text
stringlengths 11
9.77k
| label
stringlengths 2
104
|
|---|---|
We developed a sensitive assay for the rapid determination of serum methylmalonic acid concentration using capillary gas chromatography-mass spectrometry (GC/MS) with selected ion monitoring and a simple solid-phase extraction. The assay was linear up to 10,000 nmol/L and had a detection limit < 50 nmol/L, average recovery of 98% and between-day coefficient of variation at concentrations of 570 and 2206 nmol/L of 7.7% and 5.4%, respectively (n = 25). Comparison with another validated GC/MS method using sera with a wide range of methylmalonic acid concentrations (94-2020 nmol/L) revealed a slope and intercept of 0.97 and 17 nmol/L, respectively (n = 38). Methylmalonic acid concentrations determined by this assay in a group of apparently healthy individuals ranged from 64-331 nmol/L (n = 81). We conclude that the method is ideally suited for the determination of methylmalonic acid at physiological concentrations in both clinical and research laboratories.
|
Methylmalonic Acid
|
The Na+/Cl-dependent neurotransmitter transporters, a family of proteins responsible for the reuptake of neurotransmitters and other small molecules from the synaptic cleft, have been the focus of intensive research in recent years. The biogenic amine transporters, a subset of this larger family, are especially intriguing as they are the targets for many psychoactive compounds, including cocaine and amphetamines, as well as many antidepressants. In the absence of a high-resolution structure for any transporter in this family, research into the structure-function relationships of these transporters has relied on analysis of the effects of site-directed mutagenesis as well as of chemical modification of reactive residues. The aim of this review is to establish a structural context for the experimental study of these transporters through various computational approaches and to highlight what is known about the conformational changes associated with function in these transporters. We also present a novel numbering scheme to assist in the comparison of aligned positions between sequences of the neurotransmitter transporter family, a comparison that will be of increasing importance as additional experimental data is amassed.
|
Biogenic Monoamines
|
One of the most important challenges facing researchers in the field of regenerative medicine is to develop methods to introduce vascular networks into bioengineered tissues. Although cell scaffolds that slowly release angiogenic factors can promote post-transplantation angiogenesis, they cannot be used to construct thick tissues because of the time required for sufficient vascular network formation. Recently, the co-culture of graft tissue with vascular cells before transplantation has attracted attention as a way of promoting capillary angiogenesis. Although the co-cultured vascular cells can directly contribute to blood vessel formation within the tissue, a key objective that needs to be met is the construction of a continuous circulatory structure. Previously described strategies to reconstruct blood vessels include the culture of endothelial cells in a scaffold that contains microchannels or within the original vascular framework after decellularization of an entire organ. The technique, as developed by authors, involves the progressive stacking of three-layered cell sheets onto a vascular bed to induce the formation of a capillary network within the cell sheets. This approach enables the construction of thick, functional tissue of high cell density that can be transplanted by anastomosing its artery and vein (provided by the vascular bed) with host blood vessels.
|
Capillaries
|
Alzheimer's disease (AD) is characterized by the release of amyloid beta peptides (Abeta) in the form of monomers/oligomers which may lead to oxidative stress, mitochondria dysfunction, synaptic loss, neuroinflammation and, in consequence, to overactivation of poly(ADP-ribose) polymerase-1 (PARP-1). However, Abeta peptides are also released in the brain ischemia, traumatic injury and in inflammatory response. PARP-1 is suggested to be a promising target in therapy of neurodegenerative disorders. We investigated the impact of PARP-1 inhibition on transcription of mitochondria-related genes in PC12 cells. Moreover, the effect of PARP-1 inhibitor (PJ34) on cells subjected to Abeta oligomers (AbetaO) - evoked stress was analyzed. Our data demonstrated that inhibition of PARP-1 in PC12 cells enhanced the transcription of genes for antioxidative enzymes (Sod1, Gpx1, Gpx4), activated genes regulating mitochondrial fission/fusion (Mfn1, Mfn2, Dnm1l, Opa1, Fis1), subunits of ETC complexes (mt-Nd1, Sdha, mt-Cytb) and modulated expression of several TFs, enhanced Foxo1 and decreased Nrf1, Stat6, Nfkb1. AbetaO elevated free radicals concentration, decreased mitochondria membrane potential (MMP) and cell viability after 24h. Gene transcription was not affected by AbetaO after 24h, but was significantly downregulated after 96h. In AbetaO stress, PJ34 exerted stimulatory effect on expression of several genes (Gpx1, Gpx4, Opa1, Mfn2, Fis1 and Sdha), decreased transcription of numerous TFs (Nrf1, Tfam, Stat3, Stat6, Trp53, Nfkb1) and prevented oxidative stress. Our results indicated that PARP-1 inhibition significantly enhanced transcription of genes involved in antioxidative defense and in regulation of mitochondria function, but was not able to ameliorate cells viability affected by Abeta."
|
Poly (ADP-Ribose) Polymerase-1
|
In this brief response to Joona Rasanen's argument for the coherence and desirability of being able legally to change one's age, I outline a couple of reasons for thinking that the case he makes is deeply flawed. As such, I contend that we have no reason to think that age should be the kind of thing that one should be able to change legally. Moreover, we have at least one good reason for thinking that legal age change would be positively undesirable.
|
Dissent and Disputes
|
BACKGROUND: The clinical use of autologous platelet concentrates (also known as platelet-rich plasma) on the field of regenerative therapy, in the last decade has been the subject of several studies especially in equine medicine and surgery. The objectives of this study was: 1) to describe and compare the cellular population in whole blood, lower fraction (A) and upper fraction (B) of platelet concentrates, 2) to measure and compare the transforming growth factor beta 1 (TGF-beta1) concentration in plasma and both platelet concentrates after be activated with calcium gluconate or batroxobin plus calcium gluconate and, 3) to determine correlations between cell counts in platelet concentrates and concentrations of TGF-beta1. Blood samples were taken from 16 dogs for complete blood count, plasma collection and platelet concentrates preparation. The platelet concentrates (PC) were arbitrarily divided into two fractions, specifically, PC-A (lower fraction) and PC-B (upper fraction). The Platelet concentrates were analyzed by hemogram. After activated with calcium gluconate or batroxobin plus calcium gluconate, TGF-beta1 concentration was determined in supernatants of platelet concentrates and plasma. RESULTS: There were differences statistically significant (P < 0.05) for the platelet count and leukocyte count and TGF-beta1 concentration between whole blood, plasma and both platelet concentrates. A significant correlation was found between the number of platelets in both platelet concentrates and TGF-beta1 concentration. Platelet collection efficiency was 46.34% and 28.16% for PC-A and PC-B, respectively. TGF-beta1 concentration efficiency for PC activated with calcium gluconate was 47.75% and 31.77%, for PC-A and PC-B, respectively. PC activated with batroxobin plus CG showed 46.87% and 32.24% for PC-A and PC-B, respectively. CONCLUSIONS: The methodology used in this study allows the concentration of a number of platelets and TGF-beta1 that might be acceptable for a biological effect for clinical or experimental use as a regenerative therapy in dogs.
|
Calcium Gluconate
|
Fluidization, a process in which a granular solid phase behaves like a fluid under the influence of an imposed upward fluid flow, is routinely used in many chemical and biological engineering applications. It brings, to applications involving fluid-solid exchanges, advantages such as high surface to volume ratio, constant mixing, low flow resistance, continuous operation and high heat transfer. We present here the physics of a new miniaturized, microfluidic fluidized bed, in which gravity is replaced by a magnetic field created by an external permanent magnet, and the solid phase is composed of magnetic microbeads with diameters ranging from 1 to 5 mum. These beads can be functionalized with different ligands, catalysts or enzymes, in order to use the fluidized bed as a continuous purification column or bioreactor. It allows flow-through operations at flow rates ranging from 100 nL min(-1) up to 5 muL min(-1) at low driving pressures (<100 mbar) with intimate liquid/solid contact and a continuous recirculation of beads for enhanced target capture efficiencies. The physics of the system presents significant differences as compared to conventional fluidized beds, which are studied here. The effects of magnetic field profile, flow chamber shape and magnetic bead dipolar interactions on flow regimes are investigated, and the different regimes of operation are described. Qualitative rules to obtain optimal operation are deduced. Finally, an exemplary use as a platform for immunocapture is provided, presenting a limit of detection of 0.2 ng mL(-1) for 200 muL volume samples.
|
Solid Phase Extraction
|
As we move toward a value-based health care system and payment models based on individual performance of providers, nurses are faced with a dilemma. Should we as a profession actively pursue the development of individual nurse performance metrics, analysis, benchmarks, and practice standards, similar to those being implemented for physicians? Or should we wait until these metrics are imposed by payers and policymakers with little or no input from nurses?
|
Economics, Nursing
|
In angiosperms, chlorophyll biosynthesis is light dependent. A key factor in this process is protochlorophyllide oxidoreductase (POR), which requires light to catalyze the reduction of protochlorophyllide to chlorophyllide. It is believed that this protein originated from an ancient cyanobacterial enzyme that was introduced into proto-plant cells during the primary symbiosis. Here we report that PORs from the cyanobacteria Gloeobacter violaceus PCC7421 and Synechocystis sp. PCC6803 function in plastids. First, we found that the G. violaceus POR shows a higher affinity to its substrate protochlorophyllide than the Synechocystis POR but a similar affinity to plant PORs. Secondly, the reduced size of prolamellar bodies caused by a knockdown mutation of one of the POR genes, PORA, in Arabidopsis could be complemented by heterologous expression of the cyanobacterial PORs. Photoactive protochlorophyllide in the etioplasts of the complementing lines, however, was retained at a low level as in the parent PORA knockdown mutant, indicating that the observed formation of prolamellar bodies was irrelevant to the assembly of photoactive protochlorophyllide. This work reveals a new view on the formation of prolamellar bodies and provides new clues about the function of POR in the etioplast-chloroplast transition.
|
Protochlorophyllide
|
BACKGROUND/AIM: We evaluated the usefulness of topoisomerases (TOPs) expression as prognostic predictors in breast cancer. PATIENTS AND METHODS: We retrospectively investigated sixty cases with primary breast cancer. We evaluated the tumor and non-tumor mRNA levels of TOP1 and TOP2alpha using quantitative reverse-transcription polymerase chain reaction. TOP1/TOP2alpha positivity was defined as the ratio of the mRNA expression of cancer/normal tissue of >1 for both TOP1 and TOP2alpha. RESULTS: TOP1 and TOP2alpha were markedly overexpressed in breast cancer tissues compared to normal breast tissues. Of the 60 cases, 46 (76.7%) were positive for TOP1/TOP2alpha. The relapse-free survival was relatively shorter for patients with positive TOP1/TOP2alpha. There was no recurrent disease among the 14 patients who were negative for TOP1/TOP2alpha, whereas four of the 46 TOP1/TOP2alpha-positive patients had disease recurrence. CONCLUSION: Negative TOP1 or TOP2alpha expression may be useful for predicting better prognoses in breast cancer patients.
|
DNA Topoisomerases
|
INTRODUCTION: Clomiphene citrate is employed off-label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism. AIM: Our aim was to compare oral enclomiphene citrate as an alternative to topical testosterone. MAIN OUTCOME MEASURES: Blood levels of total testosterone (TT), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin-like growth factor 1 IGF-1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated. METHODS: This was a proof-of-principle, randomized, open-label, fixed dose, active-control, two-center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone. RESULTS: After discontinuation of topical testosterone, morning TT values averaged 165 +/- 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 +/- 268 and 525 +/- 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75-334 x 10(6) /mL range. The gel was ineffective in raising sperm counts above 20 x 10(6) /mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow-up, only enclomiphene citrate treatment was associated with elevated sperm counts. CONCLUSIONS: Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic-pituitary-testicular axis.
|
Enclomiphene
|
Hematopoietic SCT is currently the only curative therapy for a range of benign inherited and acquired primary hematologic disorders in children, including BM failure syndromes and hemoglobinopathies. The preferred HLA-matched sibling donor is available for only about 25% of such children. However, there has been substantial progress over the last four decades in the use of alternative donors for those without a matched sibling-including HLA-matched unrelated donors, HLA-haploidentical related donors and unrelated-donor umbilical cord blood-so that it is now possible to find a donor for almost every child requiring an allograft. Below, we summarize the relative merits and limitations of the different alternative donors for benign hematologic conditions, first generally, and then in relation to specific disorders, and suggest recommendations for selecting such an alternative donor.
|
Donor Selection
|
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder primarily affecting the white matter of the nervous system that results from a deficiency of the arylsulfatase A (ARSA). Mesenchymal stem cells (MSCs) are able to secrete ARSA and have shown beneficial effects in MLD patients. In this retrospective analysis, 10 pediatric MLD patients [mesenchymal stem cell group (MSCG)] underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received two applications of 2 x 10(6) MSCs/kg bodyweight at day +30 and +60 after HSCT between 2007 and 2018. MSC safety, occurrence of graft-versus-host disease (GvHD), blood ARSA levels, chimerism, cell regeneration and engraftment, magnetic resonance imaging (MRI) changes, and the gross motor function were assessed within the first year of HSCT. The long-term data included clinical outcomes and safety aspects of MSCs. Data were compared to a control cohort of seven pediatric MLD patients [control group (CG)] who underwent HSCT only. The application of MSC in pediatric MLD patients after allogeneic HSCT was safe and well tolerated, and long-term potentially MSC-related adverse effects up to 13.5 years after HSCT were not observed. Patients achieved significantly higher ARSA levels (CG: median 1.03 nmol.10(-6) and range 0.41-1.73 | MSCG: median 1.58 nmol.10(-6) and range 0.44-2.6; P < 0.05), as well as significantly higher leukocyte (P < 0.05) and thrombocyte (P < 0.001) levels within 365 days of MSC application compared to CG patients. Statistically significant effects on acute GvHD, regeneration of immune cells, MRI changes, gross motor function, and clinical outcomes were not detected. In conclusion, the application of MSCs in pediatric MLD patients after allogeneic HSCT was safe and well tolerated. The two applications of 2 x 10(6)/kg allogeneic MSCs were followed by improved engraftment and hematopoiesis within the first year after HSCT. Larger, prospective trials are necessary to evaluate the impact of MSC application on engraftment and hematopoietic recovery.
|
Sulfatidosis
|
BACKGROUND: Nasalis larvatus are well-known attraction for tourists in the mangrove forest of Bako National Park (BNP). Little is known regarding the infestation of helminth parasites in proboscis monkeys. Therefore, the objectives of this study are to determine the prevalence species of major helminth parasites of public health importance in proboscis monkeys in BNP. METHODS: A total of 65 faecal samples screened for helminth parasites via sodium nitrate floatation and faecal sedimentation techniques. RESULTS: A total of 14 helminth parasite species comprising of eight genera of nematodes, two species of cestodes and two trematodes were identified. Eggs of Trichuris trichiura were the most frequently encountered in proboscis monkeys. CONCLUSION: This is the first survey on the fauna of helminth parasites of proboscis monkeys living in mangrove forests, and therefore, it implies the important baseline information that increases our current knowledge for future research regarding parasite-host ecology in primates.
|
Presbytini
|
Ultrasound-assisted extraction was evaluated as a simpler and more effective alternative to conventional extraction method for the isolation of xyloglucan from apple pomace. The apple pomace samples were extracted under indirect sonication in an ultrasound cleaning bath. The ultrasound extraction was compared with the conventional method, on the productions of xyloglucan. It was found that the ultrasound-assisted extraction of xyloglucan was about three times faster than the traditional extraction method. Response surface methodology was employed to study the effect of liquid:solid ratio, KOH concentration and ultrasound-assisted extraction time on the yield of xyloglucan from apple pomace. Regression analysis was performed on the data obtained. The most relevant variable was the quadratic of liquid:solid ratio. The coefficient determination (R(2)) was good for the second-order model. The optimum combination was determined as a liquid:solid ratio of 34.4:1 (v/w), a KOH concentration of 3.3 M and an ultrasound-assisted extraction time of 2.5 h.
|
Xylans
|
The second domain of gelsolin (G2) hosts mutations responsible for a hereditary form of amyloidosis. The active form of gelsolin is Ca(2+)-bound; it is also a dynamic protein, hence structural biologists often rely on the study of the isolated G2. However, the wild type G2 structure that have been used so far in comparative studies is bound to a crystallographic Cd(2+), in lieu of the physiological calcium. Here, we report the wild type structure of G2 in complex with Ca(2+) highlighting subtle ion-dependent differences. Previous findings on different G2 mutations are also briefly revised in light of these results.
|
Gelsolin
|
The pregnane X receptor (PXR/SXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3) are nuclear receptors (NRs) involved in the regulation of many genes including cytochrome P450 enzymes (CYPs) and transporters important in metabolism and uptake of both endogenous substrates and xenobiotics. Activation of these receptors can lead to adverse drug effects as well as drug-drug interactions. Depending on which nuclear receptor is activated will determine which adverse effect could occur, making identification important. Screening for NR activation by New Molecular Entities (NMEs) using cell-based transactivation assays is the singular high throughput method currently available for identifying the activation of a particular NR. Moreover, screening for species-specific NR activation can minimize the use of animals in drug development and toxicology studies. With this in mind, we have developed in vitro transactivation assays to identify compounds that activate canine and rat PXR and CAR3. We found differences in specificity for canine and rat PXR, with the best activator for canine PXR being 10 muM SR12813 (60.1 +/- 3.1-fold) and for rat PXR, 10 muM dexamethasone (60.9 +/- 8.4 fold). Of the 19 test agents examined, 10 and 9 significantly activated rat and canine PXR at varying degrees, respectively. In contrast, 5 compounds exhibited statistically significant activation of rat CAR3 and 4 activated the canine receptor. For canine CAR3, 50 muM artemisinin proved to be the best activator (7.3 +/- 1.8 and 10.5 +/- 2.2 fold) while clotrimazole (10 muM) was the primary activator of the rat variant (13.7 +/- 0.8 and 26.9 +/- 1.3 fold). Results from these studies demonstrated that cell-based transactivation assays can detect species-specific activators and revealed that PXR was activated by at least twice as many compounds as was CAR3, suggesting that there are many more agonists for PXR than CAR."
|
Receptors, Cytoplasmic and Nuclear
|
Satellite cells represent the primary population of stem cells resident in skeletal muscle. These adult muscle stem cells facilitate the postnatal growth, remodeling, and regeneration of skeletal muscle. Given the remarkable regenerative potential of satellite cells, there is great promise for treatment of muscle pathologies such as the muscular dystrophies with this cell population. Various protocols have been developed which allow for isolation, enrichment, and expansion of satellite cell derived muscle stem cells. However, isolated satellite cells have yet to translate into effective modalities for therapeutic intervention. Broadening our understanding of satellite cells and their niche requirements should improve our in vivo and ex vivo manipulation of these cells to expedite their use for regeneration of diseased muscle. This review explores the fates of satellite cells as determined by their molecular signatures, ontogeny, and niche dependent programming."
|
Satellite Cells, Skeletal Muscle
|
Staphylococcus aureus is one of the most infectious agents among staphylococcal bacteria. Currently many strains of S. aureus have developed resistance against available antibiotics. Therefore, the treatment of infections caused by them is a major challenge. During current study, desogestrel (1), a contraceptive drug, was found to be a potent growth inhibitor of drug resistant strains of S. aureus. Therefore, in search of new and effective agents against multi-drug resistant S. aureus strains, whole-cell bio-catalytic conversion of desogestrel (1) by Cunninghamella blakesleeana ATCC 8688A at pH 7.0 and 25⯠degrees C was carried out, yielding three new metabolites, 13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-6beta,15beta,17beta-triol (2), 13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-3beta,6beta,17beta-triol (3), and 13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-20-yn-3alpha,5alpha,6beta,17beta-tetraol (4), along with a known metabolite, 13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-6beta,17beta-dihydroxy-3-one (5). Among them, compounds 1-2 showed a potent activity against S. aureus EMRSA-17, S. aureus NCTC 13277 (MRSA-252), and S. aureus NCTC 13143, and clinically isolated Pakistani strain of S. aureus in an in vitro Microplate Alamar Blue Assay (MABA). Vancomycin was used as the standard drug in this assay. In addition, compound 1 also showed a significant activity against vancomycin-resistant S. aureus (VRSA) ATCC 700699. Compounds 1-5 were also evaluated against 3T3 normal cell line (mouse fibroblast) where they all were identified as non-cytotoxic. The present study thus provides new leads for the development of anti-bacterial drugs against MDR S. aureus.
|
Desogestrel
|
The amino-terminal sequences of two polypeptides with nonsuppressible insulin-like and cell-growth-promoting activities (NSILA I and II), isolated from human serum, were determined. Of the first 31 residues, 22 are identical in NSILA I and II. Moreover, a striking structural similarity was found between NSILA and insulin B chain: 47 and 57% of residues 1-30 in NSILA I are identical to those in insulin B chain from man and tuna fish, respectively. This high degree of sequence identity is presented as evidence for homology and thus for a common evolutionary origin of insulin and NSILA. Based on these results and on these results and on biological properties of NSILA described earlier, a new designation for NSILA is proposed: insulin-like growth factor (IGF)."
|
Nonsuppressible Insulin-Like Activity
|
Nasal irrigation plays a non-negligible role in the treatment of numerous sinonasal pathologies and postoperative care. There is, however, a wide variety of protocols. The present review of the evidence-based literature sought objective arguments for optimization and efficacy. It emerged that large-volume low-pressure nasal douche optimizes the distribution and cleansing power of the irrigation solution in the nasal cavity. Ionic composition and pH also influence mucociliary clearance and epithelium trophicity. Seawater is less rich in sodium ions and richer in bicarbonates, potassium, calcium and magnesium than is isotonic normal saline, while alkaline pH and elevated calcium concentration optimized ciliary motility in vitro. Bicarbonates reduce secretion viscosity. Potassium and magnesium promote healing and limit local inflammation. These results show that the efficacy of nasal irrigation is multifactorial. Large-volume low-pressure nasal irrigation using undiluted seawater seems, in the present state of knowledge, to be the most effective protocol.
|
Nasal Lavage
|
CCL20 is the only chemokine ligand for the chemokine receptor CCR6, which is expressed by the critical antigen presenting cells, dendritic cells. Increased expression of CCL20 is likely involved in the increased recruitment of dendritic cells observed in fibroinflammatory diseases such as chronic obstructive pulmonary disease (COPD). CCL20 expression is increased by the proinflammatory cytokine IL-1beta. We have determined that IL-1beta-dependent CCL20 expression is also dependent on the multifunctional cytokine TGF-beta. TGF-beta is expressed in a latent form that must be activated to function, and activation is achieved through binding to the integrin alphavbeta8 (itgb8). Here we confirm correlative increases in alphavbeta8 and IL-1beta with CCL20 protein in lung parenchymal lysates of a large cohort of COPD patients. How IL-1beta- and alphavbeta8-mediated TGF-beta activation conspire to increase fibroblast CCL20 expression remains unknown, because these pathways have not been shown to directly interact. We evaluate the 5'-flanking region of CCL20 to determine that IL-1beta-driven CCL20 expression is dependent on alphavbeta8-mediated activation of TGF-beta. We identify a TGF-beta-responsive element (i.e. SMAD) located on an upstream enhancer of the human CCL20 promoter required for efficient IL-1beta-dependent CCL20 expression. By chromatin immunoprecipitation, this upstream enhancer complexes with the p50 subunit of NF-kappaB on a NF-kappaB-binding element close to the transcriptional start site of CCL20. These interactions are confirmed by electromobility shift assays in nuclear extracts from human lung fibroblasts. These data define a mechanism by which alphavbeta8-dependent activation of TGF-beta regulates IL-1beta-dependent CCL20 expression in COPD.
|
Chemokine CCL20
|
Monocrotophos (dimethyl (E)-1-methyl-2-(methylcarbamoyl) vinyl phosphate, or MCP), an organophosphorus insecticide, was used as a sole phosphorus source by the microorganisms isolated from the soil. None of the isolates could utilize MCP as a sole source of carbon. Two of the potential microbial isolates, Pseudomonas aeruginosa F10B and Clavibacter michiganense subsp. insidiosum SBL 11, could utilize MCP as a sole source of phosphorus. Pseudomonas aeruginosa F10B showed a lag phase of 4 h, while in the case of C. michiganense subsp. insidiosum SBL 11, it was 8 h when cultured in the presence of MCP. The generation time for both strains was increased in the medium containing MCP. It was 2.15 h for P. aeruginosa F10B in MCP medium as compared with 1.29 h in basal medium, while in case of C. michiganense subsp. insidiosum SBL 11 it was increased to 3.4 h in MCP medium as compared with 1.28 h in basal medium. These two strains were able to degrade technical MCP in shake-flask culture up to 98.9 and 86.9%, respectively, and pure MCP up to 79 and 80%, respectively, within 24 h at 37 degrees C. The optimal concentration of MCP required for the normal growth was 500 ppm. In the substrate preference study, Tris-p-nitrophenyl phosphate was the most preferred substrate followed by paraoxon. The enzyme responsible for the break down of MCP was phosphotriesterase, which was localized on the membrane-bound fraction of the disrupted cells. The gene responsible for the production of phosphotriesterase (opd) in P. aeruginosa F10B was plasmid-borne.
|
Monocrotophos
|
Idiopathic hemochromatosis is one of the most common adult genetic disorders in the Caucasian population. The clinical manifestations are various with hepatic, pancreatic, cardiac disorders.... Arthritis associated with idiopathic hemochromatosis are less well-known and differential diagnosis with other arthropathies is sometimes difficult. Early diagnosis enables rapid treatment and better prognosis.
|
Hemochromatosis
|
In response to nutrient depletion, the RelA and SpoT proteins generate the signaling molecule (p)ppGpp, which then controls a number of downstream effectors to modulate cell physiology. In Acinetobacter baumannii strain AB5075, a relA ortholog (ABUW_3302) was identified by a transposon insertion that conferred an unusual colony phenotype. An in-frame deletion in relA (DeltarelA) failed to produce detectable levels of ppGpp when amino acid starvation was induced with serine hydroxamate. The DeltarelA mutant was blocked from switching from the virulent opaque colony variant (VIR-O) to the avirulent translucent colony variant (AV-T), but the rate of AV-T to VIR-O switching was unchanged. In addition, the DeltarelA mutation resulted in a pronounced hypermotile phenotype on 0.35% agar plates. This hypermotility was dependent on the activation of a LysR regulator ABUW_1132, which was required for expression of AbaR, a LuxR family quorum-sensing regulator. In the DeltarelA mutant, ABUW_1132 was also required for the increased expression of an operon composed of the ABUW_3766-ABUW_3773 genes required for production of the surfactant-like lipopeptide acinetin 505. Additional phenotypes identified in the DeltarelA mutant included (i) cell elongation at high density, (ii) reduced formation of persister cells tolerant to colistin and rifampin, and (iii) decreased virulence in a Galleria mellonella model.IMPORTANCEAcinetobacter baumannii is a pathogen of worldwide importance. Due to the increasing prevalence of antibiotic resistance, these infections are becoming increasingly difficult to treat. New therapies are required to combat multidrug-resistant isolates. The role of RelA in A. baumannii is largely unknown. This study demonstrates that like in other bacteria, RelA controls a variety of functions, including virulence. Strategies to inhibit the activity of RelA and the resulting production of ppGpp could inhibit virulence and may represent a new therapeutic approach.
|
Guanosine Tetraphosphate
|
In this work, a novel open-source dataset for noninvasive fetal electrocardiography research is presented. It is composed of 60 high-quality electrophysiological recordings acquired between the 21st and the 27th weeks of gestation. For each acquisition, whose average duration is 30.5 s, 24 unipolar abdominal leads and three bipolar thoracic leads were included, along with a maternal respiration signal collected by a thoracic resistive belt. The chosen electrodes positioning map allows reproducing up to ten setups presented in the scientific literature. Each biopotential recording was acquired synchronously with the corresponding fetal cardiac pulsed-wave Doppler (PWD) signal, to provide complete information about the fetal cardiac cycle, both from the electrical and mechanical point of view.This is the first dataset allowing the non-invasive fetal ECG analysis even in early pregnancies with a ground truth about the fetal heart activity, given by the PWD signal. For this reason, it can be used to assess fetal ECG extraction algorithms requiring multiple channels, eventually including maternal references. This dataset is being released on Physionet by the end of June 2020 and will be continuously improved in the framework of the Non-Invasive Fetal ECG Analysis (NInFEA) project of the University of Cagliari (Italy).
|
Fetal Research
|
Particulate phosphorus (PP) is often the largest component of the total phosphorus (P) load in stormwater. Fine-resolution measurement of particle sizes allows us to investigate the mechanisms behind the removal of PP in stormwater wetlands, since the diameter of particles influences the settling velocity and the amount of sorbed P on a particle. In this paper, we present a novel method to estimate PP, where we measure and count individual particles in stormwater and use the total surface area as a proxy for PP. Our results show a strong relationship between total particle surface area and PP, which we use to put forth a simple mechanistic model of PP removal via gravitational settling of individual mineral particles, based on a continuous particle size distribution. This information can help improve the design of stormwater Best management practices to reduce PP loading in both urban and agricultural watersheds.
|
Phosphorus
|
The in vitro initial killing and post-antibiotic effect (PAE) of meropenem on five gram-negative reference strains were evaluated by bioluminescence assay of bacterial adenosine triphosphate (ATP) and viable count. Morphology studies were performed in parallel. Meropenem showed concentration-dependent long (2-5 h) PAEs on Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens when assayed by bioluminescence and induced spheroplasts at almost all concentrations. The bioluminescence PAEs reached a maximum response at 4 x MIC. These PAEs of meropenem on Escherichia coli, Klebsiella pneumoniae and Serratia marcescens were longer than corresponding PAEs of imipenem shown in previous studies. The higher affinity of meropenem than imipenem for PBP 3 might explain the longer PAEs obtained with meropenem. However, there was only a very short PAE, no PAE or even a negative PAE when viable count was used as the initial value for the PAE calculation. A strong initial decrease in viability but a less pronounced change in intracellular ATP was registered. Since this initial change in cell numbers is the initial value for the PAE calculation, the length of PAE was highly method dependent. In summary, a strong initial killing and no PAE were shown using viable count as the initial value for the PAE calculation, but a weak initial killing and long PAEs were shown when bioluminescence was used throughout the experiments.
|
Thienamycins
|
The small heat-shock protein Hsp20 (heat-shock protein 20), also known as HspB6, has been shown to protect against a number of pathophysiological cardiac processes, including hypertrophy and apoptosis. Following beta-adrenergic stimulation and local increases in cAMP, Hsp20 is phosphorylated on Ser16 by PKA (protein kinase A). This covalent modification is required for many of its cardioprotective effects. Both Hsp20 expression levels and its phosphorylation on Ser16 are increased in ischaemic myocardium. Transgenic mouse models with cardiac-specific overexpression of Hsp20 that are subject to ischaemia/reperfusion show smaller myocardial infarcts, and improved recovery of contractile performance during the reperfusion phase, compared with wild-type mice. This has been attributed to Hsp20's ability to protect against cardiomyocyte necrosis and apoptosis. Phosphomimics of Hsp20 (S16D mutants) confer improved protection from beta-agonist-induced apoptosis in the heart, whereas phospho-null mutants (S16A) provide no protection. Naturally occurring mutants of Hsp20 at position 20 (P20L substitution) are associated with markedly reduced Hsp20 phosphorylation at Ser16, and this lack of phosphorylation correlates with abrogation of Hsp20's cardioprotective effects. Therefore phosphorylation of Hsp20 at Ser16 by PKA is vital for the cardioprotective actions of this small heat-shock protein. Selective targeting of signalling elements that can enhance this modification represents an exciting new therapeutic avenue for the prevention and treatment of myocardial remodelling and ischaemic injury.
|
HSP20 Heat-Shock Proteins
|
Despite structural differences between the right-handed conformations of A-RNA and B-DNA, both nucleic acids adopt very similar, left-handed Z-conformations. In contrast to their structural similarities and sequence preferences, RNA and DNA exhibit differences in their ability to adopt the Z-conformation regarding their hydration shells, the chemical modifications that promote the Z-conformation, and the structure of junctions connecting them to right-handed segments. In this review, we highlight the structural and chemical properties of both Z-DNA and Z-RNA and delve into the potential factors that contribute to both their similarities and differences. While Z-DNA has been extensively studied, there is a gap of knowledge when it comes to Z-RNA. Where such information is lacking, we try and extend the principles of Z-DNA stability and formation to Z-RNA, considering the inherent differences of the nucleic acids.
|
Nucleic Acid Conformation
|
Analogs of GnRH constitute a new category of drugs available for the treatment of advanced prostatic cancer. The efficacy and safety of GnRH analogs in the treatment of this disease is now well established. These compounds represent an important alternative therapy for advanced prostatic cancer patients who do not wish to undergo orchiectomy or for whom DES is not tolerable because of the risk of cardiovascular complications. The advent of the monthly depot form of these drugs will make treatment more convenient and less invasive and will enhance patient compliance."
|
Gonadotropin-Releasing Hormone
|
A sustained release form of dimetindene (dimethindene maleate, Fenistil, CAS 3614-69-5) was developed based on a micropellet technique. Aim of the study was to evaluate the efficacy and duration of two doses of dimetindene in a sustained release pellet formulation with a standardised grass pollen provacation model (Vienna Challenge Chamber; VCC). The study with 12 grass pollen allergic volunteers--verified by case history, skin prick test (SPT), and radio allergo sorbent test (RAST)--was carried out in a placebo controlled, double blind, cross-over design. 12 h before a 4-h-lasting continuous challenge with permanent 1000 dactylis grass pollen in the VCC, administration of dimetindene (Fenistil R Pellets) in doses of 4 mg, 8 mg or identically appearing placebo was scheduled in three sessions. Nasal flow and resistance, nasal secretion and subjective symptoms were recorded at 15-min intervals during this long-term challenge under reproducible conditions. In comparison to placebo, dimetindene leads to a statistically significant reduction (p < 0.05) of nasal response and clinical symptoms for at least 16 h after treatment. The efficacy of 8 mg dimetindene was pronounced over 4 mg, however, the differences between both active treatments were not statistically significant. Therefore 4 mg dimetindene once a day is the adequate treatment for usual pollinotic disease conditions.
|
Dimethindene
|
Hyperosmolarity of the airway surface liquid (ASL) has been proposed as the stimulus for hyperpnoea-induced asthma. We found previously that mucociliary clearance (MCC) was increased after isocapnic hyperventilation (ISH) with dry air, and we proposed that the increase related to transient hyperosmolarity of the ASL. We investigated the effect of increasing the osmolarity of the ASL on MCC, by administering an aerosol of concentrated salt solution. MCC was measured using 99mTc-sulphur colloid, gamma camera and computer analysis in 12 asthmatic and 10 healthy subjects on three separate days, involving administration of each of the following: 1) ultrasonically nebulized 14.4% saline; 2) ultrasonically nebulized 0.9% saline; and 3) no aerosol intervention (control). The (mean +/- SD) volume of nebulized 14.4% saline was 2.2 +/- 1.2 mL for asthmatics and 3.2 +/- 0.7 mL for healthy subjects. This volume was delivered over a period of 5.4 +/- 1.3 and 6.4 +/- 0.7 min for asthmatic and healthy subjects, respectively. The airway response to 14.4% saline was assessed on a separate visit and the fall in forced expiratory volume in one second (FEV1) was 22 +/- 4% in the asthmatic and 3 +/- 2% in the healthy subjects. Compared to the MCC with the 0.9% saline and control, the hypertonic aerosol increased MCC in both groups. In asthmatic subjects, MCC of the whole right lung in 1 h was 68 +/- 10% with 14.4% saline vs 44 +/- 14% with 0.9% saline and 39 +/- 13% with control. In healthy subjects, MCC of the whole right lung in 1 h was 53 +/- 12% with 14.4% saline vs 41 +/- 15% with 0.9% saline and 36 +/- 13% with control. We conclude that an increase in osmolarity of the airway surface liquid increases mucociliary clearance both in asthmatic and healthy subjects. These findings are in keeping with our previous suggestion that the increase in mucociliary clearance after isotonic hyperventilation with dry air is due to a transient hyperosmolarity of the airway surface liquid.
|
Mucociliary Clearance
|
Advances in genetic and genomic technology changed health-care services rapidly in low and middle income countries (LMICs) in the Asia-Pacific region. While genetic services were initially focused on population-based disease prevention strategies, they have evolved into clinic-based and therapeutics-oriented service. Many LMICs struggled with these noncommunicable diseases and were unprepared for the needs of a clinical genetic service. The emergence of a middle class population, the lack of regulatory oversight, and weak capacity-building in medical genetics expertise and genetic counseling services led to a range of genetic services of variable quality with minimal ethical oversight. Some of the current shortcomings faced include the lack of awareness of cultural values in genetic health care, the variable stages of socioeconomic development and educational background that led to increased demand and abuse of genetics, the role of women in society and the crisis of gender selection, the lack of preventive and care services for genetic and birth defects, the issues of gene ethics in medicine, and the lack of understanding of some religious controversies. These challenges provide opportunities for both developing and developed nations to work together to reduce the inequalities and to ensure a caring, inclusive, ethical, and cost-effective genetic service in the region.
|
Genetic Services
|
The tumor microenvironment has recently emerged as a critical component of high-grade serous ovarian cancer (HGSC) disease progression. Specifically, cancer-associated fibroblasts (CAFs) have been recognized as key players in various pro-oncogenic processes. Here, we use mass-spectrometry (MS) to characterize the proteomes of HGSC patient-derived CAFs and compare them to those of the epithelial component of HGSC to gain a deeper understanding into their tumor-promoting phenotype. We integrate our data with primary tissue data to define a proteomic signature of HGSC CAFs and uncover multiple novel CAF proteins that are prognostic in an independent HGSC patient cohort. Our data represent the first MS-based global proteomic characterization of CAFs in HGSC and further highlights the clinical significance of HGSC CAFs.
|
Cystadenocarcinoma, Serous
|
Commonly developing in adolescence and following a chronic course, eating disorders are life-threatening psychological disorders and typically very difficult to treat despite the body of research exploring treatment options. Due to the high levels of severity and the enduring nature of eating disorders, schema therapy has been proposed as a more effective treatment than cognitive behaviour therapy. To assess the effectiveness of schema therapy in adults with eating disorders, the present systematic review was designed in accordance with PRISMA guidelines. A structured search of electronic databases and grey literature was conducted, and the Mixed Methods Assessment Tool was used to assess the quality of each article. Four articles including 151 participants were found which demonstrated that schema therapy is effective at reducing eating disorder symptoms and behaviour and general psychopathology. Despite the limitations of this study, including the scarcity of research available and varying methodologies used, the present systematic review found evidence supporting the use of schema therapy in patients with eating disorders, particularly those experiencing severe and enduring forms.
|
Schema Therapy
|
Because of jogging and aerobics, more stress fractures are occurring in women today. That they can occur unrelated to these activities in pregnant women is not quite so well known. Two cases of stress fracture of the pubic bone sustained at delivery are presented, along with discussion of the possible causes and simple treatment of such fractures.
|
Fractures, Spontaneous
|
A group of 25 patients treated with maprotiline was studied to test the question of second-generation antidepressant effectiveness in chronic pain. Of this group, 18 (72%) responded with a greater than 50% reduction in their pain syndrome. It appears that maprotiline is as effective as earlier antidepressants in the treatment of pain. The enkephalin induction hypothesis is discussed as an explanation for the mechanism of action of antidepressants in chronic pain.
|
Maprotiline
|
The deadtime characterisitcs of Anger cameras are analyzed from theoretical and experimental points of view. An investigation of two Searle Radiographics cameras revealed that they had both paralyzable and nonparalyzable components, the deadtimes of which varied with analyzer window width, the energy of the gamma rays counted, and the position of the time constant selector" switch in the A-scope module of these cameras. A mathematical model for two-component systems is presented."
|
Radionuclide Imaging
|
Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (alpha-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic alpha-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective alpha-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish alpha-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D.
|
alpha-MSH
|
All thermophilic and hyperthermophilic archaea encode homologs of dimeric Alba (Sac10b) proteins that bind cooperatively at high density to DNA. Here, we report the 2.0 A resolution crystal structure of an Alba2 (Ape10b2)-dsDNA complex from Aeropyrum pernix K1. A rectangular tube-like structure encompassing duplex DNA reveals the positively charged residues in the monomer-monomer interface of each dimer packing on either side of the bound dsDNA in successive minor grooves. The extended hairpin loop connecting strands beta3 and beta4 undergoes significant conformational changes upon DNA binding to accommodate the other Alba2 dimer during oligomerization. Mutational analysis of key interacting residues confirmed the specificity of Alba2-dsDNA interactions.
|
Desulfurococcales
|
Uretero-inguinal hernia (UIH) is a rare condition in children. We present our experience with an unexpected UIH in a male infant with associated anomalies and a literature review of pediatric cases. A full-term male newborn was referred to our hospital for microcolon and right hydroureteronephrosis. Voiding cystourethrography showed grade-IV right vesicoureteral reflux and a dilated, convoluted, ureter protruding in the right inguinal canal, suggesting a right UIH, which was uneventfully repaired at 2 months of life. UIH is a rare type of inguinal hernia in children that pediatric urologists and surgeons should be aware of. In experienced hands, and when preoperatively suspected, surgical management is safe and effective.
|
Vesico-Ureteral Reflux
|
Three children with full skin thickness friction burns of the hand caused by treadmill jogging machines are presented. The mechanism of injury, the potential hazards and poor safety precautions in design of the machine are highlighted.
|
Jogging
|
The purpose of this study was to utilize a theoretical model of bilingual speech sound production as a framework for analyzing the speech of bilingual children with speech sound disorders. In order to distinguish speech difference from speech disorder, we examined between-language interaction on initial consonant deletion, an error pattern found cross-linguistically in the speech of children with speech sound disorders. Thirteen monolingual English-speaking and bilingual Spanish-and English-speaking preschoolers with speech sound disorders were audio-recorded during a single word picture-naming task and their recordings were phonetically transcribed. Initial consonant deletion errors were examined both quantitatively and qualitatively. An analysis of cross-linguistic effects and an analysis of phonemic complexity were performed. Monolingual English-speaking children exhibited initial consonant deletion at a significantly lower rate than bilingual children in their Spanish productions; however, no other quantitative differences were found across groups or languages. Qualitative differences yielded between-language interaction in the error patterns of bilingual children. Phonemic complexity appeared to play a role in initial consonant deletion. Evidence from the speech of bilingual children with speech sound disorders supports analysing bilingual speech using a cross-linguistic framework. Both theoretical and clinical implications are discussed.
|
Speech Sound Disorder
|
Interleukin (IL)-37 is a member of the IL-1 family of cytokines. Although its broad anti-inflammatory properties are well described, the effects of IL-37 on inflammasome function remain poorly understood. Performing gene expression analyses, ASC oligomerization/speck assays and caspase-1 assays in bone marrow-derived macrophages (BMDM), and employing an in vivo endotoxemia model, we studied how IL-37 affects the expression and maturation of IL-1beta and IL-18, inflammasome activation, and pyroptosis in detail. IL-37 inhibited IL-1beta production by NLRP3 and AIM2 inflammasomes, and IL-18 production by the NLRP3 inflammasome. This inhibition was partially attributable to effects on gene expression: whereas IL-37 did not affect lipopolysaccharide (LPS)-induced mRNA expression of Il18 or inflammasome components, IL-37-transgenic BMDM displayed an up to 83% inhibition of baseline and LPS-stimulated Il1b compared to their wild-type counterparts. Importantly, we observed that IL-37 suppresses nigericin- and silica-induced ASC oligomerization/speck formation (a step in inflammasome activation and subsequent caspase-1 activation), and pyroptosis (-50%). In mice subjected to endotoxemia, IL-37 inhibited plasma IL-1beta (-78% compared to wild-type animals) and IL-18 (-61%). Thus, our study adds suppression of inflammasome activity to the portfolio of anti-inflammatory pathways employed by IL-37, highlighting this cytokine as a potential tool for treating inflammasome-driven diseases.
|
Interleukins
|
BACKGROUND AND AIMS: In peach (Prunus persica) trees, three types of shoots can be distinguished depending on the time of their appearance: sylleptic, proleptic and epicormic. On proleptic shoots, an average of ten phytomers are preformed in dormant buds prior to shoot growth after bud-break, whereas all phytomers are considered neoformed in sylleptic and epicormic shoots. However, casual observations indicated that proleptic and sylleptic shoots appear quite similar in number of phytomers and structure in spite of their different origins. The goal of this research was to test the hypothesis that both proleptic and sylleptic shoots exhibit similar growth characteristics by analysing their node numbers and bud fate patterns. If their growth characteristics are similar, it would indicate that the structure of both types of shoots is primarily under genetic rather than environmental control. METHODS: The number of phytomers and bud fate patterns of proleptic and sylleptic shoots of four peach cultivars grown in the same location (Winters, California) were analysed and characterized using hidden semi-Markov models. Field data were collected during winter 2016, just prior to floral bud-break. KEY RESULTS: Sylleptic shoots tended to have slightly fewer phytomers than proleptic shoots of the same cultivars. The bud fate patterns along proleptic and sylleptic shoots were remarkably similar for all the cultivars, although proleptic shoots started growing earlier (at least 1 month) in the spring than sylleptic shoots. CONCLUSIONS: This study provides strong evidence for the semi-deterministic nature of both proleptic and sylleptic shoots across four peach cultivars in terms of number of phytomers and bud fate patterns along shoots. It is apparent that the overall structure of shoots with similar numbers of phytomers was under similar genetic control for the two shoot types. Understanding shoot structural characteristics can aid in phenotypic characterization of vegetative growth of trees and in providing a foundation for vegetative management of fruit trees in horticultural settings.
|
Prunus persica
|
Ethylene, or its precursor 1-aminocyclopropane-1-carboxylic acid (ACC), can stimulate hypocotyl elongation in the light. It is questioned whether gibberellins (GAs) play a role in this response. Tests with light of different wavelengths demonstrated that the ethylene response depends on blue light and functional cryptochrome signalling. Levels of bio-active GA(4) were reduced in seedlings showing an ethylene response. Furthermore, ACC treatment of seedlings caused accumulation of the DELLA protein RGA, a repressor of growth. Concurrently, transcript levels of several GA biosynthesis genes were up-regulated and GA inactivation genes down-regulated by ACC. Hypocotyl elongation in response to ACC was strongly reduced in seedlings with a diminished GA signal, while being vigorously stimulated in a quadruple DELLA knock-out mutant with constitutive GA signalling. These data show that ethylene-driven hypocotyl elongation is mainly blue light-dependent and that this ethylene response, although GA dependent, hence needing a basal GA level, is not mediated by GA, but rather acts via a separate pathway.
|
Hypocotyl
|
Rhabdomyolysis, the release of myoglobin and other cellular breakdown products from necrotic muscle tissue, is seen in patients with crush injuries, drug overdose, malignant hyperthermia, muscular dystrophy, and with increasing frequency in obese patients undergoing routine procedures. For the perioperative clinician, managing the resultant shock, hyperkalemia, acidosis, and myoglobinuric acute kidney injury can present a significant challenge. Prompt recognition, hydration, and correction of metabolic disturbances may reduce or eliminate the need for long-term renal replacement therapy. This article reviews the pathophysiology and discusses key issues in the perioperative diagnosis, risk stratification, and management of rhabdomyolysis.
|
Rhabdomyolysis
|
This paper reviews changes in the ethical challenges that have arisen in military medicine over the past four decades. This includes the degree, if any, to which providers during the Vietnam conflict have carried out what we now refer to as harsh interrogation measures in an attempt to extract information from captured enemy soldiers, the extent, if any, to which the USA used medicine as a means to try to win over the hearts and minds of civilians in occupied territory and how providers should treat service members who return from the front with combat fatigue. An issue that arose during the first Gulf War in 1991 is discussed, namely US service persons being required to take botulism vaccine without their consent. Finally, present challenges are discussed including interrogation measures such as waterboarding and the ethical issues posed in the recent past by the exclusion of gay service members and those posed presently by the inclusion of transgender members. Two ethical values are suggested that have remained constant, namely giving priority to the individual needs of service personnel over those of the unit when there are no urgent combat needs and the reliance on individual virtue when what they should do is morally unclear.
|
Military Medicine
|
Hepatic differentiation from mouse embryonic stem (ES) cells via the formation of embryoid bodies (EBs) has been revealed by the expression of hepatocyte-related genes such as alpha-fetoprotein and albumin. It is known, however, that the visceral endoderm differentiates in early EBs and expresses these hepatocyte-related genes. Thus, it remains unclear whether ES cells are capable of differentiating into hepatocytes derived from definitive endoderm in vitro. In the present study, yolk sac tissues isolated from the foetal mouse were found to express many hepatocyte-related genes. Among the hepatocyte-related genes examined, cytochrome P450 7A1 (Cyp7a1) was identified as a liver-specific gene that was not expressed in the yolk sac. Cyp7a1 was induced in developing EBs, and hepatic differentiation was preferentially observed in the developing EBs in attached culture as compared to those in suspension culture. Leukaemia inhibitory factor permitted the differentiation of visceral endoderm, but inhibited the expression of gastrulation-related genes and the hepatic differentiation in cultured EBs. ES cells expressing green fluorescent protein (GFP) under the control of the Cyp7a1 enhancer/promoter showed that cultured EBs contained GFP-positive epithelial-like cells. These results demonstrate that ES cells can differentiate in vitro into hepatocytes derived from definitive endoderm.
|
Cytochrome P450 Family 7
|
The olfactory epithelium (OE) has the remarkable capability to constantly replace olfactory receptor neurons (ORNs) due to the presence of neural stem cells (NSCs). For this reason, the OE provides an excellent model to study neurogenesis and neuronal differentiation. In the present work, we induced neuronal degeneration in the OE of Xenopus laevis larvae by bilateral axotomy of the olfactory nerves. We found that axotomy induces specific- neuronal death through apoptosis between 24 and 48h post-injury. In concordance, there was a progressive decrease of the mature-ORN marker OMP until it was completely absent 72h post-injury. On the other hand, neurogenesis was evident 48h post-injury by an increase in the number of proliferating basal cells as well as NCAM-180- GAP-43+ immature neurons. Mature ORNs were replenished 21 days post-injury and the olfactory function was partially recovered, indicating that new ORNs were integrated into the olfactory bulb glomeruli. Throughout the regenerative process no changes in the expression pattern of the neurotrophin Brain Derivate Neurotrophic Factor were observed. Taken together, this work provides a sequential analysis of the neurodegenerative and subsequent regenerative processes that take place in the OE following axotomy. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1308-1320, 2017.
|
Olfactory Nerve Injuries
|
BACKGROUND: Infections with bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BoCV) are endemic to the cattle populations in most countries, causing respiratory and/or enteric disease. It has been demonstrated that herds can remain free from these infections for several years also in high prevalence areas. Organically managed (OM) dairy herds have been shown to have lower seroprevalence of both viruses compared to conventionally managed (CM) herds. The objective of this study was to challenge the hypothesis of a lower occurrence of BRSV and BoCV in OM compared to CM dairy herds. In November 2011, May 2012 and May 2013 milk samples from four homebred primiparous cows were collected in 75 to 65 OM and 69 to 62 CM herds. The antibody status regarding BRSV and BoCV was analysed with commercial indirect ELISAs. Herds were classified as positive if at least one individual sample was positive. RESULTS: The prevalence of positive herds ranged from 73.4% to 82.3% for BRSV and from 76.8% to 85.3% for BoCV among OM and CM herds, over the three sampling occasions. There was no statistically significant difference between OM and CM herds at any sampling occasion. The incidence risk of newly infected herds did not differ statistically between OM and CM herds at any sampling occasion, neither for BRSV nor for BoCV. The incidence of herds turning sero-negative between samplings corresponded to the incidence of newly infected. Bulk tank milk (BTM) samples were also sampled in the herds and analysed. Several herds were negative on individual samples but positive in BTM. Herd-level data on production, health and reproduction were retrieved from VAXA Sweden and the study herds were representative of the source population. CONCLUSION: There was no difference in prevalence of or incidence risk for BRSV or BoCV between Swedish OM and CM herds. Because the incidence of herds becoming seropositive was balanced by herds becoming seronegative it should be possible to lower the prevalence of these two infections among Swedish dairy cattle herds if biosecurity is improved."
|
Respiratory Syncytial Virus, Bovine
|
Plasma cell mucositis is a rare, benign mucosal condition with characteristic histological features of a dense polyclonal plasmacytic infiltrate. A variety of mucosal sites are affected and the presentation varies from a cobblestone to an intensely erythematous, lobulated appearance. Idiopathic cases are well documented and it has been attempted to define the entity as a hypersensitivity reaction, however reports show inconsistencies. The last two decades have highlighted an emerging association between qat (khat) chewing and plasma cell mucositis. This report provides a review of the most pertinent literature and describes two cases intimately related to qat chewing, whereby resolution occurred upon qat cessation. One case requiring systemic steroidal therapy due to severe symptoms. This highlights the need for an increased awareness amongst clinicians of a potential aetiological link between qat and plasma cell mucositis, emphasises the benefit of qat cessation and the scenarios whereby systemic steroidal therapy should be considered.
|
Catha
|
BACKGROUND: Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study. OBJECTIVE: To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study. METHODS: 12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated. RESULTS: The median survival time was 3.39 years (95% confidence interval [CI]: 2.88-3.79) for VaD without medication, 6.62 years (95% CI: 6.24-7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85-3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30-8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73-6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02-9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55-2.83) without medication, 1.46 (95% CI: 1.39-1.54) with nootropics, 1.05 (95% CI: 0.82-1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80-1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15-1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22-2.72). CONCLUSION: Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival.
|
Dihydroergocristine
|
Cylindrospermopsin (CYN), a potent hepatoxin, occurs in freshwaters worldwide. Several cyanobacterial species produce the toxin, but the producing species vary between geographical regions. Aphanizomenon flos-aquae, a common algae species in temperate fresh and brackish waters, is one of the three well-documented CYN producers in European waters. So far, no genetic information on the CYN genes of this species has been available. Here, we describe the complete CYN gene cluster, including flanking regions from the German Aphanizomenon sp. strain 10E6 using a full genome sequencing approach by 454 pyrosequencing and bioinformatic identification of the gene cluster. In addition, we have sequenced a approximately 7 kb fragment covering the genes cyrC (partially), cyrA and cyrB (partially) of the same gene cluster in the CYN-producing Aphanizomenon sp. strains 10E9 and 22D11. Comparisons with the orthologous gene clusters of the Australian Cylindrospermopsis raciborskii strains AWT205 and CS505 and the partial gene cluster of the Israeli Aphanizomenon ovalisporum strain ILC-146 revealed a high gene sequence similarity, but also extensive rearrangements of gene order. The high sequence similarity (generally higher than that of 16S rRNA gene fragments from the same strains), atypical GC-content and signs of transposase activities support the suggestion that the CYN genes have been horizontally transferred.
|
Aphanizomenon
|
BACKGROUND: Despite being one of the leading causes of disability worldwide, fewer than 10% of depressed individuals in low-resource settings have access to treatment. Mounting evidence suggests that nonspecialist workers are capable of providing counseling and case management at the community level. They often use brief psychiatric screening instruments as clinical tools to identify cases and monitor symptoms over time. In order for such tools to be used in diverse settings, they must demonstrate adequate reliability and validity in addition to cross-cultural relevance. To be used to guide routine care they also need to be flexibly adapted and sensitive to change. The goal of this paper is to assess the cross-cultural validity of brief psychiatric screening instruments in sub-Saharan Africa, identify best practices, and discuss implications for clinical management and scale-up of mental health treatment in resource-poor settings. METHOD: Systematic review of studies assessing the validity of screening instruments for depression, anxiety, and mental distress in sub-Saharan Africa using Medline and PsycINFO. RESULTS: Sixty-five studies from 16 countries assessing the validity of brief screening instruments for depression, anxiety, and/or mental distress. CONCLUSIONS: Despite evidence of underlying universality in the experience of depression and anxiety in sub-Saharan Africa, differences in the salience, manifestation, and expression of symptoms suggest the need for the local adaptation of instruments. Rapid ethnographic assessment has emerged as a promising, low-cost, and efficient strategy for doing so.
|
Mass Screening
|
Genic allozyme polymorphism and heterozygosity was studied in a large population of the evening primrose, Oenothera biennis, growing in North Haven, Connecticut. This species is a permanent structural heterozygote for the entire complement of 14 chromosomes, and is thus capable of accumulating and maintaining genic heterozygosity. A total of 11 protein species were examined, and these were judged to be controlled by 19 loci. Polymorphism occurs at 26% of the loci, with only two alleles being present at each locus. The proportion of polymorphic loci per population in organisms with normal meiotic systems is no less than in Oe. biennis, indicating that structural heterozygosity is not necessarily accompanied by a greater proportion of polymorphic loci. On the other hand, the average Oe. biennis was heterozygous at 26% of its loci, an amount considerably greater than in most other organisms. With few exceptions, all plants in the North Haven population had the same genotype. Since the species is a colonizer, it is likely that the population was founded by a single individual and retained this genotype by virtue of the genetic system.
|
Electrophoresis, Starch Gel
|
Allergic eye disease encompasses a group of hypersensitivity disorders which primarily affect the conjunctiva and its prevalence is increasing. It is estimated to affect 8% of patients attending optometric practice but is poorly managed and rarely involves ophthalmic assessment. Seasonal allergic conjunctivitis (SAC) is the most common form of allergic eye disease (90%), followed by perennial allergic conjunctivitis (PAC; 5%). Both are type 1 IgE mediated hypersensitivity reactions where mast cells play an important role in pathophysiology. The signs and symptoms are similar but SAC occurs periodically whereas PAC occurs year round. Despite being a relatively mild condition, the effects on the quality of life can be profound and therefore they demand attention. Primary management of SAC and PAC involves avoidance strategies depending on the responsible allergen(s) to prevent the hypersensitivity reaction. Cooled tear supplements and cold compresses may help bring relief. Pharmacological agents may become necessary as it is not possible to completely avoid the allergen(s). There are a wide range of anti-allergic medications available, such as mast cell stabilisers, antihistamines and dual-action agents. Severe cases refractory to conventional treatment require anti-inflammatories, immunomodulators or immunotherapy. Additional qualifications are required to gain access to these medications, but entry-level optometrists must offer advice and supportive therapy. Based on current evidence, the efficacy of anti-allergic medications appears equivocal so prescribing should relate to patient preference, dosing and cost. More studies with standardised methodologies are necessary elicit the most effective anti-allergic medications but those with dual-actions are likely to be first line agents.
|
Rhinitis, Allergic, Seasonal
|
High-intensity focused ultrasound as a trackless, noninvasive method of ablating tissue has been a concept with potential for more than 60 years. It is only in the past 10 to 15 years that technological advances in both the delivery system and the monitoring systems have allowed us to begin to truly explore this potential clinically. Although unique technical challenges remain to be overcome, this ablative technique has been successfully applied in nearly all regions of the body, even some hidden by dense bone. The possibility that HIFU may be synergistic in ways that other ablative therapies are not, with both chemotherapeutics and immune system modifiers, positions HIFU for further investigations into multidisciplinary, individualized therapy unique to the patient.
|
Diathermy
|
A healthy 12-month-old female presented with relapsing and remitting urticaria since birth that was resistant to treatment with antihistamines. A thorough history revealed extensive rheumatic disease on the father's side of the family, and subsequent genetic testing was positive for a missense variant of NLRP3, indicating cryopyrin-associated periodic fever syndrome (CAPS). CAPS encompasses a spectrum of diseases, all related to a defect in the same gene; manifestations vary in severity and presentation, but most are associated with recurrent rash and fever. Because the patient's only presenting symptom was rash, this case highlights the importance of having a high index of suspicion for cryopyrin-associated periodic fever syndrome in infants with persistent, early urticaria.
|
Chronic Inducible Urticaria
|
The interactions of bone marrow-derived mesenchymal stem cells (MSCs) and their engrafted microenvironment are an integral part of signaling control of stem cell lineage commitment. We attempted to induce bone marrow-derived MSCs to undergo epidermal lineage differentiation by manipulating the biochemical, environmental and physical properties of culture conditions in an organotypic coculture model to simulate a skin-specific microenvironment. The induction medium was optimized by varying different biomolecular supplements in a basic stratification medium. A multi-layered epidermis-like structure was established when MSCs were cultured in an optimized induction medium on a contractible fibroblast-embedded collagen gel with an air-liquid interface. The commitment into epidermal lineage was further confirmed by the expression of early and intermediate epidermalization markers - keratin 10 and filaggrin in 90.67% and 80.51% of MSCs, respectively. This study not only highlights the possibility of in vitro control of MSCs into epidermal lineage, but also suggests the therapeutic potential of bone marrow-derived MSCs for skin regeneration.
|
Keratin-10
|
Goldthioglucose induces in mice a significant increase in body weight, glucose, insulin and lipid levels. Treatment with 250 mg/kg of methanol and ethyl acetate extracts of Zingiber officinale for 8 weeks produces significant reduction in body weight, glucose, insulin and lipid levels as compared to obese control mice. The reduction in elevated glucose along with elevated insulin levels indicates that the treatment with Z. officinale improves insulin sensitivity.
|
Aurothioglucose
|
From Nov 22, 1983 through May 15, 1984, 36 crossbred steers were allotted into 3 treatment groups (12/group) and were grazed on separate 3.4-hectare pastures. On Nov 22, 1983, the steers were administered a single morantel sustained-release bolus (MSRB), orally (group 1), or a single dose of thiabendazole (TBZ; 66 mg/kg of body weight, orally; group 2), or were left untreated (group 3; controls). Animal weights, nematode egg counts in fecal specimens, and plasma pepsinogen concentrations were monitored monthly. At the termination of the study, 4 steers from each treatment group were slaughtered and necropsied and worm counts were determined. A set of parasite-free tracer calves (3/treatment group) were grazed with each treatment group for 1 month, beginning on Nov 22, 1983; a second set of tracer calves (3/group) were grazed with each treatment group for 1 month, beginning Apr 3, 1984. At the end of their respective grazing periods, tracer calves were held for 3 weeks and then were slaughtered and necropsied and their worm counts were determined. Mean nematode egg counts in fecal specimens of group 1 (MSRB treated) were significantly lower (P less than 0.05) than that of the TBZ-treated or nontreated steers. Differences in worm counts were not found between treatment groups. Differences in worm counts of tracer calves were not found among the 3 groups for November 1983 nor for April 1984. Steers treated with the MSRB had a higher mean weight gain (P less than 0.06) than did the control or TBZ-treated steers.
|
Morantel
|
Vesicular glutamate transporters (VGLUTs) are responsible for vesicular glutamate storage and exocytotic glutamate release in neurons and astrocytes. Here, we selectively and efficiently overexpressed individual VGLUT proteins (VGLUT1, 2, or 3) in solitary astrocytes and studied their effects on mechanical stimulation-induced Ca2+-dependent glutamate release. Neither VGLUT1 nor VGLUT2 overexpression changed the amount of glutamate release, whereas overexpression of VGLUT3 significantly enhanced Ca2+-dependent glutamate release from astrocytes. None of the VGLUT overexpression affected mechanically induced intracellular Ca2+ increase. Inhibition of glutamine synthetase activity by L-methionine sulfoximine in astrocytes, which leads to increased cytosolic glutamate concentration, greatly increased their mechanically induced Ca2+-dependent glutamate release, without affecting intracellular Ca2+ dynamics. Taken together, these data indicate that both VGLUT3 and the cytosolic concentration of glutamate are key limiting factors in regulating the Ca2+-dependent release of glutamate from astrocytes."
|
Vesicular Glutamate Transport Protein 2
|
Water stress triggers acclimation responses and can damage plants, which varies by species and stress levels. Ongoing climate change is projected to result in longer and more intense water stress conditions leading to an alarming increase in drought-induced forest decline. The aim of this study was to evaluate the physiological responses of leaves and stem wood anatomy from Araucaria araucana pot-grown three-year old seedlings, a conifer tree from northwestern Patagonia. Plants were subjected to moderate and severe water restriction regimes and compared to well-watered controls. Severe water stress reduced relative leaf water content and triggered an accumulation of free proline in leaves, regardless of age. Epicuticular wax extrusions increased in apical leaf stomata while photosynthetic pigments decreased, resulting in differential oxidative damage. The concentration of phenolic compounds was not affected by water restrictions. Plants exposed to restricted water regimes showed diminished middle leaf biomass and expansion (~60% of total leaves), increased stem wood density, and experienced 7% and 30% mortality rates under moderate and severe water stress, respectively. Our findings suggest that under moderate water stress, analogous to short-term droughts, A. araucana seedlings activate physiological mechanisms that allow them to withstand short periods of drought, while more severe water stress and longer droughts can be severely harmful.
|
Araucaria araucana
|
The aim of this study was to improve the quality of estimations of the first-order kinetic constant k, in Biochemical Methane Potential (BMP) tests. The results showed that existing guidelines for BMP tests are not sufficient to improve the estimation of k. The methane production of the inoculum itself exerted a major influence on the estimation of k. A flawed value in k was correlated with a high endogenous methane production. Excluding blanks that showed a distinct lag-phase of >1 day and a mean relative standard deviation >10% during the first ten days of a BMP test helped to retrieve more consistent estimates for k. For improving the repeatability in the determination of k in BMP tests, it is strongly recommended to inspect the methane production rate of the blanks. The proposed threshold values may be applied by other researchers but need further verification with different data.
|
Anaerobiosis
|
Assessment of legal age, also known as age of majority, is a controversial issue as there are few body biomarkers or evidence during late adolescence differentiating a subject from being a minor or adult. The third molar was recognized as a suitable site for age examination in late adolescence. We analyzed the development of the left mandibular third molar by the third molar maturity index (I3M) and a specific cut-off value of I3M = 0.08, established by Cameriere et al. in 2008 and used it for discriminating between minors and adult black Africans from Gaborone, Botswana. A final sample of panoramic radiographs (OPTs) of 1294 people (582 males and 712 females) aged between 13 and 23 years was evaluated. The real age decreased as I3M gradually increased. There was no statistically significant difference in the third molar development evaluated using I3M between males and females (p > 0.05) across different I3M classes. Results of 2 x 2 contingency tables for different cut-off values indicated that I3M = 0.08 was useful in discriminating between adults and minors. Precisely, for I3M = 0.08, the values of accuracy or overall fraction of correctly classified were 0.91 in males with a 95 % confidence interval (95 % CI) of 0.88 to 0.93 and 0.92 (95 % CI, 0.90 to 0.93) in females. Values of sensitivity of the test or the proportion of participants being 18 years and older were 0.88 (95 % CI, 0.87 to 0.90) in males and 0.88 (95 % CI, 0.90 to 0.93) in females, while values of specificity or proportion of individuals younger than 18 who have I3M <0.08 were 0.94 (95 % CI, 0.91 to 0.96) in males and 0.96 (95 % CI, 0.94 to 0.98) in females. Positive predictive values of the test, where the participants whose I3M <0.08 were adults, were 0.94 (95 % CI 0.91 to 0.96) in males and 0.97 (95 % CI, 0.94 to 0.98) in females, while negative predictive values of the test, where the participants whose I3M was >/=0.08 were minors, were 0.88 (95 % CI 0.85 to 0.90) in males and 0.97 (95 % CI, 0.94 to 0.98) in females. The likelihood ratios of the positive test (LR+) were 13.67 (95 % CI, 9.21 to 21.02) in males and 23.73 (95 % CI, 14.20 to 42.28) in females, while likelihood ratios of the negative test (LR-) were 0.12 (95 % CI 0.10 to 0.16) in males and 0.12 (95 % CI, 0.11 to 0.15) in females. Bayes post-test probabilities, p, were 0.94 (95 % CI 0.90 to 0.98) in males and 0.97 (95 %CI, 0.93 to 1.00) in females. These results indicate with high accuracy that I3M may be a useful alternative method in legal and forensic practice to discriminate individuals of black African origin who are around the legal adult age of 18 years in Botswana. Further studies should address the usefulness of this method and specific cut-off for different adolescent populations.
|
Molar, Third
|
Pisotriquetral instability is an often-overlooked condition that can lead to ulnar-sided wrist pain and dysfunction. Various case series and biomechanical studies have been published regarding the diagnosis and treatment of this condition. We review current methods for examining, diagnosing, and treating pisotriquetral instability.
|
Pisiform Bone
|
AIMS: Cardiac energy requirement is met to a large extent by oxidative phosphorylation in mitochondria that are highly abundant in cardiac myocytes. Human mitochondrial thioredoxin reductase (TXNRD2) is a selenocysteine-containing enzyme essential for mitochondrial oxygen radical scavenging. Cardiac-specific deletion of Txnrd2 in mice results in dilated cardiomyopathy (DCM). The aim of this study was to investigate whether TXNRD2 mutations explain a fraction of monogenic DCM cases. METHODS AND RESULTS: Sequencing and subsequent genotyping of TXNRD2 in patients diagnosed with DCM (n = 227) and in DCM-free (n = 683) individuals from the general population sample KORA S4 was performed. The functional impact of observed mutations on Txnrd2 function was tested in mouse fibroblasts. We identified two novel amino acid residue-altering TXNRD2 mutations [175G > A (Ala59Thr) and 1124G > A (Gly375Arg)] in three heterozygous carriers among 227 patients that were not observed in the 683 DCM-free individuals. Both DCM-associated mutations result in amino acid substitutions of highly conserved residues in helices contributing to the flavin-adenine dinucleotide (FAD)-binding domain of TXNRD2. Functional analysis of both mutations in Txnrd2(-/-) mouse fibroblasts revealed that contrasting to wild-type (wt) Txnrd2, neither mutant did restore Txnrd2 function. Mutants even impaired the survival of Txnrd2 wt cells under oxidative stress by a dominant-negative mechanism. CONCLUSION: For the first time, we describe mutations in DCM patients in a gene involved in the regulation of cellular redox state. TXNRD2 mutations may explain a fraction of human DCM disease burden.
|
Thioredoxin Reductase 2
|
In Vietnam, there are no accurate data on tetanus incidence to allow assessment of disease burden or vaccination program efficacy. We analyzed age structure of 786 tetanus cases admitted to a tertiary referral center in Vietnam for three separate years during an 18-year period to examine the impact of tetanus prevention programs, namely the Expanded Program on Immunization (EPI) and the Maternal and Neonatal Tetanus (MNT) initiative. Most cases were born before the initiation of EPI. Median age increased from 33 (interquartile range: 20-52) in 1994, to 46 (32-63) in 2012 (P < 0.001). Birth-year distribution was unchanged, indicating the same birth cohorts presented with tetanus in 1994, 2003, and 2012. Enzyme-linked immunosorbent assay measurements in 90 men and 90 women covered by MNT but not EPI showed 73.3% (95% confidence interval [CI]: 62.9-82.1%) of women had anti-tetanus antibody compared with 24.4% (95% CI: 15.9-34.7%) of men, indicating continued tetanus vulnerability in older men in Vietnam.
|
Tetanus Toxoid
|
Echinococcosis is a zoonotic disease with great significance to public health, and appropriate detection and control strategies should be adopted to mitigate its impact. Most cases of echinococcosis are believed to be transmitted by the consumption of food and/or water contaminated with canid stool containing Echinococcus spp. eggs. Studies assessing Echinococcus multilocularis, Echinococcus granulosus sensu stricto, and Echinococcus shiquicus coinfection from contaminated water-derived, soil-derived, and food-borne samples are scarce, which may be due to the lack of optimized laboratory detection methods. The present study aimed to develop and evaluate a novel triplex TaqMan-minor groove binder probe for real-time polymerase chain reaction (rtPCR) to simultaneously detect the 3 Echinococcus spp. mentioned above from canid fecal samples in the Qinghai-Tibetan Plateau area (QTPA). The efficiency and linearity of each signal channel in the triplex rtPCR assay were within acceptable limits for the range of concentrations tested. Furthermore, the method was shown to have good repeatability (standard deviation </=0.32 cycle threshold), and the limit of detection was estimated to be 10 copies plasmid/mul reaction. In summary, the evaluation of the present method shows that the newly developed triplex rtPCR assay is a highly specific, precise, consistent, and stable method that could be used in epidemiological investigations of echinococcosis."
|
Multiplex Polymerase Chain Reaction
|
The immunomodulative effects of elm bark extract were studied in vitro by the proliferation of splenocytes and the production capacity of three kinds of cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha] by mouse peritoneal macrophages cultured with various fractions (methanol, hexane, chloroform, ethyl acetate, butanol, and water) of elm bark extract. Splenocyte proliferation and cell viability of peritoneal macrophages were increased with concentrations of polar fractions, such as butanol and water, in the range of 1-500 microg/mL. Significantly higher levels of the production of all three cytokines were detected with supplementation of methanol extract compared with other fractions. In order to elucidate its effect in vivo, elm bark water extract was orally administrated every other day for 2 weeks. Proliferation of splenocytes and the production capacity of cytokines (IL-1beta, IL-6, and TNF-alpha) by mouse peritoneal macrophages were used as indices for immune activity. Splenocyte proliferation induced by elm bark with lipopolysaccharide or concanavalin A stimulation was enhanced at 500 mg/kg of body weight concentrations compared to that of the control group. In the case of cytokines, the highest production of IL-6 and TNF was detected at 500 mg/kg of body weight concentrations. In conclusion, this study suggests through in vitro and in vivo experiments that Ulmus davidiana var. japonica (elm bark) extracts may enhance the immunocompetent properties such as splenocyte proliferation and cytokine production capacity by activated macrophages and have a protective effect in mice.
|
Ulmaceae
|
Tumor spheroids are fast becoming commonplace in basic cancer research and drug development. Obtaining data regarding protein expression within the spheroid at the cellular level is important for analysis, yet existing techniques are often expensive, laborious, use non-standard equipment, cause significant size distortion, or are limited to relatively small spheroids. This protocol presents a new method of mounting and clearing spheroids that address these issues while allowing for confocal analysis of the inner structure of spheroids. In contrast to existing approaches, this protocol provides for rapid mounting and clearing of a large number of spheroids using standard equipment and laboratory supplies. Mounting spheroids in a pH-neutral agarose-PBS gel solution before introducing a refractive-index-matched clearing solution minimizes size distortion common to other similar techniques. This allows for detailed quantitative and statistical analysis where the accuracy of size measurements is paramount. Furthermore, compared to liquid clearing solutions, the agarose gel technique keeps spheroids fixed in place, allowing for the collection of three-dimensional (3D) confocal images. The present article elaborates how the method yields high-quality two- and 3D images that provide information about inter-cell variability and inner spheroid structure.
|
Spheroids, Cellular
|
The use of complementary and alternative medicine is wide-spread not only in Eastern countries, but also in the Western world. Despite the increasing evidence on the harmful effects induced by several naturopathic/homeopathic products, patients seem to appreciate these remedies, in particular because they consider them to be absolutely safe. This same phenomenon is common among inflammatory bowel disease (IBD) patients. As a result there is a significant request for scientific data to evaluate both the efficacy and safety of these remedies, and to support the use of such medications as adjuvant treatments to biological and synthetic drugs. We aimed to review the current evidence on efficacy and safety of some natural products that are believed to be effective in inflammatory bowel disease. Further perspectives for the clinical use of herbal products and strategies for improving knowledge about herbal products in IBD are also discussed.
|
Burseraceae
|
The incidence of congenital esophageal stenosis (CES) is approximately 1 in 25,000 to 50,000 live births. There is associated esophageal atresia in one third of cases; the remainder are classified as isolated CES. Histologically, the anomaly may include tracheobronchial remnants, a membranous diaphragm, or diffuse fibrosis of the muscularis and submucosa. The authors report their experience with three patients who had isolated CES. The patients were free of symptoms for the first 6 months of life. All had difficulty with feeding from 6 to 12 months of age, which corresponded with the introduction of solids. Most solid feedings were regurgitated. Evaluation consisted of cine-esophagogram, pH monitoring, manometry, and endoscopy, with biopsies to exclude the diagnosis of gastroesophageal reflux. All patients underwent hydrostatic dilatation, but the benefit was only transient. The patients were referred for surgical correction when symptoms recurred. Limited resection of the esophageal stenosis with primary anastomosis was performed on all three patients via a left thoracotomy. The stenoses were located in the distal third of esophagus, near the junction with the middle third. Pathological examination showed tracheobronchial remnants in one patient and fibrotic muscle in the other two. The average age at the time of surgery was 19 months. The hospital stay averaged 8 days. The contrast study 1 week postthoracotomy showed esophageal patency in all patients, with no leakage. All were discharged from the hospital, tolerating solid food. CES should be sought for in patients who present with dysphagia to solid food that begins after the first 6 months of life.(ABSTRACT TRUNCATED AT 250 WORDS)
|
Esophageal Stenosis
|
California encephalitis (CE) virus (snowshoe hare subtype) was isolated from 1 of 38 pools comprising 970 unengorged female Aedes canadensis mosquitoes and from 3 of 152 pools containing 5,676 A. communis mosquitoes which were collected in the Yukon Territory, Canada between latitudes 61 and 66 degrees N during June and July 1974. During four summers 1971 through 1974, this virus was recovered from 26 of 648 pools derived from 30,686 mosquitoes of 4 species. Isolation of CE virus from 1 of 109 pools of Aedes sp. larvae collected during May 1974 suggests maintenance of this virus over winter by transovarial transfer. Infectivity has been maintained in Culiseta inornata mosquitoes which were held continuously at 32 degrees F for 138 days. Neutralizing antibodies to CE virus were detected in 705 of 4,913 (14%) mammals collected during summers 1971 through 1974, including 430 of 1,076 (40%) snowshoe hares (Lepus americanus), 266 of 3,610 (7%) ground squirrels (Citellus undulatus) and 9 of 227 (4%) red squirrels (Tamiasciurus hudsonicus).
|
Encephalitis, California
|
Mucormycosis are opportunist infections occurring usually among predisposed patients. We report a case of an 18-year-old male with a severe thoracic trauma who developed an Absidia infection on his contused pulmonary parenchyma, without presenting the usual risk factors (diabetes mellitus, immunodeficiency). The early diagnosis using bronchoscopy has probably improved the outcome by allowing a faster treatment. After 18-months, the infectious process resolved thanks to a combination of a medical treatment composed of high-dose amphotericin B lipid formulation, itraconazole and a complementary surgical treatment.
|
Absidia
|
Na+-activated K+ currents (K(Na)) have been reported in multiple neuronal nuclei and the properties of K(Na) vary in different cell types. We have described previously the distribution of Slack, a Na+-activated K+ channel subunit. Another recently cloned Na+-activated K+ channel is Slick, which differs from Slack in its rapid activation and its sensitivity to intracellular ATP levels. We now report the localization of Slick in the rat central nervous system using in situ and immunohistochemical techniques. As for Slack, we find that Slick is widely distributed in the brain. Specifically, strong hybridization signals and immunoreactivity were found in the brainstem, including auditory neurons such as the medial nucleus of the trapezoid body. As has also been shown for Slack, Slick is expressed in the olfactory bulb, red nucleus, facial nucleus, pontine nucleus, oculomotor nucleus, substantia nigra, deep cerebellar nuclei, vestibular nucleus, and the thalamus. Slick mRNA and protein, however, also are found in certain neurons that do not express Slack. These neurons include those of the hippocampal CA1, CA2, and CA3 regions, the dentate gyrus, supraoptic nucleus, hypothalamus, and cortical layers II, III, and V. These data suggest that Slick may function independently of Slack in these regions. Computer simulations indicate that Slick currents can cause adaptation during prolonged stimuli. Such adaptation allows a neuron to respond to high-frequency stimulation with lower-frequency firing that remains temporally locked to individual stimuli, a property seen in many auditory neurons. Although it is not yet known if Slick and Slack subunits heteromultimerize, the existence of two genes that encode K(Na), that are widely expressed in the nervous system, with both overlapping and nonoverlapping distributions, provides the basis for the reported heterogeneity in the properties of K(Na) from various neurons."
|
Potassium Channels, Sodium-Activated
|
BACKGROUND: The microbiological spoilage of fishery foods is mainly due to specific spoilage organisms (SSOs), with Shewanella putrefaciens being the SSO of most chilled marine fish. Bacteriophages have shown excellent capability to control micro-organisms. The aim of this study was to determine a specific bacteriophage to prevent spoilage by reducing SSO (S. putrefaciens) levels in the marine fish Paralichthys olivaceus (olive flounder) under chilled storage. RESULTS: Chilled flounder fillets were inoculated with S. putrefaciens and treated with different concentrations of bacteriophage Spp001 ranging from 10(4) to 10(8) plaque-forming units (pfu) mL(-1) . Bacterial growth (including total viable count and SSO) of the bacteriophage-treated groups was significantly inhibited compared with that of the negative control group (P < 0.05). Sensory evaluation and biochemical parameters revealed that the bacteriophage could extend the shelf life of chilled flounder fillets (from <4 to 14 days) with good esthetic quality, even at low temperature (4 degrees C). Furthermore, bacteriophage concentrations of 10(6) and 10(8) pfu mL(-1) were more effective than the chemical preservative potassium sorbate (5 g L(-1) ). CONCLUSION: The bacteriophage Spp001 offered effective biocontrol of S. putrefaciens under chilled conditions, retaining the quality characteristics of spiked fish fillets, and thus could be a potential candidate for use in chilled fish fillet biopreservation.
|
Shewanella putrefaciens
|
BACKGROUND: Previous works have observed that younger infants with chronic hepatitis B virus (HBV) infection are more responsive to antiviral treatment. However, the underlying mechanism remains unclear. In this study, the dynamic changes of HBV quasispecies in infants with immunoprophylaxis failure were investigated to provide virological explanations for clinical management on infantile antiviral therapy. METHODS: Thirteen 7-month-old infants with immunoprophylaxis failure and their mothers were enrolled from a prospective cohort, and 8 of them were followed up to 3 years old. The sequences of HBV quasispecies were analyzed by the full-length genome clone-based sequencing, and compared among mothers and their infants at different ages. RESULTS: The results revealed that the complexity, mutation frequency and genetic distance of HBV quasispecies decreased significantly at full-length, partial open reading frames and regulatory regions of HBV genome at nucleotide level in 7-month-old infants comparing with their mothers, whereas increased significantly to near the maternal level when infants grew up to 3 years old. Furthermore, similar changes were also found in Core, PreS2, RT and P regions of HBV genome at amino acid level, especially for potential NAs-resistant mutants in RT region and immune-escape mutants in Core and PreS2 regions. CONCLUSIONS: This study uncovered the evolution of HBV quasispecies in infancy after mother-to-child transmission, which may provide the virological evidence for explaning that younger children are more responsive to antiviral therapy.
|
Quasispecies
|
INTRODUCTION: Vaginal suturing can be challenging to teach and learn due to the surgical assistant's limited operative field visualization. Data on resident training and comfort with cerclage placement using models are limited. The aim of this activity was to assess learner satisfaction with practice using a novel model allowing for full visualization during transvaginal cervical cerclage placement. METHODS: OB/GYN residents participated in a 1-hour combined lecture and hands-on cerclage training simulation with the novel model. Pre- and postsession survey responses were assessed with descriptive statistics and paired t tests. RESULTS: Twenty residents with a median of 2 (SD = 1.6) years of residency experience participated. Ninety-five percent reported no prior cerclage simulation training; 60% reported placing cerclages in practice. Pre- and posttest analysis indicated a significant decrease in perceived need for further training (M = 4.05, SD = 1.07, vs. M = 3.45, SD = 0.86; p = .024) and an increase in comfort performing a cerclage placement (M = 2.55, SD = 1.16, vs. M = 3.85, SD = 0.79; p < .001). After the simulation, residents reported more comfort in cerclage placement with decreasing supervision (M = 2.05, SD = 1.02, vs. M = 2.30, SD = 1.01; p = .021); 90% reported that learning to place a cerclage was easy. DISCUSSION: Implementing a novel, low-cost model allowing full operative field visualization significantly improved reported comfort regarding cervical cerclage placement and resulted in high satisfaction amongst residents. Future research should evaluate the training's impact on clinical skills.
|
Cerclage, Cervical
|
Tumor suppressor p53 is a transcription factor that induces growth arrest and/or apoptosis in response to cellular stress. To identify novel p53-inducible genes, we compared the expression of genes in normal mouse embryo fibroblasts (MEFs) to p53-null cells by cDNA representational difference analysis. We report here that expression of endogenous sodium channel subunit beta 3 (SCN3B) is upregulated in mouse embryonic fibroblasts by DNA damage in a p53-dependent manner. In addition, we found that SCN3B levels are upregulated in human cancer cell lines by DNA damaging agents, as well as by overexpression of p53, but not significantly by p63 or p73. Furthermore, we identified two putative p53-binding sites upstream of the first exon (RE1) and in the third intron (RE2). The p53 protein can directly interact with the putative p53-binding sites in vivo, as assessed by chromatin immunoprecipitation. A reporter gene assay revealed that these two p53-binding sites are functional response elements. The SCN3B protein appears to be localized to the endoplasmic reticulum (ER). Introduction of the SCN3B gene into T98G and Saos2 cells potently suppressed colony formation. Furthermore, we found that adenovirus-mediated transfer of SCN3B induced apoptosis when combined with anticancer agents. The results presented here suggest that SCN3B mediates a p53-dependent apoptotic pathway and may be a candidate for gene therapy combined with anticancer drugs."
|
Voltage-Gated Sodium Channel beta-3 Subunit
|
OBJECTIVE: The purpose of this study was to compare 2 film systems and several digital intraoral systems with regard to visual image quality through use of a test phantom developed for this purpose. STUDY DESIGN: The detectors used for digital imaging were as follows: Computed Dental Radiography (CDR), Digora, Dixel, and Sens-A-Ray without scintillator layer. Two types of digital images were prepared for the observer performance test: one with original gray scales and another with contrast enhancement. Images with and without enhancement from the 4 systems were displayed to 7 observers. The change in the average number of perceptible holes was plotted against exposure, and modified perceptibility curves were created and compared with curves for the film systems. The exposure level at which the maximum number of holes was perceived was defined to be optimum. The optimum exposure levels were determined for each digital system and compared with that of the film systems. At the optimum exposure, the average maximum numbers of perceptible holes in each digital system with and without contrast enhancement were compared with the maximum numbers for the film systems. The minimum exposure levels were determined to be those at which the number of perceptible holes exceeded the number for film, and the possibility of exposure reduction was evaluated. RESULTS: All digital systems except the Digora system showed lower optimum exposures than E-speed film. In all digital images without enhancement, however, the maximum number of perceptible holes was significantly lower than that for the film systems at that exposure. With contrast enhancement, all digital systems except the Sens-A-Ray system showed visibility superior to that of the film systems. With the CDR, Digora, and Dixel systems, exposures could be further reduced by a considerable amount, with greater retention of information than was associated with film. CONCLUSIONS: Our results strongly suggest that digital systems, if properly used, can exceed film systems in the detection of small mass changes.
|
Diagnosis, Oral
|
The infusion of hypertonic saline solution (HSS) is known to be beneficial to the treatment of hypovolemic hemorrhage (HH). The central mechanism of HSS-induced cardiovascular and autonomic recovery of animals subjected to HH remains unclear. Hence, the present study evaluated the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats. The wistar rats were subjected to specific lesion of noradrenergic neurons through the nanoinjections of anti-DbetaH-saporin into caudal ventrolateral medulla (A1 neurons) and nucleus of the solitary tract (A2 neurons). After recovery, mean arterial pressure (MAP) and renal sympathetic nervous activity were recorded. The HH was performed through blood withdrawal until a MAP of 60 mmHg was attained. In sham rats, HSS infusion (3M NaCl) reestablished MAP without change in HH-induced sympathoinhibition. The muscimol (agonist of GABA(A) receptor) was nanoinjected in MnPO during HH and MnPO inhibition abolished the recovery of MAP and HSS-induced sympathoinhibition. Simultaneous lesions of A1 and A2 abolished MAP restoration and sympathoinhibition after HSS infusion. These results suggest that the recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.
|
Adrenergic Neurons
|
Lon, also known as the protease La, is a homo-oligomeric ATP-dependent protease, which is highly conserved in archaea, eubacteria and eukaryotic mitochondria and peroxisomes. Since its discovery, studies have shown that Lon activity is essential for cellular homeostasis, mediating protein quality control and metabolic regulation. This article highlights the discoveries made over the past decade demonstrating that Lon selectively degrades abnormal as well as certain regulatory proteins and thus plays significant roles in maintaining bacterial and mitochondrial function and integrity. In addition, Lon is required in certain pathogenic bacteria, for rendering pathogenicity and host infectivity. Recent research endeavors have been directed toward elucidating the reaction mechanism of the Lon protease by different biochemical and structural biological techniques. In this mini-review, the authors survey the diverse biological roles of Lon, and also place special emphasis on recent findings that clarify the mechanistic aspects of the Lon reaction cycle.
|
AAA Proteins
|
Podosomes are micrometer-sized, circular adhesions formed by cells such as osteoclasts, macrophages, dendritic cells, and endothelial cells. Because of their small size and the lack of methods to visualize individual proteins and protein complexes, podosomes have long been considered a simple two-module structure with a protrusive actin core and a surrounding adhesive ring composed of integrins and cytoskeletal adaptor proteins such as vinculin and talin. In the past decade, the applications of fluorescence based techniques that circumvent the diffraction limit of conventional light microscopy took a major leap forward. Podosomes have been imaged by a variety of these super-resolution methods, and in this concise review we discuss how these super-resolution data have increased our understanding of the podosome ultra-structure and function.
|
Cell Surface Extensions
|
Phosphatidylinositol (PI) is a phospholipid molecule required for the generation of seven different phosphoinositide lipids which have a diverse range of signaling and trafficking functions. The precise mechanism of phosphatidylinositol supply during receptor activated signaling and the cellular compartmentation of the synthetic process are still incompletely understood and remain controversial despite several decades of research in this area. The synthesis of phosphatidylinositol requires the activity of an enzyme called phosphatidylinositol synthase, also known as CDIPT, which catalyzes a reversible headgroup exchange reaction on its substrate liponucleotide CDP-diacylglycerol resulting in the incorporation of inositol to generate phosphatidylinositol and the release of CMP. This protocol describes a method for locating PI synthase activity in isolated, intact biological membranes and vesicles."
|
CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase
|
Aryl acylamidase (EC 3.1.5.13; AAA) catalyzes the hydrolysis of p-nitroacetanilide (PNAA) via the standard three-step mechanism of serine hydrolases: binding of substrate (K(s)), acylation of active-site serine (k(acyl)), and hydrolytic deacylation (k(deacyl)). Key mechanistic findings that emerged from this study include that (1) AAA requires a deprotonated base with a pK(a) of 8.3 for expression of full activity toward PNAA. Limiting values of kinetic parameters at high pH are k(c) = 7 s(-1), K(m) = 20 microM, and k(c)/K(m) = 340 000 M(-1) s(-1). (2) At pH 10, where all the isotope effects were conducted, k(c) is equally rate-limited by k(acyl) and k(deacyl). (3) The following isotope effects were determined: (D)()2(O)(k(c)/K(m)) = 1.7 +/- 0.2, (D)()2(O)k(c) = 3.5 +/- 0.3, and (beta)(D)(k(c)/K(m)) = 0.83 +/- 0.04, (beta)(D)k(c) = 0.96 +/- 0.01. These values, together with proton inventories for k(c)/K(m) and k(c), suggest the following mechanism: (i) The initial binding of substrate to enzyme to form the Michaelis complex is accompanied by solvation changes that generate solvent deuterium isotope effects originating from hydrogen ion fractionation at multiple sites on the enzyme surface. (ii) From within the Michaelis complex, the active site serine attacks the carbonyl carbon of PNAA with general-base catalysis to form a substantially tetrahedral transition state enroute to the acyl-enzyme. (iii) Finally, deacylation occurs through a process involving a rate-limiting solvent isotope effect, generating conformational change of the acyl-enzyme that positions the carbonyl bond in a polarizing environment that is optimal for attack by water.
|
Acetanilides
|
The present experiment assessed the aversive quality of neuropathic and inflammatory pain in rats. Compared to sham-treated animals, L5 ligated (neuropathic) and complete Freund's adjuvant (inflammatory)-treated animals displayed an initial period of escape followed by avoidance of a preferred location of the test chamber that was associated with mechanical stimulation of the hyperalgesic paw. The onset of the avoidance behavior occurred during the first 10-15 min of behavioral testing and was maximal at 30 min. It is concluded that animals find mechanical stimulation of the hyperalgesic paw aversive and that this behavioral test paradigm is an additional method that may be used to assess nociception in rat neuropathic and inflammatory models.
|
Pain Threshold
|
DNA-dependent protein kinase (DNA-PK), composed of Ku70, Ku80, and the catalytic subunit (DNA-PKcs), is involved in double-strand break (DSB) repair by non-homologous end joining (NHEJ). DNA-PKcs defects confer ionizing radiation sensitivity and increase homologous recombination (HR). Increased HR is consistent with passive shunting of DSBs from NHEJ to HR. We therefore predicted that inhibiting the DNA-PKcs kinase would increase HR. A novel DNA-PKcs inhibitor (1-(2-hydroxy-4-morpholin-4-yl-phenyl)-ethanone; designated IC86621) increased ionizing radiation sensitivity but surprisingly decreased spontaneous and DSB-induced HR. Wortmannin also inhibits DNA-PKcs and reduces DSB-induced HR. IC86621 did not affect HR product outcome, indicating that it affects HR initiation. Thus, HR is increased in the absence of DNA-PKcs, but decreased when DNA-PKcs is catalytically inactive, suggesting interactive competition between HR and NHEJ. The effects of IC86621 and wortmannin were proportional to the level of DNA-PKcs, consistent with inhibited DNA-PKcs acting in a dominant negative manner. We propose that inhibition of DNA-PKcs blocks its autophosphorylation, prevents dissociation of DNA-PKcs from DNA ends, and thereby blocks both HR and NHEJ. By blocking the two major DSB repair pathways, DNA-PKcs inhibitors should radiosensitize at all cell-cycle stages and are therefore excellent candidates for augmenting cancer radiotherapy.
|
Wortmannin
|
CHARGE syndrome is a dominant disorder characterized by ocular colobomata, heart defects, choanal atresia, retardation of growth and development, genital hypoplasia, and ear abnormalities including deafness and vestibular disorders. The majority of individuals with CHARGE have pathogenic variants in the gene encoding CHD7, a chromatin remodeling protein. Here, we present a 15-year-old girl with clinical features of CHARGE syndrome and a de novo 6.5 Mb gain of genomic material at 2p25.3-p25.2. The duplicated region contained 24 genes, including the early and broadly expressed transcription factor gene SOX11. Analysis of 28 other patients with CHARGE showed no SOX11 copy number changes or pathogenic sequence variants. To our knowledge, this child's chromosomal abnormality is unique and represents the first co-occurrence of duplication 2p25 and clinical features of CHARGE syndrome. We compare our patient's phenotype to ten previously published patients with isolated terminal duplication 2p, and elaborate on the clinical diagnosis of CHARGE in the context of atypical genetic findings.
|
CHARGE Syndrome
|
The fundamental principles of survival analysis are reviewed. In particular, the Kaplan-Meier method and a proportional hazard model are discussed. This work is the last part of a series in which medical statistics are surveyed.
|
Statistics as Topic
|
OBJECTIVE: To determine the effect of an abdominal support wrap and transrectal abdominal palpation on intra-abdominal pressures (IAPs) measured directly from the peritoneal space. DESIGN: Prospective, experimental study. SETTING: A university-based equine research facility. ANIMALS: Ten healthy adult horses, 5 males and 5 females. INTERVENTIONS: IAPs were measured through an intraperitoneal cannula zeroed at a height midway between the height of the tuber ishii and point of the shoulder. Triplicate measurements were obtained at rest, during transrectal palpation, after placement of an abdominal support wrap, and during transrectal palpation with the support wrap still in place. Simultaneous mean arterial pressures were obtained using a tail cuff and abdominal perfusion pressures were calculated using the measured IAP minus the measured mean arterial pressures. MEASUREMENTS AND MAIN RESULTS: Baseline direct pressure measurements were subatmospheric (-4.5 +/- 3.0 cm H(2) O). IAPs were not significantly affected by transrectal palpation, but were significantly increased after placement of an abdominal support wrap (-1.19 +/- 3.01 cm H(2) O; P = 0.01). Abdominal perfusion pressures were not significantly affected by either transrectal palpation or application of the support wrap. CONCLUSION: IAPs were significantly increased after application of an abdominal support wrap commonly used after exploratory laparotomy. Further investigations are warranted to determine the clinical implications of abdominal bandaging on IAP and its implications on postoperative complications including intra-abdominal hypertension. However, transrectal abdominal palpation likely does not contribute to abdominal hypertension in normal horses.
|
Digital Rectal Examination
|
Leukotriene B4 (LTB4) is a major type of lipid mediator that is rapidly generated from arachidonic acid through sequential action of 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTA4 hydrolase (LTA4H) in response to various stimuli. LTB4 is well known to be a chemoattractant for leukocytes, particularly neutrophils, via interaction with its high-affinity receptor BLT1. Extensive attention has been paid to the role of the LTB4-BLT1 axis in acute and chronic inflammatory diseases, such as infectious diseases, allergy, autoimmune diseases, and metabolic disease via mediating recruitment and/or activation of different types of inflammatory cells depending on different stages or the nature of inflammatory response. Recent studies also demonstrated that LTB4 acts on non-immune cells via BLT1 to initiate and/or amplify pathological inflammation in various tissues. In addition, emerging evidence reveals a complex role of the LTB4-BLT1 axis in cancer, either tumor-inhibitory or tumor-promoting, depending on the different target cells. In this review, we summarize both established understanding and the most recent progress in our knowledge about the LTB4-BLT1 axis in host defense, inflammatory diseases and cancer.
|
Receptors, Leukotriene
|
An overexpression system for spinach apocytochrome b(6) as a fusion protein to a maltose-binding protein in Escherichia coli was established using the expression vector pMalp2. The fusion of the cytochrome b(6) to the periplasmic maltose-binding protein directs the cytochrome on the Sec-dependent pathway. The cytochrome b(6) has a native structure in the bacterial cytoplasmic membrane with both NH(2) and COOH termini on the same, periplasmic side of the membrane but has the opposite orientation compared to that in thylakoid. Our data also show that in the E. coli cytoplasmic membrane, apocytochrome b(6) and exogenic hemes added into a culture media spontaneously form a complex with similar spectroscopic properties to native cytochrome b(6). Reconstituted membrane-bound cytochrome b(6) contain two b hemes (alpha band, 563 nm; average E(m,7) = -61 +/- 0.84 and -171 +/- 1.27 mV).
|
Cytochromes b6
|
Triose phosphate isomerase (TIM) is responsible for the interconversion between GAP and DHAP in the glycolytic pathway. Two crystal forms belonging to space group P2(1)2(1)2(1) were obtained by the hanging-drop method and were designated A and B. Synchrotron X-ray diffraction data were collected for both forms. Form A had unit-cell parameters a = 65.14, b = 72.45, c = 93.24 A and diffracted to 2.25 A at 85 K, whereas form B had unit-cell parameters a = 73.02, b = 79.80, c = 172.85 A and diffracted to 2.85 A at room temperature. Molecular replacement was employed to solve the structures, using human TIM as a search model. Further refinement of both structures is under way and is expected to shed light on the recently reported conformational studies for rabbit TIM.
|
Triose-Phosphate Isomerase
|
BACKGROUND: The low-fluence Q-switched 1,064-nm neodymium:yttrium-aluminum-garnet laser (QSNYL) is popular for melasma treatment among Asians. OBJECTIVE: This study was to evaluate the clinical and histological effects of the low-fluence QSNYL for treatment of melasma and solar lentigenes. MATERIALS AND METHODS: In this randomized split-face clinical study, 22 patients with melasma or solar lentigo received low-fluence QSNYL weekly for 10 sessions on one cheek. The treatment efficacy was determined by Mexameter skin colorimetry, physician and patient assessment, and by evaluating histological changes. RESULTS: The treated sides had statistically significant reductions in the melanin and erythema indices (EI); 50.0% of melasma and 62.5% of solar lentigo patients had >50% clearance after the final treatment. The increased EI, vascularity, and mast cell activity in patients with melasma and large-sized solar lentigo showed no improvement. The recurrence rates were 16.7% and 12.7% for melasma and solar lentigo, respectively. Postinflammatory hyperpigmentation developed in 1 patient, but no serious side effects were noted. CONCLUSION: Low-fluence QSNYL is effective in treating melasma and small type solar lentigo in Asians. The authors' study also demonstrated that lesion thickness, vascularity, and mast cell activity can be used to predict the efficacy of the treatment of these lesions.
|
Lentigo
|
Aquatic organisms are constantly exposed to both natural and anthropogenic stressors. Under stress conditions, they elicit a cellular stress response, involving heat shock proteins (HSPs). HSPs are essential to protect proteins against aggregation and to help in the folding of native proteins or refolding of damaged ones. Because of their conservation among taxons and their inducibility after environmental/chemical stress, HSPs are commonly used as ecological and ecotoxicological biomarkers. However, the appropriate use of such molecular tools requires the investigation of the influence of biotic factors on their basal levels. As a first step in biomarker characterization, the present study aims to evaluate the impact of the reproductive cycle on the expression of the two major HSPs, Grp78 and Hsp90A in the estuarine copepod Eurytemora affinis. The constitutive expression of both genes in males was weak when compared to female levels suggesting gender-specific stress tolerance. Transcript levels gradually increased during oogenesis and maximal levels were recorded in ovigerous females. The present data support the view that the reproductive condition of individuals has to be considered as a confounding factor in stress evaluation by HSP quantification.
|
Copepoda
|
A CD8 murine monoclonal antibody-coated high-density microparticle (HDM) has been developed, which allows for the rapid depletion of CD8+ T cells from apheresis products by gravity sedimentation. We conducted a study to determine the efficacy and safety of CD8 depletion of donor lymphocyte infusions (DLI) to treat relapse after stem cell transplantation using the Eligix CD8-HDM Cell Separation System. Patients were targeted to receive 3 x 10(7) CD4+ T cells/kg. Nine patients were enrolled, three with CML, three myeloma, two CLL, and one NHL. A median of 1 x 10(10) mononuclear cells were obtained by apheresis and processed. The median depletion of CD8+ cells was 99.3% (97.8->99.5%). CD8 depletion was highly specific, with a median recovery of CD4+ cells of 75%. A median of 2.9 x 10(7) CD4+ cells/kg was infused. No infusional toxicity was noted. All CML patients achieved a complete molecular remission. A CLL patient demonstrated a complete response. One patient developed GVHD (grade II acute GVHD and subsequently chronic GVHD). The CD8-HDM Cell Separation System appears to be highly selective and effective in depleting CD8+ T cells from DLI apheresis products, and CD8-depleted DLI is capable of mediating a graft-versus-leukemia effect while minimizing GVHD.
|
Lymphocyte Depletion
|
Ameloblastoma is a locally aggressive tumor derived from odontogenic epithelium. Although benign, its clinical behavior can often exhibit malignant characteristics. It is marked by slow and persistent growth with infiltration of adjacent tissues. Almost 70% occur in the mandible in patients older than 30 years. Recurrence of ameloblastoma from inadequate treatment is frequent. Because of its slow growth, recurrences can present decades after primary surgery. A primary ameloblastoma in an area outside the mandibular, maxillary, and infratemporal fossa regions has not been described in detail to date, with only 1 possible case mentioned in the literature. The authors present a case of primary temporal bone ameloblastoma in a 17-year-old boy. The tumor originated in the left mastoid, infiltrated the lateral semicircular canal, facial nerve, and cochlea, and adhered to the sigmoid sinus and posterior cranial fossa dura. Although invasion of multiple structures in the infratemporal fossa and temporal bone leads to variable disease presentation, this case is unique because the first symptom of disease was sudden and recurring unilateral sensorineural hearing loss. Surgery required transection of the facial nerve. Histopathology confirmed primary temporal bone ameloblastoma. The difficulties in achieving wide surgical margins, diagnostics, and further management are addressed.
|
Temporal Bone
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.