticle-containing collagen significantly (n = 4, P < 0.005) enhanced the functional behavior of the rats compared with the collagen hydrogel and negative control groups as evidenced by the sciatic functional index, hot plate latency and compound muscle action potential amplitude measurements. The overall results demonstrated the applicability of the produced hydrogel for the regeneration of peripheral nerve injuries.



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Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO2 levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 x 30 s episodes of 3% CO2 and 3.0 ± 0.2% O2) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO2, O2 saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea.

NEW & NOTEWORTHY Both arousal state and concomitant CO2 levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity.



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Pretreatment with indomethacin results in increased heat stroke severity during recovery in a rodent model of heat stroke

It has been suggested that medications can increase heat stroke (HS) susceptibility/severity. We investigated whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) increases HS severity in a rodent model. Core temperature (Tc) of male, C57BL/6J mice (n = 45) was monitored continuously, and mice were given a dose of INDO [low dose (LO) 1 mg/kg or high dose (HI) 5 mg/kg in flavored treat] or vehicle (flavored treat) before heating. HS animals were heated to 42.4°C and euthanized at three time points for histological, molecular, and metabolic analysis: onset of HS [maximal core temperature (Tc,Max)], 3 h of recovery [minimal core temperature or hypothermia depth (HYPO)], and 24 h of recovery (24 h). Nonheated (control) animals underwent identical treatment in the absence of heat. INDO (LO or HI) had no effect on physiological indicators of performance (e.g., time to Tc,Max, thermal area, or cooling time) during heating or recovery. HI INDO resulted in 45% mortality rate by 24 h (HI INDO + HS group). The gut showed dramatic increases in gross morphological hemorrhage in HI INDO + HS in both survivors and nonsurvivors. HI INDO + HS survivors had significantly lower red blood cell counts and hematocrit suggesting significant hemorrhage. In the liver, HS induced cell death at HYPO and increased inflammation at Tc,Max, HYPO, and 24 h; however, there was additional effect with INDO + HS group. Furthermore, the metabolic profile of the liver was disturbed by heat, but there was no additive effect of INDO + HS. This suggests that there is an increase in morbidity risk with INDO + HS, likely resulting from significant gut injury.

NEW & NOTEWORTHY This paper suggests that in a translational mouse model, NSAIDs may be counterindicated in situations that put an individual at risk of heat injury. We show here that a small, single dose of the NSAID indomethacin before heat stroke has a dramatic and highly damaging effect on the gut, which ultimately leads to increased systemic morbidity.



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