2,075 research outputs found
Contact dermatitis presenting as non-healing wound: case report
Topical antiseptics are commonly used in the management of minor wounds, burns, and infected skin. These agents are widely used by health professionals and are often self-prescribed by patients as they are easily available over-the-counter. This case illustrates a 73 year old man who presented with a non-healing wound on his right forearm for 4 weeks. The wound started from an insect bite and progressively enlarged with increasing pruritus and burning sensation. Clinically an ill-defined ulcer with surrounding erythema and erosion was noted. There was a yellow crust overlying the center of the ulcer and the periphery was scaly. Further inquiry revealed history of self treatment with a yellow solution to clean his wound for 3 weeks. Patient was provisionally diagnosed to have allergic contact dermatitis secondary to acriflavine. Topical acriflavine was stopped and the ulcer resolved after treatment with non-occlusive saline dressing. Skin patch test which is the gold standard for detection and confirmation of contact dermatitis showed a positive reaction (2+) to acriflavine. Acriflavine is widely used as a topical antiseptic agent in this part of the world. Hence, primary care physicians managing a large variety of poorly healing wounds should consider the possibility of contact allergy in recalcitrant cases, not responding to conventional treatment. Patient education is an important aspect of management as this would help curb the incidence of future contact allergies
Adolescents and adults with Fontan circulation:insights from the PREpArE-Fontan registry
The Patient Registry for Adolescents and Adults with Stable Fontan Circulation aims to describe a contemporary cohort of Fontan patients who could be eligible for a clinical trial investigating macitentan, an endothelin receptor antagonist. This international, non-interventional, multicentre, cross-sectional, observational registry enrolled patients with “stable” Fontan circulation ≥10 years following extra-cardiac conduit or lateral tunnel procedure. Main exclusion criteria were NYHA functional class IV, reoperation of Fontan circulation, or signs of disease worsening. Patient characteristics at enrolment are described; available data were collected during a single registration visit. Of the 266 screened patients, 254 were included in this analysis. At enrolment, median (interquartile range) age was 24 (20;30) years, 37%/63% of patients were from the USA/Europe, 54% were male, 54%/47% had undergone extra-cardiac conduit/lateral tunnel procedures, and 95% were in NYHA functional class I or II. History of arrhythmia was more common in older patients and patients with lateral tunnel; overall prevalence was 19%. Most laboratory values were within the normal range but mean creatinine clearance was abnormally low (87.7 ml/min). Angiotensin-converting enzyme inhibitors were used by 48% of patients and their use was associated with creatinine clearance <90 ml/min (p = 0.007), as was Fontan completion at an older age (p = 0.007). 53.4% of patients had clinical characteristics that could potentially meet an endothelin receptor antagonist trial’s eligibility criteria. The PREpArE-Fontan registry describes a cohort of patients who could potentially participate in an endothelin receptor antagonist trial and identified early subtle signs of Fontan failure, even in “stable” patients
Dispersive charge density wave excitations and temperature dependent commensuration in Bi2Sr2CaCu2O8+{\delta}
Experimental evidence on high-Tc cuprates reveals ubiquitous charge density
wave (CDW) modulations, which coexist with superconductivity. Although the CDW
had been predicted by theory, important questions remain about the extent to
which the CDW influences lattice and charge degrees of freedom and its
characteristics as functions of doping and temperature. These questions are
intimately connected to the origin of the CDW and its relation to the
mysterious cuprate pseudogap. Here, we use ultrahigh resolution resonant
inelastic x-ray scattering (RIXS) to reveal new CDW character in underdoped
Bi2Sr2CaCu2O8+{\delta} (Bi2212). At low temperature, we observe dispersive
excitations from an incommensurate CDW that induces anomalously enhanced phonon
intensity, unseen using other techniques. Near the pseudogap temperature T*,
the CDW persists, but the associated excitations significantly weaken and the
CDW wavevector shifts, becoming nearly commensurate with a periodicity of four
lattice constants. The dispersive CDW excitations, phonon anomaly, and
temperature dependent commensuration provide a comprehensive momentum space
picture of complex CDW behavior and point to a closer relationship with the
pseudogap state
Influence of apical oxygen on the extent of in-plane exchange interaction in cuprate superconductors
In high Tc superconductors the magnetic and electronic properties are
determined by the probability that valence electrons virtually jump from site
to site in the CuO2 planes, a mechanism opposed by on-site Coulomb repulsion
and favored by hopping integrals. The spatial extent of the latter is related
to transport properties, including superconductivity, and to the dispersion
relation of spin excitations (magnons). Here, for three antiferromagnetic
parent compounds (single-layer Bi2Sr0.99La1.1CuO6+delta, double-layer
Nd1.2Ba1.8Cu3O6 and infinite-layer CaCuO2) differing by the number of apical
atoms, we compare the magnetic spectra measured by resonant inelastic x-ray
scattering over a significant portion of the reciprocal space and with
unprecedented accuracy. We observe that the absence of apical oxygens increases
the in-plane hopping range and, in CaCuO2, it leads to a genuine 3D
exchange-bond network. These results establish a corresponding relation between
the exchange interactions and the crystal structure, and provide fresh insight
into the materials dependence of the superconducting transition temperature.Comment: 9 pages, 4 figures, 1 Table, 42 reference
Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.
Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology
Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide
In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers
Microdevices for extensional rheometry of low viscosity elastic liquids : a review
Extensional flows and the underlying stability/instability mechanisms are of extreme relevance to the efficient operation of inkjet printing, coating processes and drug delivery systems, as well as for the generation of micro droplets. The development of an extensional rheometer to characterize the extensional properties of low viscosity fluids has therefore stimulated great interest of researchers, particularly in the last decade. Microfluidics has proven to be an extraordinary working platform and different configurations of potential extensional microrheometers have been proposed. In this review, we present an overview of several successful designs, together with a critical assessment of their capabilities and limitations
Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress
In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse
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Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions
A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions
Mesoscopic organization reveals the constraints governing C. elegans nervous system
One of the biggest challenges in biology is to understand how activity at the
cellular level of neurons, as a result of their mutual interactions, leads to
the observed behavior of an organism responding to a variety of environmental
stimuli. Investigating the intermediate or mesoscopic level of organization in
the nervous system is a vital step towards understanding how the integration of
micro-level dynamics results in macro-level functioning. In this paper, we have
considered the somatic nervous system of the nematode Caenorhabditis elegans,
for which the entire neuronal connectivity diagram is known. We focus on the
organization of the system into modules, i.e., neuronal groups having
relatively higher connection density compared to that of the overall network.
We show that this mesoscopic feature cannot be explained exclusively in terms
of considerations, such as optimizing for resource constraints (viz., total
wiring cost) and communication efficiency (i.e., network path length).
Comparison with other complex networks designed for efficient transport (of
signals or resources) implies that neuronal networks form a distinct class.
This suggests that the principal function of the network, viz., processing of
sensory information resulting in appropriate motor response, may be playing a
vital role in determining the connection topology. Using modular spectral
analysis, we make explicit the intimate relation between function and structure
in the nervous system. This is further brought out by identifying functionally
critical neurons purely on the basis of patterns of intra- and inter-modular
connections. Our study reveals how the design of the nervous system reflects
several constraints, including its key functional role as a processor of
information.Comment: Published version, Minor modifications, 16 pages, 9 figure
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