During migraine attacks, alterations in sensation accompanying headache may manifest as allodynia and enhanced sensitivity to light, sound, and odors. Our objective was to identify physiological ...changes in cortical regions in migraine patients using painful heat and functional magnetic resonance imaging (fMRI) and the structural basis for such changes using diffusion tensor imaging (DTI). In 11 interictal patients, painful heat threshold + 1°C was applied unilaterally to the forehead during fMRI scanning. Significantly greater activation was identified in the medial temporal lobe in patients relative to healthy subjects, specifically in the anterior temporal pole (TP). In patients, TP showed significantly increased functional connectivity in several brain regions relative to controls, suggesting that TP hyperexcitability may contribute to functional abnormalities in migraine. In 9 healthy subjects, DTI identified white matter connectivity between TP and pulvinar nucleus, which has been related to migraine. In 8 patients, fMRI activation in TP with painful heat was exacerbated during migraine, suggesting that repeated migraines may sensitize TP. This article investigates a nonclassical role of TP in migraineurs. Observed temporal lobe abnormalities may provide a basis for many of the perceptual changes in migraineurs and may serve as a potential interictal biomarker for drug efficacy.
Inappropriate antibiotic use is implicated in antibiotic resistance and resultant morbidity and mortality. Overuse is particularly prevalent for outpatient respiratory infections, and perceived ...patient expectations likely contribute. Thus, various educational programs have been implemented to educate the public.
We systematically identified public-directed interventions to promote antibiotic awareness in the United States. PubMed, Google Scholar, Embase, CINAHL, and Scopus were queried for articles published from January 1996 through January 2016. Two investigators independently assessed titles and abstracts of retrieved articles for subsequent full-text review. References of selected articles and three review articles were likewise screened for inclusion. Identified educational interventions were coded for target audience, content, distribution site, communication method, and major outcomes.
Our search yielded 1,106 articles; 34 met inclusion criteria. Due to overlap in interventions studied, 29 distinct educational interventions were identified. Messages were primarily delivered in outpatient clinics (N = 24, 83%) and community sites (N = 12, 41%). The majority included clinician education. Antibiotic prescription rates were assessed for 22 interventions (76%). Patient knowledge, attitudes, and beliefs (KAB) were assessed for 10 interventions (34%). Similar rates of success between antibiotic prescription rates and patient KAB were reported (73 and 70%, respectively). Patient interventions that did not include clinician education were successful to increase KAB but were not shown to decrease antibiotic prescribing. Three interventions targeted reductions in Streptococcus pneumoniae resistance; none were successful.
Messaging programs varied in their designs, and many were multifaceted in their approach. These interventions can change patient perspectives regarding antibiotic use, though it is unclear if clinician education is also necessary to reduce antibiotic prescribing. Further investigations are needed to determine the relative influence of interventions focusing on patients and physicians and to determine whether these changes can influence rates of antibiotic resistance long-term.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the cyanylated cysteine vibrational probe group’s ability to report on binding-induced changes along a protein–protein interface, the probe group was incorporated at several sites in a ...peptide of the calmodulin (CaM)-binding domain of skeletal muscle myosin light chain kinase. Isothermal titration calorimetry was used to determine the binding thermodynamics between calmodulin and each peptide. For all probe positions, the binding affinity was nearly identical to that of the unlabeled peptide. The CN stretching infrared band was collected for each peptide free in solution and bound to calmodulin. Binding-induced shifts in the IR spectral frequencies were correlated with estimated solvent accessibility based on molecular dynamics simulations. This work generally suggests (1) that site-specific incorporation of this vibrational probe group does not cause major perturbations to its local structural environment and (2) that this small probe group might be used quite broadly to map dynamic protein-binding interfaces. However, site-specific perturbations due to artificial labeling groups can be somewhat unpredictable and should be evaluated on a site-by-site basis through complementary measurements. A fully quantitative, simulation-based interpretation of the rich probe IR spectra is still needed but appears to be possible given recent advances in simulation techniques.
The aim of this study was to establish the maximal heart rate (HRmax)-age relation with minimal error rate.
The records of 28,137 participants (20,691 male and 7446 female, age range between 10 and ...80 yrs) who performed a maximal stress test were used in this study. Linear regressions between HRmax and age were used for the entire sample, for the male and female samples, separately, and for each section of the gender-by-age category. The equations were then contrasted to a number of equations reported in the literature. The best fitted equations were then tested on a new sample of 2449 subjects (2091 males and 358 females) for validation purposes.
Mean HRmax values were found to decrease at a faster rate in women than in men with age increase. The linear regression functions within each age category were found to be less reliable than the equations derived for the entire sample and for the female and male samples, respectively. The new and updated HRmax prediction equations are as follows: HRmax=208.609-0.716age and 209.273-0.804age for males and females, respectively, and 208.852-0.741age for the entire sample. Those equations along with the other four best equations for predicting HRmax were found to be correlated with the observed HRmax values (validation sample): 0.64 and 0.664 for males and females, respectively.
Our equations were derived from a large data set and were found to be highly sensitive for both genders. Therefore, we propose that these new formulas, with their improved accuracy, be used in healthy active and clinical populations.
Recent animal studies on the mechanism of migraine show that intracranial pain is accompanied by increased periorbital skin sensitivity. These findings suggest that the pathophysiology of migraine ...involves not only irritation of meningeal perivascular pain fibers but also a transient increase in the responsiveness (ie, sensitization) of central pain neurons that process information arising from intracranial structures and skin. The purpose of this study was to determine whether the increased skin sensitivity observed in animal also develops in humans during migraine attacks. Repeated measurements of mechanical and thermal pain thresholds of periorbital and forearm skin areas in the absence of, and during, migraine attacks enabled us to determine the occurrence of cutaneous allodynia during migraine. Cutaneous allodynia is pain resulting from a nonnoxious stimulus to normal skin. In 79% of the patients, migraine was associated with cutaneous allodynia as defined, and in 21% of the patients it was not. The cutaneous allodynia occurred either solely within the referred pain area on the ipsilateral head, or within and outside the ipsilateral head. Cutaneous allodynia in certain well‐defined regions of the skin during migraine is an as yet unreported neurological finding that points to hyperexcitability of a specific central pain pathway that subserves intracranial sensation. Ann Neurol 2000;47:614–624
Mechanosensitivity of Human Oligodendrocytes Espinosa-Hoyos, Daniela; Burstein, Suzanne R.; Cha, Jaaram ...
Frontiers in cellular neuroscience,
07/2020, Letnik:
14
Journal Article
Recenzirano
Odprti dostop
Oligodendrocytes produce and repair myelin, which is critical for the integrity and function of the central nervous system. Oligodendrocyte and oligodendrocyte progenitor cell biology is modulated in ...vitro by mechanical cues within the magnitudes observed in vivo. In some cases, these cues are sufficient to accelerate or inhibit terminal differentiation of murine oligodendrocyte progenitors. However, our understanding of oligodendrocyte lineage mechanobiology has been restricted primarily to animal models to date, due to the inaccessibility and challenges of human oligodendrocyte cell culture. Here we probe the mechanosensitivity of human oligodendrocyte lineage cells derived from human induced pluripotent stem cells. We target phenotypically distinct stages of the human oligodendrocyte lineage and quantify the effect of substratum stiffness on cell migration and differentiation, within the range documented in vivo. We find that human oligodendrocyte lineage cells exhibit mechanosensitive migration and differentiation. Further, we identify two patterns of human donor line-dependent mechanosensitive differentiation. Our findings illustrate the variation among human oligodendrocyte responses, otherwise not captured by animal models, that are important for translational research. Moreover, these findings highlight the importance of studying glia under conditions that better approximate in vivo mechanical cues. Despite significant progress in human oligodendrocyte derivation methodology, the extended duration, low yield, and low selectivity of human induced pluripotent stem cell-derived oligodendrocyte protocols significantly limit the scale-up and implementation of these cells and protocols for in vivo and in vitro applications. We propose that mechanical modulation, in combination with traditional soluble and insoluble factors, provides a key avenue to address these challenges in cell production and in vitro analysis.
Scientific evidence supports the notion that migraine pathophysiology involves inherited alteration of brain excitability, intracranial arterial dilatation, recurrent activation, and sensitization of ...the trigeminovascular pathway, and consequential structural and functional changes in genetically susceptible individuals. Evidence of altered brain excitability emerged from clinical and preclinical investigation of sensory auras, ictal and interictal hypersensitivity to visual, auditory, and olfactory stimulation, and reduced activation of descending inhibitory pain pathways. Data supporting the activation and sensitization of the trigeminovascular system include the progressive development of cephalic and whole-body cutaneous allodynia during a migraine attack. In addition, structural and functional alterations include the presence of subcortical white mater lesions, thickening of cortical areas involved in processing sensory information, and cortical neuroplastic changes induced by cortical spreading depression. Here, we review recent anatomical data on the trigeminovascular pathway and its activation by cortical spreading depression, a novel understanding of the neural substrate of migraine-type photophobia, and modulation of the trigeminovascular pathway by the brainstem, hypothalamus and cortex.
Medication overuse could interfere with the activity of critical brain regions involved in the supraspinal control of pain signals at the trigeminal and spinal level, leading to a sensitisation ...phenomenon responsible for chronic pain. We hypothesised that medication-overuse headache (MOH) patients might display abnormal processing of pain stimuli at the spinal level and defective functioning of the diffuse noxious inhibitory controls. We tested 31 MOH patients before (bWT) and after (aWT) standard inpatient withdrawal treatment, 28 episodic migraine (EM) patients and 23 healthy control subjects. We measured the threshold, the area and the temporal summation threshold (TST) of the nociceptive withdrawal reflex before, during and after activation of the diffuse noxious inhibitory controls by means of the cold pressor test. A significantly lower TST was found in both the MOH (bWT and aWT) and the EM patients compared with the controls, and in the MOH patients bWT compared with both the MOH patients aWT and the EM patients. In the MOH bWT patients the cold pressor test induced a TST increase significantly lower than that found in the MOH aWT, EM and control groups. Abnormal spinal cord pain processing and a decrease of the antinociceptive activity of the supraspinal structures in MOH patients can be hypothesised. These abnormalities could, in part, be related to the medication overuse, given that the withdrawal treatment was related to an improvement in the neurophysiological findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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